Delayed Diagnosis of Chronic Necrotizing Granulomatous Skin Lesions due to TAP2 Deficiency.

Darazam, Ilad Alavi; Hakamifard, Atousa; Momenilandi, Mana; Materna, Marie; Gharehbagh, Farid Javandoust; Shahrooei, Mohammad; Olyaei, Nasrin Alipour; Zerehpoosh, Farahnaz Bidari; Fayand, Antoine; Hatami, Firouze; Lotfollahi, Legha; Mansouri, Nahal; Casanova, Jean-Laurent; Béziat, Vivien; Mansouri, Davood

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 naïve CD8 T cell counts. Mucosal-associated invariant T (MAIT) cells and invariant natural killer T (iNKT) cell counts were increased.

DELAYED diagnosis; KILLER cells; ATP-binding cassette transporters; MAJOR histocompatibility complex; IODINE deficiency; ANTIGEN processing

Journal of Clinical Immunology, 2023, Vol 43, Issue 1, p217

0271-9142

Academic Journal

10.1007/s10875-022-01374-7