Valuable clinical indicators for identifying infantile-onset inflammatory bowel disease patients with monogenic diseases

BACKGROUND Infantile-onset inflammatory bowel disease(IO-IBD)occurs in very young children and causes severe clinical manifestations,which has poor responses to traditional inflammatory bowel disease(IBD)treatments.At present,there are no simple and reliable laboratory indicators for early screening IO-IBD patients,especially those in whom the disease is caused by monogenic diseases.AIM To search for valuable indicators for early identifying IO-IBD patients,especially those in whom the disease is caused by monogenic diseases.METHODS A retrospective analysis was performed in 73 patients with IO-IBD admitted to our hospital in the past 5 years.Based on the next-generation sequencing results,they were divided into a monogenic IBD group(M-IBD)and a non-monogenic IBD group(NM-IBD).Forty age-matched patients with allergic proctocolitis(AP)were included in a control group.The clinical manifestations and the inflammatory factors in peripheral blood were evaluated.Logistic regression analysis and receiver operating characteristic(ROC)curve analysis were used to identify the screening factors and cut-off values of IO-IBD as well as monogenic IO-IBD,respectively.RESULTS Among the 44 M-IBD patients,35 carried IL-10RA mutations,and the most common mutations were c.301C>T(p.R101W,30/70)and the c.537G>A(p.T179T,17/70).Patients with higher serum tumor necrosis factor(TNF)-αvalue were more likely to have IBD[odds ratio(OR)=1.25,95%confidence interval(CI):1.05-1.50,P=0.013],while higher serum albumin level was associated with lower risk of IBD(OR=0.86,95%CI:0.74-1.00,P=0.048).The cut-off values of TNF-αand albumin were 17.40 pg/mL(sensitivity:0.78;specificity:0.88)and 36.50 g/L(sensitivity:0.80;specificity:0.90),respectively.The increased ferritin level was indicative of a genetic mutation in IO-IBD patients.Its cut-off value was 28.20 ng/mL(sensitivity:0.93;specificity:0.92).When interleukin(IL)-10 level was higher than 33.05 pg/mL(sensitivity:1.00;specificity:0.84),or the onset age was earlier than 0.21 mo(sensitivity:0.82;specificity:0.94),the presence of diseasecausing mutations in IL-10RA in IO-IBD patients was strongly suggested.CONCLUSION Serum TNF-αand albumin level could differentiate IO-IBD patients from allergic proctocolitis patients,and serum ferritin and IL-10 levels are useful indicators for early diagnosing monogenic IO-IBD.