Hepatitis G virus/GBV-C in serum, peripheral blood mononuclear cells and bone marrow in patients with hematological malignancies

2013 ◽  
Vol 19 ◽  
pp. 195-199 ◽  
Author(s):  
Elżbieta Kisiel ◽  
Kamila Caraballo Cortez ◽  
Agnieszka Pawełczyk ◽  
Iwona Bukowska Ośko ◽  
Natalia Kubisa ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Hematological Malignancies ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Hepatitis G Virus ◽  
Blood Mononuclear Cells ◽  
Hepatitis G

Hepatitis G Viral RNA in Serum and in Peripheral Blood Mononuclear Cells and Its Relation to HCV-RNA in Patients with Clotting Disorders

1997 ◽  
Vol 77 (05) ◽  
pp. 0868-0872 ◽  
Author(s):  
Li Sheng ◽  
Ann Soumillion ◽  
Kathelijne Peerlinck ◽  
Chris Verslype ◽  
Lan Lin ◽  
...  
Keyword(s):  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Elevated Serum ◽  
Normal Serum ◽  
Hcv Rna ◽  
Peripheral Blood Mononuclear ◽  
Hepatitis G Virus ◽  
Blood Mononuclear Cells ◽  
Hepatitis G

SummaryThe hepatitis G virus (HGV) has recently been identified as a new member of the Flaviviridae family. Infection by this virus is thought to be associated with blood borne hepatitis. In this study, the presence of HCV- and HGV-RNAs in serum or plasma (175 patients) and in peripheral blood mononuclear cells (PBMC) (133 patients) was investigated in patients with clotting disorders using a sensitive reverse transcriptase polymerase chain reaction (RT-PCR). HGV-RNA was detected in serum of 26 patients (14.8%). In apparently healthy blood donors, serum HGV-RNA was detected in 4 of 358 individuals investigated (1.12%). Ninety two percent of the 26 serum HGV-RNA positive patients had coinfection with the hepatitis C virus (HGV), especially with HCV genotype lb, the most common genotype in Belgium. Of these coinfected patients, 15 (62.5%) showed elevated serum ALT levels. Two patients who were solely infected with HGV had normal serum ALT. HGV-RNA in PBMC was found in 18 patients, of whom 3 were negative for serum HGV-RNA. As in case of HCV, HGV-RNA in PBMC is preferentially sensitive to interferon treatment. Nevertheless, rapid reappearance of HGV-RNA in PBMC was observed after cessation of treatment. In one patient, persistent serum ALT elevation seems to be associated with continued HGV viremia, despite the disappearance of serum HCV-RNA.

scholarly journals Proliferation and cytolytic function of anti-CD3 + interleukin-2 stimulated peripheral blood mononuclear cells following bone marrow transplantation

Blood ◽  
1991 ◽  
Vol 78 (5) ◽  
pp. 1286-1291 ◽  
Author(s):  
E Katsanis ◽  
PM Anderson ◽  
AH Filipovich ◽  
DE Hasz ◽  
ML Rich ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Marrow Transplantation ◽  
Mononuclear Cells ◽  
Interleukin 2 ◽  
Peripheral Blood Mononuclear ◽  
Cytolytic Function ◽  
Blood Mononuclear Cells

