Citations of BMS240INSTCE
A phase 1 multidose study of SGN-30 immunotherapy in patients with refractory or recurrent CD30+ hematologic malignancies
Bartlett,Nancy L.; Younes,Anas; Carabasi,Matthew H.; Forero,Andres; Rosenblatt,Joseph D.; Leonard,John P.; Bernstein,Steven H.; Bociek,R.Gregory; Lorenz,Jennie M.; Hart,Bruce W.; Barton,Jeremy
Blood 2008;111:1848-1854.
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Abstract
Phase 1 testing of SGN-30, a chimeric monoclonal antibody for the treatment of CD30+ malignancies, was conducted in a multicenter study. To explore the safety profile and establish the maximum tolerated dose (MTD), 24 patients with refractory or relapsed Hodgkin lymphoma or CD30+ non-Hodgkin lymphoma received 6 weekly doses of intravenous SGN-30 at 4 dose levels (2, 4, 8, or 12 mg/kg). Serum concentrations of SGN-30 rose rapidly and were dose dependent. Adverse events were mild, with nausea, fatigue, and fever attributed to study treatment. One episode of hypersensitivity rash was reported. The MTD was not reached. Serious adverse events included herpes zoster (n = 2), influenza, and pneumonia. One patient with cutaneous anaplastic large cell lymphoma (8 mg/kg) achieved a complete response. Six patients, of whom 4 had Hodgkin lymphoma, achieved stable disease with durations ranging from 6 to 16 months. The pharmacokinetic profile of SGN-30 showed a biphasic disposition, and estimated half-lives ranging between 1 to 3 weeks. The 6 weekly infusions of SGN-30 resulted in approximately 2- to 3-fold accumulation in serum exposures consistently across the dose range. These results demonstrate that weekly administration of SGN-30 is safe and has modest clinical activity in patients with CD30+ tumors. This trial is registered at http://www.ClinicalTrials.gov as no. NCT00051597
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Serologic Assessment of Type 1 and Type 2 Immunity in Healthy Japanese Adults
Birmann,Brenda M.; Mueller,Nancy; Okayama,Akihiko; Hsieh,Chung Cheng; Tachibana,Nobuyoshi; Tsubouchi,Hirohito; Lennette,Evelyne T.; Harn,Donald; Stuver,Sherri
Cancer Epidemiology Biomarkers & Prevention 2004;13:1385-1391.
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Abstract
We assessed the informativeness of several serologic biomarkers of immune function using serum specimens collected in the Miyazaki Cohort Study from subjects who were seronegative for anti-human T-cell lymphotrophic virus I and anti-hepatitis C virus. To broadly characterize type 1 immune status, we measured EBV antibody titers, because titer profiles associated with cellular immune suppression are well described. We also tested for three type 2 biomarkers: total serum IgE, soluble CD23, and soluble CD30. Nonreactivity to a tuberculin purified protein derivative (PPD) skin test is indicative of diminished delayed-type hypersensitivity (type 1) responsiveness in the study population due to a history of tuberculosis exposure or Bacillus Calmette-Guerin vaccination. We therefore evaluated the serologic markers as predictors of PPD nonreactivity using logistic regression. Subjects whose EBV antibody profiles were consistent with deficient type 1 immunity were more than thrice as likely to be PPD nonreactive as persons with "normal" antibody titers. Elevated total IgE was also strongly associated with PPD nonreactivity (odds ratio 3.4, 95% confidence interval 1.2-9.9); elevated soluble CD23 had a weaker, but positive, odds ratio, whereas soluble CD30 levels were not predictive of PPD status. Therefore, PPD nonreactivity is associated, in this population, with a pattern of serum biomarkers that is indicative of diminished type 1 and elevated type 2 immunity. We conclude that, with the exception of soluble CD30, the serologic markers are informative for the characterization of type 1/type 2 immune status using archived sera from study populations of healthy adults
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CD153 in Rheumatoid Arthritis: Detection of a Soluble Form in Serum and Synovial Fluid, and Expression by Mast Cells in the Rheumatic Synovium
CARVALHO,RICARDO F.S.; ULFGREN,ANN KRISTIN; ENGSTROM,M.A.R.I.; KLINT,ERIK af; NILSSON,G.U.N.N.
The Journal of Rheumatology 2009;36:501-507.
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Abstract
Objective.A CD30-CD153 mast cell axis has been described in skin inflammations and Hodgkin's lymphoma. We investigated if a soluble form of CD153 is present in the serum and synovial fluid (SF) of patients with rheumatoid arthritis (RA), and determined whether mast cells express CD153 in the synovium of these patients. Methods.Soluble forms of CD30 and CD153 were quantified in serum and SF of patients with RA by ELISA. Consecutive sections of synovial biopsies from 12 patients were stained against tryptase (mast-cell marker), CD30, and CD153. Results.Elevated concentrations of the soluble form of CD153 were found in serum from 14/15 RA patients. In the SF, 11/20 patients had detectable levels of soluble CD153. CD30 and CD153 were expressed in all biopsies that were studied. Mast cells were present in all the synovial biopsies, and expressed CD153 in one-third of the cases. Conclusion.We observed that CD153 was expressed in the synovium of patients with RA and we were able to correlate the serum levels of soluble CD153 with SF levels in the same patients. Because CD30 can activate mast cells to release chemokines without degranulation, our finding that mast cells express CD153 in RA synovium raises the possibility that a CD30-CD153 axis may contribute to the activation of synovial mast cells in the absence of degranulation
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SERUM LEVELS OF SCD30 AND SCD40L IN SLE PATIENTS
Ciferska,H.; Horak,P.; Hermanova,Z.; Ordeltova,J.; Zadrazil,J.
EULAR Meeting Abstracts 2006;65:195-19b.
