Autoantibodies as diagnostic markers and potential drivers of inflammation in ulcerative colitis

Jodeleit, Henrika; Milchram, Lisa; Soldo, Regina; Beikircher, Gabriel; Schoenthaler, Silvia; Al-amodi, Omar; Wolf, Eckhard; Beigel, Florian; Weinhaeusel, Andreas; Siebeck, Matthias und Gropp, Roswitha (2020): Autoantibodies as diagnostic markers and potential drivers of inflammation in ulcerative colitis.
In: PLOS One 15(2), e0228615

Abstract

To date, no comprehensive analysis of autoantibodies in sera of patients with ulcerative colitis has been conducted. To analyze the spectrum of autoantibodies and to elucidate their role serum-IgG from UC patients (n = 49) and non-UC donors (n = 23) were screened by using a human protein microarray. Screening yielded a remarkable number of 697 differentially-reactive at the nominal 0.01 significance level (FDR<0.1) of the univariate test between the UC and the non-UC group. CD99 emerged as a biomarker to discriminate between both groups (p = 1e-04, AUC = 0.8). In addition, cytokines, chemokines and growth factors were analyzed by Olink's Proseek (R) Multiplex Inflammation-I 96x96 immuno-qPCR assay and 31 genes were significant at the nominal 0.05 level of the univariate test to discriminate between UC and non-UC donors. MCP-3, HGF and CXCL-9 were identified as the most significant markers to discriminate between UC patients with clinically active and inactive disease. Levels of CXCL10 (cor = 0.3;p = 0.02), CCL25 (cor = 0.25;p = 0.04) and CCL28 (cor = 0.3;p = 0.02) correlated positively with levels of anti CD99. To assess whether autoantibodies are detectable prior to diagnosis with UC, sera from nine donors at two different time points (T-early, median 21 months and T-late, median 6 months) were analyzed. 1201 features were identified with higher reactivity in samples at time points closer to clinical UC presentation. In vitro, additional challenge of peripheral mononuclear cells with CD99 did not activate CD4+ T cells but induced the secretion of IL-10 (-CD99: 20.21 +/- 20.25;+CD99: 130.20 +/- 89.55;mean +/- sd;p = 0.015). To examine the effect of CD99 in vivo, inflammation and autoantibody levels were examined in NOD/ScidIL2R gamma(null) mice reconstituted with PBMC from UC donors (NSG-UC). Additional challenge with CD99 aggravated disease symptoms and pathological phenotype as indicated by the elevated clinical score (-CD99: 1.85 +/- 1.94;+CD99: 4.25 +/- 1.48) and histological score (-CD99: 2.16 +/- 0.83;+CD99: 3.15 +/- 1.16, p = 0.01). Furthermore, levels of anti-CD99 antibodies increased (Control: 398 +/- 323;mean MFI +/- sd;Ethanol + PBS: 358 +/- 316;Ethanol + CD99: 1363 +/- 1336;Control versus

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1932-6203
• Sprache: Englisch