Ischemic heart disease and rheumatoid arthritis: Do inflammatory cytokines have a role?

BACKGROUND: The increase in Rheumatoid arthritis (RA) associated mortality is predominantly due to accelerated coronary artery and cerebrovascular atherosclerosis with increased risk of ischemic heart disease about 50% in RA patients compared to controls. OBJECTIVE: To study the pathogenesis of ischemic heart disease in RA, role of inflammatory cytokine interplay, disease activity and rheumatoid factor positivity. METHODS: Eighty RA patients and 44 healthy controls were included. All subjects were younger than 45years for females and 55years for males with exclusion of all traditional risk factors for atherosclerosis. Interleukin (IL) 1, 6 and 18 were assessed in all subjects. RA patients fulfilled ACR/EULAR 2010 criteria and were subjected to Dobutaminestress-echocardiography, diseases activity assessed by DAS-28, X-ray hands for Larsen score and function assessment by HAQ. RESULTS: RA patients had significantly higher serum IL 1, 6 and 18 than controls (p=0.00 in all). Thirty four (42.5%) patients had hypertensive reaction on Dobutamine-stress-echocardiography, four of them had ischemic change, and 46 (57.5%) had normal reaction. All patients with hypertensive reaction had positive RF (p=0.00), 10 had DAS-28>5.1, 20 had DAS-28 from 3.2 to5.1 and 4 were in remission (p=0.001). CRP was higher in patients with hypertensive reaction (p=0.003) while serum levels of IL1, 6 and 18 showed no significant difference. In all patients, serum levels of IL1, 6 and 18 showed significant positive correlation with VAS, HAQ and DAS-28 (p<0.001 in all). Only IL18 showed significant positive correlation with X-ray score in all patients. CONCLUSION: Disease activity and RF positivity play an important risk factor for ischemic heart disease in RA. Serum levels of IL1, 6 and 18 did not help much in detecting patients at risk of ischemic heart disease. Better control of RA disease activity with early remission helps in preventing cardiac complications. More studies on larger number of patients are needed for better understanding of mechanism of ischemic heart disease in RA.

Matrix Metalloproteinase-9 rs17576 Gene Polymorphism and Behçet's Disease: Is There an Association?

BACKGROUND: Clinical studies have reported a significant association between matrix metalloproteinases (MMP), particularly (MMP-9), and inflammatory diseases including Behçet's disease (BD). PURPOSE: To study the relationship between MMP-9 rs17576 gene polymorphism and the development of BD, and its relation to disease activity among Egyptian patients. METHODS: A total of 100 BD patients and 100 healthy control volunteers were genotyped for MMP-9 rs17576 polymorphism with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), followed by the confirmation of our results in random subgroups using direct DNA sequencing technique. RESULTS: The frequency of the GG genotype and G allele was significantly higher in BD patients as compared to the normal controls (p = 0.011, OR 8.61; p = 0.03, OR 1.65, respectively). There was no significant association between the MMP-9 rs17576 polymorphism and the clinical outcomes of BD. CONCLUSION: our study suggests a significant association of the MMP-9 rs17576 A/G polymorphism with increased risk of BD development in Egyptian patients.

Dysregulation of angiogenic homeostasis in systemic sclerosis.

BACKGROUND: Systemic sclerosis (SSc) is a connective tissue disorder characterized by tissue hypoxia and excessive fibrosis of skin and internal organs. OBJECTIVE: To evaluate the possible role of angiogenesis imbalance in the pathogenesis of SSc. SUBJECTS AND METHODS: Twenty-five SSc patients and 20 age- and sex-matched healthy controls were included. Assay of serum vascular endothelial growth factor (VEGF) and endostatin was done for all patients and controls using enzyme-linked immunosorbent assay. Patients were subjected to modified Rodnan skin score (mRss), pulmonary function tests (PFTS) and skin biopsies for histopathological skin thickness score assessment. RESULTS: There was significant increase in the mean levels of serum VEGF and endostatin in SSc patients compared to controls (t = 4.07, P < 0.001). Mean values of serum endostatin was significantly increased in late compared to early stages of disease (t = 6.65, P < 0.01). A significant positive correlation was found between serum levels of endostatin, mRss and histopathological skin thickness score (r = 0.99, 0.94, respectively, P < 0.01). SSc patients with ischemic manifestations had significantly higher levels of serum endostatin compared to those without ischemic manifestations (t = 6.27, P < 0.001). SSc patients with restricted PFTS had significantly higher levels of serum endostatin compared to those without pulmonary manifestations (t = 4.3, P < 0.001). CONCLUSION: Angiogenic inhibitor (endostatin) is induced and outweighs angiogenic inducer (VEGF) in late stages of SSc. Increased serum endostatin is associated with skin sclerosis severity and pulmonary fibrosis and favors SSc disease progression.