Anti-AHNAK1 Antibodies Are a Novel Diagnostic Biomarker for Systemic Lupus Erythematosus

Calcium signaling is essential for the proper function of immune cells. Recent studies have shown that the scaffold protein, AHNAK1, is important for efficient calcium signaling and NFAT activation in T cells through its ability to properly localize calcium ion (Ca²⁺) channels at the plasma membrane. Interestingly, both T cells and B cells of systemic lupus erythematosus exhibit activation signaling anomalies with dysregulated Ca²⁺ response, and enhanced Ca²⁺ signaling has emerged as a target for treatment with SLE. Therefore, we hypothesized SLE patients may have autoantibodies (Abs) against AHNAK1 because anti-AHNAK1 antibodies possibly are able to interfere with Ca²⁺ signaling through binding to AHNAK1, subsequently resulting in aberrant T cells signal transduction. In the present study, we notably found that sera from SLE patients profoundly elicit immunoreaction against AHNAK1 when compared to normal healthy controls (NHCs) or patients with other systemic autoimmune diseases, such as polymyositis/dermatomyositis (PM/DM), systemic sclerosis (SSc), Sjögren's syndrome (SjS), mixed connective tissue disease (MCTD), and rheumatoid arthritis (RA). Additionally, the expression level of AHNAK1 in peripheral blood mononuclear cells (PBMCs) from SLE patients was significantly increased compared to NHCs. We propose that measurement of serum anti-AHNAK1 antibodies can be used as a possible biomarker for the diagnosis of SLE. In addition, our data suggest that AHNAK1 antibodies may have an indicative role in the pathogenesis of SLE.