PubMed Health⌕ Search

Biomedical subjects

Emmanuelle Boulanger

Publications and source records attributed to Emmanuelle Boulanger.

16 recordsLinked to original sources
PubMed2006

Polyclonal IgG4 hypergammaglobulinemia associated with plasmacytic lymphadenopathy, anemia and nephropathy.

Marked polyclonal immunoglobulin (Ig)G4 hypergammaglobulinemia has exceptionally been reported. Here we report on two Algerian patients who presented a syndrome characterized by anemia, plasmacytic lymphadenopathy, renal manifestations, and a marked polyclonal IgG4 hypergammaglobulinemia leading to a hyperviscosity syndrome in one case. The IgG4-expressing cell percentage was significantly increased in the peripheral blood lymphocytes collected from the two patients upon diagnosis. Moreover, in contrast with normal sera, both patients' sera significantly increased the percentage of IgG4-expressing cells when incubated with CD40-stimulated normal B lymphocytes. Similar effects were obtained with the culture supernatants of the patients' activated T cells. Anti-interleukin (IL) 4 and/or anti-IL-13 antibodies were unable to antagonize the IgG4 production. IL-4 and IL-13 serum concentrations were found to be normal in the two patients. The increased IgG4 production was found to be mediated by soluble factor(s), most probably secreted by activated T cells, which did not require the signal transducer and activator of transcription 6 signaling pathway.

Adolescent↗
PubMed2006

Immunogenic HLA-B*0702-restricted epitopes derived from human telomerase reverse transcriptase that elicit antitumor cytotoxic T-cell responses.

PURPOSE: The human telomerase reverse transcriptase (hTERT) is considered as a potential target for cancer immunotherapy because it is preferentially expressed in tumor cells. To increase the applicability of hTERT-based immunotherapy, we set out to identify CTL epitopes in hTERT restricted by HLA-B*0702 molecule, a common MHC class I allele. EXPERIMENTAL DESIGN: HLA-B*0702-restricted peptides from hTERT were selected by using a method of epitope prediction and tested for their immunogenicity in human (in vitro) and HLA-B*0702 transgenic mice (in vivo). RESULTS: All the six hTERT peptides that were predicted to bind to HLA-B*0702 molecule were found to induce primary human CTL responses in vitro. The peptide-specific CD8+ CTL lines were tested against various hTERT+ tumor cells. Although differences were observed according to the tumor origin, only three CTL lines specific for p277, p342, and p351 peptides exhibited cytotoxicity against tumor cells in a HLA-B*0702-restricted manner. In addition, this cytotoxicity was inhibited by the addition of peptide-loaded cold target cells and indicated that these epitopes are naturally processed and presented on the tumor cells. Further, in vivo studies using humanized HLA-B*0702 transgenic mice showed that all the candidate peptides were able to induce CTL responses after peptide immunization. Furthermore, vaccination with a plasmid DNA encoding full-length hTERT elicited peptide-specific CTL responses, indicating that these epitopes are efficiently processed in vivo. CONCLUSIONS: Together with previously reported hTERT epitopes, the identification of new CTL epitopes presented by HLA-B*0702 increases the applicability of hTERT-based immunotherapy to treating cancer.

Animals↗
PubMed2005

Mono/oligoclonal pattern of Kaposi Sarcoma-associated herpesvirus (KSHV/HHV-8) episomes in primary effusion lymphoma cells.

Primary effusion lymphoma (PEL) is a rare lymphoma of B-cell origin, developed in serous cavities. PEL tumor cells are latently infected with Kaposi sarcoma-associated herpesvirus (KSHV) and in most cases co-infected with Epstein-Barr virus (EBV). In 15 primary PEL tumors including 10 EBV-positive cases, we analyzed the fused terminal repeat (TR) regions of KSHV episomes using pulsed-field gel electrophoresis and Southern blot. On the same genomic DNA samples, the cellular clonality was assessed by Southern blot and PCR detection of monoclonal immunoglobulin heavy chain (IGH) VDJ gene rearrangements, associated in the EBV-infected cases, with Southern blot analysis of the fused termini of EBV episomes. Monoclonal IGH gene rearrangements were detected in 13 tumors using Southern blot, in 11 cases using PCR, and in all cases considering both methods. EBV infection was monoclonal in all EBV-positive cases. However, only 5 PEL tumors were found to be monoclonally infected with KSHV. In the 10 other cases, we found a biclonal (2 bands; n = 4) or an oligoclonal pattern (3-6 bands; n = 6) of KSHV episomes. We hypothesized that the apparent discrepancy between viral and cellular clonalities in PEL might be due to several phenomena including complex mechanisms of genomic recircularization, insertion of duplicated sequences into the TR region and simultaneous infection of tumor cells with defective KSHV variants. KSHV infection of contaminating nontumoral cells, superinfection from lytically infected cells or viral integration events might also explain the oligoclonal pattern of KSHV infection. Several of these mechanisms, not mutually exclusive, might coexist in a single tumor.

