Expression profile of HLA-DRB1, RFX5, and CIITA promoters in chronic kidney disease patients from South India

Abstract

Background The present study elucidated HLA-DRB1 allele frequency, the gene expression profile of HLA-DRB1, CIITA promoters PI, PIV, and RFX5 and their association in chronic kidney disease (CKD). Patients and methods In all, 133 CKD patients and 144 healthy controls were enrolled, and qRT-PCR based expression analysis of HLA-DRB1, CIITA-PI, PIV, and RFX5 promoters was carried out. The typing of HLA-DRB1FNx01 alleles was performed by the PCR-SSP method. The immune cell profiling was performed by flow cytometry. Results Out of the 13 HLA-DRB1 alleles genotyped, increased frequencies for DRB1FNx0107 [odds ratio (OR)=2.103] and DRB1FNx0112 (OR=2.50) and decreased frequency for DRB1FNx0110 (OR=0.455) in CKD patients were observed. HLA-DRB1 expression was significantly upregulated in pooled-CKD (Fc: 1.49 ± 0.21; P<0.0001), DRB1FNx0107 (Fc: 3.10 ± 0.70; P<0.057), and DRB1FNx0112 (Fc: 3.62 ± 0.74; P<0.0001) positive CKD patients. Significantly higher levels of expressions were observed for CIITA-PI (Fc: 2.35 ± 0.23; P<0.0005) and PIV (Fc: 1.76 ± 0.23; P<0.0009) in pooled-CKD patients. With HLA-DRB1 alleles, a higher level of expressions of CIITA-PIV was observed in patients with DRB1FNx0112 (Fc: 1.45 ± 0.38; P<0.007). Interestingly, a significantly downregulated expression was observed for CIITA-PIV in patients heterozygous for DRB1FNx0112 (2.15 ± 0.24 vs. 0.16 ± 0.82; P<0.017). An upregulated RFX5 expression was observed for pooled-CKD (Fc: 1.37 ± 0.17; P<0.0001) and DRB1FNx0112 (1.40 ± 0.34; P<0.045) positive patients. Immunophenotyping analysis showed an increased CD3+ and decreased CD19+, CD4+,and CD8+ cell populations in CKD patients compared with controls. Conclusion The study confirmed the increased expression of CIITA-PI, PIV promoters, and RFX5 that in turn led to the upregulation of the DRB1 gene resulting in CKD. Thus, the study concluded the positive association of HLA-DRB1FNx0107 and DRB1FNx0112 alleles, with a differential expression of DRB1 genes as a consequence of upregulation of respective promoters in CKD pathogenesis in South India.