Thalidomide-mediated immunomodulation in a patient with IL-10RA deficiency-associated very early-onset inflammatory bowel disease.

INTRODUCTION

Very early-onset inflammatory bowel disease (VEO-IBD) is frequently triggered by monogenic defects in the pathways responsible for immune system regulation, including mutations in the interleukin-10 receptor alpha (IL-10RA) gene. Patients often show severe and refractory clinical manifestations. Thalidomide has shown immunomodulatory effects in pediatric IBD; however, its immunological effects in IL-10RA-associated VEO-IBD remain poorly defined.

METHODS

A female patient aged 2 months diagnosed with VEO-IBD was enrolled in the study. Clinical data were gathered over time. Whole-exome sequencing was utilized to uncover pathogenic variants for genomic analysis. The expression of IL-10RA was assessed using Western blotting. Flow cytometry was performed both before and after treatment to evaluate the effect of the administration of thalidomide on the populations of T and B lymphocytes, alongside the immune activation levels.

RESULTS

The patient experienced chronic diarrhea, failure to thrive, and recurrent infections. Genetic analysis revealed the presence of compound heterozygous mutations in the IL-10RA gene (c.301C>T and c.537G>A). Western blotting analysis revealed a reduction in the levels of IL-10RA protein expression. Immunophenotyping showed an increase in the percentages of γδ T cells, Th17 cells, transitional B cells, and activated CD8+ T cells before treatment. After thalidomide therapy, the symptoms of diarrhea resolved, the growth parameters improved, the proportions of γδ T cells and transitional B cells decreased, and the inflammatory markers returned to normal levels.

DISCUSSION: This study confirms the immune dysregulation caused by IL-10RA gene mutation in VEO-IBD and demonstrates that thalidomide treatment can improve clinical symptoms and modulate specific lymphocyte subsets. The immune mechanisms behind the response to thalidomide in IL-10RA-associated VEO-IBD should be further explored.