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HLA-DRB1 alleles in juvenile-onset systemic lupus erythematosus: renal histologic class correlations
B L Liphaus1, M H B Kiss, A C Goldberg
1Unidade de Reumatologia, Instituto da Criança, Universidade de São Paulo, Brasil. bernadll@icr.hcnet.usp.br
Insights
Human leukocyte antigen (HLA) DRB1 alleles are not strongly linked to clinical or autoantibody subsets in juvenile systemic lupus erythematosus (SLE). However, specific HLA-DRB1 alleles show significant associations with lupus nephritis histologic classes.
Area of Science:
- Immunogenetics
- Rheumatology
- Pediatric Autoimmunity
Background:
- Human leukocyte antigen (HLA) alleles, particularly HLA-DRB1, have been implicated in systemic lupus erythematosus (SLE) susceptibility and clinical manifestations in various ethnic groups.
- Previous studies suggest associations between specific HLA alleles and SLE autoantibodies or clinical subsets, but links to lupus renal histologic classification are less defined.
Purpose of the Study:
- To investigate the correlation between HLA-DRB1 alleles and clinical features, autoantibodies, and lupus nephritis histologic classes in a racially mixed cohort of Brazilian patients with juvenile-onset SLE.
- To determine if specific HLA-DRB1 alleles are associated with distinct clinical or serological phenotypes or renal pathology in this population.
Main Methods:
- Genomic DNA was collected from 55 pediatric patients meeting American College of Rheumatology criteria for SLE.
- HLA-DRB1 typing was performed using polymerase chain reaction with sequence-specific primers.
- Statistical analysis, including chi-square tests, was employed to assess associations between HLA-DRB1 alleles and clinical/serological data and renal histologic classes.
Main Results:
- The HLA-DRB1*15 allele was frequently observed in patients with renal, musculoskeletal, cutaneous, hematologic, cardiac, and neuropsychiatric involvement, and with anti-dsDNA, anti-Sm, anti-U1-RNP, and anti-SSA/Ro antibodies, though these associations were not statistically significant.
- Significant associations were found between specific HLA-DRB1 alleles and renal histologic classes: HLA-DRB1*17 with class I, HLA-DRB1*10 with class IIA, HLA-DRB1*15 with class IIB, and HLA-DRB1*07 with class V.
- No significant correlations were identified between HLA-DRB1 alleles and the clinical or autoantibody profiles of juvenile SLE patients.
Conclusions:
- HLA-DRB1 allele contribution to juvenile-onset SLE in this Brazilian cohort is not linked to clinical or serological subsets.
- Specific HLA-DRB1 alleles demonstrate a significant association with lupus nephritis histologic classes (I, IIA, IIB, and V), suggesting a potential role in renal pathology.
- These findings highlight a novel correlation between HLA-DRB1 alleles and lupus renal histologic classification, which warrants further investigation.
Abstract:
Human leukocyte antigens (HLA) DRB1*03 and DRB1*02 have been associated with systemic lupus erythematosus (SLE) in Caucasians and black populations. It has been observed that certain HLA alleles show stronger associations with SLE autoantibodies and clinical subsets, although they have rarely been associated with lupus renal histologic class. In the present study, HLA-DRB1 allele correlations with clinical features, autoantibodies and renal histologic class were analyzed in a cohort of racially mixed Brazilian patients with juvenile-onset SLE. HLA-DRB1 typing was carried out by polymerase chain reaction amplification with sequence-specific primers using genomic DNA from 55 children and adolescents fulfilling at least four of the American College of Rheumatology criteria for SLE. Significance was determined by the chi-square test applied to 2 x 2 tables. The HLA-DRB1*15 allele was most frequent in patients with renal, musculoskeletal, cutaneous, hematologic, cardiac, and neuropsychiatric involvement, as well as in patients positive for anti-dsDNA, anti-Sm, anti-U1-RNP, and anti-SSA/Ro antibodies, although an association between HLA alleles and SLE clinical features and autoantibodies could not be observed. The HLA-DRB1*17, HLA-DRB1*10, HLA-DRB1*15, and HLA-DRB1*07 alleles were significantly higher in patients with renal histologic class I, class IIA, class IIB, and class V, respectively. The present results suggest that the contribution of HLA- DRB1 alleles to juvenile-onset SLE could not be related to clinical or serological subsets of the disease, but it may be related to renal histologic classes, especially class I, class II A, class II B, and class V. The latter correlations have not been observed in literature.
