TY - JOUR
T1 - Intrahepatic B cell clonal expansions and extrahepatic manifestations of chronic HCV infection
AU - Sansonno, Domenico
AU - Lauletta, Gianfranco
AU - De Re, Valli
AU - Tucci, Felicia Anna
AU - Gatti, Pietro
AU - Racanelli, Vito
AU - Boiocchi, Mauro
AU - Dammacco, Franco
PY - 2004/1
Y1 - 2004/1
N2 - B cell repertoire in three biological compartments (liver, bone marrow and peripheral blood) of 30 unselected patients chronically infected with HCV has been characterized. Restriction of humoral immune response defined by enrichment of B cell clonal expansions occurred in the liver of 15 patients (50%), in the bone marrow and peripheral blood of 2 (6.7%) and 8 (26.7%) patients, respectively. An in situ hybridization technique was developed for the detection of dominant B cell clones in patients with monoclonal expansions. It was shown that morphologically distinct B cell expansion contributes to the formation of intraportal follicle-like structures. Sequence analyses of CDRH3 gene segments revealed a wide range of variations. Clones derived from the same founder were demonstrated simultaneously in the three compartments explored. The occurrence of B cell clonal expansions profoundly influenced the clinical expression of HCV infection, since it was associated with extrahepatic manifestations. In sharp contrast, no extrahepatic signs or disease occurred in patients without evidence of intrahepatic B cell clonalities. These findings emphasize the profound B cell function derangement in at least half of HCV-infected patients. Thus, the restriction of V gene usage has a direct impact on the clinical spectrum of HCV infection.
AB - B cell repertoire in three biological compartments (liver, bone marrow and peripheral blood) of 30 unselected patients chronically infected with HCV has been characterized. Restriction of humoral immune response defined by enrichment of B cell clonal expansions occurred in the liver of 15 patients (50%), in the bone marrow and peripheral blood of 2 (6.7%) and 8 (26.7%) patients, respectively. An in situ hybridization technique was developed for the detection of dominant B cell clones in patients with monoclonal expansions. It was shown that morphologically distinct B cell expansion contributes to the formation of intraportal follicle-like structures. Sequence analyses of CDRH3 gene segments revealed a wide range of variations. Clones derived from the same founder were demonstrated simultaneously in the three compartments explored. The occurrence of B cell clonal expansions profoundly influenced the clinical expression of HCV infection, since it was associated with extrahepatic manifestations. In sharp contrast, no extrahepatic signs or disease occurred in patients without evidence of intrahepatic B cell clonalities. These findings emphasize the profound B cell function derangement in at least half of HCV-infected patients. Thus, the restriction of V gene usage has a direct impact on the clinical spectrum of HCV infection.
KW - B cell immune response
KW - Cryoglobulinemia
KW - Hepatitis C virus
KW - Lymphoproliferation
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U2 - 10.1002/eji.200324328
DO - 10.1002/eji.200324328
M3 - Article
C2 - 14971038
AN - SCOPUS:1642554816
VL - 34
SP - 126
EP - 136
JO - European Journal of Immunology
JF - European Journal of Immunology
SN - 0014-2980
IS - 1
ER -