اسم المؤلف:
وسناء جمعة محمد
اسم المشرف:
محمد شمخي جبر
باسم شهاب احمد
المستخلص:
التهاب المفاصل الرثوي (Rheumatoid Arthritis) مرض جهازي التهابي مزمن يصيب المفاصل وتحديدا الاغشية الزلالية والتراكيب المفصلية، والذي يحدث للعديد من الناس وبنسبة تقارب 0.5 الى 1% من السكان في العالم. لوحظ خلال الدراسات الوبائية لمرض التهاب المفاصل الرثوي | Rheumatoid arthritis (RA) one of the most common systemic autoimmune diseases characterized by chronic joint inflammation and subsequent joint destruction. To date, it well known that RA is characteristic of the expansion of the synovium and infiltration of the inflammatory cells coupled with destruction of adjacent articular cartilage and bone. This is strongly dependent on CD4 T cell. CD4 Cells stimulate monocytes, macrophages, synovial fibroblasts, and other cells to produce cytokines such as tumor necrosis factor - ? (TNF - ?, interleukin - 1 (IL - 1), IL - 6, IL - 15, IL - 17 and metalloproteinases that produce tissue damage. TNF is a major inflammatory cytokine contributing to the pathogenesis of RA, which provides rational for development of anti - TNF biological agents in the treatment of RA.Recently have shown that IL - 37 is a key cytokine in regulating inflammatory response, mainly by inhibiting the expression, production, and function of proinflammatory cytokines. Objectives This study planned to evaluate the association of TNFRII and CD4 enhancer genes polymorphisms in development and severity of RA in Iraqi patients, evaluate IL - 37 in patients with RA and investigate the correlation between IL - 37 levels with disease activity and relation of inflammatory parameters (ESR, CRP, ACPA, and RF) with TNFRII, CD4 enhancer genes polymorphisms.Patients and methods This study was performed during the period from May to September 2015. The patients were attending the out patients' Clinic in Medical City/Baghdad Teaching hospital/rheumatology unit and the laboratory ELISA tests were done in nursing home hospital laboratory, polymerase chain reaction (RFLP) analysis was performed in the specialist private molecular laboratory (ASCO Lab) in Al - Harthia / Baghdad. Fifty patients and 50 apparently healthy control individuals, Patients received disease modifying anti rheumatic drugs (DMARDs) and newly diagnosed patients.The diagnosis of RA patients has performed under the supervision of rheumatic disease consultant physician at the consultation clinic of Baghdad teaching hospital of the medical city. Blood samples had taken from RA patients to measure (ESR), white blood cells count and hemoglobin. Also, analyze the serum levels of ACPA, RF screen CRP and estimate the levels of IL - 37 in patients and healthy individuals using ELISA test kits. TNFRII and CD4 enhancer genes polymorphisms genotyping had achieved by polymerase chain reaction restriction fragment length (PCR - RFLP).Results The results showed the estimation of RF by screening test revealed that its mean level was high among RA patients (168.87+31.62) in comparison with apparently healthy control (4.96+0.71) with highly significant difference (p<0.01). There was a higher positivity of Anti CCP in the patients sera (114.85+21.06) in comparison with apparently healthy control (1.71+0.13) (P<0.01). while the estimation of CRP showed that its level was higher among sera of RA patients (38.39+4.31) in comparison with healthy control group (16.49+2.51) (P<0.01). Furthermore, the ESR level in RA patients were higher than apparently healthy individuals (52.96+3.68) and (10.44+0.74) respectively with significance (P<0.01).The frequencies of the MM, MR, RR genotypes of TNFRII gene polymorphisms were 60%, 32%, 8% in RA patients and 52%, 42%, 6% in controls. There were no significant differences in the genotypes frequencies polymorphisms of the TNFRII 196 MR polymorphism between apparently healthy control and RA. The frequencies of AA, AG, GG genotypes of CD4 10845 A/G in patients was 36%, 42%, 22% and 8%, 44%, 48% in control group. There were significant differences in the genotypes frequencies polymorphisms of the CD4 10845A/G polymorphisms between apparently healthy control and RA patients (p<0.01). AA genotype were significantly more likely to develop RA (OR=1.355). There was significant increase in disease activity and severity in patients carries AA genotype (p<0.01).IL - 37 levels were elevated markedly in RA patients (101.31+10.41) compared with apparently healthy control (43.90+0.91) (p<0.01). More importantly, IL - 37 showed a significant correlation with disease activity (CRP) in RA patients (p<0.05). Also, IL - 37 show non - significant relationship with (MM, MR, RR) exon6 TNFRII in RA patients compared with controls, and non - significant difference between level of IL - 37 with CD4 10845 A/G genotypes compared with healthy control.Conclusion All findings suggested that TNFRII - 196R genotypes not associated with RA diagnosis. In addition, genetic polymorphisms at the CD4 enhancer gene are one of important factors that associated with susceptibility and severity of RA and can serve as a genetic marker for the risk of development of RA.
