Review articleMechanisms of autoantibody production and the relationship between autoantibodies and the clinical manifestations in Sjögren’s syndrome
Section snippets
Anti-SS-A/Ro and anti-SS-B/La autoantibodies in SS
Anti-SS-A/Ro antibody and anti-SS-B/La antibody are well-known autoantibodies usually detected by an ELISA in the sera of the patients with SS. Franceschini et al16 have reported that some techniques exist to detect these autoantibodies. One of these techniques, the RNA precipitation assay, has the highest sensitivity and specificity and is usually considered to be the reference method. They have also reported that CIE is the most reliable method for routinely detecting anti-Ro/SS-A antibodies,
ACA in SS
The ACA has also been reported as an autoantibody found in SS. Hsu et al34 recently reported that 17 of 62 (27.4%) sera of primary SS patients are positive for ACA and anti-CENP-H antibodies (Table I). Interestingly, sera from SS patients with anti-CENP-H and ACA antibodies do not contain anti-SS-A/Ro or anti-SS-B/La antibodies, suggesting that SS can be serologically divided into two groups in which the groups have anti-SS-A/SS-B antibodies or ACA/anti-CENP-H antibody. The data support the
Anti-alpha-fodrin antibodies in the pathogenesis of SS
Haneji et al37 identified 120-kd alpha-fodrin as an organ-specific autoantigen from the salivary gland of NFS/sld mouse, a model mouse of human SS (Table I). An in vitro experiment demonstrated that purified alpha-fodrin antigen could induce proliferative T cell responses as well as production of IL-2 and IFN-gamma. As sera from patients with SS reacted with purified or recombinant human alpha-fodrin protein, alpha-fodrin appears to be crucial to the development of primary SS. Yanagi et al38
Anti-type M3R autoantibodies in SS
Bacman et al44 initially reported that when using a 25-mer peptide corresponding to the extracellular domain of human M3R, anti-M3R autoantibodies can be detected by ELISA in sera from SS patients with dry eye (Table I). They reported that anti-M3R autoantibodies can serve as a new marker distinguishing SS from nonSS dry eye. Regarding LSG of SS, Beroukas et al45 detected granular staining of M3R using an affinity-purified polyclonal antibody raised against the C-terminal sequence of human M3R,
Other autoantibodies detected in SS
Except for the above autoantibodies, some other autoantibodies have been reported. With regard to RF, Markusse et al50 reported that IgA-RF was locally produced in salivary gland and measurement of IgA-RF and IgM-RF was useful as diagnosis for primary SS. Atkinson et al51 also reported that salivary flow rate was inversely correlated with serum IgA-RF concentration. Molnar et al52 reported the presence of anti-thyroid antibodies. They measured some of anti-thyroid antibodies in patients with
Conclusions and future directions
SS is a multifactorial disorder that can be induced by environmental stress, stimulation of autoantigens, and hormonal responses. However, the primary pathogenesis of SS remains unclear. In this article, the possible autoantigens related to the pathogenesis of SS were reviewed. The correlation of the autoantigen-antibody system in SS is illustrated in Fig 1. Newly suggested autoantigens were also included, such as alpha-fodrin and M3R. As autoantigens, some parts of components of viruses or
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