ABSTRACT
Polymorphism in transporter associated with antigen processing (TAP)1 gene has been observed in African American Graves' disease patients. Single strand conformational polymorphism has been used to identify variation for the locus. First-strand cDNA was generated from cell lines obtained by Epstein-Barr virus immortalization. Four variant alleles for TAP1 have been observed and the products have been sequenced to compare with the location of observed with SSCP position patterns. Variants were detected and compared with substitutions within TAP1 polypeptide which includes changing valine to leucine and three (3) silent substitutions for glycine, glutamic acid and alanine.
Subject(s)
ATP-Binding Cassette Transporters/genetics , Black People/genetics , Graves Disease/genetics , Polymorphism, Single-Stranded Conformational , ATP Binding Cassette Transporter, Subfamily B, Member 2 , Adult , Alleles , Base Sequence , DNA, Single-Stranded/analysis , Genetic Variation , Humans , Major Histocompatibility Complex , Middle Aged , Molecular Sequence Data , Polymerase Chain Reaction/methodsABSTRACT
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.
Subject(s)
Autoimmune Diseases/ethnology , Graves Disease/ethnology , HLA-DQ Antigens/analysis , Adult , Age of Onset , Autoantibodies/blood , Autoimmune Diseases/blood , Autoimmune Diseases/genetics , Autoimmune Diseases/immunology , Black People/genetics , Disease Susceptibility , Female , Gene Frequency , Graves Disease/blood , Graves Disease/genetics , Graves Disease/immunology , HLA-DQ Antigens/genetics , HLA-DR Antigens/analysis , HLA-DR Antigens/genetics , Humans , Immunoglobulins, Thyroid-Stimulating/blood , Male , Middle Aged , Thyroglobulin/blood , Thyroid Hormones/blood , White People/geneticsSubject(s)
Black People/genetics , Diabetes Mellitus, Type 1/immunology , HLA-DQ Antigens/genetics , HLA-DR Antigens/genetics , Immunity, Innate , Polymorphism, Genetic , Diabetes Mellitus, Type 2/immunology , Disease Susceptibility , Gene Frequency , HLA-DQ Antigens/analysis , HLA-DR Antigens/analysis , HLA-DR3 Antigen , Humans , Phenotype , Reference Values , United StatesABSTRACT
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.
Subject(s)
Anemia, Sickle Cell/immunology , HLA Antigens/analysis , HLA-C Antigens , Leg Ulcer/immunology , Adolescent , Adult , Female , HLA-B35 Antigen , Humans , Male , Middle AgedABSTRACT
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.
Subject(s)
Anemia, Sickle Cell/immunology , Autoantibodies/analysis , HLA Antigens/analysis , Adolescent , Adult , Aged , Antibodies, Antinuclear/analysis , Blood Transfusion , Child , Female , Genes, MHC Class II , Humans , Major Histocompatibility Complex , Male , Middle Aged , Rheumatoid Factor/analysisABSTRACT
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.
