Objective. Mixed cryoglobulinemia (MC) is a hepatitis C virus (HCV)–related immune complex disorder. Only some HCV-infected patients develop MC, which suggests that the genetic background of the host plays a key role. This study was undertaken to evaluate the contribution of host genetic factors in the pathogenesis of HCV-associated MC (HCV-MC) by analyzing allelic variants of low-affinity FcG receptor (FcGR) genes and BAFF promoter. Methods. FcGR polymorphisms (FCGR2A 131 R/H, FCGR2B 232 I/T, FCGR3A 176 V/F, and FCGR3B NA1/NA2) and BAFF promoter polymorphism -871 C/T were analyzed in 102 patients with HCV-MC and 108 patients with HCV without MC, using polymerase chain reaction–based techniques. Results. A higher prevalence of -871 T/T homozygosity (31% versus 16%; P < 0.001) and a greater frequency of T alleles of the BAFF promoter (80% versus 57%; P < 0.004) were found in the HCV-MC group than in the HCV group. A significant increase in serum BAFF concentration was significantly associated with the higher frequency of the T allele in HCV-MC (mean +/- SD 4.12 +/- 1.29 versus 2.09 +/- 0.81 ng/ml; P < 0.0005). The distribution of the FcGR genotypes was not significantly different. In the 21 HCV-MC patients treated with rituximab, the response was strictly related to F allele homozygosity (significantly reduced in 5 of 5 patients with the FCGR3A F/F genotype versus 4 of 16 with V/V or V/F; P < 0.0005). Conclusion. These results indicate the importance of host genetic background in the development of HCV-MC, suggesting that mechanisms enhancing Ig production and B cell survival may play a relevant role. Genetic FcGR variants seem to be crucial to the effectiveness of rituximab therapy.

Genetic determinants in Hepatitis C Virus-associated mixed cryoglobulinemia: role of polymorphic variants of BAFF promoter and Fc-gamma receptors / L. Gragnani; A. Piluso; C. Giannini; P. Caini; E. Fognani; M. Monti; A. Petrarca; J. Ranieri; G. Razzolini; V. Froio; G. Laffi; A.L. Zignego. - In: ARTHRITIS AND RHEUMATISM. - ISSN 0004-3591. - STAMPA. - 63 (5):(2011), pp. 1446-1451.

Genetic determinants in Hepatitis C Virus-associated mixed cryoglobulinemia: role of polymorphic variants of BAFF promoter and Fc-gamma receptors

GRAGNANI, LAURA;PILUSO, ALESSIA;GIANNINI, CARLO;CAINI, PATRIZIO;FOGNANI, ELISA;MONTI, MONICA;PETRARCA, ANTONIO;RANIERI, JESSICA;RAZZOLINI, GIULIA;FROIO, VALENTINA;LAFFI, GIACOMO;ZIGNEGO, ANNA LINDA
2011

Abstract

Objective. Mixed cryoglobulinemia (MC) is a hepatitis C virus (HCV)–related immune complex disorder. Only some HCV-infected patients develop MC, which suggests that the genetic background of the host plays a key role. This study was undertaken to evaluate the contribution of host genetic factors in the pathogenesis of HCV-associated MC (HCV-MC) by analyzing allelic variants of low-affinity FcG receptor (FcGR) genes and BAFF promoter. Methods. FcGR polymorphisms (FCGR2A 131 R/H, FCGR2B 232 I/T, FCGR3A 176 V/F, and FCGR3B NA1/NA2) and BAFF promoter polymorphism -871 C/T were analyzed in 102 patients with HCV-MC and 108 patients with HCV without MC, using polymerase chain reaction–based techniques. Results. A higher prevalence of -871 T/T homozygosity (31% versus 16%; P < 0.001) and a greater frequency of T alleles of the BAFF promoter (80% versus 57%; P < 0.004) were found in the HCV-MC group than in the HCV group. A significant increase in serum BAFF concentration was significantly associated with the higher frequency of the T allele in HCV-MC (mean +/- SD 4.12 +/- 1.29 versus 2.09 +/- 0.81 ng/ml; P < 0.0005). The distribution of the FcGR genotypes was not significantly different. In the 21 HCV-MC patients treated with rituximab, the response was strictly related to F allele homozygosity (significantly reduced in 5 of 5 patients with the FCGR3A F/F genotype versus 4 of 16 with V/V or V/F; P < 0.0005). Conclusion. These results indicate the importance of host genetic background in the development of HCV-MC, suggesting that mechanisms enhancing Ig production and B cell survival may play a relevant role. Genetic FcGR variants seem to be crucial to the effectiveness of rituximab therapy.
2011
63 (5)
1446
1451
L. Gragnani; A. Piluso; C. Giannini; P. Caini; E. Fognani; M. Monti; A. Petrarca; J. Ranieri; G. Razzolini; V. Froio; G. Laffi; A.L. Zignego
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/402599
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