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J D Bignon

Publications and source records attributed to J D Bignon.

At least 55 records · Page 3Linked to original sources

HLA-DRw52a is involved in alloimmunization against PL-A1 antigen.

The alloimmunization against the platelet PL-A1 antigen is strongly associated with a HLA class II structure in mothers of thrombocytopenic neonates. Most of the immunized women have first been shown to possess the DR3 specificity and subsequently the DRw52 allele. The 18 immunized mothers studied here by restriction fragment length polymorphism analysis had the DRw52a specificity at the DRB3 locus whatever their HLA-DRB1 gene product. This finding strongly suggests that the DRB3 chain is directly involved in the presentation of the PL-A1 antigen to the specific T cell. In addition, the similarities between DR3 and DRw52 structures due to a hypothetical gene conversion event should be considered in order to understand the high frequency of DR3 among the DRw52a-responding women. Alternatively, the high frequency of DR3 among the DRw52-responding mothers might be due to the high responder status associated with the former specificity.

Antigens, Human Platelet↗

Effect of protein A immunoadsorption on panel lymphocyte reactivity in hyperimmunized patients awaiting a kidney graft.

Six hyperimmunized patients awaiting a kidney graft underwent immunoadsorption of separated plasma through a protein-A column to remove HLA antibodies. This procedure was partially limited by constant and rapid antibody resynthesis in spite of strong immunosuppression with cyclophosphamide and prednisolone. Only two patients could be grafted with previously positive--currently negative crossmatches. The first died of infection on day 40, having developed early chronic vascular rejection and the other returned to hemodialysis on day 285 after the development of transplant glomerulopathy. However, immunoadsorption seems to be effective in removing HLA antibodies having a titer below 1/2. Such extremely hyperimmunized patients should probably be excluded from the immunoadsorption program.

Adult↗

Functional properties of HLA-DR-BON alleles associated with DQw5(w1) and with DQw7(w3): a family study.

Among the DR specificities undefined by serology, DR-BON is peculiar because RFLP cannot distinguish it from the well-defined allele DR1 even if the two specificities are very different functionally. The occurrence of two DR-BON-like alleles in the same family, one associated to the DQw5 split of DQw1 and the other associated to the DQw7 split of DQw3, enabled us to compare the properties of these alleles. The RFLP analysis showed a typical DR1-like picture for both alleles when probed with DR beta, but for one of the alleles the DQ beta probe gave a DQw7 pattern. Primary mixed lymphocyte cultures showed weak to moderate stimulation between cells from individuals identical for one haplotype and differing for the DR-blank haplotypes, but by test with cloned reagents we were not able to define differences between the two DR-blank molecules. Two-dimensional gel electrophoresis and spot-test with a probe covering the third hypervariable region of the DRB1 gene showed no difference between the two alleles. We thus think that the two DR alleles are identical and that the stimulation observed in primary cultures probably is caused by incompatibility for DQ and DP or class I.

Alleles↗

Influence of HLA-DP mismatches on primary MLR responses in unrelated HLA-A, B, DR, DQ, Dw identical pairs in allogeneic bone marrow transplantation.

The success of bone marrow transplantation relies on class I and class II HLA identity between donor and recipient but until now the impact of DP mismatches on primary mixed lymphocyte reaction (MLR I) responses has not yet been clearly established. HLA-DP typing has been performed by a RFLP method on 10 patients and their 22 selected potential donors (HLA-A, B, DR, DQ, Dw identical according to serological, RFLP and oligotyping methods). HLA-DP-matching was then correlated with MLR I responses obtained (1) in 22 HLA-A, B, DR, DQ, Dw identical donor-recipient pairs (patient series) and (2) in 30 HLA-A, B, DR, DQ, Dw identical donors pairs used as the control series. We showed that MLR I responses involving patients cells were always lower than those involving control cells (p less than 0.02 in case of two DP-mismatches and p less than 0.001 in the case of one DP-mismatch). Moreover, in the control series two or one DP mismatches influenced MLR I responses in 91% and 77% of the cases respectively; however, there was a greater scatter of response values which could be explained by the degree of sequence homology between the DP mismatched alleles. In cases with no DP mismatch, no proliferative response was observed. Overall, these results suggest that the conventional technical conditions of MLR I do not allow detection of mismatches other than the well known HLA specificities.

Bone Marrow Transplantation↗

Effect of positive crossmatch against donor B lymphocytes in kidney transplantation: a prospective one-center study.

Circulating antibodies reacting with donor lymphocytes, increasingly found in patients awaiting a kidney graft, are a cause of transplantation delays. Some of these antibodies may not be detrimental to the graft, and their recognition could be beneficial for the treatment of immunized patients. In this chapter, we report on a prospective study of 138 cases of kidney transplantation performed against a positive crossmatch (CM) on donor B lymphocytes. In all cases, a negative reaction was required on donor T lymphocytes using recipient pregraft sera. Sera of 36.3% and 43.6% of first and second-graft recipients, respectively, were also reactive on unseparated donor total lymphocytes. First grafts performed against donor B lymphocytes reacted like those with a negative CM in terms of graft survival, rejection incidence, and graft function in the first year. Surprisingly, an uncommonly high rate of success was observed in second grafts performed against a positive donor B-lymphocyte CM as compared to those with a negative B-cell CM (93.5% vs 62.8% graft survival at 2 years; p less than 0.05). In addition, these patients had a decreased rejection incidence and significantly better graft function (p less than 0.05) as compared to those grafted with a negative B-lymphocyte CM. In the 43.6% who also had a positive CM on total donor lymphocytes (negative CM on donor T cells) and would not have been grafted according to common CM policy, actuarial graft survival was 86.7%. Our results within the given procedure show that transplantation against a positive donor B-cell CM is not detrimental to a first graft.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Polyclonal rabbit gamma globulins against a human cytotoxic CD4 T cell clone. II. Use in prevention of rejection in kidney transplantation: a pilot study.

