B-Lymphocyte stimulator (BLyS) up-regulation in mixed cryoglobulinaemia syndrome and hepatitis-C virus infection.
OBJECTIVE
To investigate the role of B-Lymphocyte stimulator (BLyS) in mixed cryoglobulinaemia syndrome (MCsn), a systemic vasculitis associated with a high risk to develop lymphoma, since BLyS up-regulation may favour both autoimmunity and lymphoproliferation.


METHODS
BLyS serum levels were analysed by enzyme-linked immunosorbent assay (positive when >0.85 ng/ml) in 66 patients with MCsn, 54 (81.8%) of whom were positive for hepatitis-C virus (HCV) infection. Thirty-three HCV-positive patients without MCsn were also studied. Patients were compared with 48 healthy blood donors (HBDs). BLyS modifications after antiviral therapy were also studied.


RESULTS
A significantly higher frequency of BLyS serum positivity was detected both in MCsn patients and in HCV-positive patients without MCsn (37.9 and 30.3%, respectively) when compared with HBDs (4.2%) (P < 0.0001 vs MCsn and P = 0.0026 vs HCV-positive patients without MCsn, respectively). BLyS appeared significantly higher in MCsn (3.70 +/- 2.97 ng/ml) than in HCV-positive patients without MCsn (1.56 +/- 0.63 ng/ml; P = 0.0044). BLyS expression did not correlate with rheumatoid factor levels, cryoglobulin levels or definite MCsn-related systemic features. High BLyS levels were significantly associated only with MCsn-related overt lymphoproliferative disorder. Finally, antiviral treatment significantly increased BLyS levels, independently from HCV-RNA negativization. However, BLyS normalization was noticed after both HCV-RNA negativization and suspension of antiviral therapy by preliminary data.


CONCLUSIONS
BLyS is up-regulated and may play a pathogenetic role in a fraction of patients with MCsn, similarly to other autoimmune diseases. HCV infection likely represents the early event leading to BLyS up-regulation in this setting. BLyS is up-regulated during antiviral treatment. Overall, these data provide new insights for BLyS and virus-related autoimmunity, lymphoproliferation and possible treatment strategies.
Fabris
M
M
Division of Rheumatology, DPMSC, School of Medicine, University of Udine, 33100 Udine, Italy.
Quartuccio
L
L
Sacco
S
S
De Marchi
G
G
Pozzato
G
G
Mazzaro
C
C
Ferraccioli
G
G
Migone
T S
TS
De Vita
S
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000627:therapeutic use; D001327:Autoimmune Diseases / Q000276:immunology* / Q000821:virology; D053264:B-Cell Activating Factor / Q000097:blood*; D003449:Cryoglobulinemia / Q000276:immunology* / Q000821:virology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006526:Hepatitis C / Q000150:complications / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013577:Syndrome; D015854:Up-Regulation / Q000187:drug effects
D000998:Antiviral Agents; D053264:B-Cell Activating Factor