The rst molecular evidence of a monogenic predisposition to mycobacteria came from the study of Mendelian susceptibility to mycobacterial disease (MSMD). We aimed to study this Mendelian susceptibility to mycobacterial diseases in Moroccan kindreds through clinical, immunological and genetic analysis. MethodsPatients presented with clinical features of MSMD, were recruited into this study. We used whole blood samples from patients and age-matched healthy controls. To measure IL-12 and IFN-γ production, samples were activated by BCG plus recombinant human IFN-γ or recombinant human IL-12. Immunological assessments and genetic analysis were also done for patients and their relatives. ResultsOur study involved 22 cases from 15 unrelated Moroccan kindreds. The average age at diagnosis is 4 years. Fourteen patients (64%) were born to consanguineous parents. All patients were vaccinated with BCG vaccine, twelve of them (55%) developed loco-regional or disseminated BCG infections. The other symptomatic patients had severe tuberculosis and/or recurrent salmonellosis. Genetic mutations were identi ed on the following genes: IL12RB1 in 8 patients, STAT1 in 7 patients, SPPL2A, IFNGR1 and TYK2 in two patients and TBX21 in one patient, with different modes of inheritance. All identi ed mutations/variants altered production or response to IFN-γ or both. ConclusionSevere forms of tuberculosis and complications of BCG vaccination may imply a genetic predisposition present in the Moroccan population. In front of these infections, systematic genetic studies became necessary. BCG vaccination is contraindicated in MSMD patients and should be delayed in newborns siblings until the exclusion of a genetic predisposition to mycobacteria.

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Objective Systemic sclerosis (SSc) is a connective tissue disorder characterized by excessive fibrosis of the skin and internal organs, along with microvascular damage, and is often associated with typical autoantibodies. This study aimed to analyze the correlation between specific autoantibody profiles, clinical and paraclinical features in Moroccan patients with SSc. Methods We analyzed the presence of specific autoantibodies in 46 SSc patients using indirect immunofluorescence (IIF) on Hep-2 cells and immunodot. We then correlated the type of autoantibodies with clinical and laboratory manifestations. Results Among our patients, 86.9% were females. The mean age of patients at diagnosis was 50.21 years old, with an average diagnosis delay of 5 years. The main clinical manifestations found were Raynaud’s phenomenon (89.2%), sclerodactyly (84.8%), proximal scleroderma (67.4%), gastrointestinal involvement (50%), and interstitial lung disease (30.4%). According to the specific autoantibody profile, 14 patients were anti-topo I positive (30.4%), 8 were anti-RNP(68kDa/A/C) positive (17.4%) and 6 were anti-RNA polymerase III positive (13%). We found a significant association of Anti-RNAP III with sclerodactyly and pulmonary arterial hypertension (p < 0.05). We also found an association between anti-topo I and interstitial lung disease in 30.4% of patients. There was no significant association between the positivity for the autoantibodies and other diagnosed clinical manifestations. Conclusion Some clinical manifestations of SSc may correlate positively with the presence of specific autoantibodies. Environmental factors, ethnicity, and gene interaction may also influence this correlation. Lay summary What does this mean for patients? Systemic sclerosis (SSc) is a disease that affects the connective tissues, causing excessive skin and internal organs fibrosis and microvascular damage. Specific autoantibodies, which are antibodies that attack the body's tissues, are responsible for amplifying the immune response and targeting cells involved in the development of SSc. This study aimed to investigate the relationship between specific autoantibodies and the clinical and laboratory features of SSc in 46 Moroccan patients. The majority of patients were female, middle-aged, and of Caucasian ethnicity, with a mean age of 50 years, and duration of disease between 1 and 10 years. The most common symptoms were Raynaud’s phenomenon (89.2% of patients), sclerodactyly (84.8%), proximal scleroderma (67.4%), gastrointestinal involvement (50%), arthralgia (41.3%), interstitial lung disease (30.4%), myalgia (24%) and pulmonary arterial hypertension (10.8%). We found a correlation between anti-RNAP III and Sclerodactyly and pulmonary arterial hypertension, while anti-topo I autoantibodies were associated with interstitial lung disease. The study also noted that environmental factors, ethnicity, and genetic interactions may influence the clinical and autoantibody profile in SSc patients.

Purpose The first molecular evidence of a monogenic predisposition to mycobacteria came from the study of Mendelian susceptibility to mycobacterial disease (MSMD). We aimed to study this Mendelian susceptibility to mycobacterial diseases in Moroccan kindreds through clinical, immunological and genetic analysis. Methods Patients presented with clinical features of MSMD, were recruited into this study. We used whole blood samples from patients and age-matched healthy controls. To measure IL-12 and IFN-γ production, samples were activated by BCG plus recombinant human IFN-γ or recombinant human IL-12. Immunological assessments and genetic analysis were also done for patients and their relatives. Results Our study involved 22 cases from 15 unrelated Moroccan kindreds. The average age at diagnosis is 4 years. Fourteen patients (64%) were born to consanguineous parents. All patients were vaccinated with BCG vaccine, twelve of them (55%) developed loco-regional or disseminated BCG infections. The other symptomatic patients had severe tuberculosis and/or recurrent salmonellosis. Genetic mutations were identified on the following genes: IL12RB1 in 8 patients, STAT1 in 7 patients, SPPL2A, IFNGR1 and TYK2 in two patients and TBX21 in one patient, with different modes of inheritance. All identified mutations/variants altered production or response to IFN-γ or both. Conclusion Severe forms of tuberculosis and complications of BCG vaccination may imply a genetic predisposition present in the Moroccan population. In front of these infections, systematic genetic studies became necessary. BCG vaccination is contraindicated in MSMD patients and should be delayed in newborns siblings until the exclusion of a genetic predisposition to mycobacteria.