Interleukin-13 (IL-13)in autoimmune rheumatic diseases: relationship with autoantibody profile

Objective: Several cytokines play a role in the production of autoantibodies such as RF and ANA by B-lymphocytes; the role of IL- 13 in this process has not been previously studied. We investigated the relationship between the serum concentration of this cytokine and circulating autoantibodies. Methods: IL-13 serum levels, as well as RF and ANA, were evaluated in 282 patients with autoimmune rheumatic diseases including RA (n=84), SLE (n = 114), SS (n = 52) and Scl (n =32). Results: Serum levels of IL-13 (pg/ml) were significantly higher in patients with RA (p < 0.00003), SLE (p < 0.03), SS (p < 0.0007), or Scl (p < 0.025) compared to controls. IL-13 serian levels correlated with those of RF in RA (p < 0.00001), SLE (p < 0.003) and Scl (p < 0.03). IL- 13 levels were higher in RA (p<0.0003), SLE (p<0.005) and Scl (p<0.05) patients with RF than in patients,without RE SS patients with anti-SSA/Ro antibodies had significantly higher IL-13 levels than SS patients without this autoantibody (p < 0.04). No statistically significant correlation was found between IL-13 levels and any other antinuclear autoantibody, total immunoglobulin levels or the main clinical features of each disease. Conclusion: The evidence of higher IL- 13 levels in our RA, SLE, SS and Scl patients confirms that this cytokine is involved in the pathogenesis of autoimmune rheumatic diseases. The relationship of this cytokine with RF in RA, SLE and Scl, as well as with antiSSA/ Ro antibody in SS, strengthens the hypothesis that it plays a role in autoantibody production. However the different autoantibody synthesis by Bcells recognises different pathways depending on the underlying autoimmune disease

Anti-tissue transglutaminase antibodies in inflammatory and degenerative arthropathies

Recent studies identified tissue transglutaminase (tTG) as the antigen eliciting antiendomysial antibodies (EMA) in celiac disease (CD). Anti-tTG antibodies have therefore been proposed as a serological test for CD. Nevertheless, IgA anti-tTG but not EMA have also been found in inflammatory bowel disease patients, suggesting that these antibodies are linked to a tissue lesion rather than to an auto-immune component of CD. To confirm this hypothesis, we evaluated the presence of IgA anti-tTG in patients with inflammatory and degenerative diseases, in whom tissue lesions presented far away from the intestinal mucosa. The study was carried out on the serum and synovial fluid (SF) of 68 patients with rheumatoid arthritis (RA=33), psoriatic arthritis (PsA=26) and osteoarthritis (OA=9). In RA, PsA and OA sera, IgA anti-tTG were positive in 33%, 42% and 11% of patients, respectively. Serum anti-tTG levels were significantly higher in RA (p<0.0001), PsA (p<0.0001) and OA (p<0.02) with respect to healthy controls. SF anti-tTG levels were significantly higher in PsA (p<0.018) than in OA. A good correlation between serum and synovial fluid anti-tTG levels was found in all arthropathies This study suggests that tTG is not the only antigen of EMA and, furthermore , that IgA anti-tTG antibodies represent a general lesion-associated event. Moreover, the significant correlation between serum and synovial fluid anti-tTG levels allow us to hypothesise that these antibodies could be synthesized in the site of arthritic lesions

Role for familiarity and genetic features in the therapeutic response of psoriatic arthritis

Aim of the study: To analyze PsA patients with and without a familiar distribution for Ps and PsA, in order to better evaluate the genetic data, to verify the existence of different expression of the disease and finally to define the susceptibility to treatment in these patients. Materials and methods: 230 PsA patients were selected for familiar or sporadic distribution of the disease and were evaluated for the main clinical, demographic, radiological and laboratory features, as well as for the ongoing treatments. In each patient HLA class I (A,B,C) and II (DRB1, DQB1) antigens were typed with PCR-SSP method while MICA-A exon 5 microsatellite typing was performed by heteroduplex analysis in 122 subjects. Results: A familiar distribution for Ps and PsA was found in 68 patients (29.6%) although only two patients had familiarity for PsA. In the familiar PsA group the male prevalence was significantly higher respect to the sporadic one (p<0.001) and the more frequently involved relative was the father (28%). Mean age (p<0.006) and age at onset of Ps (p<0.004) and PsA (p<0.014) were significantly lower in familiar respect to sporadic PsA. Between the two groups no difference was found concerning the articular involvement, the radiological findings, the disease activity (including n° of painful/swollen joints), the inflammatory laboratory parameters (including ESR and CRP) and genetic aspects, incuding the frequencies of MICA-A alleles that were analysed in 30 patients with the familiar form and in 92 with the sporadic one. In the follow-up the therapeutic response to any evaluated treatment adopted for PsA did not show any significant difference in the two groups. All these results were confirmed even when the patients in the two groups were matchable for sex, age and disease duration. Conclusion: Our results confirm that familiar PsA is characterized by an early onset of the disease and by a male and fatherly predominance respect to the sporadic form, although the clinical-radiologic findings, the genetic typing and the therapeutic response do not permit us to identify any particular subset

immunohistochemical analysis of the expression of main adhesion molecules and tumor necrosis factors in the synovial membrane of psoriatic arthritis

Objective: To define the expression and pattern of the synovial distribution of adhesion molecules such as E-selectin, ICAM-1 and VCAM-1 and of TNFα and TNFβ cytokines in psoriatic arthritis (PsA), according to the synovitis duration. Methods: Cryostatic sections of the synovial membrane tissue samples were stained for the different antibodies using a standard three-stage-immunoperoxidase-labeling technique. Results: E-selectin grade of staining was higher in those patients with a shorter disease duration compared to longstanding synovitic specimens, as well as ICAM-1 expression. On the contrary a higher VCAM-1 positivity was mainly found in longstanding PsA patients. Anti-TNFa positivity was found almost in all the specimens with no difference among the two groups, while the intensity of anti-TNFβ positivity was globally higher in longstanding cases. Conclusions: Different adhesion molecules may separately participate to the synovitic process in the different phases of PsA, leading to the hypothesis of their different involvement during the disease evolution. Moreover the upregulation of TNFα and TNFβ gives evidence to their local proinflammatory effect within the synovium and to their role in perpetuating the PsA synovitis

The role of Interleukin-12 in immune-mediated rheumatic diseases

Objective: IL-12 is a proinflammatory cytokine produced by different antigen presenting cells. It has been shown to exert a critical role in inducing Th1 phenotype, thus initiating cell-mediated immune responses, but the significance of IL-12 in rheumatic diseases is not clear. Aim of the study was to determine IL-12 serum levels in immune rheumatic diseases and to analyse the relationship of this cytokine with main clinical and laboratory parameters. Methods: we analysed, by ELISA, serum IL-12 levels in 114 patients with SLE, 47 with SS, 32 with SSc, 84 with RA, 138 with PA and in 17 healthy controls. We also examined main clinical and laboratory parameters, including autoantibody profile and clinical indices of disease activity. Results: IL-12 serum levels were significantly higher in SLE and SS patients respect to controls. IL-12 serum levels were significantly higher in SLE patients compared to those affected by RA, PA and SSc. When we evaluated disease activity in SLE patients, we found significantly higher IL-12 serum levels in subjects with fever or in those without renal involvement, while no correlation was found in the other rheumatic immune diseases. Conclusions: these findings suggest that IL-12, modulating cell and humoral immune responses, is involved in the pathogenesis of immune rheumatic diseases, such as SLE and SS