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

adiponectin have a role in the pathogenesis of rheumatoid arthritis?

To elucidate the involvement of adipocytokines "Adiponectin" in the pathogenesis of rheumatoid arthritis [RA] by measuring serum and synovial fluid levels of adiponectin in RA patients and also by evaluating its expression in RA synovial tissue to find out its possible role in disease activity and severity in order to throw light on possible new strategy in the management of RA. Twenty RA patients and ten subjects with acute post traumatic knee effusion - who served as a control group-were recruited for this study. Serum adiponectin levels were measured using enzyme linked immunosorbent [ELISA]. Synovial fluid [SF] levels of adiponectin, IL-6 and pro MMP-1 were measured by ELISA. Modified disease activity score [DAS] and Larsen score were assessed in RA patients. Synovial tissue [ST] specimens were obtained from control subjects and RA patients. These specimens were assessed immunohistochemically for adiponectin and graded in a semiquantitative scale. Serum adiponectin was significantly raised in RA patients compared to controls [p<0.05]. There was a highly statistically significant increase in SF adiponectin, SF Pro MMP-1, ST adiponectin expression in RA patients compared to controls [p<0.01], while there was a significant increase in SF IL-6 in RA patients compared to controls [p<0.05]. SF adiponectin correlated positively with each of ST adiponectin expression, SF IL-6, SF pro MMP-1 [p<0.01]. A highly significant positive correlation was found between SF levels of adiponectin and each of DAS and Larsen score [p<0.01]. Adiponectin is expressed in the RA synovium and it stimulates the production of key mediators of destructive arthritis, IL-6 and pro MMP-1, so targeting the proinflammatory cascade of adiponectin may represent an exciting new therapeutic tool in RA

Role of mast cells in the pathogenesis of rheumatoid arthritis

To elucidate the involvement of mast cells in the pathogenesis of rheumatoid arthritis [RA] by finding out the cells in synovial tissue and their products in the synovial fluid. Also, by studying the ultrastructure of mast cells, in an attempt to throw light on possible new strategies in the management of this disease. Twenty RA patients and ten subjects with acute post traumatic knee effusion- who served as a control group- were recruited for this study. All synovial fluid [SF] samples were investigated for mast cell products: tryptase and histamine using radioimmunoassay [RIA]. Synovial tissue [ST] specimens were obtained from control subjects and RA patients. These specimens were stained with hematoxylin and eosin for assessment of lymphocytic infiltration and with the conventional mast cell stain "Toluidine blue". A study of the ultrastructure of synovial tissue specimens was done to further document changes of synovial mast cells. SF tryptase and histamine were highly significantly raised in RA patients in contrast to control subjects [p<0.001]. There was a statistically significant increase in ST mast cell scoring in rheumatoid synovium as compared to that of control subjects [p<0.01]. Ultrastructural study of rheumatoid synovial tissue revealed evidence of degranulation of some mast cells. There was a highly significant positive correlation between ST mast cell score, SF tryptase, SF histamine and the modified disease activity score [DAS] as well as with the severity of the disease as assessed by Larsen score [p<0.001]. A highly significant positive correlation was found between ST mast cell scoring and the histological inflammatory index [p< 0.001]. Mast cells are an important contributor of the rheumatoid process in synovium reflecting its role in disease activity and joint destruction. These findings might have important implications for understanding the pathogenesis of RA. Hence, drug therapy targeting mast cells may have a role in controlling the activity and severity of the disease

Monocyte chemotactic protein-1 production and its correlation with disease activity and T-cell subsets in synovial fluid in psoriatic arthritis patients

