Rashad Kadhim Mahmood Al-Akhras

Abstract The results of numerous studies of the biological effects of cytokines, as well as the dynamics of the activity of these molecules during physiological and pathological processes, have become the fundamental basis for the use of cytokines in clinical practice. There are three main areas of clinical use of cytokine preparations - diagnostic, therapeutic and prophylactic. The successful results of the use of cytokines in the clinic are largely associated with the leading role of impaired functioning of the immune system in the pathogenesis of the vast majority of diseases. cytokines are involved the pathogenesis of many diseases, primarily those that correlate with the development of immunopathology. Research objectives: The study was carried out on cultures of human lymphocytes obtained from peripheral blood samples from a healthy volunteer donor. Materials and methods: In our study we used many methods to do oxidative stress due using hydrogen peroxide in culture of lymphocytes that prepared by RPMI1640 medium supplemented with bovine serum, then estimating of oxidation state by using chemiluminometer and oxystat methods. The count of concentrations of cytokines by use ELISA (monoclonal and polyclonal). Results: The current study illustrated that the presence of 400 μM hydrogen peroxide in the culture medium initiates oxidative stress in human peripheral blood leukocytes. The observed oxidative stress is prolonged and is characterized by a decrease in the activity of the antioxidant system of cells 48 hours after exposure. Oxidative stress of this kind does not lead to pronounced changes in the actual protein expression of IL-1β, IL- 2, IL-4, IL-6, IL-10, and TNF, however, it causes a shift in the work of regulatory circuits that control the expression of these cytokines. Conclusion: The most pronounced change in the regulation of the studied cytokines is characterized by the loss of “direct” co-regulation of IL1β and IL10 and the prevalence of redox-dependent mechanisms of IL10 control under the conditions of the oxidative stress model that used in this study.

Background: The prevalence of Rheumatoid Arthritis (RA) has been raised in Iraq. The medical costs of such increased prevalence are high. Global studies have revealed polymorphisms of MTHFR (Methylenetetrahydrofolate Reductase) gene to be associated with Rheumatoid Arthritis (RA). This polymorphism can cause changes in various metabolic variables. Methods: The current study consists of 100 RA patients and 100 healthy control individuals. Variable parameters data included Anti-Cyclic cytrulinated peptide expression (ACCP), Rheumatoid factor (RF), C - reactive protein (CRP) in serum and Erythrocytes sedimentation rate (ESR) levels. Genotyping of MTHFR gene polymorphism is carried out by RFLP-PCR. Various statistical analyses were applied to analyze the data. Results: The estimation of immunological and biochemical data pointed out significant differences in Gender, RF, ACCP, CRP, ESR and age in RA when compared with those of the control group. The genotyping results were found to be consistent with Hardy-Weinberg equilibrium. The analysis of the genotype distribution under various inheritance models highlighted significant differences in SNP of MTHFR gene polymorphism among RA patients when compared with the control group under the dominant homozygote, heterozygote and recessive homozygote. The genotype and allele frequencies of the MTHFR SNP rs1801133; highlighted significant rises of the risk of RA CT (P =0.0335), (OR=1.9409), (95%CI 1.0532-3.5766) when compared with control subjects. We found that the CT genotype is associated with the risk of RA comparing with CC and TT genotypes. Clinical characteristics were observed to change significantly with respect to the genotype distribution (risk factors) of the investigated SNP. Conclusion: MTHFR gene polymorphism (rs1801133) is implicated in the pathogenesis of Rheumatoid arthritis in Najaf population.

ABSTRACT Background: The prevalence of Rheumatoid Arthritis (RA) has been raised in Iraq. The medical costs of such increased prevalence are high. Global studies have revealed polymorphisms of PD1 (Program Death 1) gene to be associated with Rheumatoid Arthritis (RA). This polymorphism can cause changes in various metabolic variables. Methods: The current study consists of 100 RA patients and 100 healthy control individuals. Variable parameters data included Anti-Cyclic cytrulinated peptide expression (ACCP), Rheumatoid factor (RF), C-Reactive Protein (CRP) in serum and Erythrocytes sedimentation rate (ESR) leveles. Genotyping of PD1gene polymorphism is carried out by RFLP-PCR. Various statistical analyses were applied to analyze the data. Results: The estimation of immunological and biochemical data pointed out significant differences in Gender, RF, ACCP, CRP, ESR and age in RA when compared with those of the control group. The genotyping results were found to be consistent with Hardy-Weinberg equilibrium. The analysis of the genotype distribution under various inheritance models highlighted significant differences in SNP of PD1 gene polymorphism among RA patients when compared with the control group under the dominant homozygote, heterozygote and recessive homozygote. The genotype and allele frequencies of the PD1 SNP rs11568821; genotype GA was significantly increased in RA compared with controls (45% and 24%, respectively) (P=0.0020),(OR =2.5909),(95% CI 1.4-4.7) . Subjects who carried A allele were significantly more likely to develop RA three folds AA(OR=3.3529, 95% CI=1.1691-9.6160, P=0.0244). Clinical characteristics were observed to change significantly with respect to the genotype distribution of the investigated SNP. Conclusion: PD1 gene polymorphisms (rs11568821) is implicated in the pathogenesis of Rheumatoid arthritis in Najaf population.