Abstract We evaluated the proliferation, cytolytic function, and phenotypic characteristics of anti-CD3 plus interleukin-2 (IL-2) stimulated peripheral blood mononuclear cells (PBMCs) from 44 patients with leukemia or non-Hodgkin's lymphoma (NHL) treated with multiagent chemotherapy or following bone marrow transplantation (BMT). BMT patients had decreased cell growth with only a 1.35 +/- 0.25 (autologous BMT for acute lymphoblastic leukemia [ALL]), 1.24 +/- 0.25 (autologous BMT for NHL), and 0.8 +/- 0.1 (allogeneic BMT for leukemia) mean fold increase by day 5 of culture compared with controls (4.0 +/- 0.4), P less than .001. Anti-CD3 + IL-2 activated cells from patients with ALL and NHL who had received autologous BMT and cells from patients with leukemia who underwent allogeneic BMT were more effective in lysing the natural killer (NK) sensitive target, K562, and the NK- resistant target, Daudi, compared with controls. In contrast, cytolysis of K562 and Daudi by cultured PBMCs from patients with ALL and NHL receiving multi-agent chemotherapy was similar to that of controls. Cultures from BMT recipients had a significant increase in CD16+ (autologous ALL 5.7 +/- 1.5%, P less than .01; autologous NHL 12.4 +/- 3.5%, P less than .001; allogeneic 14.3 +/- 2.9%, P less than .001) and CD56+ cells (autologous ALL 27.6 +/- 12.0%, P less than .01; autologous NHL 39.3 +/- 9.5%, P less than .001; allogeneic 42.7 +/- 7.4%, P less than .001) compared with controls (CD16+ 2.5 +/- 0.4%; CD56+ 6.9 +/- 0.9%). Stimulation of PBMCs with anti-CD3 + IL-2 is effective in generating cells with high cytolytic function post-BMT.

scholarly journals Interleukin-2 production and response to interleukin-2 by peripheral blood mononuclear cells from patients after bone marrow transplantation: II. Patients receiving soybean lectin-separated and T cell-depleted bone marrow

Blood ◽  
1987 ◽  
Vol 70 (5) ◽  
pp. 1595-1603 ◽  
Author(s):  
K Welte ◽  
CA Keever ◽  
J Levick ◽  
MA Bonilla ◽  
VJ Merluzzi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
T Cell ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Interleukin 2 ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

Abstract The ability of peripheral blood mononuclear cells (PBMC) to produce and respond to interleukin-2 (IL-2) was evaluated in 50 recipients of HLA- identical bone marrow (BM) depleted of mature T cells by soybean agglutination and E rosetting (SBA-E-BM). In contrast to our previous findings in recipients of unfractionated marrow, during weeks 3 to 7 post-SBA-E-BM transplantation (BMT), PBMC from the majority of patients spontaneously released IL-2 into the culture medium. This IL-2 was not produced by Leu-11+ natural killer cells, which were found to be predominant in the circulation at this time, but by T11+, T3+, Ia antigen-bearing T cells. The IL-2 production could be enhanced by coculture with host PBMC frozen before transplant but not by stimulation with mitogenic amounts of OKT3 antibody, thus suggesting an in vivo activation of donor T cells or their precursors by host tissue. Spontaneous IL-2 production was inversely proportional to the number of circulating peripheral blood lymphocytes and ceased after 7 to 8 weeks post-SBA-E-BMT in most of the patients. In patients whose cells had ceased to produce IL-2 spontaneously or never produced this cytokine, neither coculture with host cells nor stimulation with OKT3 antibody thereafter induced IL-2 release through the first year posttransplant. Proliferative responses to exogenous IL-2 after stimulation with OKT3 antibody remained abnormal for up to 6 months post-SBA-E-BMT, unlike the responses of PBMC from recipients of conventional BM, which responded normally by 1 month post-BMT. However, the upregulation of IL- 2 receptor expression by exogenous IL-2 was found to be comparable to normal controls when tested as early as 3 weeks post-SBA-E-BMT. Therefore, the immunologic recovery of proliferative responses to IL-2 and the appearance of cells regulating in vivo activation of T cells appear to be more delayed in patients receiving T cell-depleted BMT. Similar to patients receiving conventional BMT, however, the ability to produce IL-2 after mitogenic stimulation remains depressed for up to 1 year after transplantation.

Cytotoxic T-Cell Response to the Cancer Testis Antigen PASD1 In Multiple Myeloma: PASD1 Peptides for a Generic Vaccine to Treat PASD1-Positive Haematological Malignancies

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4294-4294
Author(s):  
Andrew J Campbell ◽  
Kamel Ait-Tahar ◽  
Suketu D. Patel ◽  
Martin Barnardo ◽  
Amanda P Liggins ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Normal Tissue ◽  
Hematological Malignancies ◽  
Mononuclear Cells ◽  
T Helper ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Cancer Testis

