Hepatitis C virus (HCV) causes mixed cryoglobulinemia (MC) by driving clonal expansion of IgM+CD27+ B cells. These cells display both the features of anergy induced by continual engagement of the B cell receptor (BCR), such as high expression of phosphorylated extracellular signal regulated kinase (pERK) and reduced lifespan, and of virus-specific exhaustion such as CD21low phenotype and defective response to ligation of BCR and Toll-like receptor 9 (TLR9). Usually MC regresses after eradication of HCV with interferon, whose immunomodulatory activity might contribute to this effect. We investigated phenotypic and functional changes in clonal B cells of MC patients with sustained virologic responses to direct-acting antivirals (DAA), which lack immunomodulatory properties. We found that high pERK expression and accelerated apoptosis revert within 4 weeks after beginning therapy, whereas clonal B cells unresponsive to TLR9 stimulation persist for at least 24 weeks although they may partially rescue normal CD21 expression. Thus, similar to mouse models, features of anergy in MC B cells rapidly revert after disengagement from HCV, whereas virus-specific exhaustion imparts a durable inhibitory imprint on cell function. Treatment of HCV+ MC with DAA provides a valuable tool for untangling the molecular mechanisms of anergy and exhaustion in human B cells.

Reversion of anergy signatures in clonal CD21low B cells of mixed cryoglobulinemia after clearance of HCV viremia / DEL PADRE, Martina; Todi, Laura; Mitrevski, Milica; Marrapodi, Ramona; Colantuono, Stefania; Fiorilli, Massimo; Casato, Milvia; Visentini, Marcella. - In: BLOOD. - ISSN 0006-4971. - STAMPA. - 1:(2017), pp. 35-38. [10.1182/blood-2017-03-771238]

Reversion of anergy signatures in clonal CD21low B cells of mixed cryoglobulinemia after clearance of HCV viremia.

DEL PADRE, MARTINA;TODI, LAURA;MITREVSKI, MILICA;MARRAPODI, RAMONA;COLANTUONO, STEFANIA;FIORILLI, Massimo;CASATO, Milvia;VISENTINI, MARCELLA
2017

Abstract

Hepatitis C virus (HCV) causes mixed cryoglobulinemia (MC) by driving clonal expansion of IgM+CD27+ B cells. These cells display both the features of anergy induced by continual engagement of the B cell receptor (BCR), such as high expression of phosphorylated extracellular signal regulated kinase (pERK) and reduced lifespan, and of virus-specific exhaustion such as CD21low phenotype and defective response to ligation of BCR and Toll-like receptor 9 (TLR9). Usually MC regresses after eradication of HCV with interferon, whose immunomodulatory activity might contribute to this effect. We investigated phenotypic and functional changes in clonal B cells of MC patients with sustained virologic responses to direct-acting antivirals (DAA), which lack immunomodulatory properties. We found that high pERK expression and accelerated apoptosis revert within 4 weeks after beginning therapy, whereas clonal B cells unresponsive to TLR9 stimulation persist for at least 24 weeks although they may partially rescue normal CD21 expression. Thus, similar to mouse models, features of anergy in MC B cells rapidly revert after disengagement from HCV, whereas virus-specific exhaustion imparts a durable inhibitory imprint on cell function. Treatment of HCV+ MC with DAA provides a valuable tool for untangling the molecular mechanisms of anergy and exhaustion in human B cells.
2017
Hepatitis C virus, mixed cryoglobulinemia, B-cell anergy
01 Pubblicazione su rivista::01a Articolo in rivista
Reversion of anergy signatures in clonal CD21low B cells of mixed cryoglobulinemia after clearance of HCV viremia / DEL PADRE, Martina; Todi, Laura; Mitrevski, Milica; Marrapodi, Ramona; Colantuono, Stefania; Fiorilli, Massimo; Casato, Milvia; Visentini, Marcella. - In: BLOOD. - ISSN 0006-4971. - STAMPA. - 1:(2017), pp. 35-38. [10.1182/blood-2017-03-771238]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/957452
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