A Rare Immunodeficiency As a Cause of Inflammatory Bowel Disease; ARPC1B Deficiency

Abstract

Actin-related protein 2/3 complex subunit 1B (ARPC1B) is involved in the control of actin polymerization. Homozygous loss-of-function mutations in ARPC1B cause immunodeficiency 71 classified as the syndromic combined immunodeficiency with congenital thrombocytopenia. Here we describe two siblings presented with homozygous mutations in the ARPC1B gene. Patient 1, a 12-year-old male, presented with bloody diarrhea, vomiting, fever and eczema starting at the age of five months. GIS endoscopic examination was compatible with Chron’s Disease. He had repeated hospitalizations due to fever, bloody diarrhea, vomiting, pneumonia, asthma, and bronchiolitis. Physical examination was normal except for marked growth retardation. Complete blood count (CBC) revealed thrombocytopenia with normal MPV values, lymphopenia as well as eosinophilia. He had high Ig A, low Ig M, and normal Ig G and Ig E levels. In the lymphocyte subgroup analysis, CD3+, CD8+ T, CD 19+ B cell and RTE percentages were low, and CD21+38+ low B cell percentages were high. Lymphocyte proliferation and Treg cell analysis were normal compared to healthy controls. Patient 2, Patient 1’s three-year-old brother started to complain of vomiting, bloody diarrhea, and eczema when he was four days old. Colonoscopy was revelaed Crohn’s Disease. He had episodes of wheezing and repeated hospitalizations for bronchiolitis. Physical examination revealed growth retardation and severe eczema. CBC was normal except for intermittent leukocytosis and eosinophilia. He had high Ig A and Ig E, low Ig M, and normal Ig G levels. In lymphocyte subgroup analysis, CD3 + T cell, RTE, naive, and CSM B cell percentages were low, CD21+38+ low B and Exhausted Cd8+ T cell percentages were high. T cell proliferative response was significantly lower than that in healthy controls. Treg cell analysis was also found to be significantly lower.Homozygous splicing mutation in the ARPC1B gene was detected in the WGS analysis of the patients. They are preparing for hematopoietic stem cell transplantation.IBD is an important finding of immune dysregulation. Advances in next-generation gene sequencing are revealing the underlying immunodeficiencies of IBDs. ARPC1B identified in our patients is an example of this. Diagnosis of patients reduces mortality and morbidity by providing new treatment options.