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Purpose: In this study, we retrospectively reviewed the use of flow cytometry (FCM) in the diagnosis of inborn errors of immunity (IEIs) at a single center in Algeria. Sharing insights into our practical experience, we present FCM based diagnostic approaches adapted to different clinical scenarios., Methods: Between May 2017 and February 2024, pediatric and adult patients presenting with clinical features suggestive of immunodeficiency were subjected to FCM evaluation, including lymphocyte subset analysis, detection of specific surface or intracellular proteins, and functional analysis of immune cells., Results: Over a nearly seven-year period, our laboratory diagnosed a total of 670 patients (372 (55.5%) males and 298 (44.5%) females), distributed into 70 different IEIs belonging to 9 different categories of the International Union of Immunological Societies classification. FCM was used to diagnose and categorize IEI in 514 patients (76.7%). It provided direct diagnostic insights for IEIs such as severe combined immunodeficiency, Omenn syndrome, MHC class II deficiency, familial hemophagocytic lymphohistiocytosis, and CD55 deficiency. For certain IEIs, including hyper-IgE syndrome, STAT1-gain of function, autoimmune lymphoproliferative syndrome, and activated PI3K delta syndrome, FCM offered suggestive evidence, necessitating subsequent genetic testing for confirmation. Protein expression and functional assays played a crucial role in establishing definitive diagnoses for various disorders. To setup such diagnostic assays at high and reproducible quality, high level of expertise is required; in house reference values need to be determined and the parallel testing of healthy controls is highly recommended., Conclusion: Flow cytometry has emerged as a highly valuable and cost-effective tool for diagnosing and studying most IEIs, particularly in low-income countries where access to genetic testing can be limited. FCM analysis could provide direct diagnostic insights for most common IEIs, offer clues to the underlying genetic defects, and/or aid in narrowing the list of putative genes to be analyzed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Tahiat, Belbouab, Yagoubi, Hakem, Fernini, Keddari, Belhadj, Touri, Aggoune, Stoddard, Niemela, Zerifi, Melzi, Aboura, Saad-Djaballah, Ferhani, Ketfi, Messaoudi, Bencharif Madani, Benhacine, Dehimi, Okka, Amroune, Fellahi, Bendahmane, Khoulani, Oukil, Soufane, Bourelaf, Boubidi, Boukhenfouf, Amine Ifri, Khelafi, Boudiaf, Khelifi Touhami, Meçabih, Boucelma, Zelaci, Gacem, Ladj, Mekki, Bensaadi, Benhalima, Zeroual, Bioud, Benameur, Bouhdjila, Bouzerar, Ibsaine, Maouche, Kedji, Smati, Boukari, Lambert, Rosenzweig, Notarangelo and Djenouhat.)

Glyphosate is an endocrine disruptor and can act on the activity of certain enzymes of metabolism subsequently altering some functions such as reproduction. The goal of the present study is to evaluate the involvement of glyphosate based-herbicide (GBH) in spermatogenesis disruption and to investigate which cells of the adult Wistar rat testis are most affected by short-term exposure to GBH. Treated groups received a diluted solution of GBH orally for 21 days (D1: 102.5 mg/Kg; D2: 200 mg/Kg; D3: 400 mg/Kg). The control group (C) received water in the same manner. Hormone levels, oxidative stress markers were evaluated, histological and morphometric analysis were performed, AR and p53 expression was conducted. Seminiferious epithelium sloughing associated to erosion of Sertoli and spermatogonia from the basement of the seminiferous tubules, with intraluminal exfoliated cells among with immature spermatids were observed. A significant change in morphometric measurement and significant decrease in AR expression in Sertoli cells were noted for all treated groups. A significant increase in NO level and p53 expression in Leydig cells were showed for animals treated with 200 and 400 mg/kg BW/day. These data demonstrate that short-term exposure to high doses of GBH has led to a disruption of certain parameters that could disturb spermatogenesis. The treatment showed that both Leydig and Sertoli cells are affected in the same manner by GBH, the activation of p53 expression in both Leydig cells and peritubular myloid cells nuclei, and the reduction in AR expression in Sertoli cells, which resulted in important testicular damage., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Conflicts of interest None declared conflicts of interest with publication of this article., (Copyright © 2024 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier B.V. All rights reserved.)

