Autoantibodies against four-and-a-half-LIM domain 1 (FHL1) in inflammatory myopathies: results from an Australian single-centre cohort

Objectives To determine the prevalence and associations of autoantibodies targeting a muscle-specific autoantigen, four-and-a-half-LIM-domain 1 (FHL1), in South Australian patients with histologically-confirmed idiopathic inflammatory myopathies (IIM) and in patients with SSc. Material and methods Sera from patients with IIM (n = 267) from the South Australian Myositis Database (SAMD), SSc (n = 174) from the Australian Scleroderma Cohort Study (ASCS) and healthy controls (HC, n = 100) were analysed for anti-FHL1 autoantibodies by Enzyme-Linked ImmunoSorbent Assay (ELISA). Results Autoantibodies to FHL1 were more frequent in patients with IIM (37/267, 13.8%) compared with SSc (12/174, 7%) (P < 0.02) and HC (2/100, 2%) (P < 0.001). The most common IIM subtypes among FHL1(+) IIM patients were (32%) and IBM (2/37, 32%). No statistically significant differences in muscular or extra-muscular manifestations of IIM were found when comparing patients who were anti-FHL1(+) with their anti-FHL1(-) counterparts. In 29/37 (78%) anti-FHL1(+) patients, no myositis-specific autoantibodies (MSA) were present. In FHL1(+) muscle biopsies, there was less frequent infiltration by CD45(+) cells (P = 0.04). There was a trend for HLA alleles DRB1*07 and DRB1*15 to be more frequent in anti-FHL1(+) compared with anti-FHL1(-) patients (9/25 vs 19/113, P = 0.09 and 8/25 vs 15/114, P = 0.09, respectively). Conclusions We report a substantial prevalence (13.8%) of anti-FHL1 autoantibodies in a large cohort of patients with histologically confirmed IIM; 75% of these cases did not have a detectable myositis-specific autoantibody. Anti-FHL1 autoantibodies were also detected in a subgroup of patients with SSc (7%), indicating that anti-FHL1 autoantibodies may not be myositis-specific. The trend towards an HLA-DR association might indicate a specific immune response to the FHL1 protein.