AUTHOR=van den Beukel Michelle D. , Stoelinga Anna E. C. , van der Meer Adriaan J. , van der Meulen Stef , Zhang Lu , Tushuizen Maarten E. , van Hoek Bart , Trouw Leendert A. 

TITLE=Antibodies against multiple post-translationally modified proteins aid in diagnosis of autoimmune hepatitis and associate with complete biochemical response to treatment

JOURNAL=Frontiers in Medicine

VOLUME=Volume 10 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2023.1195747

DOI=10.3389/fmed.2023.1195747

ISSN=2296-858X

ABSTRACT=Background: (Auto)immune mediated and cholestatic liver disease (AILD) includes autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). Especially AIH is characterized by the presence of autoantibodies and elevated serum immunoglobulins. In rheumatoid arthritis, autoantibodies against posttranslational modifications (PTMs) such as citrullination (Cit) and carbamylation (CarP) are used as diagnostic and prognostic markers, respectively. We studied the presence of six anti-PTM antibodies in patients with the three AILDs and non-AILD.Methods: Antibodies against six PTMs (malondialdehyde-acetaldehyde adducts (MAA), advanced glycation end-products (AGE), CarP, acetylation (AL), Cit, and nitration (NT)) were tested in sera of patients with AILD (n=106), non-AILD (n=101) and compared with healthy controls (HC) (n=100). Levels and positivity were correlated with clinical and biochemical features in a well-defined cohort of untreated AIH patients.Results: Anti-PTM antibodies were more often detectable in sera from AILD patients compared with HCs (anti-MAA: 67.9% vs 2.0%, anti-AGE: 36.8% vs 4.0%, anti-CarP: 47.2% vs 5.0% and anti-AL: 18.9% vs 5.0%). In untreated AIH, time to complete biochemical response (CBR) was associated with anti-MAA, anti-AGE, anti-CarP and anti-AL antibodies.Significantly more patients with at least three anti-PTM antibodies attained CBR at 12 months of treatment (13 vs 3 p=0.01).: Anti-PTM antibodies are frequently present in AILD. The presence of anti-MAA, anti-AGE and anti-CarP antibodies correlates with the presence of AIH within this cohort. In AIH, harboring at least three anti-PTM antibody responses is positively associated with CBR. Determination of anti-PTM antibodies in liver disease may have diagnostic and prognostic value. Key points • Antibodies against post-translational modifications (anti-PTM antibodies) are used as diagnostic and prognostic markers in several autoimmune diseases, such as rheumatoid arthritis • This study shows that these antibodies are often present in autoimmune mediated liver disease • Compared to cholestatic liver disease, in autoimmune hepatitis most patients harbor antibodies against multiple post-translational modifications • Such a multiple positivity was associated with complete biochemical response after