scholarly journals Somatic Hypermutations Confer Rheumatoid Factor Activity in Hepatitis C Virus-Associated Mixed Cryoglobulinemia

2013 ◽  
Vol 65 (9) ◽  
pp. 2430-2440 ◽  
Author(s):  
Edgar D. Charles ◽  
Michael I. M. Orloff ◽  
Eiko Nishiuchi ◽  
Svetlana Marukian ◽  
Charles M. Rice ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Rheumatoid Factor ◽  
Mixed Cryoglobulinemia ◽  
Factor Activity ◽  
Rheumatoid Factor Activity

Hepatitis C Virus (HCV) Infection: Serum Rheumatoid Factor Activity and HCV Genotype Correlate With Cryoglobulin Clonality

Blood ◽  
1998 ◽  
Vol 92 (9) ◽  
pp. 3486-3488 ◽  
Author(s):  
Cristian Antonescu ◽  
Claude Mayerat ◽  
Alain Mantegani ◽  
Philippe C. Frei ◽  
François Spertini ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Rheumatoid Factor ◽  
Hcv Infection ◽  
Factor Activity ◽  
Hcv Genotype ◽  
Rheumatoid Factor Activity

Sequence analysis of the immunoglobulin antigen receptor of hepatitis C virus–associated non-Hodgkin lymphomas suggests that the malignant cells are derived from the rheumatoid factor–producing cells that occur mainly in type II cryoglobulinemia

Blood ◽  
2000 ◽  
Vol 96 (10) ◽  
pp. 3578-3584 ◽  
Author(s):  
Valli De Re ◽  
Salvatore De Vita ◽  
Alessandra Marzotto ◽  
Maurizio Rupolo ◽  
Annunziata Gloghini ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Amino Acid ◽  
Rheumatoid Factor ◽  
Light Chain ◽  
Mixed Cryoglobulinemia ◽  
Amino Acid Sequences ◽  
Type Ii ◽  
E2 Protein ◽  
Immunoglobulin Receptor

Analysis of the immunoglobulin receptor (IGR) variable heavy- and light-chain sequences on 17 hepatitis C virus (HCV)-associated non-Hodgkin lymphomas (NHLs) (9 patients also had type II mixed cryoglobulinemia [MC] syndrome and 8 had NHL unrelated to MC) and analysis of intraclonal diversity on 8 of them suggest that such malignant lymphoproliferations derive from an antigen-driven pathologic process, with a selective pressure for the maintenance of a functional IgR and a negative pressure for additional amino acid mutations in the framework regions (FRs). For almost all NHLs, both heavy- and light-chain complementarity-determining regions (CDR3) showed the highest similarity to antibodies with rheumatoid factor (RF) activity that have been found in the MC syndrome, thus suggesting that a common antigenic stimulus is involved in MC syndrome and in HCV-associated lymphomagenesis. Moreover, because HCV is the recognized pathologic agent of MC and the CDR3 amino acid sequences of some HCV-associated NHLs also present a high homology for antibody specific for the E2 protein of HCV, it may be reasonable to speculate that HCV E2 protein is one of the chronic antigenic stimuli involved in the lymphomagenetic process. Finally, the use of specific segments, in particular the D segment, in assembling the IgH chain of IgR seems to confer B-cell disorders with the property to produce antibody with RF activity, which may contribute to the manifestation of an overt MC syndrome.

scholarly journals Clonal B cells in patients with hepatitis C virus–associated mixed cryoglobulinemia contain an expanded anergic CD21low B-cell subset

Blood ◽  
2011 ◽  
Vol 117 (20) ◽  
pp. 5425-5437 ◽  
Author(s):  
Edgar D. Charles ◽  
Claudia Brunetti ◽  
Svetlana Marukian ◽  
Kimberly D. Ritola ◽  
Andrew H. Talal ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
B Cells ◽  
B Cell ◽  
Rheumatoid Factor ◽  
Transcriptional Profiling ◽  
Cell Subset ◽  
Mixed Cryoglobulinemia ◽  
Memory B Cell ◽  
Peripheral B Cells

Abstract Hepatitis C virus (HCV) is associated with the B-cell lymphoproliferative disorders mixed cryoglobulinemia (MC) and non-Hodgkin lymphoma. We have previously reported that HCV+MC+ patients have clonal expansions of hypermutated, rheumatoid factor–bearing marginal zone-like IgM+CD27+ peripheral B cells using the VH1-69 gene. Here we coupled transcriptional profiling with immunophenotypic and functional studies to ascertain these cells' role in MC pathogenesis. Despite their fundamental role in MC disease, these B cells have overall transcriptional features of anergy and apoptosis instead of neoplastic transformation. Highly up-regulated genes include SOX5, CD11C, galectin-1, and FGR, similar to a previously described FCRL4+ memory B-cell subset and to an “exhausted,” anergic CD21low memory B-cell subset in HIV+ patients. Moreover, HCV+MC+ patients' clonal peripheral B cells are enriched with CD21low, CD11c+, FCRL4high, IL-4Rlow memory B cells. In contrast to the functional, rheumatoid factor–secreting CD27+CD21high subset, the CD27+CD21low subpopulation exhibits decreased calcium mobilization and does not efficiently differentiate into rheumatoid factor–secreting plasmablasts, suggesting that a large proportion of HCV+MC+ patients' clonally expanded peripheral B cells is prone to anergy and/or apoptosis. Down-regulation of multiple activation pathways may represent a homeostatic mechanism attenuating otherwise uncontrolled stimulation of circulating HCV-containing immune complexes. This study was registered at www.clinicaltrials.gov as #NCT00435201.

