None of the CCA patients had an sIgG4 value greater than 4× ULN (>560 mg/dL). Of the sera from the 50 IAC patients (9 females, 41 males), 39 (78.0%) had an IgG4 level greater than 1× ULN and 25 (50.0%) had an IgG4 value over 2× ULN. Table 1B shows the results of sIgG4 levels in the validation cohort of 161 CCA and 47 IAC patients. In summary, the median sIgG4 levels and the proportion of patients who had sIgG4 levels greater than 1× ULN and 2× ULN (140 and 280 mg/dL) in the CCA and IAC groups were

similar to the findings in the test cohort, except that 1 of the 51 (2.0%) CCA+PSC patients in the validation cohort had an sIgG4 over 4× ULN (>560 mg/dL). To help determine the ability of IgG4 to reliably distinguish IAC from CCA, we used ROC curves to identify the appropriate sIgG4 cutoffs for the two Selleck CP 690550 disease entities (Fig. 3). We found that in the test cohort an sIgG4 of over 2× ULN (>280 mg/dL) yields a specificity of 97.0% in distinguishing IAC from CCA, whereas an sIgG4 of over 4× ULN (>560 mg/dL) yields a specificity of 100%, albeit at a decreased sensitivity of 26%. Compared to the results of the test cohort, in the validation cohort the cutoff of sIgG4

of 2× ULN was less sensitive (34% versus 50%) but still highly specific (96% versus 97%). The performance of sIgG4 in discriminating IAC from all CCA in the test (T) and validation (V) cohorts is summarized in Table 2. Of the 126 CCA patients in the test cohort, 31 had associated buy Paclitaxel PSC (CCA+PSC) and the remaining 95 did not have PSC (CCA-PSC). Twenty-seven (87%) of the 31 CCA+PSC patients had hilar or extrahepatic CCA, whereas four (13%) had intrahepatic CCA. One of the CCA+PSC patients had an overlap syndrome PTK6 of PSC with autoimmune hepatitis and a normal serum IgG4 of 7.7 mg/dL. Seven (22.6%) of the 31 CCA+PSC patients had sera with elevated IgG4 and two (6.5%) of these had an sIgG4 >2× ULN; as compared with 10 (10.5%) and two (2.1%),

respectively, for CCA-PSC patients (P = 0.13 and 0.25, Fisher’s exact test). The median sIgG4 levels were higher in the CCA+PSC group than in the CCA-PSC group, but the difference did not reach statistical significance (44.1 vs 32.7, P = 0.43, rank-sum test) (Table 1A). In the validation cohort of 161 CCA patients, the proportions of CCA+PSC patients with IgG4 levels >1× ULN and >2× ULN were consistent with the proportions in the test cohort and are summarized in Table 1B. In this cohort also, CCA+PSC patients had slightly higher median sIgG4 levels compared to CCA-PSC patients, (45.7 vs 43.7, P = 0.28). Because biliary infiltration with IgG4-positive (IgG4+) plasma cells is one of the hallmarks of IAC, we examined the correlation between the sIgG4 level and the presence of biliary IgG4+ plasma cells in CCA patients in the test cohort with an sIgG4 above the upper limit of normal (17/126).