Anti-FHL1 autoantibodies in adult patients with myositis: a longitudinal follow-up analysis

Abstract

Objectives: To determine prevalence and clinical associations of anti-Four-and-a-half-LIM-domain 1 (FHL1) autoantibodies in patients with idiopathic inflammatory myopathies (IIM) and to evaluate autoantibody levels over time.

Methods: Sera at the time of diagnosis from patients with IIM (n = 449), autoimmune disease controls (DC, n = 130), neuromuscular diseases (NMDs, n = 16) and healthy controls (HC, n = 100) were analysed for anti-FHL1 autoantibodies by enzyme-linked immunosorbent assay (ELISA). Patients with IIM FHL1+ and FHL1- were included in a longitudinal analysis. Serum levels were correlated to disease activity.

Results: Autoantibodies to FHL1 were more frequent in patients with IIM (122/449, 27%) compared with DC (autoimmune DC and NMD, 13/146, 9%, P < 0.001) and HC (3/100.3%, P < 0.001). Anti-FHL1 levels were higher in IIM [median (IQR)=0.62 (0.15-1.04)] in comparison with DC [0.22 (0.08-0.58)], HC [0.35 (0.23-0.47)] and NMD [0.48 (0.36-0.80)] P < 0.001. Anti-FHL1+ patients with IIM were younger at the time of diagnosis compared with the anti-FHL1- group (P = 0.05) and were seronegative for other autoantibodies in 25%.In the first follow-up, anti-FHL1+ sample 20/33 (60%) positive at baseline had turned negative for anti-FHL1 autoantibodies. Anti-FHL1 autoantibodies rarely appeared after initiating treatment. Anti-FHL1 autoantibody levels correlated with CK (r = 0.62, P= 0.01), disease activity measured using the Myositis Disease Activity Assessment Tool (MYOACT) (n = 14, P = 0.004) and inversely with Manual Muscle Test-8 (r = -0.59, P = 0.02) at baseline.

Conclusion: Anti-FHL1 autoantibodies were present in 27% of patients with IIM; of these, 25% were negative for other autoantibodies. Other autoimmune diseases had lower frequencies and levels. Anti-FHL1 levels often decreased with immunosuppressive treatment, correlated with disease activity measures at diagnosis and rarely appeared after start of treatment.

Keywords: FHL1; autoantibody; idiopathic inflammatory myopathy; myositis.

Figure 1.

Anti-FHL1 autoantibodies in IIM and autoimmune disease controls. (A) Sera from patients with IIM (PM, DM, IBM, IMNM, ASyS, MCTD and MNOS; n = 449), HC (n = 100) and DC, including SS (n = 10), RA (n = 10), NMD (n = 16), SLE (n = 10) and SSc (n = 10), were analysed by ELISA using recombinant His-tagged FHL1. A cut-off value of 1.1 AU was calculated using a receiver operating characteristic (ROC) curve based on the HC. (B) Presence of anti-FHL1 autoantibody level by DC subgroup. Statistical analysis for (A–C) was performed using Kruskal–Wallis test with Dunn’s correction for multiple comparisons. Each point represents one individual, and horizontal lines indicate the median and interquartile range. Asterisk indicates a significant difference, *P values <0.0001. HC: healthy controls; IIM: idiopathic inflammatory myopathy; PM: polymyositis; DM: dermatomyositis; IBM: inclusion body myositis; IMNM: immune mediated necrotizing myopathy; ASyS: anti-synthetase syndrome; MCTD: mixed connective tissue disease; MNOS: myositis not-otherwise-specified; DC: disease controls; SS: Sjögren syndrome; RA: rheumatoid arthritis; NMD: neuromuscular diseases; SLE: systemic lupus erythematosus; SSc: systemic sclerosis

Figure 2.

Longitudinal analysis of anti-FHL1 autoantibodies in IIM. Legend: Longitudinally collected sera from patients with IIM (anti-FHL1+ n = 57 and anti-FHL1− n = 30), where F1 represents the sample close to diagnosis (baseline) and F2-Fn the longitudinal samples. The anti-FHL1+ groups are represented according to serology status at baseline. The longitudinal data from the anti-FHL1− sera are not represented in this figure. (A) Group anti-FHL1+ at baseline (n = 33), where the red line and symbols indicate the serum samples with high anti-FHL1 autoantibody levels during follow-up. (B) Group anti-FHL1− at baseline (n = 24), where the coloured lines indicate individual samples that became positive in F2-F3. (C) Comparison of anti-FHL1 autoantibody levels at baseline and first follow-up in sera from patients belonging to the 2A. (D) Comparison of anti-FHL1 autoantibody levels at baseline and first follow-up in sera from patients belonging to the group 2B. Each point represents one serum sample and individual; horizontal lines indicate the longitudinal follow-up. Statistical analysis for (C, D) was performed using Wilcoxon matched-pairs signed rank test. Asterisk indicates a significant difference, ***P values <0.001, NS: non-significant