Major histocompatibility complex class II deficiency in Morocco: a 26-year retrospective cohort study

Major histocompatibility complex class II (MHC-II) deficiency is a rare autosomal recessive combined immunodeficiency caused by defects in transcriptional regulators controlling HLA class II expression. The disorder is more prevalent in North Africa due to high rates of consanguinity and founder effects. Updated national data remain limited (in Morocco, up-to-date national data on this deficit remain limited). We aimed to describe the epidemiological, clinical, immunological, and genetic characteristics, as well as the outcomes of Moroccan patients with MHC-II deficiency. We conducted a retrospective cross-sectional study including 54 patients diagnosed with MHC-II deficiency at the national referral center for primary immunodeficiencies in Casablanca, between January 1998 and December 2024. The diagnosis was based on the absence or marked reduction (<5%) in HLA-DR surface expression on B lymphocytes and monocytes, as demonstrated by flow cytometry, with molecular confirmation when available. Demographic, clinical, immunological, genetic, therapeutic, and outcome data were analyzed. Included patients were issued from 47 unrelated families, and parental consanguinity was reported in 87% of cases. Median age at symptom onset was 6 months and median age at diagnosis was 19 months, reflecting a diagnostic delay of 13 months. Respiratory infections were the most frequent manifestation (96%), followed by gastrointestinal involvement (68.5%), mucocutaneous infections (75.9%), and failure to thrive (96%). Autoimmune cytopenia occurred in 20.4% of patients. Immunologic evaluation showed CD4⁺ T-cell lymphopenia in 86.7%, with hypogammaglobulinemia. Genetic testing (n = 35) identified the recurrent RFXANK founder deletion (c.338-25_338del26) in 97.1% of genotyped patients, while one patient carried a CIITA mutation. Hematopoietic stem cell transplantation (HSCT) was performed in eight patients (14.8%), with a survival rate of 62.5% among transplanted cases. Overall mortality reached 66.7%. MHC-II deficiency in Morocco is characterized by early onset, high consanguinity, and a strong RFXANK founder effect, but remains marked by delayed diagnosis and poor survival. Early clinical recognition, targeted molecular screening in high-risk families, improved access to HSCT, and optimized preventive strategies are critical to improve outcomes.