It is unclear as to whether there are prognostic implications of rectal sparing as it relates to therapeutic response or surgical outcomes. group between pANCA and Anti-CBir1. Relative rectal sparing was more common in +CBir1, 16% versus 7% (= 0.02). Calprotectin was lower in Anti-CBir1+ (Median [IQR] 1495 mcg/g [973C3333] vs 2648 mcg/g [1343C4038]; = 0.04). Vitamin D 25-OH sufficiency was associated with Anti-CBir1+ (= 0.0009). Conclusions The frequency of pANCA in children was consistent with adult observations. High titer pANCA was associated with more extensive disease, supporting the idea that the FR 167653 free base magnitude of immune reactivity may reflect disease severity. Anti-CBir1+ was more common in younger ages, suggesting host-microbial interactions may differ by patient age. toxin. Patients were all newly diagnosed with UC, and this was a clinical, endoscopic, and histologic diagnosis of UC using previously established criteria. Exclusionary criteria included any clinical, endoscopic, radiologic, or histologic evidence of CD. Age Age was evaluated by years in categories of 4C6, 7C10, 11C13, and 14C17 years old to assess trends in seropositivity across childhood and adolescence. Clinical Disease Activity Clinical activity was determined by the PUCAI (range 0C85) and endoscopic activity by the Mayo endoscopy subscore 15. PUCAI 10 denoted inactive disease/remission, 10C34 denoted mild, 35C64 denoted moderate, and 65 denoted severe disease. The baseline PUCAI was defined as the last PUCAI on or before the treatment start date, and the majority ( 60%) occurred on the scope date itself. Endoscopic Assessment Endoscopic evaluation included assessment of mucosal inflammation noting granularity, loss of vascular pattern, small superficial ulcers, mucopurulent exudate, and a line of demarcation between abnormal and normal colon in a patient whose colitis did not extend to the cecum. Note was made whether there was patchiness to the endoscopic appearance or relative rectal sparing. Disease Extent Disease extent was classified as proctosigmoiditis, left-sided colitis (to the splenic flexure), extensive colitis (to the hepatic flexure), and pancolitis (to the cecum). In analyses, we combined extensive colitis, pancolitis, and cases where a limited examination was performed due to severity of disease. Visual evidence of inflammation, not histology, was used to determine disease extent. Histology Centralized histologic examination was performed on a single rectal biopsy by one of the authors (MC) who was blinded to clinical data via a standardized scoring system that was FR 167653 free base created for PROTECT to evaluate degree of inflammation and architectural changes, and this scoring system has been previously published16. Of note, chronic features were scored as either present or absent, and these included ulcer/erosion, surface villiform changes, basal plasmacytosis, basal lymphoid aggregates, Paneth cell metaplasia, and crypt architectural abnormalities. Laboratory Assessment Hemoglobin (Hgb), hematocrit (Hct), white blood cell count (WBC), serum albumin, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were recorded from local site standard-of-care assessments, as available, within 4 weeks prior to initial UC treatment and not more than 2 days after initiating treatment. For some sites, the standard of care for milder disease did not include laboratory studies before a colonoscopy, and so the baseline window for participants with a mild PUCAI was extended to 8 weeks. Plasma albumin was measured at a central laboratory by ELISA per manufacturers instructions (Cell Biolabs, Inc., San Diego, CA) for participants with no available local serum value. We report observed values of all laboratory studies with the exception of C-reactive protein, which we report with respect to the upper limit of normal (ULN) for the local laboratory. Fecal calprotectin was determined using an ELISA (Bhlmann Laboratories AG, Sch?nenbuch, Switzerland) from stool samples collected before colonoscopy cleanout or at least 2 days after colonoscopy, but not more than 3 days after initial UC treatment 17, 18. Vitamin D 25-OH KLRD1 was performed centrally from plasma collected at baseline, and the level was defined as sufficient (30 ng/mL), insufficient (20- 30 ng/mL), or deficient ( 20 ng/mL) 19. Serology Serologic determination of pANCA, ASCA IgG and IgA, Anti-CBir1, and anti-outer membrane C (Anti-OmpC) was performed at Cedars-Sinai Hospital, FR 167653 free base Los Angeles, California, utilizing previously published methods20. Perinuclear anti-neutrophil cytoplasmic antibody was considered high-titer at a level of.