SAT0658 A LONGITUDINAL ANALYSIS OF ANTI-FHL1 ANTIBODIES IN A SWEDISH COHORT OF PATIENTS WITH IDIOPATHIC INFLAMMATORY MYOPATHIES
Authors: Angeles Shunashy Galindo-Feria, Eliška Divišová, Cátia Fernandes-Cerqueira, Maryam Dastmalchi, Edvard Wigren, Susanne Gräslund, Ingrid E. Lundberg
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Antibodies targeting a novel and muscle-specific autoantigen, the Four-and-a-half-LIM-domain 1 (anti-FHL1), have been identified in patients with idiopathic inflammatory myopathies (IIM). <h3>Objectives:</h3> The aim of this project was to evaluate when anti-FHL1 autoantibodies are present in the course of the disease and if autoantibody titers vary over time. <h3>Methods:</h3> The anti-FHL1 antibody status was obtained from a previous serological cross-sectional analysis from where we selected sera from IIM anti-FHL1<sup>+</sup> patients (n=25) and sex and age matched sera from IIM anti-FHL1<sup>-</sup>patients (n=51), and healthy controls (HCs, n=50). Levels of anti-FHL1<sup>+</sup> autoantibodies were evaluated by ELISA. Patients included in the study had at least one sample available at time of diagnosis and one consecutive serum sample within an interval of 36 months. All patients were followed at the Division of Rheumatology, Karolinska University Hospital from January 1982 to December 2017. HCs sera collected at a single time point were tested. <h3>Results:</h3> In the IIM group we included 76 patients with a total of 320 serum samples. Median follow-up time was 108 months, with median of 4 samples available per patient. In total, we identified the presence of anti-FHL1<sup>+</sup> antibodies in n=31 IIM patients, corresponding to the group of anti-FHL1<sup>+</sup> (n=25) and in anti-FHL1<sup>-</sup> (n=6) from the cross-sectional analyses. One HC had positive anti-FHL1 titers. We subdivided the patients into 4 groups: anti-FHL1<sup>+</sup>: "highly positive" (O.D.&gt;1, n=11), "intermediate positive" (1&gt;O.D.&gt;0.75, n=6), "baseline negative" that seroconverted (O.D.&gt;0.75, n= 14), and one anti-FHL1 "negative" group. All groups were compared by given OD medians at each of the point of observation. Highly positive patients had persisting high anti-FHL1 titers during the follow-up; on the contrary, both intermediate positive and baseline negative groups were fluctuating around the cut-off point. Eight of 14 (57%) patients from the group "baseline negative" seroconverted to anti-FHL1<sup>+</sup> within the first 36 months. The anti-FHL1 "negative" group presented constant low antibody titers during the longitudinal follow-up. <h3>Conclusion:</h3> Anti-FHL1 antibody positivity was detected in patients with high titers of anti-FHL1<sup>+</sup> autoantibodies in the first available serum sample or developed within the first 36 months after diagnosis and persisted over many years. A group of patients with intermediate levels had fluctuating positivity over the years. It is still unknown if the anti-FHL1 antibody titer is a marker of prognosis and/or damage in IIM; thus, clinical data needs to be addressed, and <i>in-vitro</i> experiments and biochemical characterization of this autoantibody are still required. <h3>Disclosure of Interests: </h3> Angeles Shunashy Galindo-Feria: None declared, Eliška Divišová: None declared, Cátia Fernandes-Cerqueira: None declared, Maryam Dastmalchi: None declared, Edvard Wigren: None declared, Susanne Gräslund: None declared, Ingrid E. Lundberg Grant/research support from: Dr. Lundberg has received honoraria from Bristol Myers Squibb and MedImmune and is currently receiving a research grant from Bristol Myers Squibb and from Astra Zeneca., Consultant for: She is a scientific advisor for Bristol Myers Squibb, and aTyr