Clinical, Immunological, and Molecular Findings in Five Patients with Major Histocompatibility Complex Class II Deficiency from India

Jahnavi Aluri,Snehal Mhatre,Maya Gupta,Ramprasad Vedam,Aparna Dalvi,Manasi Kulkarni,Mukesh Desai,Manisha Madkaikar,Gouri Hule,Nitin Shah,Prasad Taur

doi:10.3389/fimmu.2018.00188

Abstract

Major histocompatibility complex (MHC) class II deficiency is a rare autosomal recessive form of primary immunodeficiency disorder (PID) characterized by the deficiency of MHC class II molecules. This deficiency affects the cellular and humoral immune response by impairing the development of CD4+ T helper (Th) cells and Th cell-dependent antibody production by B cells. Affected children typically present with severe respiratory and gastrointestinal tract infections. Hematopoietic stem cell transplantation (HSCT) is the only curative therapy available for treating these patients. This is the first report from India wherein we describe the clinical, immunological, and molecular findings in five patients with MHC class II deficiency. Our patients presented with recurrent lower respiratory tract infection as the most common clinical presentation within their first year of life and had a complete absence of human leukocyte antigen-antigen D-related (HLA-DR) expression on B cells and monocytes. Molecular characterization revealed novel mutations in RFAXP, RFX5, and CIITA genes. Despite genetic heterogeneity, these patients were clinically indistinguishable. Two patients underwent HSCT but had a poor survival outcome. Detectable level of T cell receptor excision circles (TRECs) were measured in our patients, highlighting that this form of PID may be missed by TREC-based newborn screening program for severe combined immunodeficiency.

Highlights

Major histocompatibility complex (MHC) class II deficiency is a rare form of primary immunodeficiency disorder (PID) that follows an autosomal recessive pattern of inheritance
We describe here the clinical, immunological, and molecular findings of MHC class II deficiency in five patients with novel mutations for the first time from India
To the best of our knowledge, this is the first report of MHC class II deficiency from India

Summary

Introduction

Major histocompatibility complex (MHC) class II deficiency is a rare form of primary immunodeficiency disorder (PID) that follows an autosomal recessive pattern of inheritance. About two-third of these patients have a North African descent (Algeria, Morocco, and Tunisia) [1] and belong to complementation group B. MHC class II molecules on the immune cells is thought to be the underlying cause of MHC class II deficiency [3]. The MHC class II molecules referred to as human leukocyte antigens (HLAs) are polygenic and highly polymorphic cell-surface glycoproteins that assemble as α and β chain heterodimers [3]. The RFXANK, RFX5, and RFXAP proteins are three subunits of the ubiquitously expressed RFX complex, which bind directly to the promoters of all MHC class II genes and associate with other pleiotropic factors to form the MHC class II enhanceosome [1]

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