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Immunogenetic studies in habitual abortion.

Recent evidence suggests that immunological factors could play a role in the aetiology of habitual abortion. In this study, 71 couples with habitual abortion (i.e. more than 3 successive abortions) were investigated. Sharing of HLA-A, B, DR between partners was not found to be significantly increased. Anti-HLA antibodies in women against their partners' lymphocytes were found in 18.3%. After immunization with 10(7)-10(8) lymphocytes obtained from husband or unrelated donor, there was a seroconversion rate of 61% in those without antibodies initially. This was not dependent on the number of cells injected, source of cells, degree of sharing of HLA antigens or whether the couple were primary aborters (i.e. having had no advanced pregnancy), or secondary aborters. Seven pregnancies have resulted following the immunization procedure so far, 5 occurring in cross-match positive patients and 2 in cross-match negative. Growth retarded infants resulted from the pregnancy of 1 primary aborter and 2 secondary aborters.

Abortion, Habitual↗

Immunogenetic heterogeneity and associated autoimmune disorders in myasthenia gravis: a population-based survey in the province of Ferrara, northern Italy.

INTRODUCTION: The well-established relationship between myasthenia gravis (MG) and HLA antigens varies among different ethnic groups. In Caucasians B8 and/or DR3 alleles have been found associated with young MG women without thymoma and with high titres of acetylcholine-receptor antibody (AChR Ab). An increased frequency of haplotype HLA-A3, B7 and/or DR2 has been observed in older MG patients with low AChR Ab levels. So far, there is no convincing evidence for an association between a specific haplotype HLA and ocular MG or MG with thymoma. MG subjects often show other concurrent autoimmune disorders suggesting a more general inherited predisposition to autoimmunity. We performed a community-based study to verify the HLA-A, B, C, DR and DQ profile on ethnically homogeneous MG patients and with the aim to estimate the frequency of concurrent autoimmune diseases and to compare HLA phenotypes to autoimmune status in different MG patients groups. METHODS: Forty-seven patients, living in the province of Ferrara, were followed-up in our neurologic department and typed for HLA Antigens. In addition a set of immunological laboratory tests was performed. RESULTS: We found a trend towards an increased B8 and DR3 frequencies in total affected population; an association between B8 allele and early onset of generalized MG sustained by thymic hyperplasia. The DR3 allele is statistically associated with the presence of additional autoimmune disorders. CONCLUSIONS: Our data support the hypothesis of a genetically-based heterogeneity of the disease and show an increased prevalence of associate autoimmune conditions in MG patients.

Adult↗

Immunogenetic and oncogenic properties of rat trophoblast cell lines.

PROBLEM: The nature of major histocompatibility complex (MHC) antigen expression on rat placentas, trophoblast cell lines, and tumors derived from trophoblast cells was explored. METHOD OF STUDY: Cytohistochemical and flow cytometric analysis and molecular techniques. RESULTS: MHC antigen expression and genomic imprinting on the placenta and on trophoblast cells varies with the time of gestation and with the type of MHC antigen. CONCLUSIONS: There is no correlation in trophoblast cells between class I expression and cell ploidy, on the one hand, and malignant potential, on the other hand. Genomic imprinting of class I antigens in the rat placenta is a quantitative phenomenon.

Animals↗

Why did your mother reject you? Immunogenetic determinants of the response to environmental selective pressure expressed at the uterine level.

PROBLEM: Maternal "rejection" of the implanted conceptus is considered to account for a significant proportion of miscarriages (abortions) in both humans and animals. Our understanding of mechanisms has been limited, and hence, explanations for nonrejection have remained largely speculative. Losses, when they occur, could represent either random accidental failure of protective mechanisms or a more purposeful discrimination. METHOD OF STUDY: An analysis of the most recent data. RESULTS AND CONCLUSIONS: The embryo is most akin to a parasite, and pregnancy is most akin to a host-parasite interaction. If one excludes chromosome abnormalities in the embryo as a cause of death, activation of coagulation mechanisms, leading to vasculitis affecting the maternal blood supply to the implanted embryo, appears to represent a major loss-causing mechanisms--a form of ischemic autoamputation. Proinflammatory T-helper (Th) 1-type cytokines trigger this process via upregulation of a novel prothrombinase, fgl2. Th2/3 cytokines, such as interleukin (IL)-4, IL-10, and transforming growth factor (TGF)-beta 2, may antagonize the processes involved. Cytokine balance is determined by the genetics of the mother, which regulate her response to stress; endotoxin (LPS); and paternal antigens, selectively expressed on the trophoblast of the embryo, via imprinting. Based on studies in abortion-prone mice, where immunity to paternal alloantigens prevents loss, three distinct gene products in the embryo are proposed to determine the cytokine response to maternal lymphomyeloid cells in the uterus.

Abortion, Spontaneous↗

Collagen induced arthritis as an experimental model for rheumatoid arthritis. Immunogenetics, pathogenesis and autoimmunity.

