Abstract
IntroductionAnti-Ro antibodies can be found in the serum of the majority of patients with Sjögren's syndrome (SS). Immunization with a 60-kDa Ro peptide has been shown to induce SS-like symptoms in mice. The aim of this study was to investigate factors involved in salivary gland (SG) dysfunction after immunization and to test whether the induction of SS could be improved.MethodsRo60 peptide immunization was tested in Balb/c mice, multiple antigenic peptide (MAP)-Ro60 and Pertussis toxin (PTX) were tested in SJL/J mice. In addition, two injection sites were compared in these two strains: the abdominal area and the tailbase. Each group of mice was tested for a loss of SG function, SG lymphocytic infiltration, anti-Ro and anti-La antibody formation, and cytokine production in cultured cells or homogenized SG extracts.ResultsRo60 peptide immunization in the abdominal area of female Balb/c mice led to impaired SG function, which corresponded with increased Th1 cytokines (IFN-γ and IL-12) systemically and locally in the SG. Moreover, changing the immunization conditions to MAP-Ro60 in the abdominal area, and to lesser extend in the tailbase, also led to impaired SG function in SJL/J mice. As was seen in the Balb/c mice, increased IFN-γ in the SG draining lymph nodes accompanied the SG dysfunction. However, no correlation was observed with anti-MAP-Ro60 antibody titers, and there was no additional effect on disease onset or severity.ConclusionsEffective induction of salivary gland dysfunction after Ro60 peptide immunization depended on the site of injection. Disease induction was not affected by changing the immunization conditions. However, of interest is that the mechanism of action of Ro60 peptide immunization appears to involve an increase in Th1 cytokines, resulting in the induction of SG dysfunction.
Highlights
Anti-Ro antibodies can be found in the serum of the majority of patients with Sjogren’s syndrome (SS)
The pathogenic relevance of these autoantibodies is not clear and other autoantibodies involved in neuronal innervation, aquaporins, matrix metalloproteinases, and apoptosis have been identified to be involved in the pathogenesis of SS
Previous studies from our own group have shown the role of T cell related cytokines (e.g. IFN-c and IL-12) in salivary gland dysfunction [4,7,8]
Summary
Anti-Ro antibodies can be found in the serum of the majority of patients with Sjogren’s syndrome (SS). The pathogenic function of autoantibodies against Ro and La is not clear, a number of previous studies imply that enhanced pro-inflammatory cytokines, such as interferon (IFN)-c, interleukin (IL)-18 and IL17, are highly related to increased anti-Ro antibody levels in SS [6]. This suggests a possible correlation between anti-Ro antibodies and autoimmune T cell mediated responses in SS. We have set up the same model to investigate the induction of SS-like symptoms, and the role of cytokines in SG dysfunction after Ro60 peptide immunization
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