Association of human leukocyte class II antigens with rheumatic fever or rheumatic heart disease in a Brazilian population.

Abstract

BACKGROUND The incidence of rheumatic heart disease is great in Brazil. We analyzed the distribution of human leukocyte (HLA) antigens in a Brazilian population sample with rheumatic fever or rheumatic heart disease, with the aim of better understanding the mechanisms involved. METHODS AND RESULTS HLA class I (A, B, and C) and class II (DR and DQ) antigen distribution was studied in 40 patients with diagnosis of rheumatic fever or rheumatic heart disease and compared with a control group of 617 healthy individuals for class I typing, from which 118 were drawn for class II typing. A strong correlation between rheumatic fever and rheumatic heart disease and HLA-DRw53 (72.9% in the disease group versus 39% in the control group: p = 0.00061, relative risk, 4.2; etiologic fraction, 0.43) was found. We also found an increase in the frequency of HLA-DR7 (57.5% in the disease group versus 26.3% in control group: p = 0.00715; relative risk, 3.8; etiologic fraction, 0.56). HLA class I and HLA-DQ typing did not point to any association with these diseases. CONCLUSIONS HLA-DR7 and HLA-DRw53 are markers for susceptibility to rheumatic fever and rheumatic heart disease in Brazil. These results could be explained by genetic differences resulting from racial or geographical diversity.

Association of human leucocyte antigens with valvar involvement and rheumatic valvar disease development in children with acute rheumatic fever

“…Romatizmal karditli hastaların romatizmal ateşin diğer klinik bulgularını taşıyanlardan ayrı olarak incelendiği veya çoğunluğunu mitral kapak hastalığının oluşturduğu romatizmal kalp hastalığının tek başına incelendiği çalış-malarda nispeten benzer HLA ilişkileri saptandığını göz-lenmektedir. 4,11,20,[24][25][26] Stanevicha ve ark 10 yaptıkları çalışmada mitral yetersizliği olan hastalarda HLA-DRB1*07 ve DQB1*0401-2'yi multivalvüler lezyonu olanlarda HLA-DRB1*07 ve DQB1*0302'yi yüksek sıklıkta saptadıklarını bildirmektedir. Guedez ve ark 15 RKH hastalarını birden fazla kapak hastalıklı hastalar ve mitral kapak hastalığı olan (MY veya MY+mitral darlığı) olarak sınıflayıp kontrollerle karşılaş-tırmışlardır.…”

The immunology of mitral valve stenosis

“…Several different HLA alleles, in particular HLA-DR7, have been associated with RHD and the development of valvular lesions. [10][11][12][13][14] By furthering the recognition of streptococcal peptides through the HLA system, the presence of these alleles likely enhances autoimmune inflammatory processes and amplifies disease severity.…”

“…T-cell clones from heart lesions of RHD patients have shown the ability to simultaneously recognize heart tissue-derived proteins and streptococcal M5 protein peptides, 36 in particular, immunodominant peptide residues 81-96 and 83-103, 10,37 epitopes also recognized by peripheral T lymphocytes in the context of HLA-DR7. 38 Furthermore, analysis of the N-terminal portion of the M5 protein and cardiac myosin has yielded three distinct cardiac myosin epitopes targeted by molecular mimicry in the S2 and light meromyosin regions.…”

Presence of a D8/17 B lymphocyte marker and HLA-DR subgroups in patients with rheumatic heart disease

“…This is based on evidence of a familial association (4), controlled studies (5,6) and the fact that only 2-3% of individuals exposed to rheumatogenic group A streptococcal pharyngitis go on to develop ARF (1). Several studies have suggested that genetic predisposition to ARF is linked to human leukocyte antigen (HLA) class 2 alleles (7,8). However, there has been controversy concerning the nature of the susceptibility or protective alleles (9).…”