Impact of interleukin-21 in the pathogenesis of primary Sjögren's syndrome: increased serum levels of interleukin-21 and its expression in the labial salivary glands.
BACKGROUND
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.


METHODS
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.


RESULTS
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-21 expression 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.


CONCLUSIONS
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.
Division of Rheumatology, Department of Internal Medicine, Chungbuk National University Hospital, 410, Gaesin-dong, Heungduk-gu, Cheongju, 361-711, South Korea.
Kwi Young
KY
Kang
Hyun-Ok
HO
Kim
Seung-Ki
SK
Kwok
Ji Hyeon
JH
Ju
Kyung-Su
KS
Park
Dong-Il
DI
Sun
Joo Yeon
JY
Jhun
Hye Jwa
HJ
Oh
Sung-Hwan
SH
Park
Ho-Youn
HY
Kim
D000328:Adult; D015415:Biomarkers / Q000097:blood; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012469:Salivary Glands / Q000378:metabolism* / Q000473:pathology*; D012859:Sjogren's Syndrome / Q000175:diagnosis* / Q000209:etiology* / Q000378:metabolism; D000098546:Interleukin-21
D015415:Biomarkers; D007378:Interleukins; D000098546:Interleukin-21