HLA-DQ3 is associated with Graves' disease in African-Americans.

HLA heterogeneity occurs in various ethnic groups and has been significantly associated with Graves' disease. In this study we have determined that DQ3 is associated with Graves' disease in African-Americans. Human leukocyte antigen (HLA) typing of D-region antigens in 139 controls and 45 Graves' disease patients reveals significant differences for HLA-DR2, DR9, DQ1, and DQ3. The latter remained significant after correction. Increases in HLA-DR9 and DR3 are associated with increases in DQ3 and DQ2, respectively. The decrease in DR2 is associated with a decrease in DQ1. The associated increases and decreases in DR with DQ antigens probably reflect linkage disequilibrium. Patients were evaluated for autoantibodies against microsomal antigens and/or against thyroglobulin. All of the normal control volunteers were negative for thyroid antibodies and thirteen percent of patients produced autoantibodies. No significant associations were detected for antibody production, type of treatment required, age of onset, family history of Graves', status of T3, T4 levels, goiter and/or ophthalmopathy.

Polyunsaturated fatty acids result in greater cholesterol lowering and less triacylglycerol elevation than do monounsaturated fatty acids in a dose-response comparison in a multiracial study group.

Cholesterol-lowering effects of polyunsaturated and monounsaturated fatty acids were compared as they were varied in a reciprocal dose-dependent fashion in the context of a National Cholesterol Education Program (NCEP) Step 1 diet. The study population comprised 63 moderately hypercholesterolemic African American and white men and women. After a 6-wk baseline diet containing 37% of energy from total fat and 15% from saturated fat, participants consumed four diets for 6 wk each, in random order, containing 10% of energy as saturated fatty acids; 3%, 6%, 10%, and 14% of energy as polyunsaturated fatty acids; and 17%, 14%, 10%, and 6% of energy as monounsaturated fatty acids. Dietary cholesterol, fiber, plant sterol, and squalene contents were constant with all four diets. There was a progressive decrease in total (P = 0.028) and low-density-lipoprotein cholesterol (P = 0.184) across the four diets, with the greatest decrease observed in the diet with the highest content of polyunsaturated fatty acids; a small but significant decrease in high-density-lipoprotein (HDL) cholesterol that did not show a trend between the polyunsaturated and monounsaturated diets; and a trend between the four diets in triacylglycerol elevations (P = 0.029), with the smallest increment occurring in the diets highest in polyunsaturates. The magnitude of the cholesterol-lowering response was greater in those with higher baseline cholesterol and less in those who were more obese. The dietary response was similar in both ethnic groups and in both sexes. In conclusion, in an NCEP Step 1 diet containing 30% total fat, with all other known cholesterol-influencing dietary factors held constant, the substitution of polyunsaturated fatty acid for monounsaturated fatty acid from 3% to 14% resulted in a progressive decline in total cholesterol and less triacylglycerol elevations, without effect on HDL cholesterol.

Excess HLA antigens after transfusion of sickle cell patient with AIDS.

A woman with sickle cell-hemoglobin C disease developed the acquired immunodeficiency syndrome (AIDS), possibly as the result of blood transfusions administered 4 years earlier. Three months after subsequent transfusions, she had excess HLA-A and DR antigens (triplets) on her circulating lymphocytes. Three of her first-degree relatives were HLA-typed, and none had excess antigens. Family studies also indicated that the patient had at least one HLA-A antigen that was probably not inherited. These findings suggest the possibility that transient hemopoietic engraftment can occur in transfused sickle cell patients with AIDS.

Sickle cell leg ulcers are associated with HLA-B35 and Cw4.

We determined the HLA-A, B, C, and DR types in nine patients with sickle cell anemia (SS) who had leg ulcers or a history of leg ulcers, and in 29 control patients with SS without leg ulcers. Six (67%) of the nine patients with leg ulcers had HLA-B35 and each of these six patients also had HLA-Cw4. In contrast, only eight (28%) of the 29 control patients with SS had HLA-B35 and only three (10%) of these patients had both HLA-B35 and Cw4. The relative risk for development of leg ulcers in patients with SS who had both HLA-B35 and Cw4 was 17 times greater than that of patients without these antigens or who had only one antigen. The frequency of HLA-B35 was also significantly higher in patients with SS and leg ulcers than in a reference population (31%) consisting of 68 healthy black persons. These results suggest that genetic factors or an HLA-related altered immune response may contribute to the development of leg ulcers in sickle cell anemia.

Association of HLA and autoantibody in transfused sickle cell disease patients.

This study evaluates autoantibody production in sickle cell disease patients and determines whether genes in the major histocompatibility complex are associated with autoantibody responses. Rheumatoid factor was significantly increased for both male and female patients and was less prevalent in highly transfused patients. Significant increases were also detected in the incidences of antinuclear antibody for females and antismooth muscle antibody for males. Low incidence of antinuclear antibody was significantly associated with HLA-DR3. Significant associations were also found between the incidence of antinuclear antibody and both HLA-A28 and B15.

HLA-B35 is associated with red cell alloimmunization in sickle cell disease.

HLA-A, -B, -C, and DR antigens were determined in 33 patients with sickle cell disease (SCD), who had received red blood cell (RBC) transfusions. Twenty-one patients formed red cell alloantibodies after transfusions (responders) while 12 multitransfused SCD patients did not form any RBC antibodies (non-responders). We found that 67% of the SCD responder participants had HLA-B35 versus 25% of the non-responders (chi 2 = 5.3079, P = 0.0212). The frequency of B35 in non-responder SCD patients was similar to that of a normal healthy Black population consisting of 139 individuals. Calculation of the relative risk showed that sickle cell patients with B35 are six times more likely to form RBC alloantibodies after transfusion than those lacking that HLA antigen. We found no significant increase or association between any HLA-DR antigens and sickle cell disease.

HLA-DR antigens in Blacks with rheumatoid arthritis and systemic lupus erythematosus.

HLA-DR locus antigens were studied in a large population of Black Americans with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). An association was found with DR4 in RA (p less than 0.001) and DR3 in SLE (p less than 0.01). Our findings are similar to those reported in Caucasians. No significant correlations between clinical manifestations and DR locus antigens were apparent in either disease. Our results support the association of D locus antigens with disease susceptibility more than with clinical severity.