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Abstract
Background: Background:In systemic lupus erythematodes (SLE) many abnormalities in the immune system have been reported. The interaction of the B and T- cells are required to generate effective antibody responses. The interactions are provided by various ways, some of them are by subset of cytokine mediators belonging to the tumor necrosis factor (TNF) and their receptors are involved in apoptosis. For example CD40/CD40L and CD30/CD30L are said to have major effect on communication between the B and T cells. Objectives: The aim of this study was to asses levels of soluble form of CD30 (sCD30) and soluble ligand CD40 (sCD40L) from 23 patients with SLE and 10 healthy controls and to look for potential importance of their measurement for clinical praxis. Methods: The group of patients included 9 patients with lupus nephritis and 13 without lupus nephritis. We compared the serum levels of sCD30 and sCD40L with some traditional markers of SLE like levels of anti-dsDNA, C3 and C4 component of the complement and with levels of anti-C1q antibodies, antinucleosomal antibodies. The levels of sCD30 were measured by ELISA (Bender MedSystems). The levels of sCD40L were measured by ELISA (Bender MedSystems). The levels of C3 and C4 components were measured using nephelometry (Analyzer BNII Dade Behring) with diagnostic antiserum (Orion Diagnostica Company, Espoo, Finland). Anti-dsDNA and anti-nucleosome antibodies were detected by ELISA (Orgentec Diagnostika GmbH, Mainz Germany). The producer expected normal values under 20 U/ml. The levels of anti-C1q antibodies were measured by ELISA (Buhlmann, Switzerland). Results: The levels of sCD30 in all patients with SLE were 44,24{+/-} 34,65 IU/ml, in the group with lupus nephritis 58,15 {+/-} 39,46 IU/ml and in the group without lupus nephritis 33,{+/-} 19,83 IU/ml and in healthy control 16{+/-} 8,77 IU/ml. The difference between healthy controls and whole group of patients with SLE was statistically significant (p=0.0004) and the statistic significance was also found between healthy controls and subgroup with lupus nephritis (p=0,001). The levels of sCD40L in all patients with SLE were 3,47{+/-} 1, ng/ml, in the group with lupus nephritis 3,42{+/-}1,47 ng/ml and in the group without lupus nephritis 3,58{+/-} 1,40 ng/ml, and in healthy controls it was 2,96{+/-} 1,39 ng/ml. The statistically significance wasn't found between group of healthy control and the patients with the SLE and subgroup of patients with lupus nephritis. The serum levels of sCD30 correlated significantly (p[≤]0.05) with anti-C1q antibodies (r=0,42), and C3 (r=-0,56). No significant correlation were found in the case of CD40L. Conclusion: There was found statistically significant increase in serum levels of sCD30 in SLE patients. Serum levels of sCD40L did not show statistical difference between control and SLE Supported by IGA CZ NR 8406 References: Caligaris-Cappio F, Bertero MT, Converso M, Stacchini A, Vinante F, Romagnani S, Pizzolo G.: Circulating levels of soluble CD30, a marker of cells producing Th2-type cytokines, are increased in patients with systemic lupus erythematosus and correlate with disease activity. Clin Exp Rheumatol. 1995 May-Jun;13(3):339-43 Kimura K, Tsuda H, Kwangseok Y, Tamura N, Kanai Y, Kobayashi S.: Study of plasma levels of soluble CD40 ligand in systemic lupus erythematosus patients who have undergone plasmapheresis. Ther Apher Dial. 2005 Feb;9(1):64-8
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In vivo and In vitro Studies of a Novel Cytokine, Interleukin-4delta2, in Pulmonary Tuberculosis
Dheda,Keertan; Chang,Jung Su; Breen,Ronan AM; Kim,Louise U.; Haddock,Jamanda A.; Huggett,Jim F.; Johnson,Margaret A.; Rook,Graham AW; Zumla,Alimuddin
American Journal of Respiratory and Critical Care Medicine 2005;172:200502-2278OC.
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Abstract
Rationale: Tuberculosis progresses despite potent Th1 responses. A putative explanation is the simultaneous presence of a subversive Th2 response. However interpretation is confounded by IL-4delta2 (IL-4{delta}2) a splice variant and inhibitor of IL-4. Objective: To study levels of mRNA encoding IL-4 and IL4{delta}2 and their relationship to treatment and clinical parameters, in cells from lung lavage and blood from patients with pulmonary tuberculosis. Methods: IL-4{delta}2, IFN-{gamma}, IL-4 and sCD30 levels were measured by PCR and relevant immunoassays in 29 patients and matched controls lacking responses to tuberculosis-specific antigens. Results: mRNAs for IL-4 and IL-4{delta}2 were elevated in unstimulated cells from blood and lung lavage of patients vs controls (p<0.005). In controls there were low basal levels of IL-4 and IL-4{delta}2 mRNA expressed mainly by non-T cells (p<0.05). However in patients there were greater levels of mRNA for both cytokines in both T and non-T cell populations (p<0.05 compared to controls). Radiological disease correlated with the IL-4/IFN-{gamma} ratio and sCD30 (p<0.005). After chemotherapy IL-4 mRNA levels remained unchanged whilst IL-4{delta}2 increased in parallel with IFN-{gamma} (p<0.05). Sonicates of M.tuberculosis upregulated expression of IL-4 relative to IL-4{delta}2 in mononuclear cell cultures from patients (P<0.05). Conclusions: A Th2-like response, prominent in T cells, and driven by tuberculosis antigen, is present in TB and modulated by treatment; suggesting a role for IL-4 and IL-4{delta}2 in the pathogenesis of tuberculosis and their ratio as a possible marker of disease activity. The specific antigens inducing the IL-4 response require identification to facilitate future vaccine development strategies
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Soluble CD30 serum levels in atopic dermatitis and bronchial asthma and its relationship with disease severity in pediatric age
Heshmat,Nahla M.; El Hadidi,Eman S.
Pediatric Allergy and Immunology 2006;17:297-303.
