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Objectives: There is evidence that B lymphocytes play a role in the pathogenesis of systemic sclerosis (scleroderma). Stimulatory autoantibodies targeting and activating normal human fibroblasts in vitro have been demonstrated in sera from scleroderma patients. Rituximab is a monoclonal antibody which selectively targets and depletes CD20+ B lymphocytes. We investigated the biological effects of rituximab in six patients affected by scleroderma with severe skin involvement., Methods: Six patients with severe skin fibrosis, unresponsive to immunosuppressive treatment, were treated with 375 mg/m2 per week of intravenous rituximab for a total of four doses. Serum stimulatory autoantibodies to the PDGF receptor were detected. Fibroblast activation was evaluated in fibroblasts grown from skin biopsies performed at baseline and at months 3 and 6 post-treatment. The modified Rodnan's skin score, health assessment questionnaire (HAQ) and visual analogic scale (VAS) for global wellness and B lymphocyte count were performed monthly., Results: A significant reduction of anti-PDGF receptor autoantibodies was observed in the serum of all patients 3 months after treatment. Fibroblasts showed a significant downregulation of type I collagen gene expression and of the intracellular signalling triggered by anti-PDGFR autoantibodies. A decrease of the skin score and an improvement of disability indexes matched with the in vitro results. A single course of rituximab reduced scleroderma fibroblast activation in vitro and the serum levels of anti-PDGFR stimulatory autoantibodies., Conclusions: These data provide further evidence of B-cell involvement in the pathogenesis of scleroderma. Targeting B cells may be a promising treatment for scleroderma patients, and controlled clinical trials are warranted.

Objectives: To assess Chlamydophila psittaci (Cp) subclinical infection in patients with Sjögren's syndrome (SS)., Methods: Seventy-four SS patients (55.4 ±13.4 yrs; 94.6% females) were studied. Among them, 18 had salivary gland mucosa-associated lymphoid tissue (MALT) B-cell lymphoma, 20 myoepithelial sialoadenitis (MESA), and 36 no lymphoproliferative disorders (LPD). The presence of Cp DNA was assessed in peripheral blood of all patients by specific PCR protocols. Paired salivary gland samples were also investigated whenever available (34 cases), including lymphomatous and non-lymphomatous samples, as well as major and minor salivary gland tissues. As controls, 225 blood donors were analysed in the peripheral blood., Results: Overall, Cp DNA was detected in 11/74 (14.9%) SS patients vs. 1/225 (0.4%) controls (p<0.0001). Cp was detected at higher frequency in MALT lymphoma patients (6/18, 33.3%), as compared with MESA (3/20, 15%) or patients without LPD (2/36, 5.6%), (MALT lymphomas vs. others: p=0.02). A similar Cp prevalence was observed in blood vs. salivary gland tissues, however with a higher frequency in the major than in the minor salivary glands (5/18, 27.8%, vs. 1/17, 5.9%, p=0.18). Cp-positive patients were all rheumatoid factor positive (11/11, 100% vs. 40/63, 63.5% Cp-negative; p=0.014), while no difference was noticed for anti-SSA/SSB positivity., Conclusions: In the light of accepted models of MALT B-cell lymphomagenesis and considering previous data implicating Cp infection in ocular adnexa MALT lymphoma, our results suggest that Cp infection could be involved also in a fraction of patients with SS developing lymphoma. The potential therapeutic implications of these findings appear worthwhile.

Objectives: The minor salivary gland biopsy (MSGB) is widely considered an important component of the diagnostic algorithm of primary Sjögren's syndrome (pSS) and is mentioned in all the classification criteria sets for the disease. The aim of this study, coordinated by the Italian Society of Rheumatology, was to verify the inter-observer agreement on the evaluation of MSGB among different experienced Italian rheumatologic centres, in order to better standardise the diagnostic methodology., Methods: Seven centres participated in the study, providing a total of 50 MSGB samples. Each center blindly classified all the samples according to the Chisholm and Mason (CM) grading. The results were collected and analysed., Results: The inter-observer agreement was satisfactory when the samples were stratified as consistent and non-consistent with the final diagnosis of pSS (median κ =0.75; mean κ =0.70). Nonetheless, significant discrepancies in the histopathologic evaluation of MSGB emerged when the agreement was assessed on the single scores. Considering the modal CM grading for each sample as the correct grading, upon re-examination, a potential bias in the final clinical diagnosis was detected in 7 out of 50 samples., Conclusions: This study has shown significant discrepancies in the evaluation of MSGB among different rheumatologic centres in the same country. Greater standardisation of the procedure is clearly necessary, both to improve the diagnostic performance and scientific communication.