Vascular cell adhesion molecule-1 (VCAM-1) plays a central role in the pathogenesis of severe forms of vasculitis due to hepatitis C-associated mixed cryoglobulinemia.
OBJECTIVE
To better characterize the molecules involved in leukocyte tissue infiltration during hepatitis C-mixed cryoglobulinemia (HCV-MC)-associated vasculitis.


METHODS
The involvement of ELAM, ICAM-1 and VCAM-1 was evaluated in 36 patients with HCV-MC vasculitis using three different approaches: concentrations of soluble forms by specific ELISA, tissue expression by immunohistochemistry on patients nerve biopsies, endothelial expression by FACS analysis, on cells activated in vitro by cryoprecipitates purified from HCV-MC patients.


RESULTS
Concentrations of sVCAM-1 were significantly elevated in the serum of HCV-MC patients compared to HCV patients without MC, the highest concentrations being found in severe vasculitis. VCAM-1 expression was detected on blood vessels from nerve biopsies performed in patients with severe vasculitis. When added to endothelial cells in vitro, HCV-MC patients cryoprecipitate induced VCAM-1 but also ELAM and ICAM-1 expression possibly through a mechanism due to the C1q complement fraction interaction with endothelial cells, since C1q was consistently present in the cryoprecipitates.


CONCLUSIONS
VCAM-1 is mainly involved in the pathogenesis of HCV-MC-associated severe vasculitis and may be a potential interesting therapeutic target.
Kaplanski
Gilles
G
INSERM U387, Hôpital Sainte-Marguerite, 270 Boulevard Sainte-Marguerite, 13009 Marseille, France. gkaplanski@marseille.inserm.fr
Maisonobe
Thierry
T
Marin
Valérie
V
Grès
Sandra
S
Robitail
Stéphane
S
Farnarier
Catherine
C
Harlé
Jean-Robert
JR
Piette
Jean-Charles
JC
Cacoub
Patrice
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002460:Cell Line; D015922:Complement C1q / Q000032:analysis; D003449:Cryoglobulinemia / Q000097:blood / Q000209:etiology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D006526:Hepatitis C / Q000097:blood / Q000150:complications*; D019698:Hepatitis C, Chronic / Q000097:blood / Q000150:complications; D006801:Humans; D008875:Middle Aged; D012016:Reference Values; D014471:Umbilical Veins; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood*; D014657:Vasculitis / Q000097:blood / Q000209:etiology / Q000503:physiopathology* / Q000821:virology
D015415:Biomarkers; D019010:Vascular Cell Adhesion Molecule-1; D015922:Complement C1q