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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, allergies and malignancy. We aim to report for the first time the Algerian registry for IEI in children.Methods: We describe the characteristics of IEI in Algerian children from the data collected in the Algerian registry for IEI over a long period of 37 years.Results: Between 1985 and 2021, we included 887 children (530 male, 59.6%) with a mean age at diagnosis of 3.23y and a mean diagnosis delay of 2y. 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 (24.4%) and CID with syndromic features (17.9%). The most predominant diseases were severe CID (120 cases), MHC II deficiency (99 cases), agammaglobulinemia (81 cases), common variable immunodeficiency (74 cases), hyper IgE syndromes (60 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 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.

Behcet disease (BD) is a chronic multisystem disease. It stands at the crossroads between the auto-immunity and auto-inflammatory disorders. Our study aims to evaluate corticosteroids therapy effects on serum immunoglobulin isotypes and anti-phospholipid auto-anti-body production in Algerian BD patients with different clinical manifestations. We evaluated serum immunoglobulin isotypes and anti-phospholipid (anti-cardiolipin, anti-β2glycoprotein I, anti-prothrombin) auto-anti-body production using Turbidimetric or Luminex platform assays. Our study was conducted in naive active BD patients and in corticosteroid-treated patients with different clinical manifestations. Our results indicate that IgM, IgG, and IgA levels were higher in naive active patients. The increase in sera isotypes did not differ according to the clinical manifestation, except for IgA production, which was associated with an increased risk of mucocutaneous and ocular involvement. Interestingly, in corticosteroid-treated active patients, no difference was reported between each clinical subgroup. Furthermore,anti-cardiolipin, anti-β2glycoprotein I and anti-prothrombin auto-anti-body levels were elevated in naive active patients. Contrary to anti-prothrombin, high anti-cardiolipin and anti-β2glycoprotein I, production differed according to the clinical manifestations and was associated with an increased risk of mucocutaneous and ocular involvement. Importantly, corticosteroid therapy significantly reduced these immune markers regardless of the clinical manifestations. Our results suggest that high IgA production could be a risk marker of uveitis in naive active patients. Moreover, concomitant high anti-cardiolipin, anti-β2glycoprotein I and anti-prothrombin production is related to an increased risk of mucocutaneous lesions, ocular and vascular involvement. Collectively, our data indicate the importance of evaluating the corticosteroid effect on immune responses associated with BD to ensure an adequate investigation of each related clinical manifestation.

Multiple myeloma is characterized by underlying clinical and biological heterogeneity, which translates to variable responses to treatment and outcome.To assess the roles of serum free light chain (sFLC) and K/L FLC ratio (rFLC) in the diagnoses and prognoses of multiple myeloma (MM), sFLC levels and K/L ratios were measured in 112 patients with newly diagnosed multiple myeloma using the Freelite automated immunoassay.Abnormal sFLC and/or rFLC levels were detected 99.1% of the patients. The baseline sFLC predicted the overall survival (OS). The median OSs were not reached (NR) and were 30 months in the low sFLC group (sFLC-K132 mg/L or sFLC-L342 mg/L) and the high sFLC group (sFLC-K ≥ 132 mg/L or sFLC-L ≥ 342 mg/ L) (p0.001), respectively. Similarly, the rFLC successfully predicted the OS times of 29 months for group A (rFLC ≤ 0.03 or ≥ 32) and NR for group B (0.03rFLC32) (p0.001). According to the response to treatment and sFLC ratio, significant differences in the OSs were observed between the partial response group and other patients, (respectively, OS median = 28 months vs. NR, log rank p0.001). Additionally, the patients were further stratified into two groups using the novel poor-prognosis factors (rFLC32 or0.03) combined with the International Staging System parameters (beta2-microglobulin, albumin), i.e., a low-risk group (those with zero or one factor) and a high-risk group (those with two or three factors). The median OSs for the low- and high-risk groups were NR and 29 months, respectively (p = 0.001).The sFLC assay was extremely sensitive in the diagnosis of MM. In addition to its strong prognosis value, it could be a predictor of response to therapy.

Behcet’s disease (BD) is a chronic multisystemic inflammatory disease with complex etiopathogenesis. Th1-proinflammatory cytokines seem to be involved in its pathogenesis. Our current study aims to evaluate interleukin-18 (IL-18) and nitric oxide (NO) involvement in the development of different clinical manifestations of BD as well as to investigate the corticosteroid therapy effect on this production in Algerian patients. For this purpose, we evaluated in vivo and ex vivo IL-18, interferon-γ (IFN-γ) levels using ELISA and NO production by the Griess’ method in naive-active and corticosteroid-treated BD patients with different clinical manifestations. Additionally, we assessed CD40/CD40L expression by flow cytometrics assay in these groups of patients. Our results indicate that IL-18 and nitrite levels were higher in naive-active BD patients. Interestingly, this high production differed according to the clinical manifestations and was associated with an increased risk of mucocutaneous and vascular involvement. Concerning corticosteroid treated-active BD patients, no difference was observed in this production between each clinical subgroup. However, IFN-γ levels increased in all categories of active patients. Interestingly, corticosteroid therapy reduced significantly these inflammatory mediators regardless of the clinical manifestations studied. In addition, the CD40/CD40L expression differed according to the clinical presentations. Collectively, our results suggest that concomitant high production of IL-18 and NO in naive-active BD patients is related to an increased risk of mucocutaneous lesions and vascular involvement. Moreover, the relationship between these two inflammatory markers could constitute a predictable tool of BD clinical presentations and an early factor of therapy efficiency.

