Keratinocyte and lymphocyte apoptosis: relation to disease outcome in systemic lupus erythematosus patients with and without cutaneous manifestations

To investigate the relation of keratinocyte and lymphocyte apoptosis and macrophage function to disease activity and severity in SLE patients with and without cutaneous manifestations. Fifty SLE patients [25 with cutaneous manifestations [group I], 25 without cutaneous manifestations [group II]] and 20 normal controls [group III] were studied. SLEDAI score was used to assess lupus activity. Peripheral lymphocyte apoptosis by Annexin V, macrophage function by serum neopterin and immunohistochemical detection of apoptotic cells in the skin by p.53 were done. Renal biopsy was done in indicated cases. Mean SLEDAI score was significantly higher in group I than II [18.6 +/- 6, 8.8 +/- 2.7 respectively, p<0.001]. The mean percentage of peripheral apoptotic lymphocytes was significantly higher in group I compared to group II and III [55.3 +/- 21.4, 25.6 +/- 8. 7 and 19.4 +/- 3.2 respectively, p<0.001] and so was the serum neopterin level [27.5 +/- 7.3, 14.9 +/- 2.7, 9.4 +/- 1.1 respectively, p<0.001]. The mean number of P53+ve keratinocytes of group I was significantly higher than group II and III [20.6 +/- 5.4, 1.6+0.5, 1.7 +/- 0.4 respectively, p<0.001]. A higher percentage of class IV and V glomerulonephritis was found in group I [47%, 26%, respectively] compared to group II [11% both] [p<0.001]. The mean number of p53+ve keratinocyte showed a significant positive correlation to SLEDAI score, percentage of peripheral apoptotic lymphocytes and serum neopterin [p<0.001]. Accumulation of apoptotic keratinocytes and lymphocytes in SLE seems to be crucial in the pathogenesis of skin lesions and in triggering systemic disease activity and organ damage

Serum interleukin-16 level in systemic lupus erythematosus

To detect serum interleukin-16 level in patients with systemic lupus erythematosus and to find out its correlation with disease activity. The study included 30 female patients with systemic lupus erythematosus. 20 apparently healthy females with matched age represent the control group. All patients subjected to full history taking, thorough clinical assessment of disease activity using SLE Disease Activity Index [SLEDAI] serum level of IL-16 mere examined using an enzyme-linked immunosorbent assay [ELISA]. Serum level of interleukin-16 [IL-16] was significantly increased in patients with systemic lupus erythematosus compared to controls and there was a significant positive correlation between IL-16 levels and disease activity assessed by the SLEDAI score. Circulating IL-16 levels are high in SLE patients and are correlated with the disease activity so serum level of IL-16 can be used as a useful indicator of SLE disease activity

Possible role of serum levels of vascular endothelial growth factor and endostatin in rheumatoid arthritis angiogenesis imbalance

To measure serum levels of the main angiogenic inducer marker [VEGF] and the main angiogenic inhibitor marker [endostatin] in rheumatoid arthritis patients. Also, to study their correlation to clinical and laboratory variables of the disease in an attempt to provide more insight regarding their possible role in the angiogenesis imbalance and pathogenesis of RA. Twenty RA patients and fifteen age and sex matched healthy persons served as a control group underwent full history taking, thorough clinical examination, and routine rheumatological profile. Measurement of serum VEGF and endostatin levels were done using enzyme linked immunosorbent assay [ELISA] in rheumatoid arthritis patients and compared with controls. Comparison between patients with or without systemic involvement regarding serum level of VEGF was done. Correlations between serum levels of VEGF and signs of disease activity were also done. A highly significant increase in the mean values of serum VEGF was found in RA patients compared to control subjects [t=11.83, p<0.00l], while there was no statistically significant difference between both RA and control groups regarding mean values of endostatin [t=0.06, p>0.05]. In addition a highly significant increase in the mean values of serum VEGF was found in RA Patients with extra-articular manifestation [EAM] compared to Patients without EAM [t=2.98, p<0.0l]. Serum VEGF was positively correlated with ESR, DAS, and CRP [r =8.48, p<0.01; r = 0.542, p< 0.5; and r = 0.49, p< 0.5] respectively. We found an imbalance between the production of angiogenic growth factors and angiogenic inhibitors in RA. This may play an important role in the angiogenesis imbalance and pathogenesis of RA. In addition we conclude that VEGF level is related to disease activity and extra-articular manifestation of RA, so it can be considered a good indicator for evaluation of disease activity, systemic organ involvement and planning treatment strategies

Effect of progressive resistance training on glycemic control in elderly type II diabetic patients

To investigate the effect of progressive resistance training [PRT] on glycemic control in elderly type II diabetic patients. The study was conducted on 40 elderly individuals with type II diabetes. They were divided into 2 equal groups. The progressive resistance training [PRT] group received 16 weeks of PRT program plus the usual diabetic care, while the control group received a controlled exercise program plus the usual diabetic care. Glycemic control, lipid profile, resting blood pressure, muscle strength and anthropometry were evaluated for the 2 groups at baseline and at end of the study. For the PRT group we found a highly significant reduction in glycosylated hemoglobin level [HbA1c] [t=13.64, p<0.001], highly significant increase in muscle strength [t=10.19, p<0.001], trend for reduction in blood pressure and trend for reduction in triglyceride level. PRT when included with usual diabetic care for elderly people with type II diabetes is of benefit in glycemic control and at the same time is safe and well tolerated

