Rheumatoid Arthritis: Salmon I

Steinfeld SD, Demols P, Salmon I, Kiss R, Appelboom T. · Department of Rheumatology, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium. · Arthritis Rheum. · Pubmed #11665979 No free full text.

Abstract: OBJECTIVE: Tumor necrosis factor alpha (TNFalpha) is a proinflammatory cytokine involved in the pathogenesis of Sjögren's syndrome (SS), and blockade of TNFalpha may reduce the activity of the disease. The purpose of this study was to evaluate the safety and potential efficacy of infliximab, a chimeric human-mouse anti-TNFalpha monoclonal antibody, in patients with active primary SS. METHODS: This was a single-center, open-label pilot study. Sixteen patients with active primary SS received 3 infusions of infliximab (3 mg/kg) at 0, 2, and 6 weeks. Standard clinical assessment, complete ophthalmologic testing, and functional evaluation of salivary flow were performed at baseline and at weeks 2, 6, 10, and 14. RESULTS: All patients completed the study. There was statistically significant improvement in all clinical and functional parameters, including global assessments (patient's global assessment, patient's assessment of pain and fatigue, physician's global assessment), erythrocyte sedimentation rate, salivary flow rate, the Schirmer I test, tender joint count, fatigue score, and dry eyes and dry mouth. This clinical benefit was observed at week 2 and was maintained throughout the study and the 2-month followup period. The treatment was well tolerated in all patients, and no significant adverse events were seen. No lupus-like syndrome was observed, and no anti-double-stranded DNA antibodies were observed that were attributable to infliximab therapy. CONCLUSION: In patients with active primary SS, a loading-dose regimen of 3 infusions of infliximab provided a fast and significant clinical benefit without major adverse reactions. It was possible to maintain statistically significant improvement for up to 8 weeks after the third infusion.

Penaloza A, Decaestecker C, Ribaï P, Nagy N, Salmon I, Appelboom T, Danguy A, Kiss R, Steinfeld S. · Laboratory of Histology, Faculty of Medicine, Université Libre de Bruxelles, Belgium. · Clin Exp Rheumatol. · Pubmed #10609070 No free full text.

Abstract: OBJECTIVE: To investigate the composition and expression of sialic acid in the labial salivary glands (LSG) in Sjögren's syndrome (SS). METHODS: LSG of 19 patients with primary SS (n = 11) or secondary SS (n = 8) were studied. Specimens from 7 healthy women served as controls. Computer-assisted microscopy was employed to quantitatively determine the percentage of positive structures, the staining intensity and the heterogeneity for the 4 biotinylated plant lectins Tritricum vulgaris L. (WGA), Maackia amurensis (MAA), Sambucus nigra (SNA) and Canavalia ensiformis L. (Con A). RESULTS: In the acini there was a significant decrease in the staining heterogeneity of WGA in SS compared to controls; the same was observed with respect to MAA staining in the connective tissue and extralobular ducts. In the intralobular ducts, primary SS differed from normal and secondary SS mainly in terms of a decrease in the percentage of positively labeled MAA tissue. In addition, Con A stained acinar cells were significantly more numerous in secondary SS compared with primary SS. CONCLUSION: Differences in the degree of glycoconjugate sialylation were found in SS labial salivary glands, and may play a role in the disease process.

Steinfeld S, Penaloza A, Ribaï P, Decaestecker C, Danguy A, Gabius HJ, Salmon I, Appelboom T, Kiss R. · Department of Rheumatology, Erasmus Academic Hospital, Brussels, Belgium. · J Rheumatol. · Pubmed #10229404 No free full text.

Abstract: OBJECTIVE: Sjögren's syndrome (SS) is an autoimmune exocrinopathy. The mannose binding lectin (MBL), a pluripotent molecule of the innate immune system, is involved in the pathogenesis of autoimmune diseases. We investigated whether specific ligands for MBL and MBL related structures could be reliable markers in cases of SS. METHODS: The labial salivary glands of 19 patients fulfilling the diagnostic criteria for primary (n=11) and secondary SS (n=8) were studied. Seven healthy women served as controls. Computer assisted microscopy was employed to determine quantitatively the percentage of positive structures (acini, ducts, and interlobular connective tissue), the staining intensity, and the level of staining heterogeneity for 4 glycohistochemical probes including wheat germ agglutinin and concanavalin (Con A) as lectins, and mannose and N-acetylglucosamine as parts of neoglycoproteins. The data were evaluated by discriminant analysis. RESULTS: The data strongly suggest that MBL related structures, if not MBL itself, could play distinct roles in the pathogenesis of primary versus secondary SS. Further, quantitative determination of the level of expression of D-mannose and N-acetylglucosamine and their respective binding sites in labial salivary gland acini offers a powerful diagnostic tool for distinguishing primary from secondary SS. CONCLUSION: In SS labial salivary glands, determination of the level of acceptor sites for wheat germ agglutinin, Con A, D-mannose, and N-acetylglucosamine provides information on the roles played by glycoforms in SS. The methodology and data described in this paper should provide pathologists with objective diagnostic markers for SS. Our results should enhance the biological understanding of this pathology.