MHC-II deficiency in a large Algerian cohort: Clinical, immunological, and genetic characterization
Lydia Lamara Mahammed, Brahim Belaid, Koon-Wing Chan, Aida Mohand-oussaid, Ouardia Drali, Abdelhak Dehimi, Daniel Leung, Lilya Meriem Berkani, Hassiba Sakhri, Asmaa Abed, Meriem Tahir, Fatma Merah, Amina Salmi, Wassila Messadi, Souhila Melzi, Jing Yang, Xing Tian Yang, Jennifer Stoddard, Julie Niemela, Heather Kenney, Fella Dahmoune, Fairouz Guerrouche, Ahlem Mechali, Amina Saad Djaballah, Lamia Amirat, Meriem Oussalah, Yacine Inouri, Saadeddine Dib, Fatima Benbida, Chahynez Boubidi, Hind Ismahen Titri, Lynda Sekfali, Sidi Mohamed Azzouz, Amel Laredj, Fadela Bendaoud, Halima Zerguine, Djohra Hadef, Ahmed Kadi, Djazia Elhadef, Hamza Boucenna, Khadidja Benallal, Moufida Djalab, Chahrazed El Mezouar, Rachid Bouhdjila, Mimouna Bessahraoui, Nadia Bensaadi, Farih Mehdid, Malek Benakli, Farida Harieche, Rawda Aboura, Zoulikha Zeroual, Leila Smati, Salih Bendeddouche, Reda Belbouab, Azzeddine Mekki, Belkacem Bioud, Samir Mohamed Ladj, Merzak Gharnaout, Asmahane Ladjouze, Ourida Gacem, Nafissa Benhalla, Jaime Sou Rosa Duque, Sergio Rosenzweig, Luigi Daniele Notarangelo, Yu Lung Lau, Reda DjidjikMHC class II (MHC-II) deficiency is a rare inborn error of immunity caused by defects in transcriptional regulators of MHC-II expression. In this study, we characterized the clinical, immunological, and molecular features of 107 patients from 98 unrelated Algerian families. Median ages at symptom onset and diagnosis were 5 and 14 mo, respectively, with pneumonia (82%) and chronic diarrhea (73%) predominating. CD4+ T cell lymphopenia occurred in 87.6% and naïve CD4+ T cell depletion in 86.0%. Among 99 genetically characterized patients, variants were identified exclusively in RFXANK (77.8%) and RFXAP (22.2%), including two predominant mutations (RFXANK c.338-25_338del and RFXAP c.368del) and four novel variants. Exploratory comparisons suggested a more severe phenotype in patients carrying RFXAP c.368del than in those carrying RFXANK c.338-25_338del. Five of seven transplanted patients survived versus 33.3% of non-transplanted patients. As the largest MHC-II deficiency cohort reported to date, this study substantially expands current knowledge of the disease and supports targeted genetic diagnosis in North African populations.