article · Frontiers in Immunology
A 26-year study evaluated 54 patients diagnosed with major histocompatibility complex class II deficiency at a national referral centre in Casablanca, Morocco. The condition presented early in life, with a median age of symptom onset at six months and a median diagnostic delay of 13 months. Parental consanguinity was present in 87 percent of cases. The most frequent clinical presentations were respiratory infections, failure to thrive, mucocutaneous infections, gastrointestinal issues, and autoimmune cytopenia. Immunological assessments showed CD4 positive T-cell lymphopenia and hypogammaglobulinemia in the majority of patients. Genetic testing showed that over 97 percent of genotyped cases carried a recurrent RFXANK founder deletion. Overall patient mortality reached 66.7 percent, whereas haematopoietic stem cell transplantation achieved a 62.5 percent survival rate among the minority who received it.
Major histocompatibility complex class II deficiency is a life-threatening inherited immune disorder that causes recurrent severe infections in early childhood. Documenting the specific genetic cause and clinical signs in populations with high consanguinity allows healthcare providers to recognise cases faster. Earlier identification is critical because prompt interventions, such as curative stem cell transplantation, offer the best chance of reducing the high mortality rate associated with this disease.
The findings point to direct applications in clinical diagnostics, particularly the creation of targeted molecular screening kits for the identified RFXANK founder mutation. Diagnostic laboratories and clinical genetics services serving high-risk communities represent the primary users. Because the specific mutation and clinical markers are already defined in patients, developing targeted diagnostic assays represents an applied stage of research that is relatively near to real-world healthcare use.
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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.
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DOI: 10.3389/fimmu.2026.1831840
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