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Abstract
Heshmat NM, El-Hadidi ES. Soluble CD30 serum levels in atopic dermatitis and bronchial asthma and its relationship with disease severity in pediatric age. Pediatr Allergy Immunol 2006: 17: 297-303. c 2006 The Authors Journal compilation c 2006 Blackwell Munksgaard CD30 is a transmembrane molecule that may be expressed on a proportion of activated T-lymphocytes and has been reported to be a marker of Th2 phenotype. A soluble form of CD30 (sCD30) is released by CD30+ cells in vivo. Our objective was to evaluate serum sCD30 levels in children with atopic dermatitis (AD) or bronchial asthma and to investigate its relation to disease severity. This study included of 60 infants and children, of whom 18 had AD, 22 had bronchial asthma and 20 were healthy matched subjects. Severity of AD was assessed according to the objective Scoring Atopic Dermatitis (obj-SCORAD) index. Laboratory investigations included complete blood count, serum total immunoglobulin E (IgE) and serum sCD30 by ELISA. Serum levels of sCD30 in AD (77.7 +- 27.9 U/ml) and asthmatic patients (49.2 +- 21.5 U/ml) were significantly increased compared with the control group (18.2 +- 7.0 U/ml) (t = 8.8, p < 0.0001; t = 6.4, p < 0.0001, respectively). In patients with AD, sCD30 levels were shown to correlate with obj-SCORAD (r = 0.96, p < 0.0001). Patients with moderate persistent asthma had significantly elevated sCD30 levels than those with mild persistent asthma (t = 3.4, p < 0.01). In addition, sCD30 was inversely correlated to peak expiratory flow rate (r = -0.78, p < 0.0001). Levels of sCD30 did not correlate with age, disease duration or serum total IgE (p > 0.05). In conclusion, serum sCD30 levels correlate with the severity of AD and bronchial asthma. It appears to be an additional objective marker that may be useful for follow up and may help to improve research and management of these diseases
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Serum Concentrations of sCD30 and sCD40L in Patients with Malignant Bone Tumours
Holzer,Gerold; Pfandlsteiner,Thomas; Blahovec,Harald; Trieb,Klemens; Kotz,Rainer
Wiener Medizinische Wochenschrift 2003;153:40-42.
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Abstract
Summary: The aim of this study was to evaluate serum levels of both soluble CD30 (sCD30) and soluble CD40 ligand (sCD40L) in patients with malignant bone tumours and to determine their ability to serve as serum markers. Sera of 31 patients were taken at the time of diagnosis, analysed by ELISA, and the results were correlated with clinical features and compared with healthy controls. Soluble CD30 and sCD40L levels were significantly higher in all patient groups than in the healthy controls. Soluble CD30 levels showed statistically significant differences between high malignant osteosarcoma and Ewing sarcoma (P = 0.015), whereas no statistically significant correlation was seen between different types of tumours and sCD40L levels. Soluble CD30 and sCD40L seem to be of diagnostic value in osteosarcoma and Ewing sarcoma. (Wien. Med. Wschr., 2003; 153: 40-42) Serumkonzentrationen von sCD30 und sCD40L bei Patienten mit malignen Knochentumoren Zusammenfassung: Das Ziel dieser Arbeit war es, die Serumspiegel von solublem CD30 und solublem CD40L bei Patienten mit malignen Knochentumoren zu evaluieren und ihre Fahigkeit als Serummarker zu bestimmen. Die Seren von 31 Patienten, abgenommen zum Zeitpunkt der Diagnosestellung, wurden mittels ELISA analysiert und die Ergebnisse mit klinischen Parametern und den Serumspiegeln von Gesunden korreliert. Die Serumspiegel von sCD30 und sCD40L waren bei allen Patientengruppen gegenuber den Kontrollpersonen signifikant erhoht. Die Spiegel von sCD30 zeigten statistisch signifikante Unterschiede zwischen Patienten mit malignem Osteosarkom und Ewing-Sarkom (P = 0.015), wahrend sich keine Korrelation zwischen den unterschiedlichen Tumortypen und den sCD40L Spiegeln zeigte. Solubles CD30 und solubles CD40L scheint bei Osteosarkomen und Ewing-Sarkomen von diagnostischem Wert zu sein
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Effect of sublingual administration of interferon-[alpha] on the immune response to influenza vaccination in institutionalized elderly individuals
Launay,Odile; Grabar,Sophie; Bloch,Frédéric; Desaint,Corinne; Jegou,David; Lallemand,Christophe; Erickson,Robert; Lebon,Pierre; Tovey,Michael G.
Vaccine 2008;26:4073-4079.
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Abstract
A randomized double-blind placebo-controlled study was conducted to determine the effect of sublingual administration of IFN[alpha] on the immune response to influenza vaccination in elderly institutionalized individuals. Sublingual administration of 10 million IU of IFN[alpha] immediately prior to vaccination, reduced the geometric mean haemagglutination inhibitory (HAI) and IgG2 circulating antibody titers, and the secretory IgA (sIgA) response in saliva, to the New York strain of influenza A virus, 21 days post-vaccination, without detectable drug-related local or systemic toxicity. IFN treatment did not inhibit the immune response to the other components of the vaccine; the New Caledonia strain of influenza A virus, or the Jiangsu strain of influenza B virus. At the dose tested sublingual administration of IFN[alpha] reduces the immune response to influenza vaccination in elderly institutionalized individuals.
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Hepatitis C virus genotype and HIV coinfection affect cytokine mRNA levels in unstimulated PBMC but do not shift the T1/T2 balance
LEE,S.I.L.V.; WATSON,MARK W.; CLARK,B.E.N.; FLEXMAN,JAMES P.; CHENG,W.E.N.D.; FRENCH,MARTYN AH; PRICE,P.A.T.R.
Immunology and Cell Biology 2006;84:390-395.
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Abstract
Summary Rapid progression of hepatitis C virus (HCV) disease in patients with HIV/HCV may reflect different cytokine responses and be influenced by HCV genotype. This is addressed by a study of patients with HIV/HCV coinfection and infection with HCV genotype 2 or 3 (2/3). They are compared with coinfected patients infected with genotype 1 and HCV monoinfected patients matched for HCV genotype. IFN-gamma, IL-10, IL-4 and IL-4delta2 mRNA were quantified by real-time PCR in unstimulated PBMC and after in vitro stimulation with HCV core or nonstructural 3/4A antigen. In unstimulated PBMC, levels of IFN-gamma and IL-4 mRNA were lowest in HIV/HCV genotype 1 patients, intermediate in HIV/HCV genotype 2/3 patients and highest in HCV genotype 2/3 patients. Neither HCV genotype nor HIV affected levels of IL-10 mRNA in unstimulated PBMC or IFN-gamma, IL-4 and IL-10 mRNA in PBMC stimulated with HCV antigens. Levels of IL-4 and IL-4delta2 mRNA correlated in mitogen-stimulated PBMC from all patient groups but both were low in HIV/HCV genotype 1 patients. Serum soluble CD30 levels (a putative marker of a T2 cytokine environment) did not differ between patient groups. The data do not suggest a shift in the T1/T2 balance driven by HIV coinfection or HCV genotype but either may affect IL-4 bioavailability
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Immunological markers predicting outcome in patients with hepatitis C treated with interferon-alpha and ribavirin
Lee,Silvia; Macquillan,Gerry C.; Keane,Niamh M.; Flexman,James; Jeffrey,Gary P.; FRENCH,MARTYN AH; Brochier,Jean; Price,Patricia
Immunology and Cell Biology 2002;80:391-397.