Background: The aims of this study were to establish the clinical value of multi-parametric flow cytomentry (MFC) in multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS). Methods: We analyzed bone marrow aspirates from 112 MM and 17 MGUS patients by MFC, using 3 combinations of 9 color labeling: a, CD38 / CD138 / CD45 / CD56 / CD19 / CD27 / CD117 / CD20 / CD33; b, CD38 / CD138 / CD45 / cytoplasmic Kappa / cytoplasmic Lambda; and c, CD38 / CD138. MFC data were classified based on clinical features and prognosis factors. Results: Myeloma’s patients compared to MGUS group had plasma cells (PCs) with abnormal immunophenotypic patterns, including high CD56 and CD20 expression and weak or negative CD45, CD19, and CD27 expression without significant median differences in expression of CD33 and CD117. Multiple myeloma patient with low expression of CD19, CD27 or CD45, overexpression of CD56 or with a high proportion of PCs at diagnosis demonstrated shorter overall survival times. Moreover, MM patients with combined abnormal expressions of 4 or 5 antigens demonstrated shorter survival times (P = 0.001). These high-risk MFC patients were associated with poor clinical outcomes, including ISS stage III and DS stage III, low hemoglobin levels, and elevated serum beta2-microglobilin (P = 0.01, P = 0.006, P = 0.01 and P = 0.008, respectively). Conclusions: The present study highlights the benefits of assessing abnormal antigen expression for clinical uses. These measures could facilitate proper diagnosis of disorders and improve risk stratification for a targeted early treatment regimen.

Introduction Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory and multifactorial disease. Genetic predisposition seems to play an important role. The aim of this study is to explore the relationship between human leukocyte antigen (HLA)-DRB1 alleles and susceptibility, clinical and biological features of RA in an Algerian patient population. Methods Using polymerase chain reaction – sequence specific primers (SSP), 134 RA patients and 132 healthy controls were genotyped for HLA-DRB1 and HLA-DRB1*04 subtypes. Results HLA-DRB1*04 was found to have increased frequency in the RA group compared to controls (P

International audience; X linked agammaglobulinemia (XLA) is the first described primary immunodeficiency and the most common form of agammaglobulinemia. It is characterized by susceptibility to recurrent infections, profound decrease of all immunoglobulin isotypes and very low level of B lymphocytes in peripheral blood. The disorder is caused by mutations in the Bruton's Tyrosine Kinase (BTK). Nine male patients suspected to have XLA from nine unrelated families were enrolled in this study. We performed sequencing of the BTK gene in all nine patients, and in the patients' relatives when possible. The XLA diagnosis was confirmed for six patients with six different mutations; we identified a novel mutation (c.1522GN A) and five known mutations. One third of nine unrelated patients do not have mutations in BTK and thus likely suffer from autosomal recessive agammaglobulinemia in the setting of consanguinity. Our results support that the autosomal recessive agammaglobulinemia can be more common in Algeria.

The aim of the current study is to situate CDs expression (CD3+, CD4+, CD8+) and their relationship with IFNγ and NO production in Algerian patients with Behçet disease (n = 34 ). Our results revealed an elevated expression of T cells markers tested in patients in active stage of the disease in relation to IFNγ and NO increase levels. Most interestingly, we noted that CD4+/CD8+ expression correlated with IFNγ and NO production in active stage. In contrast, we observed a decrease of these mediators in inactive stage. Collectively, our results indicate a dependent relation between these parameters and inflammatory response associated with the evolutionary stage of the disease.

Presenting processed antigens to CD4+ lymphocytes during the immune response involves major histocompatibility complex class II molecules. MHC class II genes transcription is regulated by four transcription factors: CIITA, RFXANK, RFX5 and RFXAP. Defects in these factors result in major histocompatibility complex class II expression deficiency, a primary combined immunodeficiency frequent in North Africa. Autosomal recessive mutations in the RFXANK gene have been reported as being the principal defect found in North African patients with this disorder. In this paper, we describe clinical, immunological and genetic features of 11 unrelated Algerian patients whose monocytes display a total absence of MHC class II molecules. They shared mainly the same clinical picture which included protracted diarrhoea and respiratory tract recurrent infections. Genetic analysis revealed that 9 of the 11 patients had the same RFXANK founder mutation, a 26 bp deletion (named I5E6-25_I5E6+1, also known as 752delG26). Immunological and genetic findings in our series may facilitate genetic counselling implementation for Algerian consanguineous families. Further studies need to be conducted to determine 752delG26 heterozygous mutation frequency in Algerian population.

Behcet disease (BD) is a systemic chronic inflammatory disorder frequent in Algeria. As Behcet disease is considered as a vasculitis, we assessed the levels of circulating B cells by flow cytometry, antibodies (IgM, IgA, IgG) by nephelometry and auto-antibodies (ANCA, APLs) by Luminex in 70 patients with BD and 20 control subjects. The obtained results were analyzed by Mann Witney U test. We observed a significant increased B cells and antibodies levels in comparison to control group ( p 0.01 ). Patients showed different profile according to the clinical data (activity: p 0.05 , clinical expression: p 0.01 ). Autoantibodies indicated different profiles with no differences with controls in ANCA levels ( p > 0.05). In contrast, anti-phospholipids were higher during BD with aCL (anticardiolipins) revealing a significant difference ( p r = 0.760, p p