Influence of HLA-A, B, and DR matching on the outcome of kidney transplant survival in preimmunized patients.

The outcome of 893 prospectively typed (HLA-A, B, and DR) and matched cadaveric kidney transplants--all first grafts, with patients being transfused before transplantation--was studied using actuarial survival methods. The effect of HLA-A, B and DR matching was only found to be significantly beneficial to graft survival in the group of 289 presensitized recipients: 70% and 43% graft survival at two years in the case of best-matched (4-6 HLA-A, B, and DR) identities versus mismatched (0 and 1 HLA-A, B, and DR) identities, respectively (P = 0.05). Although a cumulative effect of matching for antigens belonging to the 3 HLA-A, B, and DR series was observed among the group of preimmunized recipients, a trend arose in favor of the prominent role of the HLA-B alleles. No significant difference related to HLA matching was observed in the group of nonsensitized recipients. These results confirm previous observations and support efforts to give priority for matched kidneys to preimmunized patients.

HLA-DR2 and narcolepsy.

A positive association between HLA-DR2, DQw1, and narcolepsy was documented in 23 French caucasoid narcoleptic patients, 18 who were heterozygous for DR2 and 5 who were possibly homozygous. An autoimmune mechanism of narcolepsy is proposed with three successive stages, as well as relevant methodology for further investigation. A dominant mode of inheritance of narcolepsy, with an incomplete penetrance, is suggested although not yet evidenced.

Immunogenetic study of couples with recurrent spontaneous abortions.

OBJECTIVES: Clinical observations suggest that genetic and immunologic disparity could be a factor in fecundity. The HLA system (HLA) is polymorphic and TLX (Trophoblast Lymphocyte Cross-Reactive), which is also polymorphic, seems to be linked to it. The immunologic hypothesis follows that excessive HLA and TLX-sharing could explain the rejection of a semi-allogenic blastocyst. Study objectives are therefore twofold; To determine whether or not there is significant HLA-sharing between spouses with unexplained recurrent spontaneous abortions (RSA) and to determine whether or not there is an association between some HLA specificities and RSA. STUDY DESIGN: The study includes only Caucasian couples that have had three successive spontaneous abortions. These were distributed in two groups: Group E: 18 couples either with known aetiology or with secondary RSA; Group U: seven couples with unexplained primary RSA; Control group C: 21 couples with at least two children and no spontaneous abortions. Tissue typing for HLA-A and B molecules was performed using serotyping methodology based on lymphocytotoxicity reaction. The different DRB1 alleles (class II) were determined by oligotyping with a non-radioactive reverse dot-blot methodology. RESULTS: Statistical comparison shows that the number of couples without shared specificity is not significantly different between the three groups for each locus independently and for the set of three. Our results show also that the allelic frequencies are not significantly different between the three groups. CONCLUSIONS: There is no higher HLA-sharing in couples with RSA than in fertile couples. Similarly, no particular HLA specificity can be associated with the RSA.

[HLA-A, B, C, and DR typing in rheumatoid polyarthritis]. / Les typages HLA-A, B, C, DR dans la polyarthrite rhumatoïde.

HLA-A, B, C typing were performed in 72 caucasians with rheumatoid arthritis. HLA-DR typing were accomplished in 40 patients among these 72 subjects. DR4 was clearly increased with a frequency of 55 p. 100 versus 18 p. 100 in controls. We did not find an association between DR4 and the presence of rheumatoid factor. Clinical and biological signs are similar in rheumatoid arthritis with and without DR4. Two other HLA antigens, B40 and Cw3, were increased and their frequency was twice as high in patients as compared with controls. A synthesis of six studies published in the world confirms the elevation of B40 in this disease and later on suggests the elevation of Cw3 which is often linked with B40. The association of rheumatoid arthritis with B40 and Cw3 can be explained by a linkage disequilibrium between DR4 and B40 on the one hand, between DR4 and Cw3 on the other hand.

[The place of immunology in recurring spontaneous abortion]. / Place de l'immunologie dans les avortements spontanés à répétition.

Spontaneous repeated miscarriages are often explained by an immunological mechanism. Whereas in normal pregnancy the mother develops a tolerance immune response induced by paternal antigens of fetus, she is unable to react in this variety of miscarriage. The immunological theory is supported by some solid experimental arguments, which are detailed. Antigens generating the tolerance response are probably TLX antigens, expressed on syncitiotrophoblast and cross reacting with class I HLA antigens. Diagnosis of immunological miscarriage is based on elimination of other causes and on absence in woman of antibodies directed against husband class I antigens. Tolerance immune response can be induced by injections to wife of great quantity of conjunct lymphocytes. An anti HLA, and later on anti TLX, immunization is often obtained. Several teams have applied this treatment, with frequent good results: about 80% of fecundated patients conduct a normal pregnancy until its time.

[Study of the HL-A system in Basedow's disease (author's transl)]. / Etude du système hla au cours de la maladie de basedow

HL-A typing has been carried out in 100 caucasians with Graves' disease and compared with 270 healthy controls. 25 HL-A antigens were characterized using a lymphocytotoxicity microtechnique. Analysis of the results reveals an increased incidence of HL-A8 antigen (35% in patients as compared to 16,3% in controls), with a high degree of statistical significance: p=0.0002 and corrected p X 25) = 0.005. We did not observe a clearcut correlation between the presence of HL-A8 and different characteristics of the disease: sex, age of onset, familial history, exophtalmia, goiter, severity. The knowledge of the relationships between the HL-A8 gene and several auto-immune diseases is a strong argument in favor of the auto-immune nature of Graves' disease. The association between HL-A8 and Graves' disease could be explained by a close linkage between the second HL-A locus and one or several Ir-IgG loci occupied in predisposed individuals by predisposing alleles. In these subjects, an antigenic contact with an exogenous etiological agent would induce a pathological immune response, with production of thyroid stimulating IgG.