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Abstract
Summary Type 1 (T1) cytokine responses are required for the clearance of hepatitis C virus by cytotoxic T lymphocytes, but can promote liver damage. Interferon-alpha (IFNalpha) can be expected to promote T1 cytokine responses, so treatment outcome may depend on the T1/T2 cytokine environment and levels of immune activation at baseline. This model was tested by monitoring immunological markers in a pilot study of treatment naive patients given IFNalpha2b and ribavirin, with the aim of finding markers that predict virological outcome. Soluble (s) CD26/dipeptidyl peptidase IV enzyme activity and levels of sCD30, bioavailable IL-6, sTNF-RI, IL-1ra and nitrite/nitrate (NO2-/NO3-) were measured. Levels of IL-1ra and bioavailable IL-6 were lower in patients than controls and did not change with therapy. Treatment decreased sCD26/dipeptidyl peptidase IV enzyme activities and sCD30 levels and increased NO2-/NO3- levels. High baseline sCD30 levels predicted an early (P = 0.008) and sustained (P = 0.03) virological response to therapy, suggesting treatment may be more effective in patients with a predominant T2 profile
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Association Between Serum Soluble CD30 and Serum Creatinine Before and After Renal Transplantation
Lopez-Hoyos,M.; San Segundo,D.; Benito,M.J.; Fernandez-Fresnedo,G.; Ruiz,J.C.; Rodrigo,E.; Gomez-Alamillo,C.; Benito,A.; Arias,M.
Transplantation Proceedings 2008;40:2903-2905.
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Abstract
AbstractObjectiveThere is increasing evidence that circulating levels of soluble CD30 (sCD30) may represent a biomarker for outcome in kidney transplantation. The aim of this study was to measure the pre- and posttransplantation serum levels of sCD30 in cadaveric kidney transplant recipients and correlate them with serum creatinine.Patients and MethodsSerum sCD30 was measured by a commercial enzyme-linked immunosorbent assay (ELISA) from prospective samples of 38 kidney allograft recipients serially transplanted at our center. Samples were collected at day 0 pretransplantation and at months 6, 12, 18, and 24 posttransplantation. We also studied sera from 29 patients with chronic kidney disease (CKD) at different stages of the K/DOQI guidelines, as a control group.ResultsSerum levels of sCD30 decreased significantly in samples posttransplantation compared with pretransplantation. The significant decrease after transplantation may be related to the improvement in renal function since we observed a significant correlation between serum levels of sCD30 and creatinine (sCr) at all times of the study. In addition, the patients with chronic renal failure showed a significant association between serum sCD30 and sCr (r = .454; P = .013).ConclusionsOur results did not suggest that the measurement of sCD30 may be used as a valuable biomarker in renal transplantation. Increased levels may be related to a decrease in its renal elimination.
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Pre-transplant level of soluble CD30 is associated with infection after heart transplantation
Nikaein,Afzal; Spiridon,Camelia; Hunt,Judson; Rosenthal,Jed; Anderson,Allan; Eichhorn,Erick; Magee,Mitchell; Dewey,Todd; Mack,Michael
Clinical Transplantation 2007;21:744-747.
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Abstract
Nikaein A, Spiridon C, Hunt J, Rosenthal J, Anderson A, Eichhorn E, Magee M, Dewey T, Mack M. Pre-transplant level of soluble CD30 is associated with infection after heart transplantation. Clin Transplant 2007 DOI: 10.1111/j.1399-0012.2007.00732.x c Blackwell Munksgaard, 2007 Abstract: Background: One immunologic element of the immune system is the CD30 molecule which belongs to the TNF-R superfamily. CD30 can serve as a T-cell signal transducing molecule and is expressed by a subset of activated T lymphocytes, CD45RO+ memory T cells. Augmentation of soluble CD30 during kidney transplant (Tx) rejection has been reported. Our study was to determine if the level of sCD30 prior to heart transplant (HTx) could categorize the patients (pts) into high or low immunologic risk for post-Tx outcome. Methods: Pre-Tx sera from 100 consecutive HTx recipients were studied. sCD30 was detected by ELISA using the commercially available CD30 monoclonal antibody. Level of sCD30 was correlated with two-yr Tx outcome. Results: Significant correlation was seen between the high level of sCD30 and lower incidence of infection. Four of the 35 pts with pre-Tx high level of sCD30 level (>90 U/mL) developed infection post-Tx. However, 31/65 pts who had a low level of sCD30 (<90 U/mL) developed infection post-transplantation (p < 0.0003). No remarkable differences were noted with the other clinical parameters, including mean hospitalization, 3A biopsy rejection or death. Conclusions: We report for the first time that the high level of sCD30 prior to the HTx may be associated with a higher immunologic ability of the pts and therefore, may have a protective effect in the development of infection post-Tx
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Fludarabine induces apoptosis of human T-cell leukemia virus type 1-infected T cells via inhibition of the nuclear factor-[kappa]B signal pathway
Nishioka,C.; Ikezoe,T.; Yang,J.; Koeffler,H.; Taguchi,H.
Leukemia 2007;21:1044-1049.
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Abstract
Adult T-cell leukemia/lymphoma (ATL) is a highly aggressive disease in which the human T-cell lymphotropic virus type I (HTLV-I) has been recognized as the etiologic agent. Fludarabine is a purine analog that has demonstrated significant activity in B-cell malignancies, including chronic lymphocytic leukemia and indolent non-Hodgkin's lymphoma. This study explored the effects of fludarabine on HTLV-1-infected T cells (MT-1, -2, -4 and HUT102). Fludarabine induced growth arrest and apoptosis of these cells, as measured by 3-(4,5-dimethylithiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, cell cycle analysis and annexin V staining. Moreover, exposure of HTLV-1-infected T cells to fludarabine decreased the levels of X-inhibitor of apoptosis protein in conjunction with inhibition of nuclear factor B (NF-B)/DNA-binding activity, as measured by Western blot analysis and electrophoretic mobility shift and reporter gene assays, respectively. Further studies found that fludarabine accumulated NF-B and inhibitory subunit of NF-B in cytosole in conjunction with downregulation of NF-B in nucleus, suggesting that fludarabine blocked nuclear translocation of NF-B. Taken together, fludarabine may be useful for treatment of individuals with ATL and other types of cancer in which NF-B plays a role.