Atypical Hemolytic Uremic Syndrome (aHUS) is a systemic disease due to dysregulation of the alternate complement pathway, mortality is estimated at 10% and more than 50% of patients progress to end-stage renal disease. The aim of this study was to summarize the clinical data and biological results as well as the evolution and management of patients with aHUS seen over a period of four years in one specialized department in Algeria. Our study was observational and longitudinal. The inclusion criteria were: the clinical-biological triad of aHUS and age ≤ 16 years. The type of treatment, the presence of complement mutation or anti-complement factor autoantibodies were not eligibility conditions. On inclusion and every six months, demographic data, clinical and biological history and results after treatment were collected prospectively. Our workforce consisted of 21 children with aHUS. Thirteen patients benefited from a complement study; among them, 7 had complement abnormalities. Eleven children had familial HUS; among them 8 died and 6 were less than one year old. Plasma exchanges were performed in two children. Six patients received eculizumab, with an average age of 3.6 years. After the acute phase, 9 children recovered their kidney function, one child had developed a chronic kidney disease (CKD), and 11 died, among them 8 belong to aHUS families. Fifty percent of deaths occurred in the first 3 months. At 2 years of evolution, out of 7 children having reached this stage, five had renal sequelae and four of them had CKD. The severe prognosis of this disease makes early diagnosis and treatment essential.

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., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Monogenic immune dysregulation diseases (MIDD) are caused by defective immunotolerance. This study was designed to increase knowledge on the prevalence and spectrum of MIDDs, genetic patterns, and outcomes in Middle East and North Africa (MENA). MIDD patients from 11 MENA countries (Iran, Turkey, Kuwait, Oman, Algeria, Egypt, United Arab Emirates, Tunisia, Jordan, Qatar, and Azerbaijan) were retrospectively evaluated. 343 MIDD patients (58% males and 42% female) at a median (IQR) age of 101 (42-192) months were enrolled. The most common defective genes were LRBA (23.9%), LYST (8.2%), and RAB27A (7.9%). The most prevalent initial and overall manifestations were infections (32.2% and 75.1%), autoimmunity (18.6% and 41%), and organomegaly (13.3% and 53.8%), respectively. Treatments included immunoglobulin replacement therapy (53%), hematopoietic stem cell transplantation (HSCT) (14.3%), immunosuppressives (36.7%), and surgery (3.5%). Twenty-nine (59.2%) patients survived HSCT. Along with infectious complications, autoimmunity and organomegaly may be the initial or predominant manifestations of MIDD., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare that are relevant to the content of this article., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Although lung damages are among the leading causes of death from Rheumatoid Arthritis (RA), few studies have assessed the spirometric and plethysmographic data and profile of patients with RA, particularly those with Anti-Citrullinated Peptides Antibodies Positive (ACPA+)., Aim: To compare the spirometric and plethysmographic data and profile of RA patients ACPA+ and ACPA-., Methods: This comparative pilot study was performed over a two-year period (2018-2019) in Algiers (Algeria). The study included two groups of RA non-smoker patients: 26 ACPA+ and 33 ACPA-.RA was diagnosed according to the ACR/EULAR 2010 RA classification criteria. Spirometry and plethysmography were performed. The following definitions were applied: Obstructive Ventilatory Impairment (OVI): FEV1/FVC z-score < -1.645; Restrictive Ventilatory Impairment (RVI): Total Lung Capacity (TLC) z-score< -1.645; Mixed Ventilatory Impairment (MVI): FEV1/FVC z-score < -1.645 and TLC z-score < -1.645; lung- hyperinflation: residual volume z-score > +1.645; Nonspecific Ventilatory Impairment (NSVI): FEV1z-score < -1.645, FVC z-score < -1.645, FEV1 /FVC z-score ≥ -1.645, and TLC z-score ≥ -1.645., Results: The ACPA-group was older than the ACPA+ one by ~ 10 years (63±13 vs. 53±12 years, p=0.0025; respectively). The ACPA+ and ACPA-groups included comparative percentages of patients having RVI, MVI, and NSVI (23.1 vs. 45.5%, p=0.0745; 3.8 vs. 3.0%, p=0.8654; and 7.7 vs. 6.1%, p=0.8086; respectively). Compared to the ACPA- group, the ACPA+ group included a higher percentage of patients having OVI and lung-hyperinflation (9.1 vs. 38.5%, p=0.0069; 9.1 vs. 42.3%, p=0.0029; respectively)., Conclusion: Compared to the ACPA-group, the ACPA+ one had more lung-hyperinflation and OVI, and comparative percentages of RVI, MVI, and NSVI.

