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Immunogenetic aspects of nasopharyngeal carcinoma. V. Confirmation of a Chinese-related HLA profile (A2, Singapore 2) associated with an increased risk in Chinese for nasopharyngeal carcinoma.

Histocompatibility locus A typing of 43 Malaysian Chinese and 51 Hong Kong Chinese patients with nasopharyngeal carcinoma (NPC) confirmed the association between the occurrence of A2-Sin 2 and the increased risk for NPC that was previously demonstrated in Singapore Chinese. The results support the previous interpretation that the histocompatibility locus A genotype of importance in NPC predisposition is the A2-Sin 2 haplotype. The histocompatibility locus A-linked, genetically determined NPC risk is common to Asian Chinese from at least three geographic locations.

Asian People↗

Immunogenetic analysis of rheumatoid arthritis.

Statistical association between rheumatoid arthritis (RA) and the HLA-D region antigen, HLA-DR4-MT3, was confirmed. HLA-linked immune suppression genes (Is-genes) were demonstrate, which controlled proliferative T cell response to streptococcal cell wall antigen or IgE response to cedar pollen antigen in vitro. The absence of such genes may predispose to autoimmune diseases or allergy. An HLA-linked Is-gene in negative linkage disequilibrium with HLA-DR4-MT3 was proposed to be one of the most likely genetic factors determining the resistance to RA.

Arthritis, Rheumatoid↗

Immunogenetics and immunopathology of human primary membranous glomerulonephritis: HLA-A, B, DR antigens; functional activity of splenic macrophage Fc-receptors and peripheral blood T-lymphocyte subpopulations.

In most of our patients with idiopathic membranous nephritis (MGN), we have studied the HLA-A, B, DR phenotype, the clearance of anti Rhesus D coated-51 Cr-labeled-autologous erythrocytes, and the peripheral blood T-lymphocyte subpopulations as ascertained by monoclonal antibodies (OKT3, OKT4, OKT8). The frequency of HLA-B8 antigen is 57.14% in 28 primary MGN versus 14.4% in 104 local controls (Pc less than 0.00018). The frequency of HLA-DR3 antigen is 65.38% in 26 primary MGN patients versus 20.27% in 74 local control individuals (Pc less than 0.00008). The half-life of sensitized erythrocytes is 37.30 +/- 9.55 min in 10 controls, 1963 min and 1601 min in 2 splenectomized controls, 12 min in a patient with hypersplenism, and 67.05 +/- 69.64 min in 18 idiopathic MGN patients respectively. The half-life is significantly prolonged in 6 out of 18 MGN patients. This prolongation correlates with exacerbation of the disease while normal values are obtained with remission. The OKT3 positive subpopulation (total T-lymphocytes) is 63.77 +/- 10.37% in 31 controls versus 53.74 +/- 13.81% in 22 MGN (P less than 0.002). The OKT4 positive subpopulation (helper T-cells) is 37.90 +/- 8.21% in controls versus 32.79 +/- 10.89% in MGN (P less than 0.03). The OKT8 positive subpopulation (suppressor T-cells) is 21.60 +/- 5.28% versus 20.03 +/- 5.76% respectively. The OKT4/OKT8 ratio is 1.85 +/- 0.58 in controls versus 1.74 +/- 0.69 in MGN. During exacerbation, the T-lymphocyte subset fractions are normal, whereas OKT3 and OKT4 are decreased during remission. MGN is a strongly HLA-linked disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗

Immunogenetics of Lennox-Gastaut syndrome: search for LD determinants as genetic markers of the syndrome.

In a previous work we demonstrated a strong association between HLA-B7 and the susceptibility to the Lennox-Gastaut syndrome. In this work we report some preliminary results obtained performing one-way mixed lymphocyte cultures in vitro between 15 unrelated children showing the typical EEG and clinical patterns of the syndrome. The same children were also tested against unrelated control cells from healthy donors. The low stimulation displayed by Lennox-Gastaut patients between them as compared with the higher stimulation found in patients/controls and controls/controls comparisons suggests the existence of an LD allele which may be associated with the disease.

Alleles↗

Clinical and immunogenetic studies in multicase rheumatoid families.

We have studied HLA haplotypes, autoimmune diseases and circulating autoantibodies in 23 families with multiple cases of rheumatoid arthritis; 76 per cent of rheumatoid arthritis and 70 per cent of non-rheumatoid individuals were positive for HLA-DR4. The haplotypes Bw44-Bf*S-DR4; B40-Bf*S-DR4; and B15-Bf*S-DR4 were found in 13, 9 and 7 per cent of probands respectively and the B15-Bf*S-DR4 haplotype was found between four and five times more frequently in DR4-positive rheumatoid arthritis than in DR4 positive, non-rheumatoid arthritis families. Rheumatoid arthritis segregated with a DR4 positive haplotype in 13 families and with a DR4 negative haplotype in seven. Analysis of HLA haplotype sharing showed greater than random sharing by affected siblings which is in keeping with genes within the MHS influencing susceptibility to rheumatoid arthritis. Autoimmune thyroid disorders were seen in 8 per cent of family members investigated. They were significantly more frequent in those families in which rheumatoid arthritis segregated with a non-DR4 bearing HLA haplotype. This suggests that genes for autoimmune thyroid disease might predispose to rheumatoid arthritis independently of DR4. These genes are probably not HLA-linked, as there was no trend for HLA haplotype sharing to be increased in sibling pairs with either rheumatoid arthritis and thyroid disease or rheumatoid arthritis and thyroid autoantibodies respectively.

Adolescent↗