Expression patterns of T cells-specific long noncoding RNAs in systemic lupus erythematosus patients carrying HLA risk/nonrisk alleles

Author:

Tahamoli-Roudsari Ahmad1,Rahmani Fatemeh2,Afshar Saeid3,Hajilooi Mehrdad2,Solgi Ghasem24ORCID

Affiliation:

1. School of Medicine, Department of Internal Diseases Medicine, Hamadan University of Medical Sciences, Hamadan, Iran

2. School of Medicine, Department of Immunology, Hamadan University of Medical Sciences, Hamadan, Iran

3. School of Medicine, Department of Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran

4. Cancer Research Center, Hamadan University of Medical Sciences, Hamadan, Iran

Abstract

Background Long noncoding RNAs (LncRNAs) play key roles in the regulation of gene expression and subsequently in the pathogenesis of several autoimmune diseases. This study aimed to explore the peripheral expression levels of T-cells-specific LncRNAs and transcription factors in systemic lupus erythematosus (SLE) patients carrying either human leukocyte antigens (HLA) risk or non-risk alleles. Methods Genotypes of HLA-DRB1 and HLA-DQB1 loci for 106 SLE patients were determined by PCR-SSP. In the next step, patients were stratified based on the presence of HLA-DRB1*03 and/or DRB1*16 allele groups (HLA risk alleles positive or HLA-R Pos) or carrying other DRB1 allele groups (HLA-R Neg). Then, transcript levels of LncRNAs ( IFNG-AS1, RMRP, Th2LCR, and DQ786243) and mRNAs for transcription factors ( Foxp3, Gata3, and Tbx21) were measured using qRT-PCR and compared between two subgroups of patients. Results Totally, 47 cases were classified as HLA-R Pos and 59 cases as HLA-R Neg patients. The HLA-R Pos patients showed decreased transcript levels of DQ786243 ( p = .001) and elevated expression of IFNG-AS1 ( p = .06) and T-bet mRNA ( p = .03) compared to the HLA-R Neg group. We observed significantly lower expression of Th2LCR ( p < .0001) and DQ786243 ( p = .001) and higher expression of Tbx21 ( p = .009) and Foxp3 ( p = .02) in DR3-positive versus DR3-negative patients. Likewise, decreased transcript levels of DQ786243 ( p = .02) and RMRP ( p = .003) were observed in DR16-positive versus DR16-negative patients. ROC curve analysis revealed the potential of DQ786243 and RMRP as biomarkers in SLE disease based on the carriage of HLA risk alleles. Conclusions Our results indicate that the contribution of multiple T cell subsets in SLE disease progression as judged by expression analysis of LncRNAs and transcription factors can be inspired by the inheritance of HLA risk/nonrisk alleles is SLE patients.

Funder

Hamadan University of Medical Sciences

Publisher

SAGE Publications

Subject

Rheumatology

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