RESUMO
Objective: to characterize the expression profile of chemokine receptors CCR5, CCR4 on CD4 T lymphocytes and to measure levels of the chemokine MIP-1alpha in peripheral blood and synovial fluid of patients with rheumatoid arthritis, correlating them to disease activity score, CRP titer and synovial fluid levels of IFN-gamma in a trial to explore the potential involvement of the chemokine system in rheumatoid arthritis
Methodology: the study included 15 female patients with rheumatoid arthritis [RA] diagnosed according to the American College of Rheumatology Criteria. All having active disease with knee effusion and 7 females with traumatic knee effusion served as the control group. They were all attending the out patient clinics of Rheumatology and Rehabilitation and Internal Medicine departments of Ain Shams University Hospitals. They were subjected to history taking, thorough clinical examination, assessment of disease activity using modified Disease Activity Score [DAS], laboratory investigations mainly: measurement of CRP titer, plasma and synovial fluid levels of macrophage inflammatory protein-1alpha [MIP-1alpha], synovial fluid levels of interferon gamma [IFN-gamma], expression percentage of CCR5, CCR4 on CD4 T lymphocytes of peripheral blood [PB] and synovial fluid [SF]
Results: MIP-1alpha levels were highly significantly increased in RA patients when compared to controls in both peripheral blood [PB] [t=13.7] and synovial fluid [SF] [t=8.8] . Similarly CCR5[+] CD4 T lymphocytes percentage [%] expression showed high significant increase in RA patients versus controls in PB and SF [t=4.9, t=11.7] respectively. On the contrary CCR4[+] CD4 T lymphocytes % expression showed no significant difference between both groups whether in PB [t=1.2] or SF [t=1.3]. SF levels of IFN-gamma were highly significantly increased in patients compared to controls [t= 6.3]. On comparing PB and SF in RA patients, there was high significant increase in MIP1alpha levels, CCR5[+] CD4 T lymphocytes % expression in SF versus PB [t=12.5, t=15.7] respectively, While % expression of CCR4[+] CD4 T lymphocytes showed high significant increase in PB compared to synovial fluid [t= 16.9]. SF levels of MIP-1alpha in RA patients showed highly significant positive correlations with DAS [r=0.74], CRP titer [r=0.73] and SF IFN-gamma levels [r=0.78] with no significant correlation to SF CCR4[+] CD4 T lymphocytes % expression [r= 0.28]. Among RA patients, SF CCR5[+] CD4 T lymphocytes % expression was significantly correlated with DAS [r=0.57], CRP titer [r=0.58], SF leucocytic count [r=0.54], and highly significantly correlated with SF MIP-1alpha levels [r=0.65] and SF IFN-gamma levels [r= 0.79]. On the other hand SF CCR4[+] CD4 T lymphocytes % expression showed no significant correlation with DAS [r = 0.11], CRP titer [r=0.22] or SF IFN-gamma levels [r=0.29] in RA patients
Conclusion: CCR5[+] CD4 T lymphocytes accumulate in the joints of patients with rheumatoid arthritis under the influence of high synovial fluid levels of MIP-1alpha [the ligand of CCR5]. So the interaction between CCR5 and MIP-1alpha may be critical in RA and their significant correlation with disease activity score and CRP titer; the marker of inflammation may indicate their contribution to the inflammatory process in RA. - The type 1 T helper cell bias in RA synovial fluid may be associated with the presence of CCR5 expressing lymphocytes. - MIP-1alpha and CCR5 may be important therapeutic targets in RA
RESUMO
Objective: to identify angiogenesis imbalance in systemic sclerosis [SSc] by measuring serum level of the main angiogenic inducer marker [vascular endothelial growth factor VEGF] and the main angiogenic inhibitor marker [endostatin] in order to find out their possible role in the pathogenesis of the disease
Methodology: this study was conducted on twenty five SSc patients, 15 with limited SSc [LSSc] and 10 with diffuse SSc [DSSc]. They were further classified into early LSSc, late LSSc, early DSSc and late DSSc according to Medsger and Steen, 1996, as well as 15 apparently healthy controls participated to this study. Skin involvement was assessed using the modified Rodnan Skin Score, nailfold Video Capillaroscopy [NVC] and pulmonary function tests [PFTs] were done. Serum VEGF and endostatin levels were measured using enzyme linked immunosorbent assay [ELISA]
Results: there was a statistically highly significant increase in the mean values of both serum VEGF and serum endostatin in SSc patients compared to control subjects [p<0.001]. Early DSSc and early LSSc patients had a statistically highly significant increase in the serum levels of VEGF compared to late DSSc and late LSSc patients [p<0.001]. Late LSSc patients had a statistically significant increase in the mean value of serum endostatin compared to early LSSc patients [p<0.01], as well as late DSSc patients had a statistically highly significant increase in the mean value of serum endostatin compared to early DSSc patients [p<0.001]. A highly significant positive correlation was found between serum levels of endostatin and modified Rodnan Skin Score in SSc patients [r=0.69, p<0.001], while no significant correlation was found between serum VEGF and modified Rodnan Skin Score [r=0.293, p>0.05]. SSc patients without ischemic manifestations had a statistically significant higher level of serum VEGF compared to those with ischemic manifestations [p<0.01], while SSc patients with ischemic manifestations had a statistically highly significant increase in the mean value of serum endostatin compared to those without ischemic manifestations [p<0.001]. SSc patients with early NVC pattern had highly significant increase in the mean value of serum VEGF compared to those revealing late NVC pattern [p< 0.001], while SSc patients with late NVC pattern had highly significant increase in the mean value of serum endostatin compared to those revealing early NVC pattern [p<0.001]. SSc patients with restricted PFTs had a statistically significant higher level of serum endostatin in comparison to those without pulmonary affection [p<0.001], while no significant difference regarding mean levels of serum VEGF in patients with or without restricted PFTs [p>0.05]
Conclusion: we may conclude that angiogenic inhibitor [endostatin] is induced and outweighs angiogenic inducer [VEGF] in late disease. Increased serum endostatin level is associated with skin sclerosis severity, ischemic manifestations and pulmonary fibrosis in SSc patients. This angiogenesis inhibitor favors disease progression and it is a good candidate for further evaluation of disease severity and treatment purposes