Delayed Diagnosis of Chronic Necrotizing Granulomatous Skin Lesions Due to Tap2 Deficiency Publisher Pubmed



Darazam IA^{1, 2} ; Hakamifard A^{1, 3} ; Momenilandi M^{4, 5} ; Materna M^{4, 5} ; Gharehbagh FJ¹ ; Shahrooei M^{6, 7} ; Olyaei NA^{6, 7} ; Zerehpoosh FB⁸ ; Fayand A^{4, 5, 9, 10} ; Hatami F¹ ; Lotfollahi L¹¹ ; Mansouri N¹² ; Casanova JL^{4, 5, 6, 10, 13, 14} ; Beziat V^{4, 5, 9} Show All Authors Show Affiliations
Source: Journal of Clinical Immunology Published:2023

Abstract

Major histocompatibility complex class I (MHC-I) deficiency, also known as bare lymphocyte syndrome type 1 (BLS-1), is a rare autosomal recessively inherited immunodeficiency disorder with remarkable clinical and biological heterogeneity. Transporter associated with antigen processing (TAP) is a member of the ATP-binding cassette superfamily of transporters and consists of two subunits, TAP1 or TAP2. Any defect resulting from a mutation or deletion of these two subunits may adversely affect the peptide translocation in the endoplasmic reticulum, which is an important process for properly assembling MHC-I molecules. To date, only 12 TAP2-deficient patients were reported in the literature. Herein, we described two Iranian cases with 2 and 3 decades of delayed diagnosis of chronic necrotizing granulomatous skin lesions due to TAP2 deficiency without pulmonary involvement. Segregation analysis in family members identified 3 additional homozygous asymptomatic carriers. In both asymptomatic and symptomatic carriers, HLA-I expression was only 4–15% of the one observed in healthy controls. We performed the first deep immunophenotyping in TAP2-deficient patients. While total CD8 T cell counts were normal as previously reported, the patients showed strongly impaired naive CD8 T cell counts. Mucosal-associated invariant T (MAIT) cells and invariant natural killer T (iNKT) cell counts were increased. © 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.