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Pregnancy in patients with rheumatic disease: anti-inflammatory cytokines increase in pregnancy and decrease post partum
Ostensen,M.; Forger,F.; Nelson,J.L.; Schuhmacher,A.; Hebisch,G.; Villiger,P.M.
Annals of the Rheumatic Diseases 2005;64:839-844.
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Abstract
Objective: To investigate changes in the levels of circulating cytokines with a focus on the Th1/Th2 balance during and after pregnancy in patients with rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), and ankylosing spondylitis (AS). Methods: Plasma and serum samples of 34 pregnant patients, 19 with RA, 6 with JIA, and 9 with AS, and of 30 healthy pregnant women, 20 non-pregnant patients, and 10 non-pregnant healthy women were analysed for levels of interferon {gamma} (IFN{gamma}), interleukin (IL) 1{beta}, IL10, IL1 receptor antagonist (IL1Ra), soluble tumour necrosis factor receptor (sTNFR), and soluble CD30 (sCD30) by ELISA. Clinical assessment and blood sampling in pregnant women was done once in each trimester and 6, 12, and 24 weeks post partum. Disease activity in the patients was evaluated by validated clinical instruments and correlated with circulating levels of cytokines. Results: Low levels of IL10 were found sporadically, whereas IFN{gamma} and IL1{beta} were below detection level in the samples tested. Significantly higher concentrations of sTNFR and IL1Ra were measured in pregnant than in non-pregnant subjects. An increase of IL1Ra from the second to the third trimester correlated with improvement of disease activity in patients with RA and AS. Compared with non-pregnant patients and the other pregnant women, patients with RA showed markedly raised levels of sCD30 during pregnancy. Conclusions: IFN{gamma} and IL10, markers of a Th1 and Th2 response, respectively, were either low or undetectable in the cohorts analysed. The increase of cytokine inhibitors IL1Ra and sTNFR was related to pregnancy and was independent of an underlying disease. These anti-inflammatory mediators seem to affect disease activity
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Evaluation of posttransplantation soluble CD30 for diagnosis of acute renal allograft rejection
Pelzl S,Opelz G,Daniel V,Wiesel M,Süsal C.
Transplantation 2003;75:421-423.
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Abstract
BACKGROUND: Posttransplantation measurement of soluble CD30 (sCD30) may be useful for identifying kidney graft recipients at risk of impending graft rejection in the early posttransplantation period. METHODS: We measured plasma sCD30 levels and evaluated the levels in relation to the diagnosis of rejection. RESULTS: Receiver operating characteristic curves demonstrated that on posttransplantation days 3 to 5, sCD30 allowed a differentiation of recipients who subsequently developed acute allograft rejection (n=25) from recipients with an uncomplicated course (n=20, P<0.0001) (area under the receiver operating characteristic curve 0.96, specificity 100%, sensitivity 88%) and recipients with acute tubular necrosis in the absence of rejection (n=11, P=0.001) (area under the receiver operating characteristic curve 0.85, specificity 91%, sensitivity 72%). CONCLUSIONS: sCD30 measured on posttransplantation days 3 to 5 offers a noninvasive means for differentiating patients with impending acute allograft rejection from patients with an uncomplicated course or with acute tubular necrosis.
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Soluble CD30 as a predictor of kidney graft outcome
Pelzl S,Opelz G,Wiesel M,Schnülle P,Schönemann C,Döhler B,Süsal C.
Transplantation 2002;73:3-6.
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Abstract
BACKGROUND: In the present study, we investigated whether the soluble form of CD30 (sCD30), a marker for T helper 2-type cytokine-producing T cells, is increased in sera of potential kidney graft recipients. We also investigated whether the pretransplantation serum sCD30 content is related to kidney graft survival. METHODS: Pretransplantation sera of 844 cadaver kidney recipients from three transplant centers in Germany were tested for serum sCD30 content using a commercially available ELISA kit. RESULTS: Kidney graft recipients showed a significantly higher serum sCD30 content than healthy controls (P<0.0001). High sCD30 serum content was associated with graft rejection. The 2-year graft survival rate in recipients with a high pretransplantation serum sCD30 was 68+/-6%, significantly lower than the 86+/-1% rate in recipients with a low sCD30 (P<0.0001). Importantly, high sCD30 was indicative of an increased risk of graft loss even in recipients without lymphocytotoxic alloantibodies. CONCLUSION: These data show that an elevated pretransplantation serum sCD30 reflects an immune state that is detrimental for kidney graft survival.
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CD30L up-regulates CD30 and IL-4 expression by T cells
Rossi,F.M.; Degan,M.; Mazzocut-Zecchin,L.; Di Francia,R.; Aldinucci,D.; Pinto,A.; Gattei,V.
FEBS Letters 2001;508:418-422.
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Abstract
CD30L is frequently expressed on acute myeloid leukemia (AML) blasts. Its presence is associated with the co-expression of interleukin-4 (IL-4) receptor and with the expansion of specific T-helper 2 (Th2) cell subsets producing IL-4 and expressing CD30. Recombinant CD30L-bearing cells up-regulated the expression of surface CD30 and increased the production of IL-4 and soluble (s) CD30 by co-cultured T cells. These findings were confirmed with AML blasts expressing surface CD30L, where blocking anti-CD30 antibodies completely abolished the release of sCD30 and reduced the production of IL-4. Our data indicates a direct role of CD30L+ neoplastic cells in driving the immune response toward a Th2-polarized non-protective state.
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Plasma levels of soluble interleukin 2 receptor, soluble CD30, interleukin 10 and B cell activator of the tumour necrosis factor family during follow-up in vasculitis associated with proteinase 3-antineutrophil cytoplasmic antibodies: associations with disease activity and relapse
Sanders,J.-S.F.; Huitma,M.G.; Kallenberg,C.G.M.; Stegeman,C.A.
Annals of the Rheumatic Diseases 2006;65:1484-1489.