Abstract Abstract 4294 Multiple myeloma (MM) is a bone marrow localized plasma cell tumor comprising 1% of all cancers and 10–15% of hematological malignancies. Despite significant advances in treatment, such as bortezomib, patients currently only have a 5-year survival rate of approximately 35%. The identification of improved therapeutic options therefore remains a priority. There is increasing evidence for a role of the immune system in tumor progression. Examples include the remission of some leukemias and lymphomas in immunocompetent patients while allogeneic stem cell transplantation also has a graft-versus-tumor effect in MM. The immunotherapeutic targeting of tumor-associated antigens (TAAs) on MM cells therefore represents an important approach for improved treatment of this disease. MM cells express a number of TAAs, of which cancer testis antigens (CTAs) are of particular interest. Their restricted normal tissue distribution combined with widespread expression in tumors makes them attractive immunotherapeutic targets whilst minimizing potential problems with autoimmunity. Reports of cytotoxic T cells (CTLs, the major effector cells in tumor immunity) and CD4-positive T-helper cells recognizing the NY-ESO-1 and MAGE CTAs in patients with MM suggests the presence of a spontaneous immune response to these molecules, which can be boosted through vaccination with CTAs such as NY-ESO-1. We previously identified PAS (Per ARNT Sim) domain containing 1 (PASD1) protein as a novel diffuse large B-cell lymphoma (DLBCL)-associated CTA. Importantly, PASD1 has a restricted normal tissue distribution but is present in a range of hematological malignancies, including MM. Subsequent in vitro studies have identified immunogenic PASD1 peptides that elicit PASD1-driven CTL or CD4-positive T-helper responses in peripheral blood mononuclear cells from DLBCL patients. Studies using a pre-clinical in vivo murine model have confirmed the immunogenicity of the PASD1 CTL peptides. These critical steps support the use of PASD1 as a potential immunotherapeutic target in DLBCL. The current study was performed to ascertain whether the PASD1 CTL peptides were immunogenic in MM patients and thus have utility for immunotherapy in this disease. Blood samples were obtained from 9 post-treatment myeloma patients attending the John Radcliffe Hospital following informed consent. Peripheral blood mononuclear cells were incubated with the PASD1 CTL peptides PASD1(1)38-47 (QLLDGFMITL) and PASD1(2)167-175 (YLVGNVCIL). A gamma-interferon ELISPOT release assay was performed after 8–10 days. The results are summarized in Table 1.Table 1:Gamma-IFN response to PASD1 in patients with MM.PatientsMHC Class I*Gamma-IFN response to peptides/50,000 cellsPASD1(1)PASD1(2)HIV-1PHADSA*0201+2+/−112+/−41+/−1100+/−14MWA*0201+52+/−244+/−220+/−266+/−8DMA*0201− A*2601+28+/−246+/−68+/−298+/−10JBA*0201+0+/−00+/−02+/−088+/−12JYA*0201+–––72+/−10DAA*0201−2+/−20+/−00+/−082+/−10GGA*0201−58+/−268+/−244+/−288+/−10MDA*0201−52+/−228+/−242+/−292+/−12RSA*0201––––*Results were considered positive if the number of spots in the test wells were at least twice that found in the irrelevant HIV-1 cultures. A significant gamma-interferon response was detected to one or both of the PASD1 peptides in 2/4 A*0201-positive evaluable patients. Analysis of the SYPETHI web-based algorithm predicted the PASD1 peptides used here to be immunogenic in the context of A*2601 and this was confirmed in the one A*2601+ patient studied here. No significant response was detected in the 3 A*0201 and A*2601-negative patients. Double immunolabeling studies using antibodies to PASD1 and CD138 showed PASD1 to be present in a subset of tumor cells in all 7 patients with evaluable ELISPOT data. Our findings demonstrate the immunogenicity of both the PASD1(1) and PASD1(2) peptides in patients with MM. These ‘generic’ peptides therefore represent vaccine candidates for inclusion in a vaccine targeting multiple PASD1-positive hematological malignancies. Disclosures: Banham: University of Oxford: Patents & Royalties. Pulford:Leukaemia and Lymphoma Research: Patents & Royalties.

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