Autoantibodies against C5aR1, C3aR1, CXCR3, and CXCR4 are decreased in primary Sjogren’s syndrome

Yue, Xiaoyang; Deng, Fengyuan; Chen, Juan; Ju, Youlun; Zheng, Jiangjun; Chen, Yan; Huang, Qiaoniang; Gao, Xing; Liu, Zuguo; Luo, Jiao; Müller, Antje; Heidecke, Harald; Riemekasten, Gabriela; Petersen, Frank; Yu, Xinhua

doi:10.1016/j.molimm.2020.12.027

Cited by 5 publications

(4 citation statements)

References 52 publications

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“…While PCS patients analyzed here were median seven months post-infection, ME/CFS patients in these previous studies were mainly analyzed much later in the disease course. Lower GPCR AAB levels were found in vascular diseases such as acute coronary syndrome or vasculitis and in progressive lung involvement in rheumatic disease, too (26,88,91). One explanation could be that lower levels of circulating AABs result from AAB binding to their target molecules upregulated in the post-infection inflammatory endothelium or tissue in PCS patients.…”

Section: Discussionmentioning

confidence: 99%

“…The CXCL10-CXCR3 axis is also likely to play an essential role in COVID-19-induced tissue injury and fibrosis, including pulmonary and cardiac fibrosis, endothelitis, and endothelial damage. In Sjogren’s Syndrome, an autoimmune disease with a high prevalence of fatigue, anti-CXCR3 AAB levels were also diminished and negatively correlated with circulating lymphocyte counts ( 88 ).…”

Section: Discussionmentioning

confidence: 99%

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Dysregulated autoantibodies targeting vaso- and immunoregulatory receptors in Post COVID Syndrome correlate with symptom severity

Sotzny

Filgueiras²,

Kedor³

et al. 2022

Front. Immunol.

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Most patients with Post COVID Syndrome (PCS) present with a plethora of symptoms without clear evidence of organ dysfunction. A subset of them fulfills diagnostic criteria of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Symptom severity of ME/CFS correlates with natural regulatory autoantibody (AAB) levels targeting several G-protein coupled receptors (GPCR). In this exploratory study, we analyzed serum AAB levels against vaso- and immunoregulatory receptors, mostly GPCRs, in 80 PCS patients following mild-to-moderate COVID-19, with 40 of them fulfilling diagnostic criteria of ME/CFS. Healthy seronegative (n=38) and asymptomatic post COVID-19 controls (n=40) were also included in the study as control groups. We found lower levels for various AABs in PCS compared to at least one control group, accompanied by alterations in the correlations among AABs. Classification using random forest indicated AABs targeting ADRB2, STAB1, and ADRA2A as the strongest classifiers (AABs stratifying patients according to disease outcomes) of post COVID-19 outcomes. Several AABs correlated with symptom severity in PCS groups. Remarkably, severity of fatigue and vasomotor symptoms were associated with ADRB2 AAB levels in PCS/ME/CFS patients. Our study identified dysregulation of AAB against various receptors involved in the autonomous nervous system (ANS), vaso-, and immunoregulation and their correlation with symptom severity, pointing to their role in the pathogenesis of PCS.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Dysregulated autoantibodies targeting vaso- and immunoregulatory receptors in Post COVID Syndrome correlate with symptom severity

Sotzny

Filgueiras²,

Kedor³

et al. 2022

Front. Immunol.

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“…The beneficial effects of the C5aR antagonist avacopan in AAV demonstrate the relevance of both C5a and the GPCR C5aR (6,7). Previously, we detected that circulating antibodies directed against various GPCR were decreased in GPA in comparison to healthy donors as well as other autoimmune diseases (8,16). Accordingly, here we report that anti‐GPCR antibodies recognizing C5aR and C3aR displayed lower values in AAV when compared to healthy donors.…”

Section: Discussionmentioning

confidence: 98%

Low Concentrations of C5a Complement Receptor Antibodies Are Linked to Disease Activity and Relapse in Antineutrophil Cytoplasmic Autoantibody–Associated Vasculitis