Adult↗
PubMed2005

Prognostic factors and outcome of human herpesvirus 8-associated primary effusion lymphoma in patients with AIDS.

PURPOSE: Primary effusion lymphoma (PEL) is a rare high-grade B-cell non-Hodgkin's lymphoma associated with Kaposi sarcoma-associated herpesvirus/human herpesvirus 8 (KSHV/HHV-8) infection, and is mostly observed in the course of HIV infection. The prognosis is poor, with reported median survival time shorter than 6 months. To date, no prognostic factor has been identified in this subset of lymphoma. PATIENTS AND METHODS: We describe here a large series of HIV-infected patients with PEL, including 28 cases diagnosed in six centers during an 11-year time period. Prognosis analysis was performed using a Cox proportional hazard regression model. Statistically significant covariates were further analyzed in a forward, stepwise multivariate model. RESULTS: After a median follow-up of 3.8 years (range, 10 months to 10.8 years), nine patients (32%) were still alive, and eight of them remained progression free. The median survival was 6.2 months, and the 1-year overall survival rate was 39.3%. Fourteen patients (50%) achieved complete remission, with a 1-year disease-free survival rate at 78.6%. In a multivariate analysis, only a performance status more than 2 (hazard ratio, 5.84; 95% CI, 1.76 to 19.33) and the absence of highly active antiretroviral therapy (HAART) before PEL diagnosis (hazard ratio, 3.26; 95% CI, 1.14 to 9.34) were found to be independent predictors for shorter survival. CONCLUSION: Based on a retrospective series of 28 patients, two prognostic factors were identified as being independently associated with impaired clinical outcome in HIV-related PEL--(1) a poor performance status and (2) the absence of HAART before PEL diagnosis.

Acquired Immunodeficiency Syndrome↗
PubMed2004

Human herpesvirus 8 (HHV-8)-associated peritoneal primary effusion lymphoma (PEL) in two HIV-negative elderly patients.

Human herpesvirus 8 (KSHV/HHV-8) is associated with all forms of Kaposi sarcoma (KS), with a rare high-grade B-cell non-Hodgkin lymphoma characterized by serous effusions in body cavities called primary effusion lymphoma (PEL) and with some forms of multicentric Castleman disease (MCD). Although mostly observed during AIDS, such disorders have also been described with a lower incidence in human immunodeficiency virus-negative patients. We describe here the features of two novel cases of AIDS-unrelated PEL. Two patients, a 78-year-old man (case 1) and a 86-year-old woman (case 2), both of French origin, presented exudative ascitic effusion containing numerous KSHV/HHV-8(+) EBV(-) large lymphomatous cells of B-cell clonal origin, characterized by a CD45(+) CD30(+) CD19(-) CD20(-) immunophenotype. The PEL tumor cells harbored a homogenous and isolated trisomy 12 in case 1 and an aberrant expression of the T-cell lineage antigen CD7 in case 2. Both patients were lymphopenic at the time of PEL diagnosis and rapidly died with progressive lymphoma. Moreover, patient 2 had a previous history of classic KS and MCD clinically improved after treatment with all-trans-retinoid acid and a concomitant metastatic breast adenocarcinoma. Compared to AIDS-related PEL, these two cases displayed distinct features in particular the advanced age of patients, as observed for Mediterranean KS, and the absence of EBV coinfection.

Aged↗
PubMed2004

Severe ADAMTS13 deficiency in adult idiopathic thrombotic microangiopathies defines a subset of patients characterized by various autoimmune manifestations, lower platelet count, and mild renal involvement.

