Increased serum levels of the chemokine CXCL13 and up-regulation of its gene expression are distinctive features of HCV-related cryoglobulinemia and correlate with active cutaneous vasculitis.
Chemokine CXCL13, also known as BCA-1 (B cell-attracting chemokine-1) or BLC (B-lymphocyte chemoattractant), is a major regulator of B-cell trafficking. Hepatitis C virus (HCV) infection may be associated with B-cell dysfunction and lymphoproliferative disorders, including mixed cryoglobulinemia (MC). This study evaluates circulating levels of CXCL13 protein and specific mRNA expression in chronically HCV-infected patients with and without MC. Compared with healthy controls and HCV-infected patients without MC, CXCL13 serum levels were significantly higher in MC patients. The highest CXCL13 levels strongly correlated with active cutaneous vasculitis. CXCL13 gene expression in portal tracts, isolated from liver biopsy tissues with laser capture microdissection, showed enhanced levels of specific mRNA in MC patients with active cutaneous vasculitis. Specific CXCL13 gene mRNA expression was also up-regulated in skin tissue of these patients. These findings paralleled specific deposits of CXCL13 protein both in the liver and in the skin. Our results indicate that up-regulation of CXCL13 gene expression is a distinctive feature of HCV-infected patients. Higher levels of this chemokine in the liver as well as in the skin of patients with active MC vasculitis suggest a possible interrelation between these biologic compartments.
Sansonno
Domenico
D
Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine and Clinical Oncology, University of Bari Medical School, Bari, Italy. d.sansonno@dimo.uniba.it
Tucci
Felicia Anna
FA
Troiani
Laura
L
Lauletta
Gianfranco
G
Montrone
Michele
M
Conteduca
Vincenza
V
Sansonno
Loredana
L
Dammacco
Franco
F
D000328:Adult; D000368:Aged; D001483:Base Sequence; D016022:Case-Control Studies; D054382:Chemokine CXCL13 / Q000097:blood* / Q000235:genetics* / Q000378:metabolism; D003449:Cryoglobulinemia / Q000097:blood* / Q000150:complications* / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D005260:Female; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000150:complications* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000378:metabolism / Q000473:pathology; D017445:Skin Diseases, Vascular / Q000097:blood* / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D014657:Vasculitis / Q000097:blood* / Q000150:complications* / Q000235:genetics / Q000378:metabolism / Q000473:pathology
C110663:CXCL13 protein, human; D054382:Chemokine CXCL13; D017931:DNA Primers; D012333:RNA, Messenger