Algerian Registry for Inborn Errors of Immunity in Children: Report of 887 Children (1985-2021).

INTRODUCTION: Inborn errors of immunity (IEI) represent a heterogeneous large group of genetic disorders characterized by susceptibility of affected individuals to recurrent infections, autoimmune/inflammatory diseases, allergy, and malignancy. We aimed to report for the first time the Algerian registry for IEI in children. METHODS: We described the characteristics of IEI in Algerian children from the data collected in the Algerian registry for IEI between 1985 and 2021. RESULTS: Over a period of 37 years, we included 887 children (530 male, 59.6%) with a mean age at diagnosis of 3.23 years and a mean diagnosis delay of 2 years. The prevalence rate was estimated at 1.97/100,000 inhabitants or 5.91/100,000 children. The parental consanguinity was found in 52.6%. The most prevalent category was combined immunodeficiencies (CID) (35.5%), followed by predominantly antibody deficiencies (24.5%) and CID with syndromic features (18.3%). The most predominant diseases were severe CID (134 cases), MHC II deficiency (99 cases), agammaglobulinemia (82 cases), common variable immunodeficiency (78 cases), hyper IgE syndromes (61 patients), ataxia-telangiectasia (46 patients), Wiskott-Aldrich syndrome (40 patients) and chronic granulomatous disease (39 cases). The clinical presentation was dominated by lower respiratory tract infections (69%), failure to thrive (38.3%), and chronic diarrhea (35.2%). Genetic analysis was performed in 156 patients (17.6%). The global mortality rate was 28.4% mainly caused by CID. CONCLUSION: This is the first report of the Algerian registry for IEI in children. Data is globally similar to that of the Middle East and North African (MENA) registries with high consanguinity, predominance of CID, and significant mortality. This registry highlights the weak points that should be improved in order to provide better patient care.

Diagnostic and Predictive Contribution of Autoantibodies Screening in a Large Series of Patients With Primary Immunodeficiencies.

Objectives: To evaluate the diagnostic and predictive contribution of autoantibodies screening in patients with primary immunodeficiencies (PIDs). Methods: In the present study, PID patients and healthy controls have been screened for 54 different autoantibodies. The results of autoantibodies screening in PID patients were correlated to the presence of autoimmune diseases. Results: A total of 299 PID patients were included in this study with a predominance of antibody deficiencies (27.8%) followed by immunodeficiencies affecting cellular and humoral immunity (26.1%) and complement deficiencies (22.7%). Autoimmune manifestations were present in 82 (27.4%) patients. Autoimmune cytopenia (10.4%) was the most common autoimmune disease followed by gastrointestinal disorders (10.0%), rheumatologic diseases (3.7%), and endocrine disorders (3.3%). Autoantibodies were found in 32.4% of PID patients and 15.8% of healthy controls (P < 0.0005). Anti-nuclear antibodies (ANA) (10.0%), transglutaminase antibody (TGA) (8.4%), RBC antibodies (6.7%), anti-smooth muscle antibody (ASMA) (5.4%), and ASCA (5.0%) were the most common autoantibodies in our series. Sixty-seven out of the 82 patients with autoimmune manifestations (81.7%) were positive for one or more autoantibodies. Eleven out of the 14 patients (78.6%) with immune thrombocytopenia had positive platelet-bound IgM. The frequencies of ASCA and ANCA among patients with IBD were 47.4% and 21.0% respectively. All patients with celiac disease had TGA-IgA, while six out of the 11 patients with rheumatologic diseases had ANA (54.5%). Almost one third of patients (30/97) with positive autoantibodies had no autoimmune manifestations. ANA, rheumatoid factor, ASMA, anti-phospholipid antibodies and ANCA were often detected while specific AID was absent. Despite the low positive predictive value of TGA-IgA and ASCA for celiac disease and inflammatory bowel disease respectively, screening for these antibodies identified undiagnosed disease in four patients with positive TGA-IgA and two others with positive ASCA. Conclusion: The present study provides valuable information about the frequency and the diagnostic/predictive value of a large panel of autoantibodies in PIDs. Given the frequent association of some AIDs with certain PIDs, screening for corresponding autoantibodies would be recommended. However, positivity for autoantibodies should be interpreted with caution in patients with PIDs due to their low positive predictive value.