The significance of ADAMTS13 deficiency in adult thrombotic microangiopathy (TMA) remains controversial. In an attempt to define the characteristics of adult TMA with severe ADAMTS13 deficiency, we determined 2 groups of patients on the basis of ADAMTS13 activity (undetectable or detectable). Clinical presentation, laboratory values, autoimmune manifestations, and outcome were compared between the groups. Patients were included retrospectively from 12 centers. All fulfilled the diagnosis criteria of TMA. Patients with a history of transplantation, cancer and chemotherapy, and Centers for Disease Control and Prevention (CDC) stage C human immunodeficiency virus (HIV) infection were not included. Forty-six patients were included. Thirty-one patients had an undetectable ADAMTS13 activity (<5%), and the remaining 15 patients had ADAMTS13 activity of >25%. Severe ADAMTS13 deficiency was associated with a plasmatic inhibitor in 17 cases (55%), suggesting an immune-mediated mechanism. Patients with undetectable ADAMTS13 were more frequently of Afro-Caribbean origin than patients with detectable ADAMTS13 activity (48.4% vs 13.3%, respectively; p = 0.03). As opposed to patients with detectable ADAMTS13 activity, patients with severe ADAMTS13 deficiency displayed various autoimmune manifestations that consisted of nondestructive polyarthritis (4 cases) associated in 1 case with malar rash and extramembranous glomerulonephritis, discoid lupus (3 cases), and autoimmune endocrinopathies, Raynaud phenomenon, and sarcoidosis-like disease (1 case each). In patients with severe ADAMTS13 deficiency, antinuclear antibodies, anti-double-stranded DNA antibodies, and anticardiolipin antibodies were positive in 22 (71%) cases, 3 (9.7%) cases, and 1 (3.2%) case, respectively. One patient fulfilled the criteria for the diagnosis of systemic lupus erythematosus. During follow-up, 1 patient with severe ADAMTS13 deficiency developed antinuclear antibodies, and 3 others developed anti-double-stranded DNA antibodies, in association with neurologic manifestations and anticardiolipin antibodies in 1 case. Patients with severe ADAMTS13 deficiency also had a lower platelet count (12 x 10(9)/L; range, 2-69 x 10(9)/L) and less severe renal failure (estimated glomerular filtration rate: 78 mL/min; range, 9-157 mL/min) than patients with detectable ADAMTS13 activity (49.5 x 10(9)/L; range, 6-103 x 10(9)/L; p = 0.0004, and 15.8 mL/min; range, 5.6-80 mL/min; p < 0.0001, respectively). End-stage renal failure occurred in 1 patient with severe ADAMTS13 deficiency and in 3 patients with detectable ADAMTS13 activity (3.2% vs 21.4%, respectively; p = 0.08). Flare-up and relapse episodes and survival were comparable between the groups. Taken together, these data indicate that adult idiopathic thrombotic thrombocytopenic purpura, as defined by severe ADAMTS13 deficiency, may occur preferentially in a particular ethnic group, and is characterized by severe thrombocytopenia, mild renal involvement, and a wide spectrum of autoimmune manifestations that may be completed during follow-up. Indeed, apparently idiopathic thrombotic thrombocytopenic purpura may be considered a specific autoimmune disease.

ADAM Proteins↗
PubMed2004

Novel gamma-2-herpesvirus of the Rhadinovirus 2 lineage in gibbons.

We obtained 475 nucleotides of the DNA polymerase gene of a novel human herpesvirus 8 homolog sequence in a gibbon. The finding of this new gibbon virus, which clusters with a related chimpanzee virus in the rhadinovirus 2 genogroup, suggests the existence of a novel gamma-2-herpesvirus in humans.

Animals↗
PubMed2003

Improved survival in HIV-related Hodgkin's lymphoma since the introduction of highly active antiretroviral therapy.

OBJECTIVE: To evaluate the evolving characteristics of HIV-related Hodgkin's lymphoma (HL) and survival of affected patients since the introduction of highly active antiretroviral therapy (HAART). DESIGN AND METHODS: A retrospective single-institution study was performed over a 15-year follow-up period. For statistical analysis, patients were categorized into a pre-HAART period (1987-1996, n = 61) and a post-HAART period (1997-2001, n = 47). RESULTS: HL characteristics were similar in both groups. The chemotherapy regimens used did not differ significantly, although the MOPP/ABV regimen (mechlorethamine, vincristine, procarbazine substituted by cyclophosphamide since 2000, and prednisone /adriamycin, bleomycin, vinblastin) has progressively replaced the ABVD regimen (adriamycin, bleomycin, vinblastin, dacarbazine). A slight increase in the complete response rate was noted in the post-HAART population (74.5%) versus the pre-HAART population (64.5%), and the probability to relapse was not different between the two groups. Patients diagnosed since 1997 had a higher probability for prolonged survival with a median survival time not reached versus 19 months in the pre-HAART period. The estimate 2-year survival probability was 45% [95% confidence interval (CI), 32.3-57.8% in the pre-HAART period, and 62% (95% CI, 46.7-77.1%) in the post-HAART period ( P= 0.03). This decreased mortality was associated with a decrease in AIDS-associated deaths. In the post-HAART period, 12 patients were naive to any antiretroviral therapy and 31 were already on HAART at the time of HL diagnosis. Twenty of them had a plasma HIV-RNA below 500 copies/ml. The response rate and the overall survival were not statistically different in these patients. CONCLUSIONS: HL still occurs in patients with HAART-induced HIV suppression. However, overall survival has significantly improved since the introduction of HAART.

