Autoantibodies have been associated with autoimmune diseases. However, studies have identified autoantibodies in healthy donors (HD) who do not develop autoimmune disorders. Here we provide evidence of a network of immunoglobulin G (IgG) autoantibodies targeting G protein-coupled receptors (GPCR) in HD compared to patients with systemic sclerosis, Alzheimer’s disease, and ovarian cancer. Sex, age and pathological conditions affect autoantibody correlation and hierarchical clustering signatures, yet many of the correlations are shared across all groups, indicating alterations to homeostasis. Furthermore, we identify relationships between autoantibodies targeting structurally and functionally related molecules, such as vascular, neuronal or chemokine receptors. Finally, autoantibodies targeting the endothelin receptor type A (EDNRA) exhibit chemotactic activity, as demonstrated by neutrophil migration toward HD-IgG in an EDNRA-dependent manner and in the direction of IgG from EDNRA-immunized mice. Our data characterizing the in vivo signatures of anti-GPCR autoantibodies thus suggest that they are a physiological part of the immune system.

COVID-19 shares the feature of autoantibody production with systemic autoimmune diseases. In order to understand the role of these immune globulins in the pathogenesis of the disease, it is important to explore the autoantibody spectra. Here we show, by a cross-sectional study of 246 individuals, that autoantibodies targeting G protein-coupled receptors (GPCR) and RAS-related molecules associate with the clinical severity of COVID-19. Patients with moderate and severe disease are characterized by higher autoantibody levels than healthy controls and those with mild COVID-19 disease. Among the anti-GPCR autoantibodies, machine learning classification identifies the chemokine receptor CXCR3 and the RAS-related molecule AGTR1 as targets for antibodies with the strongest association to disease severity. Besides antibody levels, autoantibody network signatures are also changing in patients with intermediate or high disease severity. Although our current and previous studies identify anti-GPCR antibodies as natural components of human biology, their production is deregulated in COVID-19 and their level and pattern alterations might predict COVID-19 disease severity.

Background: Metabolites of tryptophan, produced via the kynurenine pathway (kynurenines), have been linked to Alzheimer’s disease (AD) in small cohorts with conflicting results. Objective: To compare differences in plasma kynurenine levels between AD and controls and identify potential associations with cognition. Methods: The study included 65 histopathologically-confirmed AD patients and 65 cognitively-screened controls from the Oxford Project to Investigate Memory and Ageing (OPTIMA) cohort. Cognition was assessed using the Cambridge Cognitive Examination (CamCog). Tryptophan, kynurenines, neopterin, and vitamin B6 forms were measured in plasma by liquid chromatography-tandem mass spectrometry. Non-parametric statistics, logistic regression and standardized robust regressions were applied with a false discovery rate of 0.05. Results: Tryptophan, xanthurenic acid, 3-hydroxyanthranilic acid, and quinolinic acid were lower in AD (Odds ratios (ORs) 0.24 –0.47; p-values <0.001 –0.01). Pyridoxal 5’phosphate did not differ between AD and controls. Kynurenine, anthranilic acid, quinolinic acid, and markers of immune activation (neopterin, kynurenine/tryptophan ratio, and the PAr index (Pyridoxic acid/(Pyridoxal 5’phosphate + Pyridoxal)) increased with age (β 0.31 –0.51; p-values <0.001 –0.006). Xanthurenic acid decreased with age (β: –0.42, p < 0.001). Elderly AD patients with high quinolinic acid performed worse on the CamCog test, indicated by a significant age*quinolinic acid interaction (β 0.21, p < 0.001). Conclusion: Plasma concentrations of several kynurenines were lower in patients with AD compared to controls. Low xanthurenic acid occurred in both AD and with aging. Inflammation-related markers were associated with age, but not AD. However, elevated QA was associated with poor cognition in older AD patients.

In-hospital delirium is associated with adverse outcomes and is underdiagnosed, limiting research and clinical follow-up. To compare the incidence of in-hospital delirium determined by chart-based review of electronic medical records (D-CBR) with delirium discharge diagnoses (D-DD). Furthermore, to identify differences in symptoms, treatments and delirium triggers between D-CBR and D-DD. The community-based cohort included 2,115 participants in the Hordaland Health Study born between 1925 and 1927. Between 2018 and 2022, we retrospectively reviewed hospital electronic medical records from baseline (1997–99) until death prior to 2023. D-DD and D-CBR were validated using The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria for delirium. Of the 2,115 participants, 638 had in-hospital delirium. The incidence rate (IR) of D-CBR was 29.8 [95% confidence interval 28, 32] per 1,000 person-years, whereas the IR by D-DD was 3.4 [2.8, 4.2]. The IR ratio was 9.14 (P < 0.001). Patients who received pharmacological treatment for delirium (n = 121, odds ratio (OR) 3.4, [2.1, 5.4], P < 0.001), who were affected by acute memory impairment (n = 149, OR 2.8, [1.8, 4.5], P < 0.001), or change in perception (n = 137, OR 2.9, [1.8, 4.6] P < 0.001) had higher odds for D-DD. In contrast, post-operative cases (OR 0.2, [0.1, 0.4], P < 0.001) had lower odds for D-DD. Underdiagnosis of in-hospital delirium was a major issue in our study, especially in less severe delirium cases. Our findings emphasise the need for integrating systematic delirium diagnostics and documentation into hospital admission and discharge routines.