Clinical, Immunological, and Genetic Findings in Iranian Patients With Mhc-Ii Deficiency: Confirmation of C.162Delg Rfxank Founder Mutation in the Iranian Population Publisher Pubmed



Mousavi Khorshidi MS¹ ; Seeleuthner Y^{2, 3} ; Chavoshzadeh Z⁴ ; Behfar M^{5, 6} ; Hamidieh AA^{5, 6} ; Alimadadi H⁷ ; Sherkat R⁸ ; Momen T⁹ ; Behniafard N^{10, 11} ; Eskandarzadeh S¹² ; Mansouri M⁴ ; Behnam M^{13, 14} ; Mahdavi M¹ ; Heydarazad Zadeh M⁴ Show All Authors
Source: Journal of Clinical Immunology Published:2023

Abstract

Purpose: Major histocompatibility complex class II (MHC-II) deficiency is a rare inborn error of immunity (IEI). Impaired antigen presentation to CD4 + T cells results in combined immunodeficiency (CID). Patients typically present with severe respiratory and gastrointestinal tract infections at early ages. Hematopoietic stem cell transplantation (HSCT) is the only curative therapy. Methods: We describe the clinical, immunologic, and genetic features of eighteen unrelated Iranian patients with MHC-II deficiency. Results: Consanguinity was present in all affected families. The median age at the initial presentation was 5.5 months (range 7 days to 18 years). The main symptoms included failure to thrive, persistent diarrhea, and pneumonia. Autoimmune and neurologic features were also documented in about one-third of the patients, respectively. Thirteen patients carried RFXANK gene mutations, two carried RFX5 gene mutations, and three carried a RFXAP gene mutation. Six patients shared the same RFXANK founder mutation (c.162delG); limited to the Iranian population and dated to approximately 1296 years ago. Four of the patients underwent HSCT; three of them are alive. On the other hand, nine of the fourteen patients who did not undergo HSCT had a poor prognosis and died. Conclusion: MHC-II deficiency is not rare in Iran, with a high rate of consanguinity. It should be considered in the differential diagnosis of CID at any age. With the limited access to HSCT and its variable results in MHC-II deficiency, implementing genetic counseling and family planning for the affected families are mandatory. We are better determined to study the c.162delG RFXANK heterozygous mutation frequency in the Iranian population. © 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.