Th1/Th2 cytokine imbalance in patients with Sjögren syndrome secondary to hepatitis C virus infection.
OBJECTIVE
To investigate if the serum immunologic profile, as delineated by serum circulating levels of Th1/Th2 cytokines and autoantibodies, is different in patients with Sjögren syndrome (SS) with and without hepatitis C virus (HCV) infection.


METHODS
This study included 20 patients with HCV-related SS and 47 consecutive patients with primary SS. All fulfilled 4 or more of the modified 1996 European criteria for SS. Serum levels of interleukin (IL)-2 (pg/mL), srIL-2 (pM), tumor necrosis factor (TNF)-alpha (pg/mL), IL-6 (pg/mL), and IL-10 (pg/mL) were determined using enzyme immunoassay. We also analyzed the following immunologic tests: anti-nuclear antibodies (ANA), anti-mitochondrial antibodies (AMA), anti-parietal cell antibodies (PCA), anti-smooth muscle antibodies (SMA), anti-liver-kidney microsome antibodies type-1 (LKM-1), anti-Ro/SS-A, anti-La/SS-B, rheumatoid factor (RF), complement factors (C3 and C4), and cryoglobulins.


RESULTS
Of the 20 patients with HCV-related SS, 18 were women and 2 men (mean age, 66 years). Patients with HCV-related SS had a different cytokine profile compared with patients with primary SS, with higher circulating levels of IL-6 (73.6 v 33.0 pg/mL, P =.045), IL-10 (6.7 v 3.1 pg/mL, P =.01), srIL-2 (124.6 v 72.7 pM, P =.001), and TNF-alpha (59.8 v 31.7 pg/mL, P =.003). The main immunologic features were ANA, detected in 75% of patients, RF in 63%, cryoglobulinemia in 50%, hypocomplementemia in 40%, SMA in 30%, PCA in 25%, anti-Ro/SS-A in 25%, AMA in 20% and anti-La/SS-B in 16%. When compared with primary SS patients, those with HCV-related SS had a higher prevalence of AMA (20% v 2%, P =.025), hypocomplementemia (40% v 11%, P =.015), and cryoglobulinemia (50% v 12%, P =.003).


CONCLUSIONS
Although chronic HCV infection may mimic the main clinical, histologic and immunologic features of primary SS, patients with HCV-related SS showed some differentiated characteristics, including a predominant Th2 pattern and a higher frequency of cryoglobulinemia and hypocomplementemia (features closely related to HCV). This suggests that the SS observed in some HCV patients should be interpreted as one of the extrahepatic manifestations of chronic HCV infection.
Ramos-Casals
Manuel
M
Department of Autoimmune Diseases, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clínic, School of Medicine, University of Barcelona, Barcelona, Catalonia, Spain. mramos@clinic.ub.es
García-Carrasco
Mario
M
Cervera
Ricard
R
Filella
Xavier
X
Trejo
Olga
O
de la Red
Gloria
G
Gil
Víctor
V
Sánchez-Tapias
José Ma
JM
Font
Josep
J
Ingelmo
Miguel
M
D001323:Autoantibodies / Q000032:analysis; D016207:Cytokines / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications / Q000276:immunology*; D006801:Humans; D016753:Interleukin-10 / Q000097:blood; D007376:Interleukin-2 / Q000097:blood; D008297:Male; D012859:Sjogren's Syndrome / Q000209:etiology / Q000276:immunology* / Q000503:physiopathology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D001323:Autoantibodies; D016207:Cytokines; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10