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

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 (FDRIn 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/ScidIL2Rγnull 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 Ethanol + CD99: p = 0.03). In a highly inflammatory environment, frequencies of pro-inflammatory M1 monocytes (CD14+ CD64+: unchallenged 8.09±4.72; challenged 14.2±8.62; p = 0.07; CD14+ CD1a+: unchallenged 16.29 ±6.97; challenged 43.81±14.4, p = 0.0003) increased and levels of autoantibodies in serum decreased in the NSG-UC mouse model. These results suggest that autoantibodies are potent biomarkers to discriminate between UC and non-UC and indicate risk to develop UC. In an inflammatory environment, auto-antibodies may promote the pathological phenotype by activating M1 monocytes in the NSG-UC animal model and also in patients with UC.