HLA Class II Associations With Rheumatic Heart Disease Are More Evident and Consistent Among Clinically Homogeneous Patients

Abstract

Significant increases in DRB1*0701 and DQA1*0201 alleles and DRB1*0701-DQA1*0201 haplotypes were found in patients. Removal of the MVL patients from analysis increased the strength of HLA associations among the MVD sample. The frequency of DQA1*0103 allele was decreased and the DQB1*0603 allele was absent from the patient group, suggesting that these alleles may confer protective effects against RHD. DQ alleles in linkage disequilibrium with DR alleles appear to influence risk/protection effect: whereas the DRB1*13-DQA1*0501-3-DQB1*0301 haplotype showed a trend toward risk, the DRB1*13-DQA1*0103-DQB1*0603 haplotype was absent in the RHD sample. Our data indicate that certain class II alleles/haplotypes are associated with risk or protection from RHD and that these associations appear to be stronger and more consistent when analyzed in patients with relatively more homogeneous clinical manifestations.

Association Between Angiotensin I-Converting Enzyme Gene Insertion/Deletion Polymorphism and Risk of Rheumatic Heart Disease

“…Although no specific "RF gene" has been identified, several studies have suggested that genetic susceptibility to RF and RHD is linked to HLA class II alleles/haplotypes (HLA-DR2 in American blacks, HLA-DR4 in American Caucasians, HLA-DQA1 *0104 and DQB1 *05031 in Japanese, and HLA-DRB1 *0701 and DQA1 *0201 alleles and DRB1 *0701-DQA1 *0201 haplotype in Egyptians). [15][16][17] The most common lesion of acute rheumatic endocarditis is mitral valvulitis. MS usually results from repeated episodes of carditis alternating with healing and is characterized by the deposition of fibrous tissue in the valves and chordae tendineae.…”

“…(36) 8 (15) 29 (47) 22 (35) 11 (18) 23 (23) 46 (46) 31 ( (14) 23 (43) 23 (43) 12 (19) 23 (37) 27 (44) 18 (18) 45 (45) Guedez reported that MVD patients experienced a significant 5-fold fewer acute recurrent RF episodes compared with the multivalvular lesion patients, with mean rates of RF recurrence of 0.7 and 3.3, respectively. 17) The extent of original inflammation, and recurrence of RF are not the only predictors of the crippling process. Ultimately, the deformed valve is subject to nonspecific fibrosis and calcification.…”

Susceptibility to severe streptococcal sepsis: use of a large set of isogenic mouse lines to study genetic and environmental factors

“…This human pathogen causes a wide variety of conditions ranging from sore throat to invasive life-threatening diseases (reviewed in Cunningham 6 ), and the same strain of pathogen leads to different outcomes in different individuals. 7 Our laboratory provided direct evidence that the highly polymorphic human leukocyte antigen (HLA) genes confer high risk or protection in rheumatic heart disease; 8 as well as in streptococcal toxic shock (STSS) and necrotizing fasciitis (NF). 9,10 In GAS sepsis, allelic variation in HLA class II molecules plays a major role in modulating infection severity, primarily because they serve as binding and signaling receptors for superantigens, 11,12 which are the primary trigger of the severe inflammatory responses that can lead to organ failure and shock.…”

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

“…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. RKH olan hastalarda ve mitral kapak hastalığı olan hastalarda HLA-DRB1*0701 ve DQA1*0201 antijenlerini kontrollere göre yüksek sıklıkta bulmuşlar, birden fazla kapak tutulumu olan hastalar için benzer bir ilişki tespit etmemişlerdir.…”

“…RKH olan hastalarda ve mitral kapak hastalığı olan hastalarda HLA-DRB1*0701 ve DQA1*0201 antijenlerini kontrollere göre yüksek sıklıkta bulmuşlar, birden fazla kapak tutulumu olan hastalar için benzer bir ilişki tespit etmemişlerdir. Hastalık gruplarını homojenize etmeye yönelik bu iki çalışmada 10,15 da daha çok kronik romatizmal kapak hastalıklı hastalara odaklanılmış ve hastaların ilk atak özellikleri dikkate alınmamıştır. Her iki çalışmada da ilk atak özellikleri açık olmadığından bizim çalışmamızdaki gibi ilk başvuruda yapılacak doku tiplendirmesinin ilerisi için yol gösterici olup olamayacağı hakkında fikir verememişlerdir.…”