Adult↗
PubMed2003

Combined chemotherapy including high-dose methotrexate in KSHV/HHV8-associated primary effusion lymphoma.

Primary effusion lymphoma (PEL) is a rare KSHV/HHV8-associated high-grade non-Hodgkin's lymphoma (NHL) of B-cell origin, characterized by serous effusions in body cavities. Most patients are HIV-infected homosexual men with severe immunosuppression and other KSHV/HHV8-associated diseases such as Kaposi's sarcoma (KS). The prognosis is poor with a median survival of less than 6 months in most cohorts. The achievement of a sustained complete remission is rare. High-dose chemotherapy regimens are warranted to improve complete remission rate and survival. Seven patients with AIDS-associated PEL were treated with a combined chemotherapy including high-dose methotrexate followed by leucovorin rescue. In all cases, KSHV/HHV8 sequences were detected in the effusion samples using quantitative PCR assays. Five patients had a pre-existing KS, associated in three cases with multicentric Castleman's disease (MCD). Upon diagnosis, 6 patients received antiretroviral therapy, which was maintained during chemotherapy in 5 of them. At time of analysis, 3 out of 7 patients were in complete remission 18, 26, and 78 months after PEL diagnosis. Three patients died with a progressive PEL at 22, 67, and 153 days after diagnosis, and 1 patient died 9 months after PEL diagnosis with a MCD-associated plasmablastic NHL. Complete remission was obtained in 3 out of 7 patients treated for AIDS-associated PEL with combined chemotherapy containing high-dose methotrexate.

Acquired Immunodeficiency Syndrome↗
PubMed2003

High-dose plasma infusion versus plasma exchange as early treatment of thrombotic thrombocytopenic purpura/hemolytic-uremic syndrome.

Thrombotic thrombocytopenic purpura and adult hemolytic-uremic syndrome (TTP/HUS) have a substantial mortality rate even with currently available treatments. Although therapeutic plasma exchange is the recommended treatment of TTP/HUS, this cumbersome procedure may not be available for all patients in an emergency. In this context, plasma infusion may represent an alternative first-line therapy. We compared the effectiveness of high-dose plasma infusion (25-30 mL/kg per day) and therapeutic plasma exchange as first-line treatment of adult TTP/HUS at a single center. Two groups of patients with TTP/HUS were identified according to their initial therapy, that is, high-dose plasma infusion (19 patients) and therapeutic plasma exchange (18 patients). Clinical charts and outcomes were retrospectively analyzed. Endpoints for comparison were the duration of platelet counts below 150 x 10 /L and LDH levels above normal values; the volumes of plasma administered and the duration of treatment; complete remission, relapse, and mortality rates; and treatment-related complications. Patients of the 2 groups had comparable clinical and laboratory features on admission. Sixteen patients achieved complete remission in each group. Median times to recovery of platelet counts and LDH levels were comparable between the 2 groups. Eight patients in the high-dose plasma infusion (HD-PI) group were switched to therapeutic plasma exchange because of fluid overload (6 patients), persistent biologic disturbances (1 patient), or unresponsiveness to high-dose plasma infusion treatment (1 patient). This latter patient had severe TTP/HUS that remained refractory to therapeutic plasma exchange and vincristine, and rapidly died. All 7 remaining patients achieved complete remission with therapeutic plasma exchange. Four patients in the HD-PI group and 3 patients in the therapeutic plasma exchange (TPE) group died. In the HD-PI group, 5 patients experienced a transient nephrotic-range proteinuria during treatment. Main complications in the TPE group were collapse (1 patient) and central venous catheter infection (2 patients) or thrombosis (1 patient). Three patients in each group relapsed. High-dose plasma infusion may be an efficient treatment of TTP/HUS in patients who cannot have early plasma exchange. However, the large volumes of plasma required to reach complete remission may result in fluid overload, which may necessitate subsequent therapeutic plasma exchange.

Adult↗
PubMed2002

Analysis of TCR, pT alpha, and RAG-1 in T-acute lymphoblastic leukemias improves understanding of early human T-lymphoid lineage commitment.

