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Annals of the Rheumatic Diseases 02/2002; 61(1):91-2. · 8.73 Impact Factor
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ABSTRACT: Tumor necrosis factor alpha (TNFalpha) has been described as a citokine involved in gastrointestinal mucosal inflammation in Crohn's disease. A single infusion of the chimeric mouse/human monoclonal antibody cA2 anti-TNFalpha has been established as a new therapeutical procedure. The aim of these study was to determine the effect of the monoclonal antibody cA2 on lymphocyte and monocyte TNFalpha-producing cells. Initially the patient, with severe Crohn's disease (Crohn's disease activity index CDAI > 350), presented a higher number of peripheral blood TNFalpha-producing cells than healthy controls. The patient received two cA2 treatments throughout one year due the severe activity of the disease. Before treatment the patient had a large number of TNFalpha producer cells. A dramatic reduction in lymphocyte and monocyte TNFalpha producing cells, together a clinical remission (CDAI < 150), was shown after the treatments. Four months after the first cA2 treatment, the patient had a clinical response associated with an important increment of TNFalpha-producing cells that extended increasing until the second cA2 treatment was averaged. These results suggest that the clinical activity of the Crohn's disease correlates with peripheral TNFalpha-expressing cells. The cA2 antibody, as well as of neutralize soluble TNFalpha, also removes TNFalpha-producer cells, which may collaborate with the anti-TNFalpha activity of the antibody treatment.
Human antibodies 02/2001; 10(2):91-4.
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Transplantation Proceedings 01/1999; 30(8):4177-9. · 1.00 Impact Factor
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Transplantation Proceedings 01/1999; 30(8):3952-4. · 1.00 Impact Factor
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Clinical Chemistry 06/1997; 43(5):848-9. · 7.91 Impact Factor
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ABSTRACT: Hepatitis B vaccine is effective in producing protection against hepatitis B virus (HBV) infection in hemodialysis (HD) patients, but the antibody response is variable. To identify those factors implicated in the vaccine response, in a prospective study over a 24-month period, we vaccinated 80 seronegative patients on HD (group A) and monitored clinical, biochemical, and immunologic parameters. The protective immunity acquired by vaccination was compared with that developed through HBV infection in 22 age-matched HD patients (group B). The anti-HBs antibody-seronegative patients followed a four-dose vaccination schedule (0, 1, 2, and 6 months) with 40 microg DNA-recombinant hepatitis B vaccine. One month after vaccination, 77.5% of the patients had seroconverted, and 72.5% achieved high antibody response, whereas 22.5% were nonresponders. Patients aged younger than 40 years seroconverted 100%; those aged 40 to 60 years, 75% (P < 0.01); and patients older than 60 years, 74% (P < 0.001). No differences between responders and nonresponders concerning sex, time on HD, HD dose, nutritional status, hemoglobin level, HD membrane, iPTH level, calcitriol treatment, or number of transfusions during vaccination were found. The presence of other factors, such as recombinant human erythropoietin (rHuEPO) therapy or hepatitis C virus (HCV) infection, did not significantly influence antibody responses to hepatitis B immunization. A greater frequency of DR3 (53.8% v 25.7%, P < 0.05), DR7 (53.8% v 18.6%, P < 0.01), and DQ2 (76.9% v 44.1%, P < 0.05), and a lesser frequency of A2 (7.7% v 37.2%, P < 0.05) were found in nonresponders compared with responders. Eighteen months after vaccination, the analysis showed similar antibody titers but lower seroconversion rates in group A as compared with group B. In conclusion, unresponsiveness to hepatitis B vaccine in HD patients was related to factors such as older age, the presence of DR3, DR7, and DQ2, and the absence of A2 alleles. Although the seroprotection produced by the vaccine was less than that achieved through natural HBV infection, our protocol of vaccination was sufficiently immunogenic and provided lasting protection.
American Journal of Kidney Diseases 03/1997; 29(2):239-45. · 5.43 Impact Factor
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New England Journal of Medicine 09/1996; 335(7):523-4. · 53.30 Impact Factor
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ABSTRACT: In healthy subjects, previous studies have demonstrated a great interindividual variability in the ability for tumor necrosis factor-alpha (TNF-alpha) production. The gene for TNF-alpha is closely linked to and located in the major histocompatibility complex (MHC) and it has been suggested that these interindividual differences may be HLA related. Since TNF-alpha is likely to be an important mediator in renal allograft rejection, we investigated the role of HLA antigens on TNF-alpha production rates by peripheral blood mononuclear cells (PBMC) from renal transplant recipients during stable graft function. HLA-DR2-positive recipients showed significantly lower spontaneous TNF-alpha production than DR2-negative patients (p < 0.001). Upon stimulation with OKT3, HLA-DR2-positive patients also showed significantly lower TNF-alpha production than DR2-negative subjects (p < 0.001). HLA-DR3-positive recipients, however, showed significantly higher spontaneous TNF-alpha production than DR3-negative individuals (p < 0.05). These results suggest that differences in TNF-alpha production, both spontaneous and induced, may be due to the expression of certain DR allotypes.
Nephron 02/1995; 71(2):180-3. · 13.26 Impact Factor
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ABSTRACT: The influence of calcium-channel blocker treatment on in-vitro TNF alpha production by peripheral blood mononuclear cells (PBMC) from renal transplant recipients treated with cyclosporin was studied.
