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

Abstract

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.

Keywords: DM; IBM; PM; SSc, anti-FHL1 autoantibodies; myositis-associated autoantibodies; myositis-specific autoantibodies.

Fig. 1

Characteristics of IIM subgroups (A) Sera from patients with IIM (DM, PM, IBM, IMNM and MNOS; n = 267), SSc (n = 174) and HC (n = 100) were analysed by ELISA using recombinant His-tagged FHL1. A cut-off value of 1.06 AU was calculated using a receiver operating characteristic (ROC) curve based on the HC. (B) Frequency of IIM patients presenting MSA and MAA in anti-FHL1⁺ group. (C) Representative histological findings in the muscle biopsy regarding the frequency of marked atrophy (grade 4) and the infiltration by CD68⁺ and CD45⁺ cells. (D) Comparison of the frequency of atrophy in the muscle biopsy by IIM subgroup in IBM and IMNM in anti-FHL1⁺ and anti-FHL1^– groups. Statistical analysis for (A) was performed using Kruskal–Wallis test with Dunn’s correction for multiple comparisons. Statistical analysis for (C–D) was performed using a 2-tailed Mann–Whitney U test. Each data point in (A) represents one individual and horizontal bars indicate the mean values. Asterisk indicates a significant difference, *P-values < 0.05, **P-values < 0.01. HC: healthy controls; IIM: idiopathic inflammatory myopathy; IMNM: immune mediated necrotizing myopathy; MAA: myositis-associated autoantibodies; MNOS: myositis not-otherwise-specified; MSA: myositis-specific autoantibodies.