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BackgroundInborn errors of immunity (IEI) predispose patients to various infectious and non-infectious complications. Thanks to the development and expanding use of flow cytometry and increased awareness, the diagnostic rate of IEI has markedly increased in Algeria the last decade.AimThis study aimed to describe a large cohort of Algerian patients with probable IEI and to determine their clinical characteristics and outcomes.MethodsWe collected and analyzed retrospectively the demographic data, clinical manifestations, immunologic, genetic data, and outcome of Algerian IEI patients - diagnosed in the department of medical immunology of Beni Messous university hospital center, Algiers, from 2008 to 2021.ResultsEight hundred and seven patients with IEI (482 males and 325 females) were enrolled, 9.7% of whom were adults. Consanguinity was reported in 50.3% of the cases and a positive family history in 32.34%. The medium age at disease onset was 8 months and at diagnosis was 36 months. The median delay in diagnosis was 16 months. Combined immunodeficiencies were the most frequent (33.8%), followed by antibody deficiencies (24.5%) and well-defined syndromes with immunodeficiency (24%). Among 287 patients tested for genetic disorders, 129 patients carried pathogenic mutations; 102 having biallelic variants mostly in a homozygous state (autosomal recessive disorders). The highest mortality rate was observed in patients with combined immunodeficiency (70.1%), especially in patients with severe combined immunodeficiency (SCID), Omenn syndrome, or Major Histocompatibility Complex (MHC) class II deficiency.ConclusionThe spectrum of IEI in Algeria is similar to that seen in most countries of the Middle East and North Africa (MENA) region, notably regarding the frequency of autosomal recessive and/or combined immunodeficiencies.

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X-linked severe combined immunodeficiency (X-SCID) is caused by mutations of IL2RG, the gene encoding the interleukin common gamma chain (IL-2Rγ or γc) of cytokine receptors for interleukin (IL)-2, IL-4, IL-7, IL-9, IL-15, and IL-21. Hypomorphic mutations of IL2RG may cause combined immunodeficiencies with atypical clinical and immunological presentations. Here, we report a clinical, immunological, and functional characterization of a missense mutation in exon 1 (c.115G>A; p. Asp39Asn) of IL2RG in a 7-year-old boy. The patient suffered from recurrent sinopulmonary infections and refractory eczema. His total lymphocyte counts have remained normal despite skewed T cell subsets, with a pronounced serum IgE elevation. Surface expression of IL-2Rγ was reduced on his lymphocytes. Signal transducer and activator of transcription (STAT) phosphorylation in response to IL-2, IL-4, and IL-7 showed a partially preserved receptor function. T-cell proliferation in response to mitogens and anti-CD3/anti-CD28 monoclonal antibodies was significantly reduced. Further analysis revealed a decreased percentage of CD4+ T cells capable of secreting IFN-γ, but not IL-4 or IL-17. Studies on the functional consequences of IL-2Rγ variants are important to get more insight into the pathogenesis of atypical phenotypes which may lay the ground for novel therapeutic strategies.

Kidney transplantation is a major risk factor for severe forms of coronavirus disease 2019 (COVID-19). The dynamics and the persistence of the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in this immunocompromised population remain largely unknown. This study aimed to evaluate the persistence of humoral and cellular immune response in kidney transplant recipients (KTRs) and to establish whether immunosuppressive therapy influenced long-term immunity in this population. We report here the analysis of anti-SARS-CoV-2 antibodies and T cell-mediated immune responses in 36 KTRs compared to a control group who recovered from mild COVID-19. After a mean time of 5.22 ± 0.96 months post symptom onset for kidney transplant recipients, 97.22% of patients and 100% of the control group displayed anti-S1 immunoglobulin G SARS-CoV-2 antibodies (p > 0.05). No significant difference was reported in the median of neutralizing antibodies between the groups (97.50 [55.25–99] in KTRs vs. 84 [60–98] in control group, p = 0.35). A significant difference in SARS-CoV-2-specific T cell reactivity was found in the KTRs compared to the healthy controls. The levels of IFNγ release after stimulation by Ag1, Ag2 and Ag3 were higher in the control group compared to the kidney transplant group (p = 0.007, p = 0.025 and p = 0.008, respectively). No statistically significant correlation between humoral and cellular immunity was found in the KTRs. Our findings indicated that humoral immunity persisted similarly for up to 4 to 6 months post symptom onset in both the KTRs and the control group; however, T cell response was significantly higher in the healthy population compared to the immunocompromised patients.