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 YKL-40 in rheumatoid arthritis and its correlation with disease activity

To determine the serum level of YKL-40 in rheumatoid arthritis [RA] patients and to find out its correlation with the disease activity. The study was conducted on 20 RA patients recruited from the Rheumatology and Rehabilitation Department of Ain Shams University Hospitals, as well as 10 apparently healthy individuals who served as a control group. Patients with liver disease, myocardial infarction or malignancies were excluded. Also patients taking slow-acting drugs or had intra-articular injections in the previous month before the study were not included. All the patients and the controls were subjected to complete history taking, thorough clinical examination, radiological and laboratory tests. Serum YKL-40 level was measured in the patients and the controls using ELISA test. Serum YKL-40 level was significantly higher in RA patients as compared to the control group. Serum YKL-40 level showed a positive significant correlation with the disease duration, the parameters of disease activity in RA patients and with the disease severity as assessed with Larsen's radiological score. Measurement of serum YKL-40 level in RA patients is a laboratory test that can be used as a new parameter other than the conventional markers of inflammation, which are ESR and serum CRP level. Also, it helps to asses the disease activity as well as the progression and the destructive effect of the disease on the joints

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

Undifferentiated polyarthritis: is it a hiddrn form of RA? The value of anticyclic citrullinated peptide antibodies as a diagnostic and prognostic marker for rheumatoid arthritis

The study was undertaken to assess the value of anti-cyclic citrullinated peptide antibodies [anti-CCP] in comparison to anti-perinuclear factor [APF] and IgM rheumatoid factor [IgM RF] in the early diagnosis of rheumatoid arthritis [RA] in patients with undifferentiated polyarthritis [UPA]. Serum samples of sixty patients with UPA [not fulfilling any of the ACR criteria for the diagnosis of any of the connective tissue diseases] and of other twenty age and sex matched healthy volunteers act as a control group was tested for IgM RF, APF and anti-CCP antibodies at first visit. Follow-up and reassessment of all patients was done monthly till the end of the study after one year. Measurement of APF was done by indirect immunofluorescence [IIF] and anti-CCP was done by enzyme linked immunosorbent assay [ELISA]. Forty two [70%] out of 60 UPA patients met the revised criteria of diagnosis of RA after one year of follow-up. A positive anti-CCP test was highly specific for RA [specificity 88.8%] being found in 30 [71.5%] out of 42 RA patients and its sensitivity was [71.4%]. IgM RF had the highest sensitivity [76%] and it was less specific for RA [66.6%] while the specificity and the sensitivity of APF were 77.7% and 52.38%, respectively. There was a highly significant association between anti-CCP antibodies positive RA patients and high disease activity score as well as disease severity score [p<0.001] while there was significant association between IgM RF and APF positive RA patients separately and high disease activity score [p<0.02 and 0.01, respectively] as well as disease severity score [p<0.05 and 0.01, respectively]. These results suggest that anti-CCP antibody is a highly specific serologic marker for RA and its determination is of value in the diagnosis of early cases of RA. Furthermore, anti-CCP may have prognostic significance because of their association with more severe and active form of RA