Presenter of 2 Presentations
IS018 - FROM COVID-19 TO AUTOIMMUNE DISEASES AND BACK? (ID 851)
Abstract
Abstract Body
Coronavirus Disease 2019 (COVID-19) is a heterogenous disease with a high variability of clinical symptoms and complications. Here, immune perturbation is a hallmark with ambivalent roles of the involved immune compartments. Among other cell lineages, the plasma cell compartment, responsible for antibody production, is affected by this dichotomy between mounting fast immune defence and potentially deleterious autoimmunity: while neutralizing antibodies against protein structures of SARS-CoV-2 were produced as part of the physiological immune response, growing evidence hints towards a broad activation of plasma cells. Therefore, we have performed a systematic screening for abs confirming induction of diverse functional abs by SARS-CoV-2 infection, targeting several immunomodulatory proteins such as cytokines/chemokines and their respective receptors, which belong to the group of G-protein coupled receptors (GPCR). Abs against GPCR have been linked before to chronic diseases such as systemic sclerosis, sharing many clinical features with COVID-19, or to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), one of the most common symptoms in post-COVID-19 syndrome. In addition, as also shown before in autoimmune diseases, these abs reveal specific correlations with other antibodies and these correlations became disrupted with the severity of Covid-19 infection. We have identified several antibodies discriminating mild from severe live-threatening COVID-19 such as abs directed to the angiotensin receptor type-1 (AT1R). As recently identified, AT1R abs are involved in the development of interstitial lung disease as well as in skin inflammation and in fibrotic pathways. AT1R abs act on immune cells such as monocytes and induce a signalling via their Fab fragment to produce profibrotic and inflammatory cytokines and chemokines. In HEK cells, they only act synergistically with their natural ligand angiotensin II. We found a disruption of ab correlations depending on the severity of COVID-19. Other interesting anti-GPCR abs in COVID-19 infection are abs directed to the thrombin receptor PAR-1, which are linked to alterations in the coagulation system. COViD-19 infection is also characterized by increased abs directed to the chemokine receptor CXCR3, which were linked before to the presence of interstitial lung disease in systemic sclerosis. Taken together, our studies support our hypothesis that natural IgG abs cause and modulate diseases in general and not only autoimmune diseases. The identification of their individual function could explain physiology as well as pathophysiology and should be a focus to develop better therapies.
O132 - CONFOUNDING INFLUENCES ON FIBROMYALGIA AND AUTOANTIBODIES DIRECTED TO NEURO- AND VASOREGULATORY MOLECULES NEED TO BE CONSIDERED IN BIOMARKER RESEARCH (ID 739)
Abstract
Background and Aims
Fibromyalgia syndrome (FMS) is often present in autoimmune diseases and biomarkers are currently missing. In this study, we aimed to delineate changes in natural autoantibodies (AAB) directed to neuro- and vasoregulatory molecules and potentially confounding factors.
Methods
Sera from 91 patients with primary FMS (pFMS), 24 patients with secondary FMS (sFMS) and 31 healthy controls (HC) were analysed for the presence of 27 different natural AAB directed to e.g., cholinergic, opioid, cannabinoid, endothelin or complement receptors or angiotensin system molecules by individual ELISAs (CellTrend GmbH, Luckenwalde, Germany). Linear regression adjusted for potential confounders was used to compare AAB-levels between groups. Random forest analysis was applied to differentiate between pFMS and HC by measuring the Area Under the Curve Receiver operating characteristics (AUC-ROC).
Results
Patients with pFMS differed in levels of some of the investigated AAB compared to HC. After adjustment for age (linear and squared) and sex, only some differences in the AAB levels remain significant, none of which remained significant after further adjustment for BMI. Random forest analysis revealed an AUC-ROC that was influenced by covariate adjustment to a non-negligible degree.
Conclusions
AAB might be potential biomarkers for pFMS and could provide a link to understand how acquired conditions interact with the immune system. However, these results highlight the important role of correct covariate adjustment for research on biomarkers supposed to classify FMS or other diseases. In FMS for instance, adjusting for BMI might be correct or incorrect due to its unclear causal relation to disease state and AAB levels.