MHC-II deficiency among Egyptians: novel mutations and unique phenotypes

Publication date: Available online 28 August 2018

Source: The Journal of Allergy and Clinical Immunology: In Practice

Author(s): Rabab E. El Hawary, Andrea A. Mauracher, Safa S. Meshaal, Alia Eldash, Dalia S. Abd Elaziz, Radwa Alkady, Sohilla Lotfy, Lennart Opitz, Nermeen M. Galal, Jeannette A. Boutros, Jana Pachlopnik Schmid, Aisha M. Elmarsafy

Abstract

Background

Major histocompatibility complex class (MHC-II) deficiency leads to defective CD4+ T cell function that results from impaired antigen presentation. A genetic disorder in one of four genes results in this syndrome that is associated with the clinical phenotype of combined immunodeficiency.

Objectives

We describe the clinical, immunological and molecular characteristics of 10 Egyptian patients from 9 different families having presented with MHC-II deficiency between 2012 and 2017.

Methods

An initial diagnosis based on the combination of clinical features and low HLA- DR expression by flow cytometry was confirmed by genetic analyses.

Results

Symptoms included failure to thrive (n=9), persistent diarrhea (n=5) and pneumonia (n=8). Septicemia due to coagulase-negative staphylococci (n=1) and Candida krusei (n=1) was diagnosed. Nine patients orally received the live attenuated polio vaccine and three patients developed acute flaccid paralysis thereafter. Nine patients received the BCG vaccine and none developed obvious signs of BCGitis. Four patients carried RFXANK gene mutations, 3 carried RFX5 gene mutations, one carried a CIITA gene mutation and none carried RFXAP gene mutation. 6/7 detected mutations were previously unreported mutations: c.431T>C, c.247_250delTCAG and c.600delG in RFXANK, c.116+1G>A and c.715C>T in RFX5 and c.929delA in CIITA.

Conclusion

Given that Egypt is a North African country with a high rate of consanguinity, MHC-II deficiency is not rare. However, the molecular defects differ from those reported in nearby countries. Early diagnosis must be based upon suspicious clinical signs and laboratory diagnosis since the defect can be missed by T cell receptor excision circles based neonatal screening.