Heat shock protein 27 and its regulatory molecules express differentially in SLE patients with distinct autoantibody profiles

• Downregulation of HSP27 specifically in anti-ENA+ SLE patients.
• HSP27 expression correlated inversely with caspase 3 and PARP expression.
• Brn3a specifically downregulated in anti-ENA+ subgroup, may regulate HSP27 expression.
• Overexpression of hsa-miR-939 in specific subset of SLE patient could contribute for decreased Brn3a expression.
• SLE patients with distinct autoantibody profile have differential immunoregulatory mechanisms.

Generation of autoantigens of nuclear origin, like dsDNA and extractable nuclear antigens (ENA) have largely been associated with dysregulated apoptosis and defective clearance of apoptotic debris in SLE. Heat shock protein (HSP) 27 has been reported to have anti-apoptotic properties hence it was of interest to study the expression of HSP27 and its regulatory molecule Brn3a and hsa-miR-939 in SLE patients with distinct autoantibodies specificities. SLE patients were categorized into three subsets based on their distinct sero-positivity for either anti-dsDNA antibody alone (anti-dsDNA+ group) or anti-ENA antibody alone (anti-ENA+ group) or both (anti-dsDNA+ ENA+ group). We investigated the mRNA and protein expression of HSP27 and Brn3a in peripheral blood leukocytes (PBLs) by real-time reverse transcriptase PCR and Western blotting. Expression of apoptosis markers caspase 3 and poly (ADP-ribose) polymerase (PARP) was determined by Western blotting. Hsa-miR-939 expression was determined using TaqMan® miRNA assay. In this study, we report significant downregulation of HSP27 in anti-ENA+ patients and increased expression of caspase 3 and PARP in both anti-ENA+ and anti-dsDNA+ SLE subsets. A negative correlation was observed between the expression of HSP27 and apoptosis markers caspase 3 and PARP. Decreased Brn3a expression was observed in anti-ENA+ SLE patients, which correlated positively with HSP27 expression. Expression of hsa-miR-939, which has a potential target site for Brn3a 3′ UTR, was also elevated specifically in anti-ENA+ patients. The decreased expressions of HSP27, Brn3a along with elevated levels of hsa-miR-939 are selectively associated with anti-ENA+ patients and HSP27 was observed to be inversely associated with apoptosis. These findings are suggestive of distinct regulatory processes operative in SLE patient subsets with different autoantibody specificities.