Background: Inborn errors of immunity (IEIs) are a heterogeneous group of genetic defects of immunity, which cause high rates of morbidity and mortality mainly among children due to infectious and non-infectious complications. The IEI burden has been critically underestimated in countries from middle- and low-income regions and the majority of patients with IEI in these regions lack a molecular diagnosis., Methods: We analyzed the clinical, immunologic, and genetic data of IEI patients from 22 countries in the Middle East and North Africa (MENA) region. The data was collected from national registries and diverse databases such as the Asian Pacific Society for Immunodeficiencies (APSID) registry, African Society for Immunodeficiencies (ASID) registry, Jeffrey Modell Foundation (JMF) registry, J Project centers, and International Consortium on Immune Deficiency (ICID) centers., Results: We identified 17,120 patients with IEI, among which females represented 39.4%. Parental consanguinity was present in 60.5% of cases and 27.3% of the patients were from families with a confirmed previous family history of IEI. The median age of patients at the onset of disease was 36 months and the median delay in diagnosis was 41 months. The rate of registered IEI patients ranges between 0.02 and 7.58 per 100,000 population, and the lowest rates were in countries with the highest rates of disability-adjusted life years (DALY) and death rates for children. Predominantly antibody deficiencies were the most frequent IEI entities diagnosed in 41.2% of the cohort. Among 5871 patients genetically evaluated, the diagnostic yield was 83% with the majority (65.2%) having autosomal recessive defects. The mortality rate was the highest in patients with non-syndromic combined immunodeficiency (51.7%, median age: 3.5 years) and particularly in patients with mutations in specific genes associated with this phenotype (RFXANK, RAG1, and IL2RG)., Conclusions: This comprehensive registry highlights the importance of a detailed investigation of IEI patients in the MENA region. The high yield of genetic diagnosis of IEI in this region has important implications for prevention, prognosis, treatment, and resource allocation., (© 2021. The Author(s).)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Tahiat, Yagoubi, Ladj, Belbouab, Aggoune, Atek, Bouziane, Melzi, Boubidi, Drali, Bendahmane, Iguerguesdaoune, Taguemount, Soufane, Oukil, Ketfi, Messaoudi, Boukhenfouf, Ifri, Bencharif Madani, Belhadj, Benhala, Khiari, Cherif, Smati, Arada, Zeroual, Bouzerar, Ibsaine, Maouche, Boukari and Djenouhat.)

Introduction: Determining the profile of COVID-19 patients with low pulsed hemoglobin saturation in oxygen (SpO2) could help clinicians identify those with a poor prognosis., Aim: To identify and to compare the clinical, biological and radiological data of Algerian patients hospitalized for COVID-19 and divided according to the SpO2 measured at admission, at rest, and in ambient air., Methods: A prospective study was carried out on Algerian patients hospitalized for COVID-19 during the period from March 9 to April 30, 2020. The general characteristics of the patients and the clinical, biological and radiological data were determined., Results: 86 patients were included in the study [G1: SpO2 >95% (n=51) and G2: SpO2 ≤95% (n=35)]. Compared to G1, G2 was older (48±14 vs. 61±12 years, p=0.0001), included more patients aged ≥ 50 years (37.2 vs. 80.0%, p=0.0001), having an arterial-hypertension (21.6 vs. 45.7%, p=0.0180), a cancer (0.0 vs. 14.3%, p=0.0054), an anemia (25.6 vs. 56.3%, p=0.0069), a leukocytosis (4.7 vs. 21.9%, p=0.0236), a biological inflammatory syndrome (82.5 vs. 100%, p=0.0142), a hyper-uremia (7.0 vs. 37.5%, p=0.0185), a hyper-creatininaemia (4.7 vs. 18.8%, p=0.0356), a tissue damage (41.0 vs. 66.7%, p=0.0341), a diffuse ground-glass opacity (52.0 vs. 71.4%, p=0.0397), band condensations (30.0 vs. 54.3%, p=0.0244), a severe extension (2.0 vs. 25.7%, p=0.0008), and included fewer patients who complained from diarrhea (49.0 vs. 22.9%, p=0.0145), having a nodular ground-glass (66.0 vs. 40.0%, p=0.0177) and a slight extension (78.0 vs. 40.0%, p=0.0004)., Conclusion: Criteria associated with low SpO2 in hospitalized COVID-19 patients were advanced age, a history of arterial-hypertension and cancer, high frequencies of certain biological abnormalities or radiological signs. The diarrhea symptom, the radiological appearance of nodular ground glass, and a slight extension of the radiological lesions appear as protective elements.