[HLA B8 and Graves' disease (author's transl)]. / Système HLA et maladie de Basedow

HLA typing has been carried out in 100 caucasions with Graves' disease and compared with 270 healthy controls. 25 HL-A antigens were characterized using a lymphocytotoxicity micro-technique. Analysis of the results reveals an increased incidence of HLA-B8 antigen (35% in patients as compared to 16.3% in controls) with a high degree of statistical significance: p = 0.0002 and corrected p (X 25) = 0.005. We did not observe a clear-cut correlation between the presence of HLA-B8 and different characteristics of the disease: sex, age of onset, familial history, exophtalmia, goiter, severity. The knowledge of the relationships between the HLA B8 gene and several auto-immune diseases is a strong argument in favor of the auto-immune nature of Graves' disease. The association between HLA B8 and Graves' disease could be explained by a close linkage between the second HLA locus and one or several Ir-IrG loci, occupied in predisposed individuals by "predisposing" alleles. In these subjects, an antigenic contact with an exogenous etiological agent would induce a pathological immune response, with production of thyroid stimulating IgG.

[Intra-conjugal immunotherapy and the pathology of reproduction. Experiences at the Center for the Treatment of Sterility, Montpellier-Nîmes]. / Immunothérapie intraconjugale et pathologie de la reproduction. Expérience du Centre de Traitement de la Stérilité Montpellier-Nîmes.

81 patients who had consulted for infertility, of whom 26 had recurrent spontaneous abortions (RSA), 28 unexplained infertility (UI), and 27 with difficulties for implantation following in vitro fertilization (IVF) were tested by a cross-match for the presence of the partner's lymphocyte antibodies. When the result was negative, leucocyte transfusions were carried out (200 million of the partner's lymphocytes in 3 successive injections at intervals of one month). Positive antipaternal cytotoxic antibodies were found in 81% of cases. There was, however, no benefit in groups of unexplained infertility or implantation difficulties. In the RSA group there was a 50% recurrence of spontaneous abortions.

Psoriatic arthritis and HLA antigens.

HLA groups including the characteristics of 25 antigens were determined in 108 patients suffering from psoriatic arthritis. These included 18 patients with central forms (pelvospondylitis), and 90 patients with peripheral forms (polyarthritis with or without sacroiliitis). Analysis of the results leads to the following conclusions: central psoriatic arthrisis is strongly associated with B27 and BW38, less closely with B13 and slightly with BW17. Peripheral psoriatic arthritis has the same relationship with the HLA system as has psoriasis without arthropathy.

[Calculation of the proportion of men excluded from paternity by HLA typing of the mother and child]. / Calcul de la proportion d'hommes exclus de paternité par les typages HLA de la mère et de l'enfant.

When filiation research shows that paternity is possible, French legislation recommends the calculation of two coefficients: 1. paternity probability (CP); 2. percentage of random men excluded from paternity by genetic markers of the mother and the child (PEme). A method is proposed, allowing the determination of PEme for the HLA system and PEme for the various systems employed. The calculations, relatively simple, can be worked out quickly and without risk of error, using a computer. We successively look at simple cases, complex cases and unusual cases: maternal death, consanguinity problems, racial problems. HLA-A, B, C, DR, DQ typing almost always leads to the exclusion of more than 98% of innocent men (PEme greater than 0.98). The HLA system clearly appears to be the most conclusive of the systems utilized by experts.

[HLA and narcolepsy]. / HLA et narcolepsie.

A very strong association has been shown to exist between HLA-DR2/Dw2 and narcolepsy, both in Caucasoid and Mongoloid people. The gene responsible for susceptibility, HLA or linked with HLA, is probably transmitted as an autosomal dominant trait with incomplete penetrance. The investigation of DR2 is useful for the diagnosis of minor or incomplete forms in narcolepsy and in the detection of exposed subjects in families. This association opens up horizons concerning the mechanism of narcolepsy. Several hypotheses are discussed, in particular that of a multifactorial disease, in which an environmental agent and DR2 antigen, functioning as the product of an Ir gene, would play a role.

[Relation between Ia antigens and Ir gene products. A theory on the development of the immune response]. / Relations entre antigènes Ia et produits des gènes Ir. Une théorie sur le déroulement de la réponse immunitaire.

To explain the relations between Ia and Ir, we propose the following hypothesis. It would exist an antigen specific factor released by T lymphocytes. This factor would be constituted by two parts: a variable fragment forming the antigenic receptor of T cells and coded by Ir genes, a constant fragment transmitting a helper or suppressor signal and carrying Ia antigens. Ia antigens would allow a mutual recognition between macrophages, T lymphocytes and B lymphocytes and a recognition by these cells of some mediators released during immune response. Ir genes products would allow the antigen recognition, if they correspond to the antigenic receptor of T lymphocytes.

[Relations between Ia antigens and the products of Ir genes. A theory of the evolution of the immune response]. / Relations entre antigènes Ia et produits des gènes Ir. Une théorie sur le déroulement de la réponse immunitaire.

To explain the relations between Ia and Ir, we propose the following hypothesis. It would exist an antigen specific factor released by T lymphocytes. This factor would be constituted by two parts: a variable fragment forming the antigenic receptor of T cells and coded by Ir genes, a constant fragment transmitting an helper or suppressor signal and carrying Ia antigens. Ia antigens would allow a mutual recognition between macrophages, T lymphocytes and B lymphocytes and a recognition by these cells of some mediators released during immune response. Ir genes products would allow the antigen recognition, if they correspond to the antigenic receptor of T lymphocytes.