Characterization of HLA-B*3921 and confirmation of HLA-B*4415, two variant HLA-B alleles identified in the Omani population.

We describe a variant HLA-B*39 allele present in two individuals from Oman, which has been officially named HLA-B*3921. In addition we confirm the existence of HLA-B*4415, an allele closely related to HLA-B*4501 differing only at the Bw4/Bw6 epitope.

Histocompatibility antigens in Omanis: Comparison with other Gulf populations and implications for disease association.

BACKGROUND: This is the first comprehensive report of HLA antigens in Omanis, and the first application of HLA sequence-specific primer (SSP) DNA typing in a Gulf population. The objective was to compare the findings with other Gulf populations and assess their implications for disease association. PATIENTS AND METHODS: HLA typing was carried out on 321 healthy Omanis. One hundred and twenty-six of these were typed for Class II antigens by low-resolution SSP DNA typing. The results were compared with other HLA antigen frequencies recorded from Kuwait and Saudi Arabia. RESULTS: The Omani population was characterized by a very high incidence of HLA-DR2 (66%), with associated HLA-DQ1 (76%) and a reduced incidence of DR4, DR7 and DR53. The incidence of DR2 is the highest recorded worldwide. HLA-A11, A32, B17, B35 and B40 were significantly higher than in Kuwait and Saudi Arabia, and A9, B21(B50) significantly lower (Pc<0.05). HLA-B27 is very low in the Omani population (0.3%). The high incidence of HLA-DR2 in Oman and disparities in the frequency of other antigens would indicate that there has not been any significant migration from northern Arabia. Class II DNA typing revealed that DR16 was the predominant split of DR2 (63%), with DR15 being 18% and both DR15 and 16 being found in 6%, giving a total of 87% for A centAADR2A centAA-associated antigens (serology of the same individuals gave a DR2 incidence of 74%). The major disparity between serology and DNA typing was in the definition of DR4 (serology 8%, DNA 14%) and DR51 (53% vs. 70%). CONCLUSION: The frequency of many HLA antigens in Omanis differs significantly from frequencies found in the populations of Kuwait and Saudi Arabia, possibly reflecting different migration patterns. The high incidence of HLA-DR2 in Oman may have important implications for disease association.

HLA antigens in Omanis with blinding trachoma: markers for disease susceptibility and resistance.

AIM: To determine the presence of HLA antigens in people with blinding trachoma. METHODS: Fifty Omanis with blinding trachoma were serologically typed for HLA A, B, C, DR, and DQ antigens and DNA typed for class II DR beta and DQ beta alleles and compared with a population of 100 healthy controls. RESULTS: chi 2 analysis of serological reactions did not reveal any significant differences in HLA antigen frequencies after correction of probability, although DR4, DR7, and DR53 were completely absent in the patients and all of the patients were HLA DQ1 positive. In the case of DQ1 the relative risk was 22.6 (95% confidence interval of 20.7-24.7). Class II DNA low resolution DR beta typing showed a significant increase in HLA DR16 (pc = 0.036, relative risk = 3.8) and a significant decrease in HLA DR53 (pc = 0.018, relative risk = 0.05). CONCLUSION: The finding that HLA DR16 (a DR2 subtype) is associated with susceptibility to blinding trachoma, a disease that is caused by an intracellular micro-organism, is consistent with reports of an HLA DR2 association with leprosy and tuberculosis, diseases also caused by an intracellular micro-organism. Similarly, resistance to leprosy is associated with HLA DR53 as is the case with blinding trachoma described here. It is postulated that HLA DR2 or subtypes in association with HLA DQ 1 may enable an intracellular micro-organism to enter the cell or are involved in presentation of peptides derived from intracellular micro-organisms to T lymphocytes initiating a delayed hypersensitivity or autoimmune reaction. These findings are the first report that genetic factors are of major importance in the development and protection against blinding trachoma.

HLA antigens in an Omani population with dilated cardiomyopathy.

We have investigated the frequency of HLA antigens in 50 Omanis with idiopathic dilated cardiomyopathy to establish whether there are ethnic/racial differences in the reported HLA associations with this disease. There were no statistically significant HLA-A, B, C, DR or DQ antigen frequency differences between the patients and 247 healthy Omanis. THe reported association of HLA-DR4 with idiopathic dilated cardiomyopathy in the Caucasian population does not apply to the Omanis. This confirms the heterogeneity of this disease and points to ethnic/racial origins as important factors when examining the HLA association. This is particularly pertinent as HLD-DR4 has been strongly linked to autoantibody formation in idiopathic dilated cardiomyopathy in Caucasians. The lack of any HLA antigen association in Omanis would argue against the proposed HLA-linked autoimmune pathology of idiopathic dilated cardiomyopathy.

Lymphocytotoxins in sera from highly sensitized multiparous dialysis patients: antibody class, relationship with the HLA and with paternal antigens.

1. Sera from 11 highly sensitized multiparous dialysis patients were studied in order to define the target antigens, antibody class and relationship with paternal HLA class I antigens of the underlying lymphocytotoxic antibodies. All sera contained lymphocytotoxic antibodies to over 70% of a panel of lymphocytes from 24 donors (panel reactivity greater than 70%). 2. Inhibition of cytotoxic activity against paternal lymphocytes by monoclonal antibodies to HLA framework determinants indicated that all 11 sera contained lymphocytotoxic antibodies to paternal class I antigens. In addition, five sera contained lymphocytotoxic antibodies to paternal class II antigens. 3. In order to determine the extent to which lymphocytotoxic antibodies were directed to paternal antigens, the panel reactivity of sera was compared before and after absorption with paternal peripheral blood lymphocytes. Over 50% of panel reactivity was absorbed from eight out of 11 sera, and in three of these 11 over 80% was absorbed. In the majority of patients this change in panel reactivity could be ascribed to binding of lymphocytotoxic antibodies to specific paternal class I antigens. 4. Digestion of sera with dithiothreitol had no significant effect on panel reactivity, indicating that the lymphocytotoxic antibodies were of immunoglobulin G class. 5. No sera reacted with either autologous lymphocytes or K562 cells, indicating an absence of autoantibodies. 6. These studies imply that panel-reactive lymphocytotoxic antibodies in the sera of highly sensitized multiparous patients are those which mediate hyperacute renal allograft rejection. Their development may be related to secondary humoral responses to antigens in blood transfusions from donors who share paternal class I specificities.

HLA antigens and familial benign hypercalcaemia.

We have determined the blood groups and HLA haplotypes in 15 members in four generations of a large kindred with familial benign hypercalcaemia (familial hypocalciuric hypercalcaemia). No linkage was seen between the disorder and ABO or Rh blood groups or the HLA antigens.

HLA antigens in a Scottish psoriatic population.

Sixty-one patients in the Dundee area suffering from psoriasis were typed for HLA-A and HLA-B antigens. On the basis of the typing results, the patients were divided into three groups, and studied with respect to sex, age of onset and familial incidence of the disease. The frequency of HLA-A1 appeared to be increased and HLA-B7 decreased but HLA-B13 and HLA-B17 were highly significantly increased (P less than 10(-6) and P less than 10(-10) respectively) in the psoriatic group compared to 204 controls. Of particular interest was a highly significant association of HLA-A1 with HLA-B17 in psoriatic patients. Family studies showed HLA-B17 to be a useful genetic marker for psoriasis in the families of B17 positive patients. Considerations of age of onset, familial incidence and typing data suggest that there is heterogeneity of genetic susceptibility to psoriasis and that one probable mechanism is the dominant inheritance of a "disease allele" in linkage disequilibrium with the allele coding for HLA-B17.