Comparison Of Clinical Phenotypes Between Different Ages Of IBD Onset,Analysis Of Phenotypic And Genotypic Characterization Of Monogenic IBD

First partBackground:The incidence of inflammatory bowel disease(IBD)is dramatically increased during the recent years.The clinical characterization is different based on the different ages of disease onset,especially with the disease onset below the six years of age.There were no large clinical studies based on the different ages of IBD onset in China.The objective of this single-center study was to compare the clinical phenotypes of different groups based on the ages of disease onset at a tertial hospital in southern China.Methods:A retrospective analysis of children 0 to 18 years of age diagnosed with IBD according to Porto criteria was performed at a tertiary hospital in south China from 2005 to 2017.Patients’ data including sex,first symptoms and time of disease onset,time of disease diagnosis,symptoms,laboratory findings,endoscopic findings,pathological changes,family history,surgical history,medication history,and prognosis were collected,and these data were compared between infantile onset IBD(IO-IBD),very early onset IBD(VEO-IBD),early onset IBD(EO-IBD)and late onset IBD(LO-IBD).Results:Of the 127 IBD patients identified during the 12-year study period,the ratio of male to female was 1.52:1.0.Crohn’s disease(CD)was the predominant diagnosis in each group.105 patients(82.68%)were diagnosed with CD,7.09%of the patients were diagnosed with ulcerative colitis(UC),and 10.24%of the patients were diagnosed with IBD unclassified(IBDU).The median age of diagnosis was 125 M(IQR:3 to 199 M).35.43%of the patients with the disease onset before six years and with the peak incidence of 10 to 18 year of age.No positive family history was found in our study.Symptoms of diarrhea,bloody stools and growth failure in 10-IBD group were significantly more common compared with other groups(p=0.001,p=0.000 and p=0.004,respectively).Perianal disease complications in io-IBD occurred more than in other groups(p=0.024).There were no significantly differences between the laboratory investigations including C reactive protein(CRP),erythrocyte sedimentation rate(ESR)and the level of serum albumin among the four groups.The predominant disease location in 10-CD was colonic involvement(73.33%),and intestinal involvement was rare.CD patients 0-6 yrs old primarily presented with colonic disease(51.52%),and patients older than six years of age primarily presented with both colonic and small bowel disease(54.17%).The incidence of intestinal stricture and perfusion were higerst in the VEO-IBD group(38.89%).Capsule endoscopy was effective in the diagnosis of small intestinal bowel disease,and the main findings were ulcerative lesions.Noncaseating granulomas were found most commonly in LO-CD(13.33%),other findings were chronic inflammation,chronic ulcer and increase of eosinophils.VEO-IBD patients need higher rate of immunosuppressant(68.18%)and infliximab(50%).The abdominal surgery in the VEO-IBD group was the highest(p=0.025).The death rate in VEO-IBD group was secondary to the IO-IBD group.Conclusions:CD was the predominant diagnosis in the four groups in this cohort.IO-IBD mainly preseted with darhhea,bloody stool and perianal diseases.The predominant disease location in the patient below six years were clonic disease and colonia and small bowel involvement were in predominance in the patient older than six years old.And VEO-IBD patients showed more severe clinical course compared with other goups in our study.Second partObjectives:The aim of this study was to analyze the clinical differences between monogenic and non-monogenic very early onset inflammatory bowel disease(VEO-IBD)and to investigate the phenotypic and genotypic characterization of monogenic IBD through genetic testing.Methods:A retrospective analysis was performed in children aged 0 to 6 years diagnosed with VEO-IBD in a tertiary hospital in southern China from 2005 to 2017.Clinical data of VEO-IBD patients were collected,and the genetic characteristics were analyzed using whole exome sequencing(WES)and target gene panel sequencing(TGPS).Results:A total of 54 VEO-IBD patients,including 57.41%of patients with disease onset before the age of two years,were included in this study.The ratio of male to female was 2.18:1.While the diagnosis of Crohn’s disease(CD)or CD-like intestinal manifestations accounted for 72.22%of VEO-IBD cases,ulcerative colitis(UC)or UC-like intestinal manifestations and IBD unclassified(IBDU)accounted for 9.26%and 20.37%of cases,respectively.Nine patients(16.67%)were identified to have monogenic IBD by genetic testing according to their clinical presentation.The median age of disease onset in the monogenic group was less than that of the non-monogenic IBD group with 1 M(IQR:0,72 M),19.5 M(IQR:0,72 M),respectively,p=0.008.And the median age of disease diagnosis in monogenic group were less than that of non-monogenic IBD group with 18 M(IQR:4 to 78 M)and 43.5 M(IQR:3 to 173 M),respectively,p=0.021.The incidence of perianal disease in the monogenic group was higher than that of the non-momogenetic group(p=0.001).There were no significant differences between the Z-scores of weight for age and height for age between the two groups.Laboratory findings demonstrated similar results in the two groups.Next generation sequencing was performed in 16 patients.Five patients were observed to have IL-10 receptor mutation,two patients had chronic granulomatous disease(CGD),one patient had common variable immunodeficiency disease(CVID)and one patient had XIAP deficiency.Conclusions:There was a high proportion of monogenic IBD in the VEO-IBD group.Monogenic IBD and non-monogenic IBD showed similar clinical features.Furthermore,next generation sequencing played an important role in the diagnosis of VEO-IBD patients with high risks of monogenic IBD.IL-10RA mutation was predominant in our study.