The type II collagen (CII) induced arthritis animal model (CIA) provides opportunities to study the nature of autoimmune reactions leading to arthritis and may be used as a model for rheumatoid arthritis (RA). Thus, in similarity with RA, the CIA model, when induced with autologous CII, shows a chronic and progressive disease course. The susceptibility to both RA and CIA are correlated to the expression of certain MHC class II allotype genes. In both diseases are autoantibodies to CII and rheumatoid factors produced. Immunohistopathology of affected joints show in both diseases a dominance of activated macrophages/fibroblasts with a significant infiltration of activated T cells and an infiltration of granulocytes. We do here suggest that both RA and CIA are dependent on a synergy between delayed type hypersensitivity and immune complex mediated inflammatory mechanisms and that CIA provides opportunities for studies of immunospecific reactions leading to arthritis.

Animals↗

Immunogenetic control of experimental collagen-induced arthritis in rats. II. ECIA susceptibility and immune response to type II collagen (CALF) are linked to RT1.

The segregation of genes controlling ECIA susceptibility and the level of immune response to native calf type II collagen were determined in the F2 progeny of matings between WF (RT1u/u; ECIA-susceptible; high responders) and LEW.B3 (RT1n/n; ECIA-resistant; low to intermediate responders). RT1n/n F2 progeny showed resistance to ECIA, low skin test reactivity to type II collagen and intermediate levels of IgG anti-collagen antibodies (-log2 of 6.2 +/- 2.6; mean +/- SD, n = 10). RT1u/u and RT1u/n F2 progeny were susceptible to ECIA and were high responders to type II collagen by skin testing and IgG antibody titres (-log2 of 12.1 +/- 1.3, mean +/- SD, n = 26). Although all rats that developed arthritis were also high responders to type II collagen one group of immature F2 progeny, RT1u/u and RT1u/n, showed high anti-collagen immune responses in the absence of detectable arthritis. The data indicate that genes linked to RT1.A control susceptibility to ECIA and at least part of the immune response to native calf type II collagen in WF and LEW.B3 rats.

Animals↗

Immunogenetic studies of spontaneous abortion in mice. III. Non-H-2 antigens and gestation.

CBA/J (H-2k) females, mated with DBA/2 J (H-2d) or DBA/1 J (H-2q) males, exhibit a high rate of fetal resorption. In contrast, when H-2 identical CBA substrains (i.e. CBA/Ca and CBA/N) are used, this phenomenon is not observed. On the other hand, before mating with DBA/2 J males, pre-immunization of CBA/J females with spleen cells coming from BALB/c J or (DBA/2 x BALB/c J) F1 males (and not from other H-2d identical males whatever their Mls alleles) has significantly decreased the fetal resorption rate. Thus, immunization against determinants other than classical H-2d (K, I, D, L) antigens (transmitted as a dominant character and different from Mls determinants) can elicit anti-abortive effects. Furthermore, it was observed that the spleen cell endowed with the anti-abortive effects was neither a T nor a B lymphocyte. In contrast, peritoneal cells were able to reproduce the phenomenon, indicating that it may be mediated by a cell of the macrophage-monocyte lineage. Finally, a first gestation was substituted for allo-immunization of CBA/J females. The anti-abortive effects of a first pregnancy by BALB/c J males (and not by other H-2k syngeneic or H-2d allogeneic males) was observed in the course of a second pregnancy sired by DBA/2 J males. These data can be interpreted in terms of maternal recognition of an antigen present on both macrophages and trophoblast cells and necessary for a successful gestation, which is coded for by genes outside the K, I, D, L regions.

Abortion, Veterinary↗

Immunogenetic analysis of successful and rejected bone marrow grafts within one family.

We report the case of an Indonesian patient who required urgent bone marrow transplantation for acute leukaemia and who received successive transplants from two siblings. The first transplant failed while the second was successful. There were some uncertainties in serological typing due to the presence of cross-reacting HLA-B alleles, lack of paternal typing and the use of Caucasoid sera for Indonesian patients. Distinction between the two donors was also difficult. Interestingly, the use of a new DNA technique identified the presence of differences between the patient and the first unsuccessful donor but not the second successful donor.

Adult↗

Immunogenetics of autoimmune diseases in Asian Indians.

The HLA class II molecules play a critical role in the processing and presentation of specific peptides derived from autoantigens of pancreatic beta cells or gluten for T cell scrutiny in IDDM and CD. In the present study, extended DR3-positive haplotypes associated with autoimmunity in northern Indian patients have been reported. The haplotype A26-B8-DR3 was the most common autoimmunity-favoring haplotype encountered among these patients. This association is, indeed, unique to Indian autoimmune patients, as it replaces the otherwise most commonly associated Caucasian haplotype A1-B8-DR3 (AH8.1) in this population. Further, CD patients revealed 100% association with DQB1*0201 along with DQA*0501 (97%) either in cis or trans configuration.

Asian People↗