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Abstract
Objectives: To evaluate whether T cell activation, as reflected by levels of soluble interleukin 2 receptor (sIL2R), soluble CD30 (sCD30), IL-10 and B cell activator of the tumour necrosis factor family (BAFF) at diagnosis and during initial follow-up, is predictive for persistent or renewed antineutrophil cytoplasmic antibody (ANCA) positivity and clinical relapse in patients with vasculitis associated with proteinase 3-antineutrophil cytoplasmic antibodies (PR3-ANCA). Methods: 87 Patients with PR3-ANCA-associated vasculitis and at least 2 years of follow-up were included in the study. At diagnosis, and at 3, 6, 12, 18 and 24 months after diagnosis, cytoplasmic ANCA titres were detected by indirect immunofluorescence (IIF), and PR3-ANCA, sIL2R, sCD30, IL-10 and BAFF levels were assessed by ELISA. 31 healthy volunteers provided plasma samples for comparison. Levels of immune markers were related to ANCA positivity and relapse during follow-up. Results: Plasma levels of sIL2R, sCD30 and BAFF were higher in patients than in controls at all time points. Plasma levels of sIL2R, sCD30 and IL-10 were higher at diagnosis and relapse than during remission. At 18 months, sCD30 (p<0.001) and sIL2R levels (p = 0.01) were significantly higher in PR3-ANCA-positive patients (detected by ELISA) than in PR3-ANCA-negative patients. ANCA-positive patients detected by ELISA or IIF at 24 months had significantly higher plasma sCD30 levels (p = 0.02 and p = 0.03, respectively) than ANCA-negative patients. Conclusion: Increased T cell activation in patients with ANCA-associated vasculitis in remission during and after immunosuppressive treatment is associated with persistent or renewed ANCA positivity
754
Strong human leukocyte antigen matching effect in nonsensitized kidney recipients with high pretransplant soluble CD30
Süsal C,Pelzl S,Opelz G
Transplantation. 2003;76:1231-1232.
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Abstract
The influence of human leukocyte antigen (HLA) matching on graft survival is greater in patients with preformed lymphocytotoxic antibodies than in nonsensitized patients. Pretransplant serum soluble CD30 (sCD30) affects graft outcome independently of presensitization status. The impact of HLA compatibility on kidney transplant survival was analyzed in 3980 nonsensitized first cadaveric kidney recipients in relation to the pretransplant serum sCD30 content. Although HLA compatibility influenced graft outcome only marginally in nonsensitized recipients with low sCD30 (at 3 years: P=0.0095; at 5 years: P=0.1033), a strong HLA matching effect was observed in nonsensitized recipients with high sCD30 (at 3 years: P<0.0001; at 5 years: P=0.0001). Nonsensitized patients with high pretransplant sCD30 benefit from an HLA well-matched kidney. Patients should be tested for sCD30 while on the waiting list for a kidney transplant, and HLA well-matched kidneys should be allocated to patients with high sCD30.
1303
Identification of Highly Responsive Kidney Transplant Recipients Using Pretransplant Soluble CD30
Süsal,Caner; Pelzl,Steffen; Dohler,Bernd; Opelz,Gerhard
Journal of the American Society of Nephrology 2002;13:1650-1656.
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Abstract
The identification of high immunologic responders is desirable for the selection of appropriate immunosuppressive regimens. With the collaboration of 29 transplant centers in 15 countries, we investigated whether the pretransplant serum content of soluble CD30 (sCD30), a marker for the activation state of Th2-type cytokine producing T cells, is a useful predictor of kidney graft outcome. Pretransplant sera of 3899 cadaver kidney recipients were tested for serum sCD30 concentration using a commercially available enzyme-linked immunosorbent assay kit. Subsequent kidney graft survival was analyzed. The 5-yr graft survival rate in 901 recipients with a high pretransplant serum sCD30 ([>=]100 U/ml) was 64 {+/-} 2%, significantly lower than the 75 {+/-} 1% rate in 2998 recipients with low sCD30 (<100 U/ml) (P < 0.0001). High sCD30 was associated primarily with graft loss and not with patient death. The sCD30 effect on graft survival was evident in first transplants as well as in retransplants, in presensitized patients with lymphocytotoxic antibodies as well as in nonsensitized patients, and in patients who received HLA well-matched kidneys as well as in patients who received poorly matched grafts. Recipients with a high pretransplant sCD30 needed significantly more rejection treatment after the first posttransplant year and continued to lose grafts at a higher rate during the 5-yr follow-up period, indicating that pretransplant sCD30 predicts not only the risk of acute rejection but also of chronic allograft nephropathy.
124
Elevated pretransplantation soluble CD30 is associated with decreased early allograft function after human lung..
Shah,A.S.; Leffell,M.S.; Lucas,D.; Zachary,A.A.
Human Immunology 2009;70:101-103.
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Abstract
Early allograft function after lung transplantation is variable. Clinical criteria have limited predictive value for early graft function. Recipient immunologic state before LTx may affect early lung function. We investigated the association between pretransplantation soluble CD30 (sCD30), a marker of Th2-type T-cell activation, and early clinical parameters of allograft function. Between September 2002 and January 2007, a total of 80 transplantations were performed at Johns Hopkins Hospital. Of the patients, 43 had a pretransplantation sCD30 level determined. Pre- and postoperative patient variables were collected, and patients were stratified into two groups: sCD30 <20 (low sCD30) and >20 (high sCD30). High sCD30 (n = 26) and low sCD30 (n = 17) groups were similar in age, gender, and ischemia time. In the high sCD30 group, a higher percentage of patients had pulmonary fibrosis and a lower percentage had emphysema. Oxygenation at 48 hours was significantly worse in the high sCD30 group as compared with the low sCD30 (p = 0.003). Moreover, prolonged intubation and 90-day mortality were greater in the high sCD30 group. This represents the first report of the use of sCD30 as a marker for early allograft function in human lung transplanation. Increased pretransplantation recipient sCD30 appears to be associated with decreased early post-transplantation gas exchange, prolonged intubation, and early mortality.
2701
Soluble CD30 concentrations in ESRD patients with and without panel reactive HLA antibodies
Vaidya,Smita; Partlow,David; Barnes,Titus; Thomas,Phillip; Gugliuzza,Kristin
Clinical Transplantation 2006;20:461-464.
