HLA class II antigens in rheumatic fever Analysis of the DR locus by restriction fragment-length polymorphism and oligotyping

Weidebach, Wagner Felipe de Souza; Goldberg, Anna Carla; Chiarella, Josely Marchi; Guilherme, Luiza; Snitcowsky, R; Pileggi, F; Kalil, Jorge

doi:10.1016/0198-8859(94)90024-8

Cited by 52 publications

(33 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Our previous results have shown an association between RF and the HLA-DR7, DR53 haplotype (12,29) in the Brazilian population. Since HLA-DR53 is in linkage disequilibrium with DR4, DR7, and DR9 antigens, not all HLA-DR53 molecules carry HLA-DR7.…”

Section: Resultsmentioning

confidence: 75%

See 1 more Smart Citation

T-Cell Reactivity against Streptococcal Antigens in the Periphery Mirrors Reactivity of Heart-Infiltrating T Lymphocytes in Rheumatic Heart Disease Patients

et al. 2001

Self Cite

View full text Add to dashboard Cite

T-cell molecular mimicry between streptococcal and heart proteins has been proposed as the triggering factor leading to autoimmunity in rheumatic heart disease (RHD). We searched for immunodominant T-cell M5 epitopes among RHD patients with defined clinical outcomes and compared the T-cell reactivities of peripheral blood and intralesional T cells from patients with severe RHD. The role of HLA class II molecules in the presentation of M5 peptides was also evaluated. We studied the T-cell reactivity against M5 peptides and heart proteins on peripheral blood mononuclear cells (PBMC) from 74 RHD patients grouped according to the severity of disease, along with intralesional and peripheral T-cell clones from RHD patients. Peptides encompassing residues 1 to 25, 81 to 103, 125 to 139, and 163 to 177 were more frequently recognized by PBMC from RHD patients than by those from controls. The M5 peptide encompassing residues 81 to 96 [M5(81-96) peptide] was most frequently recognized by PBMC from HLA-DR7 ؉ DR53 ؉ patients with severe RHD, and 46.9% (15 of 32) and 43% (3 of 7) of heart-infiltrating and PBMC-derived peptide-reactive T-cell clones, respectively, recognized the M5(81-103) region. Heart proteins were recognized more frequently by PBMC from patients with severe RHD than by those from patients with mild RHD. The similar pattern of T-cell reactivity found with both peripheral blood and heart-infiltrating T cells is consistent with the migration of M-protein-sensitized T cells to the heart tissue. Conversely, the presence of heart-reactive T cells in the PBMC of patients with severe RHD also suggests a spillover of sensitized T cells from the heart lesion.Rheumatic fever (RF) is a sequel of group A streptococcal throat infection and remains an important health problem in developing countries. About 30% of RF patients develop rheumatic heart disease (RHD), with high morbidity and cost to the public health system. Molecular mimicry between streptococcal antigens, mainly the M protein, and heart tissue proteins is proposed as an important factor leading to the heart lesions found in RHD patients. Several studies have been performed with human peripheral blood mononuclear cells (PBMC) showing reactivity against the streptococcal cell wall and tissue antigens (20,25). CD4 ϩ T cells are the predominant population at the site of heart lesions (23, 16).Yoshinaga et al. (30) reported that T-cell lines derived from heart valve specimens and PBMC from RF patients react with cell wall and membrane streptococcal antigens. These lymphocytes did not cross-react with M protein or mammalian cytoskeletal proteins. Autoreactivity to heart antigens caused by streptococcal infections was also suggested by results of immunization in which peripheral T lymphocytes from RHD patients stimulated in vitro with streptococci were able to recognize a 50-to 54-kDa myocardial protein fraction (7). Our group previously reported intralesional T-cell clones, from surgical fragments of patients with severe RHD, capable of recognizing immunodominant...

show abstract

Section: Resultsmentioning

confidence: 75%

“…Given the previously reported association of the HLA-DR7, DR53 haplotype with RF-RHD (12,29), we also assessed the ability of RHD-associated HLA molecules DR7 and DR53 to bind and present immunodominant M5 peptides.…”

mentioning

confidence: 99%

T-Cell Reactivity against Streptococcal Antigens in the Periphery Mirrors Reactivity of Heart-Infiltrating T Lymphocytes in Rheumatic Heart Disease Patients

et al. 2001

Self Cite

View full text Add to dashboard Cite

show abstract

“…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.…”

Section: Discussionunclassified

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

Yazıcı¹

2012

Sakarya Med J

View full text Add to dashboard Cite

Objective: It was aimed to study the relation between HLA antigens and valvar involvement at fist atack in patiens with acute rheumatic fever (ARF). Also we purposed to study the same relation in patients who develop rheumatic valvar disease during follow up period. Material and Method:Tissue typing of 80 patiens whose average age was 10.6±2.6 years (median 5-18 years) was performed by Polimerise Chain Reaction (PCR).The control group consisted of 63 healthy persons. The patients were subgrouped accoring to the manifestations at first attack. The relation between HLA antigens and valvar involvement was studied in these groups, at fist atack and after at least one year follow up period.Results: HLA DQ8 (P<0.05) in cases of isolated carditis with aortic (AI) and mitral insufficiency (MI) at first attack, and HLA DR7 (P<0.05), DR8 (P<0.05) and DQ8 (P<0.05) in the same group with remaining aortic+mitral insufficency after the first year, were more frequent than controls. By the first year HLA B27 (P<0.05) was more frequent than controls in patients with remaining isolated mitral insufficiency in this subgroup. HLA B57 (p<0.05) and HLA B61 (p<0.05) were found more frequent in poliartritis+carditis patients with mitral+aortic insufficiency at first attack. After follow up period more than one year, in patients with remaining isolated MI, HLA-DRB1*04 (p<0.05) and DQB!*08 (p<0.05) in patients with remaining isolated AI and HLA-DRB!*07 (p<0.05) in patients with remaining MI+AI were found more ferquent than controls. In chorea+carditis subgroup at first attack, HLA B13 (p<0.05) was more frequent in patients with isolated MI, and HLA-A1 and B49 (p<0.05) in patients with MI+AI.In this subgroup HLA-B27 (p<0.05) was found more ferquent in patients with remaining isolated MI after follow up period more than one year. Conclusion:The results of our study pointed out that HLA Class II antigens may be more determinig on the development of rheumatic valvar disease. But it is concluded that the results of our study should be supported by wider studies including more number of patients in each subgroups.

