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Genetic testing provides great support to validate the clinical diagnosis of inborn errors of immunity (IEI). However, the high cost and advanced technology make these tests inaccessible to a large proportion of patients in low-income countries. In the present study, we aim to evaluate the Moroccan experience in genetic testing and to report the main molecular features and difficulties encountered in genetic diagnosis.We performed a multi-center retrospective analysis of all patients with a molecular diagnosis and registered in the national registry between 2010 and 2022. To estimate the impact of the newly identified mutations, we calculated the Combined Annotation Dependent Depletion (CADD) score and the mutation significance cutoff (MSC) for each variant.A total of 216 (29%) patients received a genetic diagnosis out of 742 patients with IEI included in the registry. All genetic tests were performed in the context of thesis projects (40%) or international collaborations (60%). A set of 55 genetic defects were identified, including 7 newly reported: SNORA31, TBX21, SPPL2A, TYK2, RLTPR, ZNF341, and STAT2 GOF. Genetic diagnoses were more frequent in the defects of innate and intrinsic immunity with a percentage of 78%, while antibody deficiencies had a lower frequency with a percentage of 17.5%. Only one genetic diagnosis has been made in the complement deficiency group. The most commonly used molecular techniques were Sanger sequencing (37%) followed by targeted gene sequencing (31%).The thesis projects and collaborations were beneficial as they allowed us to provide a definitive genetic diagnosis to 29% of the patients and to contribute to the identification of new genetic defects and mutations. These results offer insight into the progress made in genetic diagnoses of IEI in Morocco, which would provide a baseline for improving the clinical management of patients with IEI.

Severe combined immunodeficiency (SCID) is a heterogeneous group of primary immunodeficiency diseases (PIDs) characterized by a lack of autologous T lymphocytes. This severe PID is rare, but has a higher prevalence in populations with high rates of consanguinity. The epidemiological, clinical, and immunological features of SCIDs in Moroccan patients have never been reported. The aim of this study was to provide a clinical and immunological description of SCID in Morocco and to assess changes in the care of SCID patients over time. This cross-sectional retrospective study included 96 Moroccan patients referred to the national PID reference center at Casablanca Children’s Hospital for SCID over two decades, from 1998 to 2019. The case definition for this study was age

Le Syndrome hyper IgM est un déficit immunitaire héréditaire bien connu, décrit pour la première fois en 1961. Il est causé par un défaut au niveau des lymphocytes B, caractérisé par un taux sérique normal ou élevé des IgM et un taux bas ou nul des IgG, IgA, IgE résultant d'une déficience de la commutation isotypique. Ses manifestations cliniques sont dominées par les infections à répétition, surtout du tube digestif, de la sphère ORL et des poumons. Le syndrome est causé par un défaut de commutation de classe d'immunoglobuline dans les cellules B, et une diminution de la capacité des monocytes à induire la prolifération des lymphocytes T. Le résultat net de tous ces défauts est la susceptibilité accrue aux infections opportunistes à Pneumocystis jiroveci, Cryptosporidium spp et d'autres organismes intracellulaires, ainsi qu'une fréquence élevée d'infections bactériennes et virales. L'intérêt de ce projet est d'illustrer l'importance de la compréhension des mécanismes physiopathologiques associés à cette susceptibilité accrue aux infections, ce qui permettra une meilleure prise en charge diagnostique et thérapeutique des patients atteint du Syndrome hyper IgM (SHIM).

The importance of community-acquired infections due to extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE) has been increasingly recognized in recent years. This study aimed to determine the prevalence of intestinal carriage of ESBL-PE in the community in Casablanca, Morocco.During 6 months (2013), 93 fecal samples were examined for ESBL-PE. Isolates expressing an ESBL phenotype were investigated for the presence of genes encoding β-lactamases and plasmid-mediated quinolone resistance. Conjugation experiments were done to determine the mobility of ESBL genes.The prevalence of fecal carriage of ESBL-PE was 4.3% (4/93; 95% CI, 0.2-8.4). Klebsiella pneumoniae (n = 2), Enterobacter cloacae (n = 2), Escherichia coli (n = 1), and Serratia odorifera (n = 1) were the ESBL-producing species. Four (66.7%) of these isolates were multidrug-resistant. The blaSHV-12 (n = 5) was the most frequent ESBL gene detected, followed by blaCTX-M-15 (n = 3).The non-ESBL gene detected was blaTEM-1 (n = 5). One isolate harbored the qnrB1 variant. RESULTS of conjugation experiments indicated that blaSHV-12 + blaTEM-1 + qnrB1 and blaCTX-M-15 + blaTEM-1 genes were co-transferred and that these genes were carried by a conjugative plasmid of high molecular weight (125 kb).Our results show the importance of the intestinal tract as a reservoir for ESBL-PE in the community in Morocco.