Epidemiological and immunochemical parameters of monoclonal plasma cell dyscrasias of 2121 cases in Algeria.

BACKGROUND: Plasma cell dyscrasias (PCD) are a heterogeneous group of diseases characterized by the expansion of monoclonal bone marrow plasma cells that produce a monoclonal immunoglobulin (M-component). PURPOSE: This is a retrospective study that describes the epidemiological, immunochemical features and etiology of monoclonal gammopathies diagnosed between 1998 and 2016 in the Teaching Hospital Beni-Messous of Algiers. PATIENTS AND METHODS: 2121 cases of monoclonal gammopathies (MG) were collected during this period. Serum/urine protein electrophoresis, serum/urine immunofixation and serum free light chain measurements were used to demonstrate M protein. RESULTS: The middle age of the patients at the time of the diagnosis were 62.96 ± 13.19 years with extremes ranging from 07 to 99 years. The study included 1013 (47, 76 %) men and 1108 (52, 23 %) women with a sex ratio 0,91. Isotypes repartition was: IgG (60.91 %), IgA (17.91 %), light chain (10.46 %), IgM (6.6 %), IgD (1.03 %) and IgE (0.09 %) of cases. The most frequent diagnosis was: Multiple Myeloma (55.20 %), followed by monoclonal gammopathy of undetermined significance (34.13 %). CONCLUSION: In our study, two particularities were noted. There is no male predominance in Algerian PCD patients. Moreover, we observed a higher frequency of light chain multiple myeloma and lower frequency of IgM isotype compared to western studies.

Association study of single nucleotide polymorphisms of IL23R and IL17 in rheumatoid arthritis in the Algerian population.

OBJECTIVE: Previous studies implicated that IL17/IL23 pathway and TH17 cells play an important role in autoimmune inflammation. Genome wide association studies have identified multiple single nucleotide polymorphisms (SNPs) in the IL23R and IL17 genes region associated with rheumatoid arthritis (RA). METHODS: In this study, we investigated the association of IL23R, IL17A and IL17F genes SNPs with RA susceptibility in the Algerian population. 343 patients with RA and 323 healthy subjects were genotyped for IL23R (rs11209026, rs1343151, rs10489629), IL17F (rs763780, rs2397084) and IL17A (rs2275913) variants by TaqMan technology. RESULTS: There was no evidence of a genetic association between IL23R, IL17F and IL17A SNPs and RA susceptibility in our population. However, IL23R rs1343151 variant enhanced the development of RF IgM and IgG positive (+) RA as compared with RF IgM and IgG negative (-) RA (OR 2.29, p = 0.004 and OR 0.64, p = 0.014 respectively). Also, IL23R rs10489629 was associated with all RF isotypes positive disease (IgM+: OR 2.16, p = 0,006; IgG+: OR 0.64, p = 0,004 and IgA+: OR 1.54, p = 0,013). A moderate association of IL17A rs2275913 with RF IgA- RA subgroup was shown (OR 1.95, p = 0,039). Moreover, our data showed a correlation between IL23R and IL17F variants and the parameters of disease activity such as HAQ score and disease duration. CONCLUSION: The current study emphasizes the lack of association of IL23R and IL17 polymorphisms with RA susceptibility in the Algerian population. However, the data showed the relationship between IL23R and IL17A polymorphisms and the production of the different RF isotypes in RA patients.

Association of rs6822844 within the KIAA1109/TENR/IL2/IL21 locus with rheumatoid arthritis in the Algerian population.

