Autoantibodies against specific post-translationally modified proteins are present in patients with lupus and associate with major neuropsychiatric manifestations. Issue 1 (21st April 2022)

• Record Type: Journal Article
• Authors: Monahan, Rory C; van den Beukel, Michelle D; Borggreven, Nicole V; Fronczek, Rolf; Huizinga, Tom W J; Kloppenburg, Margreet; Steup-Beekman, Gerda M; Trouw, Leendert A
• Is Part Of: RMD open. Volume 8:Issue 1(2022)
• Publication Date: 2022-04-21
• Subjects: lupus erythematosus, systemic -- autoantibodies -- epidemiology; Musculoskeletal system -- Diseases -- Periodicals; Rheumatism -- Periodicals; 616.7005
• DOI: 10.1136/rmdopen-2021-002079
• Languages: English
• ISSNs: 2056-5933

Abstract

Abstract : Background: Although autoantibodies are an important hallmark of systemic lupus erythematosus (SLE), most are not specific for SLE or any of its clinical manifestations. Autoantibodies against post-translationally modified (PTM) proteins have been studied extensively in rheumatoid arthritis and associate with disease progression. While PTMs have also been detected in patients with SLE, studies on anti-PTM antibodies remain scarce. We studied the presence of anti-PTM antibodies in SLE and neuropsychiatric SLE (NPSLE), a manifestation that lacks serological markers. Methods: IgG antibody responses against six PTMs (malondialdehyde–acetaldehyde adducts (MAA), advanced glycation end-products (AGE), carbamylation (CarP), citrullination, acetylation and nitration) were tested using ELISA in sera of 349 patients with SLE (mean age 44±13 years; 87% female) and compared with 108 healthy controls. Levels and positivity were correlated with clinical features and SLE manifestations. Results: Anti-MAA, anti-AGE and anti-CarP antibodies were more prevalent in SLE compared with controls (MAA: 29% vs 3%, AGE: 18% vs 4%, CarP: 14% vs 5%, all p≤0.0001). Anti-MAA and anti-AGE antibodies correlated with clinical manifestations and serological inflammatory markers. Patients with major NPSLE showed higher positivity of anti-MAA (39% vs 24%, p=0.01) and anti-CarP antibodies (20% vs 11%, p=0.04) than patients without major NPSLE. In addition, anti-PTM antibody levels correlated with brain volumes, an objective measure of nervous system involvement. Conclusions: In our NPSLE cohort, a subset of patients with SLE have anti-PTM antibodies against MAA, AGE and CarP modified proteins. Interestingly, anti-MAA and anti-CarP were more prevalent in NPSLE, a manifestation for which no biomarkers exist.