Peripheral blood lymphocytes apoptosis in juvenile idopathic arthritis: relation to disease activity and type of onset

Abnormalities in the mechanisms regulating apoptosis may have a role in the pathogenesis of autoimmune disorders. The aim of this study was to evaluate the incidence of apoptosis of peripheral blood [PB] lymphocytes in children with juvenile idiopathic arthritis [JIA] and correlating it with CD95 [APO-1/Fas] antigen expression and serum levels of sFas and interleukin-15 [IL-15] in different types of onset and activity of the disease. PB lymphocytes apoptotic index [AI], CD95 [APO-1/Fas] antigen expression, serum levels of sFas and IL-15 were detected in 30 cases of JIA and 20 healthy controls. Results were correlated with the type of onset, activity of the disease and acute phase indicators [ESR, CRP]. The mean values of AI, CD95, sFas and IL-15 were higher in children with JIA than in healthy controls. Significant difference was only found for AI especially with systemic type of onset and high activity. Also the levels of IL-15 increased with activity especially in the systemic type. Moreover, AI showed a significant positive correlation with ESR and CRP but not with IL-15, CD95, or sFas. AI of lymphocytes was high in systemic onset JIA and in active disease and correlated with ESR and CRP, but not with IL-15, CD95 expression or serum sFas

Simultaneous combined measurement of antikeratin antibody and rheumatoid factor: additive value in the diagnosis of rheumatoid arthritis

Rheumatoid arthritis [RA] is a systemic inflammatory autoimmune disease of unknown etiology characterized by chronic polyarthritis. Its highly variable and unpredictable course is the underlying reason for the search for new and more sensitive and specific laboratory markers. The only serologic test routinely used in RA assessment is the determination of rheumatoid factor [RF] in the serum. Although RF has sensitivity up to 80%, still it lacks specificity. To evaluate a new marker "antikeratin antibody" [AKA] regarding its sensitivity and specificity and its relation to disease activity. Also the combined RF and AKA, does it add to the diagnosis of RA. Sera from 88 consecutive RA patients, 40 disease controls and 50 healthy controls were tested for RF with latex agglutination and AKA with indirect immunofluorescence assay that used rat esophagus as a substrate. The proportion of RA patients who had AKA [49/88] was higher than in healthy controls 4/50 [X[2]=28.6, p<0.001], and in disease controls 5/40 [X[2] =19.2, p<0.001]. AKA gives weaker sensitivity than RF [55.7%], but stronger specificity [87.5% versus other rheumatic, and 92% versus healthy controls]. The frequency of AKA positivity was higher among patients who had severe disease [being positive in 41/50 of active RA patients], this gives a highly significant association p<0.001. Also, AKA shows significant positive association with RF+ve results [45/71]. Combined results of both AKA and RF gave overall best results as both positive results gave a sensitivity of 97.7%, and both negative results gave a specificity of 97.5% versus rheumatic and 98% versus healthy controls. AKA adds a valuable diagnostic tool in the diagnosis of RA. It is more specific than RF. Its positivity is associated with active RA disease. Combined AKA and RF measurement gives the best sensitivity and specificity for diagnosing rheumatoid disease than each test individually

Serum and synovial fluid levels of MMP-3 and TIMP-1 in rheumatoid arthritis and osteoarthritis

Matrix metalloproteinases [MMPs] are cytokine-modulated enzymes that play an important role in the pathogenesis of RA by inducing bone resorption and cartilage destruction. Tissue inhibitors of metalloproteinases [TIMPs] are naturally occurring MMPs inhibitors. In rheumatoid arthritis [RA], there is a disturbed balance between MMPs and TIMPs favoring proteolysis. This study was performed to evaluate the significance of measuring the serum and synovial fluid [SF] levels of MMP-3 and TIMPs in RA and osteoarthritis [OA] patients in an attempt to provide more insight in their role in the pathogenesis of those two diseases. Serum levels of MMP-3 and TIMP-1 were measured from 30 RA, 20 OA patients and 20 healthy controls using double-antibody ELISA. Also, their levels were measured in the SF of 14 RA and 9 OA patients. RA disease activity was assessed using the Multivariate Analysis of Mallya and Mace and joint erosions were assessed using Larsen score. Serum and SF levels of MMP-3 and TIMP-1 were significantly higher in RA than OA patients and in OA patients than controls. Their levels were significantly higher in the SF than in the serum. Serum and SF TIMP-1: MMP-3 ratio was significantly lower in RA as compared to OA patients and normal controls and this ratio was significantly lower in the SF than in the serum of RA patients. Serum levels of MMP-3 and TIMP-1 correlated strongly with clinical and laboratory parameters of rheumatoid disease activity, and the serum levels of MMP-3 showed a significant positive correlation with the number of joint erosions but TIMP-1 levels did not show this positive correlation. Serum and SF MMP-3 and TIMP-1 levels were significantly higher in RA than OA patients and normal controls. They appear to play a critical role in joint inflammation and destruction, especially MMP-3, which may serve as an additional marker for assessment of RA disease activity and severity