Introduction: Aucune étude antérieure n'a élaboré le profil des patients Algériens hospitalisés pour COVID-19. L'objectif de cette étude était de déterminer le profil clinique, biologique et tomodensitométrique des patients Algériens hospitalisés pour COVID-19., Méthodes: Une étude prospective était menée auprès des patients hospitalisés pour COVID-19 (période: 19 mars-30 avril 2020). Les données cliniques, biologiques et radiologiques, le type de traitement reçu et la durée de l'hospitalisation étaient notés., Résultats: Le profil clinique des 86 patients atteints de COVID-19 était un homme non-fumeur, âgé de 53 ans, qui était dans 42% des cas en contact avec un cas suspect/confirmé de COVID-19 et ayant une comorbidité dans 70% des cas (hypertension artérielle, diabète sucré, pathologie respiratoire chronique et allergie, cardiopathie). Les plaintes cliniques étaient dominées par la triade «asthénie-fièvre-toux» dans plus de 70% des cas. Les anomalies biologiques les plus fréquentes étaient: syndrome inflammatoire biologique (90,1%), basocytémie (70,8%), lymphopénie (53,3%), augmentation de la lactico-deshydrogénase (52,2%), anémie (38,7%), augmentation de la phosphokinase (28,8%) et cytolyse hépatique (27,6%). Les signes tomodensitométriques les plus fréquents étaient: verre dépoli (91,8%), condensations alvéolaires (61,2%), verre dépoli en plage (60,0%), et verre dépoli nodulaire (55,3%). Un traitement à base de «chloroquine, azithromycine, zinc, vitamine C, enoxaparine, double antibiothérapie et ± corticoïdes» était prescrit chez 34,9% des patients. La moyenne de la durée d'hospitalisation était de 7±3 jours., Conclusion: La connaissance des profils des formes modérées et sévères du COVID-19 contribuerait à faire progresser les stratégies de contrôle de l'infection en Algérie., Competing Interests: Les auteurs ne déclarent aucun conflit d´intérêts., (© Abdelbassat Ketfi et al.)

Anti-citrullinated cyclic peptide antibodies (ACPA) were initially considered very specific for the diagnosis of rheumatoid arthritis (RA), and can predict the prognosis of the disease. However, these antibodies can be detected in other autoimmune diseases, including systemic lupus erythematosus (SLE), the most common manifestation of which is inflammatory arthritis, which is often found in early-stage rheumatoid arthritis. The aim of our study is to evaluate the prevalence of ACPA antibodies and to analyze the profiles of their associations with autoantibodies specific to lupus, in order to look for a possible rhupus overlap syndrome in our patients. This is a retrospective study, carried out at the immunology unit, at Blida University Hospital, Algeria, involving 96 lupus patients, diagnosed according to the criteria of the American college of rheumatology (ACR). ACPA have been identified by the ELISA technique. ACPA was positive in 14,56% of our patients, whereas anti-DNA, anti-Sm and rheumatoid factor (RF) autoantibodies were positive, respectively in 47.09%, 35.41%, and in 26.04% of our patients. In addition, the presence of ACPA with anti DNA was found in 12.5% of patients. Of the 14 with ACPA+, 57.14% had arthritis. Our results confirm that ACPA auto-antibodies do not represent a pathognomonic criterion of RA. This sometimes makes the differential diagnosis with lupus difficult especially at the beginning of the disease.

Since the introduction of the most expensive drug in the world (Eculizumab) in the therapeutic arsenal of many diseases involving the alternative complement pathway (ACP) in their pathophysiology, the unmet need to perform simple ACP assays affordable for all countries has become one of the major challenges of the contemporary medicine. The assay currently used is AH 50 , despite it still challenging for several laboratories. This educational chapter consists of a detail protocol of standardized hemolytic assay AP 100 and aims to help clinical laboratories over the world and especially those of the developing and low income countries to perform it. The procedure is essentially the same as for the timed lysis assay and dilution methods (AP 50 ) except the concentration of ACP buffer and the chicken erythrocyte density used to make the gels. In clinical field, AP 100 has at least nine applications in disease diagnosis and follow-up. AP 100 has many advantages over the AH 50 as it is more reliable for the Eculizumab monitoring and more practical with a purpose to be stored and transported for several weeks. AP 100 is a portable and easy to use device both at the bedside and in the companion medical care.

Background: Der p 5 is an important allergen of Dermatophagoides pteronyssinus that plays a key role in allergic airway diseases. Its three dimensional structure (PDB 3MQ1) consists of three anti-parallel α-helices arranged in a helical bundle. Aggregation of Der p5 can modulate its allergenicity. This study aimed to identify the key residues of IgE binding epitopes of Der p 5., Methods: IgE binding epitopes of Der p 5 were characterized as follow. An in silico prediction of the epitope was performed with the help of SEPPA program. We also made a mapping of the epitope by using an overlapping library of peptides that encompass the sequence of mature Der p 5. Finally, an alanine scanning mutagenesis allowed us to define the key residues of the allergen involved in its interaction with IgE. The integrity of the structure of the different protein's mutants was assessed by far UV circular dichroism., Results: The presented data indicate that the major epitope sequence of Der p 5 is 90DRLMQRKDLDIFEQYNLEM108. Residues L98, D99, I100, F101, E102 and Y104 appear to be important for IgE binding., Conclusion: This study highlighted the residues of Der p 5 essential for IgE binding. The identification of the major residues epitope of Der p 5 allergen may participate in the selection and engineering of new hypoallergens used in immunotherapy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)