Antiblast globulins (GAB) were prepared by immunization of rabbits with activated T lymphocytes (AT) derived from a rejected kidney allograft. AT consisted of a CD4+ (CD3+, CD2+ TCR alpha+ beta+) clone cytotoxic for HLA DR8-positive targets. The immunizing cells were adapted to industrial growth conditions by repetitive stimulations with an EBV-transformed line from the kidney donor and recombinant IL-2. In the pilot study, GAB (1.0-1.5 mg/kg/day) was given in 12-hr infusions, in association with prednisone (Pred) 1 mg/kg/day and azathioprine (Aza) 2 mg/kg/day, as prophylactic treatment of rejection in 12 kidney-transplanted patients during the first 2 weeks postgrafting. GAB dosage was further adapted according to the level of circulating E-rosette-forming T cells (ERFT). Cyclosporine A (8 mg/kg/day) was given at day 14 as a monotherapy after Pred and Aza were progressively tapered. No patient died, but one kidney was lost from surgical complication. No rejection occurred under GAB treatment; 41% of patients had at least one episode in the first 3 months and 16% from 3 to 9 months. GAB side effects were minor (skin rash: 2, low grade fever: 4) except for one acute serum sickness. Platelet and white blood cell counts were unchanged, but there was a significant decrease in hemoglobin during the 2 weeks of GAB infusions. Few infectious episodes occurred (3 bacterial, 2 viral). GAB monitoring showed a dramatic drop in T11+, T3+, T4+, and T8+ circulating T cells (less than 10% of normal values between days 3 and 14), whereas EFRT cells had a delayed and somewhat lower decrease (less than 10% after day 6 only). Consequently, mean GAB doses had to be raised to 1.3 mg/kg/day at day 4 and 1.6 at days 8 and 14. This pilot study suggests that this new bioreagent should be of major interest in the prophylaxis and treatment of rejection in allograft recipients. A controlled study is in progress.

Animals↗

[Platelet phenotyping and study of alloantibodies using flow cytometry].

In this study, we describe a flow cytometric technic for the detection and characterization of platelet allo antibodies and for platelets grouping in the platelet group PLA. This new technique is a variant of the platelet suspension immuno fluorescence test. It is rapid, simple, sensitive and specific. So it is very useful in the cases of neonatal thrombocytopenia and posttransfusion purpura. Moreover, anti-HLA antibodies don't obstruct the detection of anti-PLA1 antibodies.

Antigens, Human Platelet↗

Prognostic value of Langerhans cells in the epidermis of HIV patients.

We measured the number of Langerhans cells in clinically normal epidermis and the number of T4 lymphocytes in the plasma in 24 patients infected with HIV, and related these to the stage of the disease. A correlation is demonstrated between the numbers of Langerhans cells and T4 lymphocytes. Numbers of Langerhans cells were lower in patients with disease stages III and IV than in those with disease stage II. Thus Langerhans cell numbers could be of prognostic value in this disease.

Acquired Immunodeficiency Syndrome↗

Definition of DRw10 specificity by restriction fragment length polymorphism.

The purpose of this study was the RFLP characterization of the DRw10 specificity. Twenty-two DRw10 cells were tested: the DNAs were digested by seven restriction enzymes and hybridized with DR beta, DQ beta and DQ alpha probes. Hybridization with DR beta revealed a pattern particular to the DRw10 specificity, with a specific TaqI 12.5Kb fragment. Hybridization with both DQ-specific probes showed that DRw10 is always associated with a special DQw1 subtype: DQw5. Furthermore, at DR and DQ levels, the 22 DRw10 cells behaved homogeneously.

Alleles↗

HLA class II genes polymorphism in DR4 giant cell arteritis patients.

We have previously reported a significant increase of HLA-DR4 antigen frequency in giant cell arteritis (GCA). This finding suggested an important role of immunogenetic factors in this syndrome. Recent data suggest that inherited susceptibility to several autoimmune diseases was associated with specific DR4 associated DQ beta alleles. DNAs from 27 DR4 positive patients with GCA were digested with Taq I and Bam HI, analysed on 0.7% agarose gel and hybridized with DR beta, DQ alpha and DQ beta probes. DR beta hybridization produced no variant detectable within DR4. DQ beta probe confirmed two clusters among DR4 associated DQW3 alleles: DQW 3.1 (Bam HI 360 Kb) and DQw 3.2 (Taq I 1.9 Kb and Bam HI 11 Kb). Among our 27 DR4 positive patients, 34% were DQW 3.1 and 66% were DQW 3.2. These frequencies are the same as those observed in healthy controls.

DNA↗