Relevance of autoantibody profile with HLA-DRB1 and -DQB1 alleles in a group of Iranian systemic lupus erythematosus patients

Ashkan Rasouli-Saravani; Ahmad Tahamoli-Roudsari; Zahra Basiri; Mahboobeh Babaei; Alireza Fazaeli; Ghodratollah Roshanaei; Mehrdad Hajilooi; Ghasem Solgi

doi:10.1016/j.imlet.2021.06.004

Relevance of autoantibody profile with HLA-DRB1 and -DQB1 alleles in a group of Iranian systemic lupus erythematosus patients

Immunol Lett. 2021 Sep:237:11-16. doi: 10.1016/j.imlet.2021.06.004. Epub 2021 Jun 26.

Authors

Ashkan Rasouli-Saravani¹, Ahmad Tahamoli-Roudsari², Zahra Basiri², Mahboobeh Babaei², Alireza Fazaeli², Ghodratollah Roshanaei³, Mehrdad Hajilooi¹, Ghasem Solgi⁴

Affiliations

¹ Department of Immunology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
² Department of Internal Diseases Medicine, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
³ Department of Biostatistics and Epidemiology, School of Health, Hamadan University of Medical Sciences, Hamadan, Iran.
⁴ Department of Immunology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran; d. Psoriasis Research Center, Department of Dermatology, Farshchian Hospital, Hamadan University of Medical Sciences, Hamadan, Iran.. Electronic address: gh.solgi@umsha.ac.ir.

PMID: 34186156
DOI: 10.1016/j.imlet.2021.06.004

Abstract

Background: One of the most relevant genetic components in systemic lupus erythematosus (SLE) is human leukocyte antigen (HLA) gene complex which plays a central role in autoimmune responses. This study aimed to explore the associations of HLA-DRB1/-DQB1 alleles and haplotypes with SLE risk and the appearance of autoantibodies in SLE disease.

Methods: A total of 127 SLE patients and 153 ethnically matched healthy controls were enrolled. HLA-DRB1 and HLA-DQB1 alleles were determined by PCR-SSP method and then HLA alleles and haplotypes frequencies were compared between two groups and among the patients in terms of autoantibodies spectrum.

Results: We found that HLA-DRB1*03 and HLA-DRB1*16 alleles were significantly associated with increased risk (P = 0.008, P_C=0.05 and P = 0.002, P_C=0.02 respectively) and DRB1*01 conferred a potential protective role for disease (P = 0.03, P_C=0.13). Similar associations were observed at haplotype level; DRB1*03~DQB1*02 (OR1.91,P = 0.01, P_C=0.08), DRB1*16~DQB1*05 (OR3.65,P = 0.004,P_C=0.06) and DRB1*01~DQB1*05 (OR0.36,P = 0.04, P_C=0.22). Remarkably, we observed significantly associations of DRB1*03 with the appearance of anti-SSA/Ro (P_C=0.02), anti-SSB/La (P_C=0.002) and anti-coagulant (P = 0.007), DRB1*15 with anti-SSA/Ro (P_C=0.04), DRB1*16 with anti-Sm (P_C=0.02), DRB1*04 with anti-β2gpI (P_C=3 * 10^-5), anti-cardiolipin (P = 0.002) and rheumatoid factor (P = 0.004) and DRB1*13 with anti-Sm (P_C=0.02) and anti-β2gpI (P_C=0.01) antibodies. Also, negative associations of DRB1*04 with anti-Sm, anti-SSA/Ro, DQB1*03 with anti-Sm and DRB1*11 with anti-Sm and anti-β2gpI were observed.

Conclusions: We identified DRB1*03 and DRB1*16 as risk alleles and DRB1*01 as a potential protective allele for SLE disease. More importantly, we found a close link between genetic susceptibility for SLE and autoantibodies status that was more evident for DRB1*03 allele.

Keywords: Autoantibody; HLA-DQB1; HLA-DRB1; Systemic lupus erythematosus.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Alleles
Antibodies, Antinuclear / immunology
Autoantibodies / immunology*
Autoantigens / immunology
Case-Control Studies
Female
Genes, MHC Class II*
Genetic Predisposition to Disease
Genotype
HLA-DQ beta-Chains / genetics
HLA-DQ beta-Chains / immunology*
HLA-DRB1 Chains / genetics
HLA-DRB1 Chains / immunology*
Haplotypes / immunology
Humans
Iran
Lupus Erythematosus, Systemic / ethnology
Lupus Erythematosus, Systemic / genetics
Lupus Erythematosus, Systemic / immunology*
Male
Middle Aged

Substances

Antibodies, Antinuclear
Autoantibodies
Autoantigens
HLA-DQ beta-Chains
HLA-DQB1 antigen
HLA-DRB1 Chains