Anti-MAA and anti-AGE both negatively correlated with levels of complement factors C3 and C4 (p0.002) and correlated positively with erythrocyte sedimentation rate (ESR) (p 0.001), ANA (p=0.02/0.03), anti-double-stranded DNA (p0.005) and anti-Smith (p=0.02). were tested using ELISA in sera of 349 individuals with SLE (mean age 4413 years; 87% female) and RET-IN-1 compared with 108 healthy regulates. Levels and positivity were correlated with medical features and SLE manifestations. Results Anti-MAA, anti-AGE and anti-CarP antibodies were more prevalent in SLE compared with settings (MAA: 29% vs 3%, AGE: 18% vs 4%, CarP: 14% vs 5%, all p0.0001). Anti-MAA and anti-AGE antibodies correlated with medical manifestations and serological inflammatory markers. Individuals 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 individuals without major NPSLE. In addition, anti-PTM antibody levels correlated with mind volumes, an objective measure of nervous system involvement. Conclusions In our NPSLE cohort, a subset of individuals with SLE have anti-PTM antibodies against MAA, AGE and CarP revised proteins. Interestingly, anti-MAA and anti-CarP were more prevalent in NPSLE, a manifestation for which no biomarkers exist. strong class=”kwd-title” Keywords: lupus erythematosus, systemic; autoantibodies; epidemiology Important communications What is already known about this subject? Post-translationally revised (PTM) proteins and anti-PTM antibodies are explained in many diseases, such as rheumatoid arthritis, in which anti-PTM antibodies are associated with disease progression. What does this study add? We demonstrate the presence of several anti-PTM antibodies (anti-malondialdehydeCacetaldehyde adducts, anti-advanced glycation end-products and anti-carbamylation) in individuals with systemic lupus erythematosus (SLE) and their association with different aspects of disease activity in SLE and neuropsychiatric SLE (NPSLE). How might this impact on medical practice or further developments? As virtually no biomarkers exist for NPSLE, anti-PTM antibodies are a potential candidate. Long term studies should further set up the potential part of anti-PTM antibodies in NPSLE. Intro Systemic lupus erythematosus (SLE) is definitely a heterogeneous autoimmune disease characterised by a global loss of self-tolerance. Although autoantibodies are an important hallmark of SLE, many autoantibodies are not specific for SLE or specific SLE manifestations, such as neuropsychiatric involvement (NPSLE).1 Many different types of biomarkers exist and may be applied in different contexts for diagnostic, prognostic and predictive purposes.2 In rheumatoid arthritis (RA), the recognition of anti-citrullinated protein antibodies (ACPAs), antibodies (Abs) directed against a post-translational changes (PTM), offers facilitated the diagnostic process and created fresh insights in its pathophysiology.3 4 Noteworthy, the presence of specific anti-PTM Abs also facilitates discrimination between phenotypes within RA, as they associate with more severe RA.5C8 It is possible that Abs against PTMs may also contribute to the identification of specific phenotypes in individuals with SLE. PTMs can occur naturally, as part of physiological functions, or may be the result of enzymatic or chemical processes.9 10 SLE has been associated with a dysregulated metabolic state and elevated levels of reactive oxygen species,11 which enhances the formation of PTMs. In some situations, immune reactions against PTMs can develop, leading to anti-PTM Abdominal muscles.12 To day, anti-PTM Ab studies in SLE have mainly focused on ACPA and anti-carbamylated protein (anti-CarP) Abs, which associated with improved joint damage.13C16 Several anti-PTM Abs have been associated with general disease activity (SLE Disease Activity Index (SLEDAI)) in lupus.17C19 In addition, RET-IN-1 phospholipid 2-glycoprotein-1 is reported to be modified by PTMs making it more antigenic.20 Around 35% of all individuals with SLE are positive for Abs against these phospholipids, which are associated with antiphospholipid syndrome.21 Overall, studies on anti-PTM Abs in individuals with SLE remain limited and RET-IN-1 techniques to measure anti-PTM Abs vary greatly.18 19 Based on previous studies, we hypothesised that SLE activity can lead to the generation of PTMs on relevant antigens and that there is specificity in breaking tolerance towards these neoantigens. In this study, we focused on IgG antibodies against six different PTMs, selected based on their association with activity in additional diseases and variance in location in the protein, configuration and reversibility. We targeted to first study the presence of these six anti-PTM Abs in individuals with SLE RET-IN-1 using a standardised method to assess specific anti-PTM Ab reactivities. Second, we targeted to assess the association between anti-PTM Abs and medical phenotypes of SLE, in particular NPSLE, for which virtually no biomarkers exist. Additionally, both the subjective medical analysis of NPSLE and objective evidence of nervous system involvement, namely radiological measurements, were assessed. Methods Study design and population Individuals visiting the NPSLE medical center of the Leiden University or RET-IN-1 college Medical Center between 2007 and 2019 with the medical analysis of SLE and authorized informed consent were included in this study. The NPSLE medical ABCG2 center is definitely a tertiary referral center in.