Increasing evidence suggests that the rs6822844, within KIAA1109/TENR/IL2/IL21 gene cluster on 4q27, is strongly associated with rheumatoid arthritis (RA) in the Caucasian population. The aim of this study is to investigate the possible association between the SNP rs6822844 and susceptibility to RA in the Algerian Maghreb population, and to explore the association with the clinical and immunological features of RA. The polymorphism rs6822844 was genotyped in 323 RA patients and 323 healthy individuals using the TaqMan assay. A strong association of IL2/IL21 with RA susceptibility was detected in the Algerian population [odds ratio (OR) = 2.57 (95% confidence interval (CI) 1.74-3.83), P = 10(-4) ]. Our results revealed that IL2/IL21 predisposed to disease development in both autoantibody positive and negative disease. Meanwhile, the association was stronger in RA patients with anti-cyclic citrullinated peptides (ACPA) positive than those with ACPA negative [OR = 2.30 (95% CI 1.53-3.51), P = 10(-4) and OR = 1.98 (95% CI 1.01-4.22), P = 0.037, respectively]. Moreover, our findings showed a moderate association of the rs6822844 polymorphism with disease activity (P = 0.014). This study indicates for the first time that there is a strong association between IL2/IL21 rs6822844 variant and susceptibility to RA in the Algerian population, and that this association was independent from the autoantibodies status of RA patients.

IgD multiple myeloma: Clinical, biological features and prognostic value of the serum free light chain assay.

IgD multiple myeloma (MM) is a rare subtype of myeloma, it affects less than 2% of patients with MM. To evaluate the clinical and prognostic attributes of serum free light chains (sFLCs) analysis, we examined 17 cases of IgD MM. From 1998 to 2012, we obtained 1250 monoclonal gammapathies including 590 multiple myeloma and 17 patients had IgD MM. With preponderance of men patients with a mean age at diagnosis of: 59±12years. Patients with IgD MM have a short survival (Median survival=9months). The presenting features included: bone pain (75%), lymphadenopathy (16%), hepatomegaly (25%), splenomegaly (8%), associated AL amyloidosis (6%), renal impairment function (82%), infections (47%), hypercalcemia (37%) and anemia (93%). Serum electrophoresis showed a subtle M-spike (Mean=13.22±10g/L) in all patients associated to a hypogammaglobulinemia. There was an over-representation of Lambda light chain (65%); high serum ß2-microglobulin in 91% and Bence Jones proteinuria was identified in 71%. The median rate of sFLCs κ was 19.05mg/L and 296.75mg/L for sFLCs λ. sFLCR was abnormal in 93% of patients and it showed concordance between baseline sFLCR and the survival (P=0.034). The contribution of FLC assay is crucial for the prognosis of patients with IgD MM.

[Common variable immunodeficiency (CVID): clinical and immunological features of 29 Algerian patients]. / Déficit immunitaire commun variable (DICV) : caractéristiques cliniques et immunologiques de 29 patients algériens.

PURPOSE: Common variable immunodeficiency (CVID) is the commonest symptomatic primary immunodeficiency. It is characterized by a defect of antibody production, recurrent respiratory tract infections and increased occurrence of auto-immune discords and lymphoproliferative disease. METHODS: This retrospective study was conducted on 29 patients fulfilling the classical CVID definition. Blood tests included immunoglobulin measurement and lymphocyte subpopulations phenotyping. RESULTS: This study includes 29 patients. The mean age at diagnosis was 23years. Recurrent upper and lower bacterial respiratory tract infections were common in almost all patients. Five patients developed auto-immune conditions and six had lymphoproliferative disease. Decreased IgG was found in almost all patients. Low IgA and IgM levels were found in 89.6 % and 65.5 % of cases respectively. Abnormal T and/or B phenotype was found in 75 % of cases; the most common abnormalities were decreased circulating B (54.2 %) and T CD4+ (41.7 %) cells and inversion of the CD4/CD8 ratio (70.8 %). Patients with decreased circulating B and T CD4+ cells were significantly more likely to have auto-immune cytopenias and lymphoproliferative disease. CONCLUSIONS: Our study confirms the heterogeneity of CVID. A patient's classification is necessary to define homogeneous groups of patients and to characterize specific molecular abnormalities in each group.

NOD2/CARD15 and IL23R genetic variability in 204 Algerian Crohn's disease.

