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IMPACT OF THE IL28B RS12979860 CT POLYMORPHISM ON THE CYTOMEGALOVIRUS REACTIVATION IN AUTOLOGOUS STEM CELL TRANSPLANT PATIENTS
Author(s): ,
Ombretta Annibali
Affiliations:
Unit of Hematology, Stem Cell Transplantation, Transfusion Medicine and Cellular Therapy, Department of Medicine,UNIVERSITÀ CAMPUS BIO-MEDICO for the Rome transplant Network,Roma,Italy
,
Elisabetta Riva
Affiliations:
UOS of Virology,UNIVERSITÀ CAMPUS BIO-MEDICO ROMA,Roma,Italy
,
Livia Piccioni
Affiliations:
UOS of Virology,UNIVERSITÀ CAMPUS BIO-MEDICO ROMA,Roma,Italy
,
Valeria Tomarchio
Affiliations:
Unit of Hematology, Stem Cell Transplantation, Transfusion Medicine and Cellular Therapy, Department of Medicine,UNIVERSITÀ CAMPUS BIO-MEDICO for the Rome transplant Network,Roma,Italy
,
Erika Circhetta
Affiliations:
Unit of Hematology, Stem Cell Transplantation, Transfusion Medicine and Cellular Therapy, Department of Medicine,UNIVERSITÀ CAMPUS BIO-MEDICO ROMA,Roma,Italy
,
Chiara Sarlo
Affiliations:
Unit of Hematology, Stem Cell Transplantation, Transfusion Medicine and Cellular Therapy, Department of Medicine,UNIVERSITÀ CAMPUS BIO-MEDICO for the Rome transplant Network,Roma,Italy
,
Luca Franceschini
Affiliations:
Hematology and Stem Cell Transplant Unit,University Tor Vergata for The Rome Transplant Network,Roma,Italy
,
Manuela Rizzo
Affiliations:
Hematology and Stem Cell Transplant Unit,University Tor Vergata for The Rome Transplant Network,Roma,Italy
,
Giulia Ciangola
Affiliations:
Hematology and Stem Cell Transplant Unit,University Tor Vergata for The Rome Transplant Network,Roma,Italy
,
Pierpaolo Berti
Affiliations:
Unit of Hematology, Stem Cell Transplantation, Transfusion Medicine and Cellular Therapy, Department of Medicine,UNIVERSITÀ CAMPUS BIO-MEDICO ROMA,Roma,Italy
,
Tommasangelo Petitti
Affiliations:
Unit of Hygiene Public Health and Statistics,UNIVERSITÀ CAMPUS BIO-MEDICO ROMA,Roma,Italy
,
Maria Cantonetti
Affiliations:
Hematology and Stem Cell Transplant Unit,University Tor Vergata for The Rome Transplant Network,Roma,Italy
,
Maria Cristina Tirindelli
Affiliations:
Unit of Hematology, Stem Cell Transplantation, Transfusion Medicine and Cellular Therapy, Department of Medicine,UNIVERSITÀ CAMPUS BIO-MEDICO ROMA,Roma,Italy
,
William Arcese
Affiliations:
Hematology and Stem Cell Transplant Unit,University Tor Vergata for The Rome Transplant Network,Roma,Italy
Giuseppe Avvisati
Affiliations:
Unit of Hematology, Stem Cell Transplantation, Transfusion Medicine and Cellular Therapy, Department of Medicine,UNIVERSITÀ CAMPUS BIO-MEDICO for the Rome transplant Network,Roma,Italy
(Abstract release date: 05/19/16) EHA Library. Annibali O. 06/09/16; 135086; PB2186
Dr. Ombretta Annibali
Dr. Ombretta Annibali
Contributions
Abstract
Abstract: PB2186

Type: Publication Only

Background
CMV infection represents one of the main cause of morbility and mortality after stem cell transplantation (SCT).  Type III interferons (IFNs), including IFNl1 (IL29), IFNl2 (IL28A) and IFNll3 (IL28B), are thought to display potent antiviral and  immunomodulatory properties in vivo, which may partially overlap with those exerted by type I IFNs. Type I and Type III IFNsl both generate an antiviral state by triggering the JAK-STAT pathway, ultimately upregulating the expression of interferon-stimulated genes. Rs12979860  single nucleotide polymorphism (SNP) in IL28B gene region is well known to influence the spontaneous and treatment-induced clearance in HCV infection. Although  the relevance of such a SNP in other virCMV infection represents one of the main cause of morbility and mortality after stem cell transplantation (SCT).  Type III interferons (IFNs), including IFNl1 (IL29), IFNl2 (IL28A) and IFNll3 (IL28B), are thought to display potent antiviral and  immunomodulatory properties in vivo, which may partially overlap with those exerted by type I IFNs. Type I and Type III IFNsl both generate an antiviral state by triggering the JAK-STAT pathway, ultimately upregulating the expression of interferon-stimulated genes. Rs12979860  single nucleotide polymorphism (SNP) in IL28B gene region is well known to influence the spontaneous and treatment-induced clearance in HCV infection. Although  the relevance of such a SNP in other viral infections is still debated, Bravo et al. recently documented a protective effect of the T allele against CMV infection in the Allogeneic SCT  (Journal of Medical Virology 2014,86:838).al infections is still debated, Bravo et al. recently documented a protective effect of the T allele against CMV infection in the Allogeneic SCT  (Journal of Medical Virology 2014,86:838).

