High values of CXCL10 serum levels in mixed cryoglobulinemia associated with hepatitis C infection.
OBJECTIVE
No study has evaluated circulating CXCL10 in patients with mixed cryoglobulinemia (MC) and hepatitis C virus (HCV) chronic infection. The aim of this study is to measure inteferon-inducible protein 10 (CXCL10/IP-10), interferon-gamma (IFN-gamma), and tumor necrosis factor alpha (TNF-alpha) (Th1 cytokines) in a series of cryoglobulinemic patients and to correlate this parameter to the clinical phenotype.


METHODS
Serum CXCL10, IFN-gamma, and TNF-alpha were assayed in 102 patients with hepatitis C-associated cryoglobulinemia (MC + HCV), in 102 sex- and age-matched patients with type C chronic hepatitis without cryoglobulinemia (HCV+), and in 102 sex- and age-matched controls.


RESULTS
Cryoglobulinemic patients showed significantly higher mean CXCL10 serum levels than controls (P < 0.0001) or HCV+ patients (P < 0.0001) (397 +/- 132 pg/mL, 92 +/- 53 pg/mL, 280 +/- 149 pg/mL, respectively). Moreover, CXCL10 was significantly increased in 30 cryoglobulinemic patients with active vasculitis compared to those without it (460 +/- 104 pg/mL vs 369 +/- 139 pg/mL, respectively; P < 0.001). Both groups of MC + HCV patients with or without active vasculitis had serum CXCL10 significantly higher than HCV+ patients (P < 0.001, P= 0.02, respectively). IFN-gamma levels were not significantly different in MC + HCV than in HCV+ patients or controls. Serum TNF-alpha levels were significantly higher in MC + HCV than in HCV+ patients or controls (median [interquartile range]: 12.0 [9.8], 5.7 [5.4], 1.3 [2.1] pg/mL, respectively; P < 0.0001).


CONCLUSIONS
The study demonstrates high CXCL10 and TNF-alpha serum levels in patients with hepatitis C-associated cryoglobulinemia. Moreover, in MC + HCV patients, increased CXCL10 levels were significantly associated with the presence of active vasculitis.
Antonelli
Alessandro
A
Department of Internal Medicine, University of Pisa School of Medicine, Pisa, Italy.
Ferri
Clodoveo
C
Fallahi
Poupak
P
Ferrari
Silvia Martina
SM
Sebastiani
Marco
M
Ferrari
Daniela
D
Giunti
Marco
M
Frascerra
Silvia
S
Tolari
Simone
S
Franzoni
Ferdinando
F
Galetta
Fabio
F
Marchi
Santino
S
Ferrannini
Ele
E
D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D054357:Chemokine CXCL10 / Q000097:blood*; D003378:Counterimmunoelectrophoresis; D003449:Cryoglobulinemia / Q000097:blood* / Q000209:etiology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology; D018937:Hepatitis C Antibodies / Q000032:analysis; D019698:Hepatitis C, Chronic / Q000097:blood / Q000150:complications* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012367:RNA, Viral; D012189:Retrospective Studies; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D015415:Biomarkers; C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D018937:Hepatitis C Antibodies; D012367:RNA, Viral; D014409:Tumor Necrosis Factor-alpha