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Abstract
Vaidya S, Partlow D, Barnes T, Thomas P, Gugliuzza K. Soluble CD30 concentrations in ESRD patients with and without panel reactive HLA antibodies. Clin Transplant 2006: 20: 461-464. c Blackwell Munksgaard, 2006 Background: In this retrospective study we compared accuracy of panel reactive antibodies (PRA) with serum soluble CD30 (sCD30) contents in predicting acute rejection crisis post-renal transplant. Methods: Pre-transplant sera from 115 patients were evaluated for their PRA and sCD30 concentrations. All patients received calcineurin inhibitor-based immunosuppressive therapy. Objective measurements for rejection were biopsy-proven acute rejection (AR) episodes within first six months of the transplant. Post-transplant sera of patients with AR were tested for the presence of donor-specific HLA antibodies (DSA). Results: Overall AR rate was 16% (18/115). Patients positive for PRA and sCD30 tests were at significantly higher risk for AVR compared with those patients negative for both the tests (36% vs. 5%, p = 0.01). Among negative PRA patients risk for AR was significantly elevated if they were also tested positive for sCD30 concentrations (21% vs. 5%, p = 0.04). Of the 18 patients with AR, 14 were positive for sCD30, and 13 of them (93%) developed DSA post-transplant (p = 0.001). Conclusion: These data showed that patients positive for sCD30 contents are at high risk for the development of DSA and AR post-transplant regardless of their pre-transplant PRA
572
Soluble CD30 is a predictor of Bronchiolitis Obliterans Syndrome after lung transplantation
Van de Graaf,E.A.; Bauwens,A.A.; Van Kessel,D.A.; Van Ginkel,W.G.J.; Otten,H.G.
Journal of Heart and Lung Transplantation 2006;25:84-84.
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Abstract
In kidney transplantation circulating levels of soluble CD30 (sCD30) are an indicator for graft outcome (J Am Soc Nephrol 2002;13:1650). In this study we investigated the value of sCD30 in predicting the bronchiolitis syndrome (BOS) after lungtransplantation...
1105
Both Th1- and Th2-derived cytokines in serum are elevated in Graves' ophthalmopathy
Wakelkamp,I.M.M.J.; Gerding,M.N.; Van Der Meer,J.W.C.; Prummel,M.F.; Wiersinga,W.M.
Clinical and Experimental Immunology 2000;121:453-457.
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Abstract
Increased serum cytokine levels have been reported in patients with autoimmune thyroid disease, but less is known about their levels in patients with Graves' ophthalmopathy (GO). It is not known whether GO is a cell-mediated or humoral autoimmune disease. We investigated whether serum cytokines are elevated in GO patients and whether the cytokines were Th1- or Th2-derived. In addition, elevated cytokines might reflect the activity of GO, and thus we investigated whether cytokine levels could predict the clinical response to orbital radiotherapy. We studied 62 consecutive patients with moderately severe untreated GO and 62 healthy controls, matched for sex, age and smoking habits. Serum concentrations of IL-1RA, sIL-2R, IL-6, sIL-6R, tumour necrosis factor-alpha (TNF-alpha) RI and II and sCD30 were measured using highly sensitive ELISAs, in the patients before and 3 and 6 months after radiotherapy. All patients were euthyroid, with anti-thyroid drugs, before and during the entire study period. All baseline cytokine and cytokine receptor levels were significantly elevated in GO patients compared with healthy controls, except for IL-1RA. The levels did not correlate with parameters of the thyroid disease, nor with the duration, activity or severity of GO. However, backward logistic regression analysis showed that IL-6, sCD30 and TNFalphaRI were able to predict a beneficial response to orbital radiotherapy. We therefore conclude that both Th1- and Th2-derived cytokines are elevated in GO patients compared with its controls. IL-6, sCD30 and TNFalphaRI had some value for predicting therapeutic outcome to orbital irradiation, and may thus reflect active eye disease
580
Pre- and post-transplant monitoring of soluble CD30 levels as predictor of acute renal allograft rejection
Wang,D.; Wu,G.J.; Wu,W.Z.; Yang,S.L.; Chen,J.H.; Wang,H.; Lin,W.H.; Wang,Q.H.; Zeng,Z.X.; Tan,J.M.
Transplant Immunology 2007;17:278-282.
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Abstract
Identification of renal graft candidates at high risk of impending acute rejection (AR) and graft loss may be helpful for patient-tailored immunosuppressive regimens and renal graft survival. To investigate the feasibility with soluble CD30 (sCD30) as predictor of AR, sCD30 levels of 70 patients were detected on day 0 pre-transplant and day 1, 3, 5, 7, 10, 14, 21, and 30 post-transplant. AR episodes in 6 months were recorded and then patients were divided into Group AR (n = 11) and Group UC (n = 59). Results showed that the patients had higher pre-transplant sCD30 levels than healthy people. A significant decrease of sCD30 was observed on the first day post-transplant and continued until day 14 post-transplant. Soluble CD30 presented a stable level from day 14 to 30 post-transplant. Pre-transplant sCD30 levels of Group AR were much higher than those of Group UC (P < 0.001). Patients of Group AR also had higher sCD30 levels than those of Group UC on day 1, 3, 5, 7, 10 and 14 (P < 0.001). The sCD30 level presented a significantly delayed decrease in the patients of Group AR. Statistical results showed that the highest value of area under ROC curve (0.95) was obtained on day 5 post-transplant, suggesting that sCD30 levels on day 5 are of high predictive value. Therefore, sCD30 level may be a good marker of increased alloreactivity and of significant predictive value. It's necessary to monitor the variation of sCD30 in the early period post-transplant.
1112
Post-Transplant sCD30 and Neopterin as Predictors of Chronic Allograft Nephropathy: Impact of Different Immunosuppressive Regimens
Weimer,R.; Susal,C.; Yildiz,S.; Staak,A.; Pelzl,S.; Renner,F.; Dietrich,H.; Daniel,V.; Kamali-Ernst,S.; Ernst,W.; Padberg,W.; Opelz,G.
American Journal of Transplantation 2006;6:1865-1874.