NOD2/CARD15 and IL23R gene variants play an important role in the susceptibility to Crohn's disease (CD). Studies of genotype-phenotype relationship suggest that these variants are associated with the development of the disease and specific phenotype. Preliminary reports analyzing the association between these variants have never been made on Algerian CD's. In a case-control design, 204 Algerian with CD diagnosed for at least 5years and 201 controls were included were genotyped for single nucleotide polymorphisms (SNP) in the NOD2/CARD15 gene R702W (SNP8, rs2066844), G908R (SNP12, rs2066845) and IL23R R381Q (rs11209026) gene variants were determined using the TaqMan SNP genotyping assays. NOD2/CARD15 908R was carried by 3% of the patients and none in control subjects (χ(2)=8.6, Pc=0.003, OR=13.20). NOD2/CARD15 702W was associated to CD outcome (χ(2)=17.2, Pc=0.00003, OR=12.5) and early onset of disease (group A1, χ(2)=19.3, Pc=1.10(-5), OR=14.05, PM-H=2.10(-6)). IL23R 381Q variants was more frequent in CD's patients than controls (χ(2)=8, Pc=0.005, OR=3.48), it was associated to earlier onset (group A1, χ(2)=7.1, Pc=0.007, OR=1.04, PM-H=0.002), extra-intestinal manifestations (EIM) outcome (χ(2)=10.6, Pc=0.001, OR=1.05, PM-H=0.002) and ileocolonic location (χ(2)=6.8, Pc=0.009, OR=1.05, PM-H=0.001). In this Algerian cohort, NOD2/CARD15 and IL23R variants were associated with CD's outcomes and linked to a particular clinical phenotype.

[Interleukin-1 and the interleukin-1 receptor antagonist gene polymorphisms study in patients with rheumatoid arthritis]. / Étude des polymorphismes des gènes de l'interleukine-1 et de l'antagoniste du récepteur de l'interleukine-1 chez des patients atteints de polyarthrite rhumatoïde.

OBJECTIVES: One of the most important pro-inflammatory cytokines in the pathophysiology of rheumatoid arthritis (RA) is interleukin 1 (IL-1). The purpose of this study is to evaluate the association between IL-1B (-511), IL-1 (+3953), IL-1 RN variable number of tandem repeat (VNTR) polymorphisms and the occurrence in Algerian patients with rheumatoid arthritis. We also analyze their correlations with clinical and biological phenotypes. PATIENTS AND METHODS: One hundred and forty-seven patients with RA (119 women, 28 men) and 127 controls (70 women, 57 men) were included in the study. The analysis of two polymorphisms of IL-1B-511 and IL-1B+3953 was done by PCR-RFLP. Analysis of IL1-RN VNTR polymorphism was performed by PCR. RESULTS: No significant difference in genotype, allelic and haplotype distribution at the three polymorphisms was observed between RA patients and controls. However, the genotype (T/T) polymorphism of IL-1B-511 is more frequent in the group of patients with positive ACPA compared with negative ACPA group (Pc=0.01, OR=4.65). Moreover, we noted that the haplotype (IL-1RN* 1/IL-1B-511T/IL-1B+3953C) was more frequent (Pc=0.03, OR=2.05) in the positive ACPA group. CONCLUSION: The association between the allele 1 of IL-1 RN VNTR, T allele of IL1B-511 and C allele of IL1-B +3953 polymorphisms seems to predispose to the synthesis of ACPA and therefore to the occurrence of ACPA positive RA. Further studies with a larger number of patients are needed to define the real role of IL-1 in the susceptibility to or severity of RA.

Constitutive nitric oxide synthase gene polymorphisms and house dust mite respiratory allergy in an Algerian patient group.

Genetic polymorphisms in neuronal nitric oxide synthase (NOS1) and calmodulin-dependent endothelial NOS (NOS3) genes are known to influence the course of allergic respiratory disorders. We investigated the role of NOS1 -84 G-->A and NOS3 -786 T-->C, 894 G-->T and 27 base pair (bp) repeat polymorphisms in 125 patients suffering from asthma and/or rhinitis and monosensitized against Dermatophagoides pteronyssinus (Dpter) and 111 controls from Algeria. We found a higher frequency of the -786 C NOS3 allele in patients than in controls [corrected P value (Pc) = 0.04], especially in female cases (Pc = 0.02) and that the 'ab' genotype of the 27-bp polymorphism was significantly associated with specific immunoglobulin E production against Dpter (P = 0.006). This study brings further support for the participation of NOS3 gene polymorphism in the pathogenesis of respiratory allergic disorders.