Sequence analysis of the immunoglobulin antigen receptor of hepatitis C virus–associated non-Hodgkin lymphomas suggests that the malignant cells are derived from the rheumatoid factor–producing cells that occur mainly in type II cryoglobulinemia

Blood ◽  
2000 ◽  
Vol 96 (10) ◽  
pp. 3578-3584 ◽  
Author(s):  
Valli De Re ◽  
Salvatore De Vita ◽  
Alessandra Marzotto ◽  
Maurizio Rupolo ◽  
Annunziata Gloghini ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Amino Acid ◽  
Rheumatoid Factor ◽  
Light Chain ◽  
Mixed Cryoglobulinemia ◽  
Amino Acid Sequences ◽  
Type Ii ◽  
E2 Protein ◽  
Immunoglobulin Receptor

Abstract Analysis of the immunoglobulin receptor (IGR) variable heavy- and light-chain sequences on 17 hepatitis C virus (HCV)-associated non-Hodgkin lymphomas (NHLs) (9 patients also had type II mixed cryoglobulinemia [MC] syndrome and 8 had NHL unrelated to MC) and analysis of intraclonal diversity on 8 of them suggest that such malignant lymphoproliferations derive from an antigen-driven pathologic process, with a selective pressure for the maintenance of a functional IgR and a negative pressure for additional amino acid mutations in the framework regions (FRs). For almost all NHLs, both heavy- and light-chain complementarity-determining regions (CDR3) showed the highest similarity to antibodies with rheumatoid factor (RF) activity that have been found in the MC syndrome, thus suggesting that a common antigenic stimulus is involved in MC syndrome and in HCV-associated lymphomagenesis. Moreover, because HCV is the recognized pathologic agent of MC and the CDR3 amino acid sequences of some HCV-associated NHLs also present a high homology for antibody specific for the E2 protein of HCV, it may be reasonable to speculate that HCV E2 protein is one of the chronic antigenic stimuli involved in the lymphomagenetic process. Finally, the use of specific segments, in particular the D segment, in assembling the IgH chain of IgR seems to confer B-cell disorders with the property to produce antibody with RF activity, which may contribute to the manifestation of an overt MC syndrome.

scholarly journals Involvement of chemokines and type 1 cytokines in the pathogenesis of hepatitis C virus-associated mixed cryoglobulinemia vasculitis neuropathy

2005 ◽  
Vol 52 (9) ◽  
pp. 2917-2925 ◽  
Author(s):  
David Saadoun ◽  
Ivan Bieche ◽  
Thierry Maisonobe ◽  
Tarik Asselah ◽  
Ingrid Laurendeau ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Mixed Cryoglobulinemia

scholarly journals Membranoproliferative glomerulonephritis associated with hepatitis C virus infection.

1993 ◽  
Vol 4 (6) ◽  
pp. 1288-1293
Author(s):  
D M Burstein ◽  
R A Rodby
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Virus Infection ◽  
Membranoproliferative Glomerulonephritis ◽  
Membranous Glomerulonephritis ◽  
Mixed Cryoglobulinemia ◽  
Virus Genome ◽  
Hepatitis C Virus Infection ◽  
Hepatitis C Virus Antibody ◽  
Work Up

The hepatitis C virus genome has been recently sequenced and cloned, allowing the identification of patients exposed to this virus, which is now felt to be the principal cause of "non-A, non-B" hepatitis. The hepatitis B virus has long been implicated in the pathogenesis of several glomerulopathies including membranoproliferative glomerulonephritis, mixed cryoglobulinemia, and membranous glomerulonephritis. Several authors have recently reported an association between hepatitis C virus infection and glomerular disease. The case of a patient with chronic hepatitis C virus infection who developed the nephrotic syndrome 3 months after liver transplantation is described. Serologic testing was significant for an elevated rheumatoid factor, circulating cryoglobulins, and a mildly depressed C4 level. Hepatitis C virus antibody and viral RNA (by polymerase chain reaction) were present in both the serum and cryoglobulin fraction. A renal biopsy demonstrated membranoproliferative glomerulonephritis. It is believed that persistent infection with the hepatitis C virus is responsible for an immune complex-mediated glomerulonephritis in this patient. Because hepatitis C has now been pathogenetically linked to several glomerulopathies, testing for this virus should be considered in the serologic work-up of the patient with glomerulonephritis.

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