Impact of interleukin-21 in the pathogenesis of primary Sjogren's syndrome: increased serum levels of interleukin-21 and its expression in the labial salivary glands
- Equal contributors
1 Division of Rheumatology, Department of Internal Medicine, Chungbuk National University Hospital, 410, Gaesin-dong, Heungduk-gu, Cheongju, 361-711, South Korea
2 Division of Rheumatology, Department of Internal Medicine, Gyongsang University, 90, Chilam-dong, Jinju, 660-702, South Korea
3 Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, 505, Banpo-Dong, Seocho-Gu, Seoul, 137-701, South Korea
4 Department of Otolaryngology-Head and Neck Surgery, College of Medicine, The Catholic University of Korea, 505, Banpo-Dong, Seocho-Gu, Seoul, 137-701, South Korea
5 Rheumatism Research Center, Catholic Institutes of Medical Science, The Catholic University of Korea, 505, Banpo-Dong, Seocho-Gu, Seoul, 137-701, South Korea
Arthritis Research & Therapy 2011, 13:R179 doi:10.1186/ar3504
See related editorial by Scofield, http://arthritis-research.com/content/13/6/137Published: 26 October 2011
Interleukin (IL)-21 is a cytokine that controls the functional activity of effector T helper cells and the differentiation of Th17 cells, and promotes B-cell differentiation. To test whether IL-21 participates in the pathogenesis of primary Sjögren's syndrome (SS), serum IL-21 level was measured and IL-21 expression in the labial salivary glands (LSG) was examined.
Serum IL-21 levels in 40 primary SS, 40 rheumatoid arthritis (RA), and 38 systemic lupus erythematosus (SLE) patients and 20 healthy controls were measured. Serum IL-21 levels of SS patients were assessed for correlations with laboratory data, including anti-nuclear antibody, anti-Ro/La antibodies, globulin, immunoglobulin (Ig) class, and IgG subclass. LSGs from 16 primary SS and 4 controls with sicca symptoms were evaluated for IL-21 and IL-21 receptor (IL-21R) expression by immunohistochemistry. Confocal microscopy was performed to further characterize the IL-21 positive cells.
Primary SS patients had significantly higher serum IL-21 levels than controls, and these increments correlated positively with levels of IgG, IgG1. Serum IgG1 levels correlated with anti-Ro antibody titers. Immunohistochemical analyses showed that lymphocytic foci and the periductal area of the LSGs from SS patients expressed high levels of IL-21 and lower levels of IL-21R, whereas the control LSGs showed minimal expression of both antigens. The more the lymphocyte infiltrated, IL-21expression in LSGs showed a tendency to increase. Confocal microscopic analyses revealed that IL-21 expressing infiltrating lymphocytes in the LSGs of SS patients also expressed CXCR5.
Primary SS is associated with high serum IL-21 levels that correlate positively with serum IgG, especially IgG1, levels. The expression of IL-21 is increased as more lymphocytes infiltrated in LSGs. These observations suggest that IL-21 may play an important role in primary SS pathogenesis.