Aims
 the current study was aimed at investigating whether the IL28B polymorphism Rs12979860 may affect the CMV reactivaction in the setting of Autologous  SCT (Auto-SCT).

Methods
From October 2014, 67 patients undergoing an Auto-SCT for hematological malignancies  were included in the study. The patients, with a median age of 56 years (range, 16-66 yrs),  were distributed according to the underlying disease as follows: 75% had Multiple Myeloma, 16% non Hodgkin Lymphoma, 6% Hodgkin Lymphoma and 3% Acute Myeloid Leukemia. The Rs12979860 IL28B SNP (C/T) genotype was determined by Melthing analysis on DNA derived from peripheral blood samples. CMV DNAemia was determined by quantitative Real-Time PCR with a limit detection of 50 copies/mL (Artus, Qiagen). Patients were monitored for CMV DNAemia weekly for three months after transplantation.

Results
According to the lowest frequency of TT genotype harboring in general population, the detected genotypes were CC in 31 patients ( 46%) CT in 27 ( 40%) and TT in only 9 (14 %) . Although not statistically significant, a CMV reactivation (symptomatic and asymptomatic) was higher in patients carrying TT genotype (n=7 ;77.7%) with respect to patients carrying CC (n21.;67.7%) and CT genotype (n=12; 44.4%). According to the logistic regression analysis,  the incidence of CMV reactivation was significantly lower in patients carrying IL-28B CT compared to the cumulative group of patients with CC and TT genotype (44.4% versus 70% ; p=0.039, CI 95%,  OR 2.91) (codominat genetic model).

Conclusion
Our data  suggest  that in the Auto-SCT setting the carriage of IL-28B CT genotype  might express a protective effect  against CMV infection

Session topic: E-poster

Keyword(s): Cytomegalovirus
Abstract: PB2186

Type: Publication Only

Background
CMV infection represents one of the main cause of morbility and mortality after stem cell transplantation (SCT).  Type III interferons (IFNs), including IFNl1 (IL29), IFNl2 (IL28A) and IFNll3 (IL28B), are thought to display potent antiviral and  immunomodulatory properties in vivo, which may partially overlap with those exerted by type I IFNs. Type I and Type III IFNsl both generate an antiviral state by triggering the JAK-STAT pathway, ultimately upregulating the expression of interferon-stimulated genes. Rs12979860  single nucleotide polymorphism (SNP) in IL28B gene region is well known to influence the spontaneous and treatment-induced clearance in HCV infection. Although  the relevance of such a SNP in other virCMV infection represents one of the main cause of morbility and mortality after stem cell transplantation (SCT).  Type III interferons (IFNs), including IFNl1 (IL29), IFNl2 (IL28A) and IFNll3 (IL28B), are thought to display potent antiviral and  immunomodulatory properties in vivo, which may partially overlap with those exerted by type I IFNs. Type I and Type III IFNsl both generate an antiviral state by triggering the JAK-STAT pathway, ultimately upregulating the expression of interferon-stimulated genes. Rs12979860  single nucleotide polymorphism (SNP) in IL28B gene region is well known to influence the spontaneous and treatment-induced clearance in HCV infection. Although  the relevance of such a SNP in other viral infections is still debated, Bravo et al. recently documented a protective effect of the T allele against CMV infection in the Allogeneic SCT  (Journal of Medical Virology 2014,86:838).al infections is still debated, Bravo et al. recently documented a protective effect of the T allele against CMV infection in the Allogeneic SCT  (Journal of Medical Virology 2014,86:838).

Aims
 the current study was aimed at investigating whether the IL28B polymorphism Rs12979860 may affect the CMV reactivaction in the setting of Autologous  SCT (Auto-SCT).

Methods
From October 2014, 67 patients undergoing an Auto-SCT for hematological malignancies  were included in the study. The patients, with a median age of 56 years (range, 16-66 yrs),  were distributed according to the underlying disease as follows: 75% had Multiple Myeloma, 16% non Hodgkin Lymphoma, 6% Hodgkin Lymphoma and 3% Acute Myeloid Leukemia. The Rs12979860 IL28B SNP (C/T) genotype was determined by Melthing analysis on DNA derived from peripheral blood samples. CMV DNAemia was determined by quantitative Real-Time PCR with a limit detection of 50 copies/mL (Artus, Qiagen). Patients were monitored for CMV DNAemia weekly for three months after transplantation.

Results
According to the lowest frequency of TT genotype harboring in general population, the detected genotypes were CC in 31 patients ( 46%) CT in 27 ( 40%) and TT in only 9 (14 %) . Although not statistically significant, a CMV reactivation (symptomatic and asymptomatic) was higher in patients carrying TT genotype (n=7 ;77.7%) with respect to patients carrying CC (n21.;67.7%) and CT genotype (n=12; 44.4%). According to the logistic regression analysis,  the incidence of CMV reactivation was significantly lower in patients carrying IL-28B CT compared to the cumulative group of patients with CC and TT genotype (44.4% versus 70% ; p=0.039, CI 95%,  OR 2.91) (codominat genetic model).

Conclusion
Our data  suggest  that in the Auto-SCT setting the carriage of IL-28B CT genotype  might express a protective effect  against CMV infection

Session topic: E-poster

Keyword(s): Cytomegalovirus

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