Hepatitis C Virus (HCV) in Lymphocyte Subsets and in B Lymphocytes Expressing Rheumatoid Factor Cross-reacting Idiotype in Type II Mixed Cryoglobulinaemia

Overview

Journal Clin Exp Immunol

Publisher Oxford University Press

Specialty Allergy & Immunology

Date 2000 Dec 21

PMID 11122246

Citations 12

Authors

A Fornasieri

P Bernasconi

M L Ribero

R A Sinico

M Fasola

J Zhou

G Portera

A Tagger

A GIBELLI

G DAmico

Affiliations

Soon will be listed here.

Abstract

The IgMk rheumatoid factors (RF) of type II mixed cryoglobulinaemia (MC) react, in 95% of cases, with MoAbs against the cross-reactive idiotypes (CRI) Cc1 or Lc1 (corresponding to the products of the VH1 and VH4 genes). MC is closely associated with HCV infection, a virus which infects lymphocytes and may replicate in B cells. It has been suggested that HCV may induce clonal selection of B cells producing monoclonal IgMk RF in type II MC. To verify whether HCV is enriched in B cells, and in the subsets expressing Cc1 and Lc1 CRI, we studied peripheral blood lymphocytes from eight patients with MC and HCV RNA-positive sera. Seven patients had RF reacting with anti-Cc1, the other with anti-Lc1 CRI. Total lymphocytes, T cells, B cells, and Cc1+ or Lc1+, Cc1- or Lc1- B cells were purified using MoAb-coated magnetic beads. Lymphocyte subsets were then diluted to give a range of 1 x 106-1 x 103 cells and tested for HCV RNA by reverse transcriptase-polymerase chain reaction. HCV was found exclusively in B cells in seven out of eight patients. In three patients HCV was enriched in the Cc1+ cells. In one of these patients, HCV was found exclusively in Cc1+ cells, with Cc1- cells being HCV-. The data indicate that B cells from type II MC patients are almost constantly infected by HCV. In selected cases, B cell subsets expressing IgMk RF CRI are the prevalent cell type infected by HCV. Our data suggest HCV involvement in B cell dysregulation leading to cryoprecipitable IgMk RF production.

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References

Franzin F, Efremov D, Pozzato G, Tulissi P, Batista F, Burrone O . Clonal B-cell expansions in peripheral blood of HCV-infected patients. Br J Haematol. 1995; 90(3):548-52. DOI: 10.1111/j.1365-2141.1995.tb05582.x. View

Muller H, Kallinowski B, Solbach C, Theilmann L, Goeser T, Pfaff E . B-lymphocytes are predominantly involved in viral propagation of hepatitis C virus (HCV). Arch Virol Suppl. 1994; 9:307-16. DOI: 10.1007/978-3-7091-9326-6_31. View

Agnello V . The etiology and pathophysiology of mixed cryoglobulinemia secondary to hepatitis C virus infection. Springer Semin Immunopathol. 1997; 19(1):111-29. DOI: 10.1007/BF00945029. View

Donato F, Tagger A, Chiesa R, Ribero M, Tomasoni V, Fasola M . Hepatitis B and C virus infection, alcohol drinking, and hepatocellular carcinoma: a case-control study in Italy. Brescia HCC Study. Hepatology. 1997; 26(3):579-84. DOI: 10.1002/hep.510260308. View

Muratori L, Gibellini D, Lenzi M, Cataleta M, Muratori P, Morelli M . Quantification of hepatitis C virus-infected peripheral blood mononuclear cells by in situ reverse transcriptase-polymerase chain reaction. Blood. 1996; 88(7):2768-74. View

Ono M, Winearls C, Amos N, Grennan D, Gharavi A, PETERS D . Monoclonal antibodies to restricted and cross-reactive idiotopes on monoclonal rheumatoid factors and their recognition of idiotope-positive cells. Eur J Immunol. 1987; 17(3):343-9. DOI: 10.1002/eji.1830170307. View

Sinico R, Winearls C, Sabadini E, Fornasieri A, Castiglione A, DAmico G . Identification of glomerular immune deposits in cryoglobulinemia glomerulonephritis. Kidney Int. 1988; 34(1):109-16. DOI: 10.1038/ki.1988.152. View

Agnello V, Chung R, Kaplan L . A role for hepatitis C virus infection in type II cryoglobulinemia. N Engl J Med. 1992; 327(21):1490-5. DOI: 10.1056/NEJM199211193272104. View

Fong S, Chen P, Fox R, Goldfien R, Radoux V, Silverman G . The diversity and idiotypic patterns of human rheumatoid factors in disease. Concepts Immunopathol. 1988; 5:168-91. View

10.

Ferri C, Monti M, La Civita L, Longombardo G, Greco F, Pasero G . Infection of peripheral blood mononuclear cells by hepatitis C virus in mixed cryoglobulinemia. Blood. 1993; 82(12):3701-4. View

11.

DAmico G, Colasanti G, Ferrario F, Sinico R . Renal involvement in essential mixed cryoglobulinemia. Kidney Int. 1989; 35(4):1004-14. DOI: 10.1038/ki.1989.84. View

12.

Crouzier R, Martin T, Pasquali J . Monoclonal IgM rheumatoid factor secreted by CD5-negative B cells during mixed cryoglobulinemia. Evidence for somatic mutations and intraclonal diversity of the expressed VH region gene. J Immunol. 1995; 154(1):413-21. View

13.

Schott P, Polzien F, Ramadori G, Hartmann H . In vitro reactivity of cryoglobulin IgM and IgG in hepatitis C virus-associated mixed cryoglobulinemia. J Hepatol. 1998; 28(1):17-26. DOI: 10.1016/s0168-8278(98)80197-9. View

14.

Pascual M, Perrin L, Giostra E, Schifferli J . Hepatitis C virus in patients with cryoglobulinemia type II. J Infect Dis. 1990; 162(2):569-70. DOI: 10.1093/infdis/162.2.569. View

15.

Shokri F, Mageed R, Maziak B, Talal N, Amos N, Williams B . Lymphoproliferation in primary Sjögren's syndrome. Evidence of selective expansion of a B cell subset characterized by the expression of cross-reactive idiotypes. Arthritis Rheum. 1993; 36(8):1128-36. DOI: 10.1002/art.1780360814. View

16.

De Vita S, Sansonno D, Dolcetti R, Ferraccioli G, Carbone A, Cornacchiulo V . Hepatitis C virus within a malignant lymphoma lesion in the course of type II mixed cryoglobulinemia. Blood. 1995; 86(5):1887-92. View

17.

Ferri C, La Civita L, Longombardo G, Lombardini F, Pasero G, Zignego A . Hepatitis C virus in mixed cryoglobulinemia and B cell lymphoma. Clin Exp Rheumatol. 1994; 12(1):89-90. View

18.

Brouet J, Clauvel J, DANON F, Klein M, SELIGMANN M . Biologic and clinical significance of cryoglobulins. A report of 86 cases. Am J Med. 1974; 57(5):775-88. DOI: 10.1016/0002-9343(74)90852-3. View

19.

Zignego A, Macchia D, Monti M, Thiers V, Mazzetti M, Foschi M . Infection of peripheral mononuclear blood cells by hepatitis C virus. J Hepatol. 1992; 15(3):382-6. DOI: 10.1016/0168-8278(92)90073-x. View

20.

Misiani R, Bellavita P, Fenili D, Borelli G, Marchesi D, MASSAZZA M . Hepatitis C virus infection in patients with essential mixed cryoglobulinemia. Ann Intern Med. 1992; 117(7):573-7. DOI: 10.7326/0003-4819-117-7-573. View