Serological profiling of Crohn’s disease and ulcerative colitis patients reveals anti-microbial antibody signatures

Figure 1 Phylogenetic tree of microbes studied with their corresponding number of proteins analyzed. A: Fifty species of bacteria with 1173 proteins were segregated into 6 phyla; B: Thirty-three species of viruses with 397 proteins were segregated into 10 phyla.

Figure 2 Sequence homology of target antigens of validated antibodies and overlap of antibodies among Crohn’s disease and ulcerative colitis. A: Heatmap showing sequence homology among target antigens for antibodies with validated performance of ≥ 14% sensitivity at 96% specificity comparing Crohn’s disease (CD) patients with healthy controls; B: CD_IgG, ulcerative colitis (UC)_IgG, CD_IgA and UC_IgG represent the overlap of anti-microbial antibodies of IgG and IgA isotypes in CD and UC patients with ≥ 14% sensitivity at 96% specificity against healthy controls in the discovery set. CD: Crohn’s disease; UC: Ulcerative colitis.

Figure 3 Receiver operating characteristic curves to discriminate Crohn’s disease, ulcerative colitis, and healthy controls. A: Receiver operating characteristic (ROC) curve for Crohn’s disease (CD) vs healthy controls. Area under the curve (AUC) values of novel anti-flagellin antibodies (HP_0115, CK_LafA, CK_LafA.1, VC_flaD, VC_flaB, VC_flaE, VC_flaA) and anti-non-flagellin antibodies (BVU_0562, SP_1992, PMI_RS06815, SF_Lpp) was 0.73 and 0.75, respectively. The AUC value obtained with a combination of novel anti-flagellin and anti-non-flagellin antibodies was 0.81; B: ROC curve for ulcerative colitis (UC) vs healthy controls. The AUC value obtained with a combination of 7 markers was 0.87; C: ROC curve for CD vs UC. The AUC value obtained with a combination of 7 markers was 0.82.

Figure 4 Spearman’s rank correlation coefficient heatmap of anti-microbial antibodies and autoantibodies in Crohn’s disease patients. The names of anti-microbial antibodies are colored in blue while autoantibodies are colored in black.