show abstract

“…The HLA association in ARF/RHD has been investigated in several studies (7,(13)(14)(15)(16)(17)(18)(19)(20)(21). Although the data seem to support the hypothesis that such a link exists, a consistent association with specific allele(s)/haplotypes has been lacking (9).…”

Section: Discussionmentioning

confidence: 99%

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

Karakurt¹,

Celıloğlu²,

Özgen³

et al. 2011

Anadolu Kardiyol Derg

View full text Add to dashboard Cite

ÖZETAmaç: Bu çalışmanın amacı, romatizmal kalp hastalığı olan hastalarda HLA-DR subgrupları ve HLA dışı B lenfosit belirteci olan D8/17 belirteç oranlarını araştırmaktı. Yöntemler: Bu enine-kesitli gözlemsel çalışmaya romatizmal kalp hastalığı olan 35 çocuk ve erişkin hasta ile kontrol grubu olarak sağlıklı 35 çocuk ile sağlıklı 12 erişkin alınmıştır. Hasta ve kontrol grubunda yer alan bireyler renkli Doppler ve 2 boyutlu ekokardiyografi ile değerlendiril-dikten sonra D8/17 B lenfosit markeri ve HLA-DR subgrupları için kan örnekleri alındı. B lenfosit D8/17 ekspresyonu akım sitometrisi kullanılarak değerlendirildi. HLA-DR subgupları ise ilgili primerler kullanılarak PCR yöntemi ile değerlendirildi. İstatistiksel analiz için gruplar arası karşılaş-tırmada Ki-kare, eşleştirilmemiş t ve Mann-Whitney U testleri ile değerlendirildi. Bulgular: D8/17 eksprese eden B lenfosit yüzdesi hasta grubunda kontrol grubuna göre istatistiksel olarak anlamlı olarak yüksek bulundu (%77.3±15.6' ya karşın %67.7±20.0, p=0.013). HLA DRB5 (%37.6'ya karşın %13.6, p=0.007) ve HLA DRB1*15 (%31.8'e karşın %9.0, p=0.008) ekspresyonu hasta grubunda anlamlı olarak yüksek bulunurken, DRB4 ekspresyonu (%29.5'e karşın %50.0, p=0.049) kontrol grubunda hasta grubuna göre anlamlı olarak yüksek bulundu. Sonuç: Çalışmamızda HLA DR subgrupları ve D8/17 ekspresyonu romatizmal kalp hastalığı ile arasında ilişki bulunduğunu desteklemektedir. Sonuçlarımızın desteklenmesi daha fazla çalışmaya ihtiyaç vardır. (Anadolu Kardiyol Derg 2011; 11: 314-8) Anahtar kelimeler: Romatizmal kalp hastalığı, insan lökosit antigen DR altgrupları, D8/17 beta lenfosit antigeni, akım sitometrisi ABSTRACT Objective: The aim of our study was to investigate the association of HLA antigens and a non-HLA protein D8/17 with rheumatic heart disease and its pattern of cardiac involvement. Methods: This cross-sectional observational study included 35 children and 12 adult patients who have rheumatic heart disease and 35 healthy children and 12 healthy adult controls. After physical examination, all patients and control group members were evaluated with 2D and colorcoded echocardiography. B-lymphocyte D8/17 expression was tested by a flow cytometry assay. HLA genotyping was performed using polymerase chain reaction sequence-specific primers. In statistical analysis, Chi-square, unpaired t and Mann-Whitney U tests were used for comparison groups. Results: The percentage of the D8/17-expressing B lymphocytes of the patient group was significantly higher than of the control group (77.3±15.6% vs. 67.7±20.0%, p=0.013). When compared with the control group, the HLA DRB5 (38.6% vs. 13.6%, p=0.007) and HLA DRB1*15 (31.8% vs. 9.0%, p=0.008) expression levels of the patient group were significantly higher and the DRB4 expression of the patient group was significantly lower (29.5% vs. 50.0%, p=0.049). Conclusion: Our findings support the association between HLA Class 2 subgroups and rheumatic heart disease, and an association between D8/17 expression and rheumatic heart disease. Further studies in...

show abstract

HLA class II antigens in rheumatic fever Analysis of the DR locus by restriction fragment-length polymorphism and oligotyping

Cited by 52 publications

References 11 publications

T-Cell Reactivity against Streptococcal Antigens in the Periphery Mirrors Reactivity of Heart-Infiltrating T Lymphocytes in Rheumatic Heart Disease Patients

T-Cell Reactivity against Streptococcal Antigens in the Periphery Mirrors Reactivity of Heart-Infiltrating T Lymphocytes in Rheumatic Heart Disease Patients

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

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

Contact Info

Product

Resources

About