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Abstract
Immunological monitoring for chronic allograft nephropathy (CAN) is of great potential interest. We assessed serum soluble CD30 (sCD30) together with in vitro Th2-type responses (IL-4, IL-10, CD4 helper activity) and neopterin in a prospective study of 84 renal transplant recipients with 2-year follow-up. Patients were randomized to CsA/Aza, CsA/MMF and Tacr/Aza, respectively, to analyze the effect of immunosuppression on posttransplant sCD30 and neopterin. ATG induction and acute rejections did not alter sCD30 levels whereas CMV disease was associated with transient upregulation of sCD30 (p = 0.003 at 4 months) and sustained upregulation of neopterin (corrected for graft function (Neo/CR) p = 0.005 at 2 years). Tacr versus CsA treatment proved to be an independent variable associated with downregulation of 1-year sCD30, which was positively related to Neo/CR (p = 0.007 and 0.01, respectively; logistic regression). Importantly, increased 1-year sCD30 and Neo/CR were associated with decreased glomerular filtration rate at 2 years (p = 0.02 and p < 0.0005, respectively) and evidence of CAN (p < 0.0005). High 1-year sCD30 could not be attributed to enhanced Th2-type responses and was not associated with HLA antibody formation. Our data suggest that elevated sCD30 and neopterin predict graft deterioration by CAN. Tacr effectively downregulates these responses and might be of advantage in patients with elevated sCD30 or neopterin
1441
sCD30 and Neopterin as Risk Factors of Chronic Renal Transplant Rejection: Impact of Cyclosporine A, Tacrolimus, and..
Weimer,R.; Susal,C.; Yildiz,S.; Streller,S.; Pelzl,S.; Staak,A.; Renner,F.; Dietrich,H.; Daniel,V.; Feuring,E.
Transplantation Proceedings 2005;37:1776-1778.
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Abstract
High pretransplantation sCD30 levels have been shown to be associated with lower 5-year kidney graft survival in mainly Cyclosporine A (CsA)-treated recipients (Collaborative Transplant Study database). To analyze the effect of different immunosupressive regimens (CsA/Azathioprine [Aza], CsA/Mycophenolate Mofetil [MMF], Tacrolimus [Tacr]/Aza) on sCD30, we assessed serum sCD30 and neopterin together with in vitro cytokine responses in a prospective randomized study of 84 renal transplant recipients before, 4 months, and 1 year after transplantation. Panel-reactive antibody (PRA) formation, HLA matching, ATG induction therapy, and acute rejections had no impact on sCD30 levels, whereas cytomegalovirus (CMV) infections induced an up-regulation of sCD30 4 months posttransplantation (P = .003). Whereas MMF showed no effect on sCD30 compared with Aza therapy, we found a significant impact of Tacr versus CsA treatment (1-year sCD30 =60 U/mL: 14/42 (33%), CsA; 1/38 (3%), Tacr; P < .0005). Chronic rejection 2 years posttransplantation was associated with elevated 1-year sCD30 (P = .001) and neopterin levels (P = .006). Our data indicate that the Th2 activation marker sCD30 provides a risk factor for chronic rejection independent of classical immunological risk factors and may be down-regulated using Tacr treatment.
1118
ATG induction therapy: long-term effects on Th1 but not on Th2 responses
Weimer,Rolf; Staak,Anne; Susal,Caner; Streller,Sabine; Yildiz,Sevgi; Pelzl,Steffen; Renner,Fabrice; Dietrich,Hartmut; Daniel,Volker; Rainer,Lucy; Kamali-Ernst,Shirin; Ernst,Wolfgang; Padberg,Winfried; Opelz,Gerhard
Transplant International 2005;18:226-236.
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Abstract
Antithymocyte globulin (ATG) induction therapy is associated with an increased long-term risk of infection- and cancer-related death. To analyze long-term effects of ATG induction on lymphocyte function, we prospectively assessed CD4 helper function, B-cell/monocyte and cytokine responses in 84 renal transplant recipients (ATG, n = 44) up to 1 year post-transplant. A PWM-driven allogeneic coculture system was used to assess helper function of CD4+ T cells and T-cell-dependent B-cell responses. SAC I was used for T-cell-independent stimulation of B-cell cultures. In vitro cytokine secretion and serum soluble CD30 (sCD30) were determined by enzyme-linked immunosorbent assay (ELISA). ATG induced a persistent decrease of peripheral blood lymphocyte counts compared with non-ATG treatment because of a predominant decrease of CD4+ T cells (4 months, 1 year; P < 0.0005) which was associated with a decreased CD28 expression (1 year, P = 0.02) and CD4 cell interleukin 2 (IL-2) response (4 months, P < 0.0005). However, Th2 responses (CD4 help, CD4 cell IL-4 and IL-10 responses, sCD30), which proved to be predictive of graft outcome, were not affected, and neither was the secretion of the lymphoma growth factors IL-6 and IL-10 by B cells and monocytes. Our data show that ATG induction therapy in immunological high-risk patients induces a profound long-term decrease in cell counts and Th1 but not Th2 responses of CD4+ T cells which may explain long-term effects on infection and post-transplant lymphoproliferative disease (PTLD) incidence because of inadequate T-cell control
114
Serum levels of the homeostatic B cell chemokine, CXCL13, are elevated during HIV infection
Widney DP,Breen EC,Boscardin WJ,Kitchen SG,Alcantar JM,Smith JB,Zack JA,Detels R,Martínez-Maza O.
J Interferon Cytokine Res. 2005;25:702-706.
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Abstract
HIV infection is associated with B cell dysfunction, which includes B cell hyperactivation, hypergammaglobulinemia, impaired production of antibodies against specific antigens, and a loss of B cell memory. Because lymph node architecture is progressively destroyed during HIV infection, it is possible that normal B cell trafficking is impaired as well, which could be a cause or a result of these abnormalities. Because the homeostatic chemokine, CXCL13 (BLC, BCA-1), is a major regulator of B cell trafficking, we assessed circulating levels of this molecule in HIV infection. Serum levels of CXCL13 were seen to be progressively elevated in HIV disease. Serum levels of CXCL13 correlated strongly with those of the inflammation-associated chemokine, inducible protein-10 (IP-10), in subjects who had advanced HIV disease, and more moderately with levels of soluble CD30 (sCD30), sCD27, and sCD23. CXCL13 levels also correlated moderately with viral load and showed a significant decline after use of highly active antiretroviral treatment (HAART). Elevated levels of CXCL13 could cause impaired or altered trafficking of B cells during HIV infection and could contribute to the previously reported loss of CXCR5, the receptor for CXCL13, from the surface of circulating B cells in HIV infection.
1304