Psoriatic arthritis [PsA] is a chronic inflammatory arthritis characterized by infiltration of the skin and joints with activated T lymphocytes. The latter have been implicated in both the initiation and maintenance of inflammatory lesions at these sites and it is mediated by the local production and secretion of chemotactic cytokines. To evaluate the role of monocyte chemotactic protein-1 [MCP-1] in the immunopathogenesis of PsA. Also, to find out whether evidence exists for a causal relationship between MCP-1 levels in synovial fluids and T cells recruitment to lesional sites during acute and chronic synovitis and its relation to disease activity in psoriatic arthritis patients. Thirty PsA patients were recruited for this study. They were subdivided into two groups: Group I: 15 patients with synovitis less than 6 months' duration [acute PsA]. Group II: 15 patients with synovitis more than 6 months' duration [chronic PsA]. The clinical activity of the disease was assessed by using modified disease activity score 28 [DAS28]. Their results were compared to 15 healthy age and sex matched volunteers [group III]. Peripheral blood [PB] and synovial fluid [SF] were obtained from PsA arthritis patients; also PB was obtained from normal controls. Immune cell populations in PB and SF samples were assessed with immunofluorescent labeling and flow cytometry, levels of soluble MCP-1 were determined in PB and SF samples with quantitative ELISA. DAS28 was significantly higher in group I [acute PsA] patients than group II [chronic PsA patients] [p<0.01]. CD4+, CD8+ T cells were significantly elevated in SF as compared to PB of acute but not chronic PsA patients and the majority of these cells expressed CD45RO [p<0.01]. Plasma MCP-1 levels were elevated in PsA [whether acute or chronic] relative to normal controls [p<0.01]. SF MCP-1 levels were significantly higher than paired plasma samples in acute PsA patients only [p<0.01]. A highly significant positive correlation was observed between MCP-1 levels in SF and DAS28 and also with T cell numbers in SF of acute PsA patients [p<0.01]. The elevated concentration of MCP-1 is concomitant with T cell infiltration in SF of acute PsA patients. This suggests that MCP-1 mediated chemotaxis is involved in the recruitment of T lymphocytes particularly memory cells into the synovial fluid in PsA during acute synovitis which is associated clinically with severely active disease and thus could be considered as an early inflammatory marker in acute PsA

Immunological effects of estrogen on CD40 ligand expression on T cells of systemic lupus erythematosus female patients

Systemic lupus erythematosus [SLE] predominantly affects women during their reproductive years. Its pathogenesis has been postulated to involve T cells hyperactivity that can be induced by over-expression of signaling molecules such as CD40 ligand [CD40L] on T cells. This is supposed to lead to B cells proliferation, differentiation and autoantibodies production. To investigate the immunological effects of estrogen on CD40L expression on T cells in vivo as well as its relation to disease activity in SLE female patients. Thirty SLE female patients were included in this study. They are subdivided into two groups: Group Ia: 15 SLE patients during their reproductive years and Group IIa: 15 post menopausal SLE patients. The clinical activity of the disease was assessed with SLE disease activity index [SLEDAI]. The results were compared to two control groups: Group Ib: 10 normal females during their reproductive years and Group IIb: 10 normal postmenopausal women. Routine investigations were performed. Serum estradiol was assessed with electrochemiluminescence immuno-assay. Whole blood was used to determine CD40L expression on T lymphocytes with direct immunofluorescence technique. Renal biopsy was performed for SLE patients only. CD40L expression on T cells was significantly higher in group Ia than in group IIa [p<0.01]. Also it was significantly higher in group Ia than that in group Ib [p<0.01]. There was no significant difference between both groups regarding estrogen level [p>0.05]. In spite of that, SLEDAI score was significantly higher in group Ia than that in group IIa [p<0.01]. Also 24 hrs urinary protein was significantly elevated in group Ia than that in group IIa [p<0.01] while creatinine clearance and serum C3 level were significantly reduced in group Ia than that in group IIa. Of group Ia 66.7% had WHO class IV and V glomerulonephritis [GN] as compared to only 6.7% of group IIa [p<0.01]. There was a non-significant difference between groups IIa and IIb regarding CD40L expression on T cells [p>0.05]. Also, there was a significant correlation between CD40L expression on T cells, estrogen level and SLEDAI score in groups Ia and IIa patients [p<0.01]. On the other hand, there was a non-significant correlation between CD40L expression on T cells and estrogen level in groups Ib and IIb [p>0.05]. Estrogen plays an important role in the pathogenesis of SLE through increasing the expression of CD40L on T cells in SLE female patients, but not in normal females. This action is dose-dependent as we found that CD40L expression on T cells was significantly higher in SLE female patients during their reproductive years than during their postmenopausal years. Again, its level correlated well with markers of disease activity i.e. SLEDAI