Klapa

Müller

Koch

et al. 2023

Arthritis & Rheumatology

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Objective To examine concentrations of circulating antibodies targeting C3a and C5a complement receptors in antineutrophil cytoplasmic autoantibody (ANCA)–associated vasculitis (AAV) and analyze their association with disease activity. Methods Concentrations of antibodies against C3a and C5a complement receptors (anti‐C3aR and anti‐C5aR) and plasma complement fragments C3a and C5a were determined in patients with AAV (n = 110; granulomatosis with polyangiitis [GPA; n = 82] or microscopic polyangiitis [MPA; n = 28]), systemic lupus erythematosus (SLE) patients as disease controls (n = 36), and healthy donors (n = 220). C3aR and C5aR expression by circulating neutrophils, monocytes, and T cells was analyzed using flow cytometry. Clinical data were assessed at time of serum sampling and during follow‐up for 60 months. Results In AAV, anti‐C3aR and anti‐C5aR antibodies were decreased (P = 0.0026 and P ≤ 0.0001, respectively). In remission, anti‐C3aR antibody concentrations rose to values comparable to healthy donors, whereas anti‐C5aR antibody concentrations did not. In GPA, anti‐C5a and anti‐C5aR antibody concentrations inversely correlated with each other (r = −0.6831, P = 0.0127). In newly diagnosed GPA, decreased concentrations of anti‐C5aR antibodies but not anti‐C3aR antibodies were associated with disease activity (P = 0.0009). Moreover, low anti‐C5aR antibodies were associated with relapse in GPA (hazard ratio 3.54, P = 0.0009) and MPA (hazard ratio 4.41, P = 0.0041). The frequency of C5aR‐expressing cells within T cell populations was increased in GPA (P = 0.0021 for CD4+ T cells; P = 0.0118 for CD8+ T cells), but not in MPA. Conclusion Low concentrations of anti‐C5aR antibodies reflect disease activity and are associated with an increased risk for relapse in AAV.

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“…Zahra et al found that HIST1H4 was involved in the pathogenesis of HELLP syndrome and was closely related to autoimmunity as one of the hub genes with the highest degree of connectivity [ 45 ]. Yue reported that the number of autoantibodies against C3AR1 decreased in pSS [ 46 ]. Moreover, our results showed that 10 hub genes all had good diagnostic efficiency.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic markers and potential therapeutic agents for Sjögren’s syndrome screened through multiple machine learning and molecular docking

Zhou

Wang

Zhang

et al. 2023

Clinical and Experimental Immunology

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Primary Sjögren's syndrome(pSS) is a chronic inflammatory autoimmune disease, which mainly damages patients' exocrine glands. Sensitive early diagnostic indicators and effective treatments for pSS are lacking. Using machine learning methods to find diagnostic markers and effective therapeutic ways for pSS is of great significance. In our study, first, 1643 differentially expressed genes (DEGs; 737 were upregulated and 906 were downregulated) were ultimately screened out and analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes based on the date sets from the Gene Expression Omnibus. Then, support vector machine, Least absolute shrinkage and selection operator regression, random forest, and weighted correlation network analysis were used to screen out feature genes from DEGs. Subsequently, the intersection of the feature genes was taken to screen 10 genes as hub genes. Meanwhile, the analysis of the diagnostic efficiency of 10 hub genes showed their good diagnostic value for pSS, which was validated through immunohistochemistry on the paraffin sections of the labial gland. Subsequently, a multi-factor regulatory network and correlation analysis of hub genes were performed, and the results showed that ELAVL1 and IGF1R were positively correlated with each other but both negatively correlated with the other seven hub genes. Moreover, several meaningful results were detected through the immune infiltration landscape. Finally, we used molecular docking to screen potential therapeutic compounds of pSS based on the hub genes. We found that the small molecules DB08006, DB08036, and DB15308 had good docking scores with ELAVL1 and IGF1R simultaneously. Our study might provide effective diagnostic biomarkers and new therapeutic ideas for pSS.

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Autoantibodies against C5aR1, C3aR1, CXCR3, and CXCR4 are decreased in primary Sjogren’s syndrome

Cited by 5 publications

References 52 publications

Dysregulated autoantibodies targeting vaso- and immunoregulatory receptors in Post COVID Syndrome correlate with symptom severity

Dysregulated autoantibodies targeting vaso- and immunoregulatory receptors in Post COVID Syndrome correlate with symptom severity

Low Concentrations of C5a Complement Receptor Antibodies Are Linked to Disease Activity and Relapse in Antineutrophil Cytoplasmic Autoantibody–Associated Vasculitis

Diagnostic markers and potential therapeutic agents for Sjögren’s syndrome screened through multiple machine learning and molecular docking

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