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 IIM and in patients with systemic sclerosis (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 analyzed 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 polymyositis (PM, 12/37, 32%) and inclusion body myositis (IBM, 12/37, 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 + (p= 0.04) cells. 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.

Idiopathic inflammatory myopathies: one year in review 2022

“…Recent evidence has confirmed and extended previous data on myositis associated auto-antibodies anti-Four-anda-half-LIM-domain 1 (antiFHL1) (30), which recognise a muscle-specific antigen, have been observed in some seron- egative IIM and systemic sclerosis patients (31). Anti-RuvBL1/2 antibodies were also found in patients with IIM/ systemic sclerosis overlap syndrome without other known autoantibodies, in association with nuclear fine or coarse speckled HEp-2 IIF pattern (32).…”

Distinct HLA associations with autoantibody-defined subgroups in idiopathic inflammatory myopathies

“… 21 , 22 , 23 We are also aware that the subgroup negative for all analysed autoantibodies may contain patients positive for new MSA, such as anti-FHL1, or autoantibodies that were either not analysed or removed from the analysis due to substantial missing data (e.g., anti-HMGCR, -Ku, -cN1A). 24 Moreover, ethnic background was available for only 28% of the patients included, so ancestry could not be adjusted for in the different models. Despite the potential misclassification resulting from our autoantibody assessment strategy and possible presence of unmeasured confounders, this study allowed us to use unsupervised clustering to define IIM subgroups based on serological profiles, evaluate HLA associations, and contrast traditional clinical and histopathological classification.…”