We compared spontaneous and OKT3-induced TNF alpha production of 12 renal transplant recipients treated with calcium-channel blocker therapy with that of 18 renal transplant recipients who were never treated with a calcium antagonist.
The two groups were similar with regards to age, time after transplantation, dosage of immunosuppressive drugs, and blood cyclosporin levels. Spontaneous (481 +/- 161 versus 319 +/- 74 pg/ml, n.s.) and OKT3-induced (745 +/- 182 versus 632 +/- 112 pg/ml, n.s.) TNF alpha production were similar in both groups.
The results indicate that in cyclosporin-treated renal transplant recipients calcium-channel blockers do not affect TNF alpha production.
Nephrology Dialysis Transplantation 02/1995; 10(6):871-3. · 3.40 Impact Factor
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ABSTRACT: The aim of this study was to investigate the differences in LH, FSH, PRL and testosterone levels in 20 men on haemodialysis and 26 men following renal transplantation. Nineteen of the renal transplant recipients were receiving cyclosporin, azathioprine, and prednisone, while the seven remaining individuals received azathioprine and prednisone. A subgroup of eight patients were also studied longitudinally while undergoing maintenance haemodialysis and after transplantation. The results show that successful renal transplantation resulted in a normalization of hormone levels in either the cross-sectional or longitudinal groups, the degree of which was unaffected by treatment modality. Cyclosporin given in therapeutic doses does not alter the pituitary-testicular function in renal transplant recipients.
Nephrology Dialysis Transplantation 02/1994; 9(10):1453-5. · 3.40 Impact Factor
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Nephron 02/1993; 63(1):118. · 13.26 Impact Factor
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Transplantation Proceedings 01/1993; 24(6):2542-4. · 1.00 Impact Factor
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Transplantation Proceedings 01/1993; 24(6):2596-9. · 1.00 Impact Factor
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ABSTRACT: We have investigated the genotype and allelic distribution of germline restriction fragment length polymorphisms of the T-cell receptor beta chain, segment C beta, and two variable segments which are in linkage disequilibrium, V beta 8 and V beta 11, in 42 insulin-dependent diabetes mellitus (IDDM) patients and in 51 healthy blood donors used as controls. Recently, several works have reported contradictory results showing or not showing an association between polymorphic alleles of the C beta gene and diabetes type I. We found no significant differences in the allele, genotype, and haplotype distribution of the gene segments studied, between IDDM patients and control populations.
Human Immunology 07/1991; 31(2):77-80. · 2.84 Impact Factor
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ABSTRACT: Conversely to the well-established association of DR2/Dw2 with multiple sclerosis (MS) susceptibility in Caucasoids, several studies have found an association of DR4 in populations from Mediterranean origin. We have studied the distribution of the different DR4B1 subtypes in Spanish MS patients. Oligonucleotide probes were selected in order to type samples amplified by polymerase chain reaction (PCR) from Spanish DR4+ MS patients (25) and controls (28). No DR4B1 subtypes were found to be increased in MS. MS susceptibility linked to DR4 may be due to the presence of shared functional epitopes common to the different HLA-DR4B1 subtypes.
Journal of Neuroimmunology 07/1991; 32(3):279-83. · 2.96 Impact Factor
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Nucleic Acids Research 03/1991; 19(3):685. · 8.03 Impact Factor
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ABSTRACT: In this report we describe the linkage between genes encoding human complement components C6, C7, and C9. Polymorphisms have been described at the DNA level for the C7 and C9 genes. We have studied 20 individuals by Southern blot analysis with four C6 cDNA subclones to detect restriction fragment length polymorphisms (RFLPs). We have found a Taq I polymorphism defined by two alleles of 8.0 (C6 H) and 6.0 (C6 L) kilobases (kb). RFLP segregation for the C6, C7, and C9 loci in informative families allowed us to estimate the maximum Lod scores at a recombination fraction of theta = 0.0 (C6-C7), theta = 0.0 (C7-C9), and theta = 0.0 (C6-C9). Significant linkage disequilibrium was found between C6 and C7 and between C7 and C9 loci in directly determined haplotypes of unrelated parents. Data from this study show that the genes encoding the human terminal complement components C6, C7, and C9 define a cluster in the short arm of chromosome 5. We propose that the clusters involving the C8A and C8B and the C6, C7, and C9 genes be referred to as MACI and MACII, respectively.
Immunogenetics 02/1991; 33(3):184-7. · 2.93 Impact Factor
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Nucleic Acids Research 10/1990; 18(18):5581. · 8.03 Impact Factor
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Nucleic Acids Research 05/1990; 18(7):1929. · 8.03 Impact Factor
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ABSTRACT: We have investigated the genotype and allelic distribution of germline restriction fragment length polymorphisms of the T-cell receptor β chain, segment Cβ, and two variable segments which are in linkage disequilibrium, Vβ8 and Vβ11, in 42 insulin-dependent diabetes mellitus (IDDM) patients and in 51 healthy blood donors used as controls. Recently, several works have reported contradictory results showing or not showing an association between polymorphic alleles of the Cβ gene and diabetes type I.We found no significant differences in the allele, genotype, and haplotype distribution of the gene segments studied, between IDDM patients and control populations. Human Immunology 31 77–80 (1991)
Human Immunology. 31(2):77-80.
