Hematopoietic Cell Transplantation for MHC Class II Deficiency.

Su Han Lum,Su Han Lum,Mary A Slatter,Mary A Slatter,Andrew R Gennery,Andrew R Gennery,Andrew R Gennery,Benedicte Neven,Mary A Slatter

doi:10.3389/fped.2019.00516

Abstract

Major histocompatibility complex (MHC) class II deficiency is a rare and fatal primary combined immunodeficiency. It affects both marrow-derived cells and thymic epithelium, leading to impaired antigen presentation by antigen presenting cells and delayed and incomplete maturation of CD4+ lymphocyte populations. Affected children are susceptible to multiple infections by viruses, Pneumocystis jirovecii, bacteria and fungi. Immunological assessment usually shows severe CD4+ T-lymphocytopenia, hypogammaglobulinemia, and lack of antigen-specific antibody responses. The diagnosis is confirmed by absence of constitutive and inducible expression of MHC class II molecules on affected cell types which is the immunologic hallmark of the disease. Hematopoietic cell transplantation (HCT) is the only established curative therapy for MHC class II deficiency but it is difficult as affected children have significant comorbidities at the time of HCT. Optimization organ function, implementing a reduced toxicity conditioning regimen, improved T-cell depletion techniques using serotherapy and graft manipulation, vigilant infection surveillance, pre-emptive and aggressive therapy for infection and newer treatments for graft-versus-host disease have improved the transplant survival for children with MHC class II deficiency. Despite persistent low CD4+ T-lymphopenia reported in post-HCT patients, transplanted patients show normalization of antigen-specific T-lymphocyte stimulation and antibody production in response to immunization antigens. There is a need for a multi-center collaborative study to look at transplant survival of HCT and long-term disease outcome in children with MHC class II deficiency in the modern era of HCT.

Highlights

Major histocompatibility complex (MHC) class II deficiency, known as bare lymphocyte syndrome type II, is a rare autosomal recessive combined immunodeficiency and was first described in 1980s [1]
The immunologic hallmark of the disease is the absence of constitutive and inducible expression of MHC class II molecules on all cell types which leads to impaired antigen presentation by HLA-DR, HLA-DQ, and HLA-DP molecules on antigen presenting cells (APC) [2]
The reported incidence of MHC class II deficiency ranges from 5% of severe combined immunodeficiency (SCID) in Canada to 20–30% of SCID in Kuwait and in North Africans Countries [4, 5]

Summary

INTRODUCTION

Major histocompatibility complex (MHC) class II deficiency, known as bare lymphocyte syndrome type II, is a rare autosomal recessive combined immunodeficiency and was first described in 1980s [1]. In MHC class II deficiency, the MHC locus itself is intact in patients and it is a monogenic disease caused by mutations in the genes encoding for four regulatory factors controlling transcription of MHC class II genes. These regulatory factors are CIITA (class II transactivator), RFX5 (regulatory factor 5), RFXAP (RFXassociated protein), and RFXANK (RFX-associated ankyrincontaining protein) (Figure 1). A multidisciplinary team with participation of respiratory physicians, gastroenterologists, dietitians, play therapies and other supportive groups are required in all the phases in order to achieve the best outcome possible This consists of donor selection, appropriate stem cell source and optimal conditioning regimen. If no family donor is found, a search of the national or international

MFD marrow

Findings

SUMMARY