Prevalence of BTK mutations in male Algerian patterns with agammaglobulinemia and severe B cell lymphopenia.

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.1522G>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.

Clinical, immunological and genetic features in eleven Algerian patients with major histocompatibility complex class II expression deficiency.

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.

Lung function data of North-African patients with rheumatoid arthritis: a comparative study between anti-citrullinated peptides antibodies positive and negative patients.

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.

Autoantibody profile in a cohort of Algerian patients with systemic sclerosis.

AIM: To describe the autoantibody profile in a cohort of Algerian patients with systemic sclerosis (SSc) and to determine clinical associations between SSc-related autoantibodies, disease subtypes and specific clinical features. METHODS: Consecutive Algerian patients with SSc were included in the present study. In addition to clinical characterization, all subjects underwent autoantibody testing using indirect immunofluorescence, immunoenzymatic, and line immunoblot assays. RESULTS: A total of 150 patients were included in this study, 103 (68.7%) had limited cutaneous SSc (lcSSc), 42 (28%) had diffuse cutaneous SSc (dcSSc) and 5 (3.3%) had sine cutaneous scleroderma. One hundred thirty-five (90.0%) patients were positive for SSc-related autoantibodies, including 63 (42%) with more than one autoantibody. The two most frequent autoantibodies were anti-topoisomerase I (ATA) (76; 50.7%) and anti-SSA/Ro (49; 32.7%). Only 23 (15.3%) patients were positive for anticentromere; 9 (6%) were positive for anti RNA polymerase III; 5 (3.3%) for anti-U3 RNP; 3 (2%) for anti Th/To; 25 (16.7%) for anti-U1 RNP; 11 (7.3%) for anti-PM/Scl and 4 (2.7%) for anti-Ku. Anti-topoisomerase I was associated with dcSSc (p <0.0001), interstitial lung disease (ILD) (p <0.0001) and digital ulcers (p <0.0001). Anti-U3 RNP was associated with pulmonary arterial hypertension (PAH) (p=0.031). CONCLUSION: Notable similarities and differences in the prevalence of SSc-related autoantibodies were found in our population when compared to other ethnic groups. ATA and anti-U3 RNP may be a reliable biomarker for ILD and PAH. Further studies should be conducted to better understand the ethnic influence on disease expression and autoantibody production.

Th17 pathway genes polymorphisms in Algerian patients with systemic sclerosis.

OBJECTIVE: TH17 cells have involved in the pathogenesis of several autoimmune diseases including systemic sclerosis (SSc). The aim of our study was to investigate an association of IL-17A, IL-17F, IL-21, IL-23R and STAT3 genes with SSc susceptibility, and clinical and immunological phenotypes. PATIENTS AND METHODS: The case-control study included 136 patients suffering from SSc and 317 healthy controls of the Algerian population. Eight single nucleotide polymorphisms (SNP) of genes encoding TH17 pathway were genotyped using TaqMan allelic discrimination assays. These SNPs are: IL-17A (rs2275913), IL17F (rs2397084 and rs763780), IL-21 (rs6822844), IL-23R (rs10489629, rs11209026 and rs1343151) and STAT3 (rs2293152). RESULTS: The current study showed a significant association of rs2397084 SNP (p = 0.049 and p = 0.036 for the TT genotype and the T allele, respectively) and rs6822844 SNP (p = 6.6ₓ10-4 for the G allele) with systemic sclerosis (SSc) susceptibility. Also, we found an association of rs2275913 SNP (pc = 0.015 and p = 0.005 for the GG genotype and the G allele, respectively) and rs6822844 SNP (pc = 0.024 for the TT genotype) with digestive involvement. Also an association with anti RNAPIII antibodies production have been found with rs6822844 SNP (pc = 0.012 and pc = 0.029 for the GT genotype and the T allele, respectively). Association of rs10489629 SNP with digital infarcts (p = 0.043 for the C allele), interstitial lung disease (p = 0.045 for the CT genotype) and anti SSA antibodies production (p = 0.001 and p = 0.008 for the CT genotype and the T allele, respectively) have been showed. Finally an association of rs1343151 SNP with digital infarcts (p = 0.028 for the A allele), and with interstitial lung disease (p = 0.025 for the AG genotype) have also been found. CONCLUSION: The study revealed that IL-17F and IL-21 genes were associated with systemic sclerosis (SSc) susceptibility and that IL-17A, IL-17F, IL-21 and IL-23R genes influence the clinical and immunological features, which suggest the implication of TH17 cells in SSc pathogenesis.

Association study of human leukocyte antigen-DRB1 alleles with rheumatoid arthritis in Algerian patients.

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 < 0.001, OR = 3.14), and was associated with anti-citrullinated protein antibodies positivity (ACPA) (P = 0.01, OR = 2.35). In contrast, HLA-DRB1*07 was found to have a decreased frequency in patients compared to controls (P = 0.003, OR = 0.44) and significant decrease was observed in patients with the rheumatoid factor (RF) positivity subgroup (P = 0.009, OR = 0.29). HLA-DRB1*04:05 was associated with RA (P = 0.005, OR = 3.41), whereas, HLA-DRB1*04:02 showed a protective effect against RA (P = 0.003, OR = 0.20). CONCLUSIONS: HLA-DRB1*04 was associated with increased risk for RA and ACPA positivity, while HLA-DRB1*07 was associated with reduced risk for RA and RF synthesis in Algerian patients.