T-acute lymphoblastic leukemias (T-ALLs) derive from human T-lymphoid precursors arrested at various early stages of development. Correlation of phenotype and T-cell receptor (TCR) status with RAG-1 and pT alpha transcription in 114 T-ALLs demonstrated that they largely reflect physiologic T-lymphoid development. Half the TCR alpha beta lineage T-ALLs expressed a pre-TCR, as evidenced by RAG-1, pT alpha, and cTCR beta expression, absence of TCR delta deletion, and a sCD3(-), CD1a(+), CD4/8 double-positive (DP) phenotype, in keeping with a population undergoing beta selection. Most TCR gamma delta T-ALLs were pT alpha, terminal deoxynucleotidyl transferase (TdT), and RAG-1(lo/neg), double-negative/single-positive (DN/SP), and demonstrated only TCR beta DJ rearrangement, whereas 40% were pT alpha, TdT, and RAG-1 positive, DP, and demonstrated TCR beta V(D)J rearrangement, with cTCR beta expression in proportion. As such they may correspond to TCR alpha beta lineage precursors selected by TCR gamma delta expression, to early gamma delta cells recently derived from a pT alpha(+) common alpha beta/gamma delta precursor, or to a lineage-deregulated alpha beta/gamma delta intermediate. Approximately 30% of T-ALLs were sCD3/cTCR beta(-) and corresponded to nonrestricted thymic precursors because they expressed non-T-restricted markers such as CD34, CD13, CD33, and CD56 and were predominantly DN, CD1a, pT alpha, and RAG-1 low/negative, despite immature TCR delta and TCR gamma rearrangements. TCR gene configuration identified progressive T-lymphoid restriction. T-ALLs, therefore, provide homogeneous expansions of minor human lymphoid precursor populations that can aid in the understanding of healthy human T-cell development.

Adolescent↗
PubMed2002

Systemic non-Hodgkin lymphoma in HIV-infected patients with effective suppression of HIV replication: persistent occurrence but improved survival.

The incidence of systemic non-Hodgkin lymphoma (NHL) has only slightly decreased since the introduction of highly active antiretroviral therapy (HAART), suggesting that current antiretroviral strategies do not eliminate the lymphoma risk. This study evaluates the evolving characteristics of HIV and NHL between the pre-HAART and the post-HAART periods in 246 HIV-infected NHL patients from a single institution. Major HIV-related characteristics were similar in the two periods. Most patients in the post-HAART period presented with unknown (23%), untreated (16%), or uncontrolled (37%) HIV infection. Despite an increased frequency of advanced stage IV disease in the post-HAART period (68% vs. 53%, p =.03), the overall survival has improved, with a 2-year survival probability of 61.6% versus 35.9%, (p <.001). This was associated with an increased complete remission rate (69% vs. 55%, p =.04) and the generalization of more intensive chemotherapy regimens. Most patients (76%) who developed NHL in the post-HAART period had uncontrolled HIV replication. However, 27 patients (24%) developed NHL despite an effective viral suppression at NHL diagnosis. Patients who were naive to any antiretroviral therapy at NHL diagnosis had an overall survival probability very similar to that of patients with controlled HIV replication. Improvement in the overall survival rate in the post-HAART period was associated with more intensive chemotherapy regimens, increased complete remission rate, and a likely benefit of continuation or introduction of HAART.

Adult↗
PubMed2002

High incidence of Kaposi sarcoma-associated herpesvirus-related non-Hodgkin lymphoma in patients with HIV infection and multicentric Castleman disease.

Multicentric Castleman disease (MCD) is a distinct type of lymphoproliferative disorder associated with inflammatory symptoms and interleukin 6 (IL-6) dysregulation. In the context of human immunodeficiency virus (HIV) infection, MCD is associated with Kaposi sarcoma-associated herpesvirus, also called human herpesvirus type 8 (KSHV/HHV8). Within a prospective cohort study on 60 HIV-infected patients with MCD, and a median follow-up period of 20 months, 14 patients developed KSHV/HHV8-associated non-Hodgkin lymphoma (NHL): 3 "classic" KSHV/HHV8(+) Epstein-Barr virus-positive (EBV(+)) primary effusion lymphoma (PEL), 5 KSHV/HHV8(+) EBV(-) visceral large cell NHL with a PEL-like phenotype, and 6 plasmablastic lymphoma/leukemia (3/3 KSHV/HHV8(+) EBV(-)). The NHL incidence observed in this cohort study (101/1000 patient-years) is about 15-fold what is expected in the general HIV(+) population. MCD-associated KSHV/HHV8(+) NHL fell into 2 groups, suggesting different pathogenesis. The plasmablastic NHL likely represents the expansion of plasmablastic microlymphoma from the MCD lesion and progression toward aggressive NHL. In contrast, the PEL and PEL-like NHL may implicate a different original infected cell whose growth is promoted by the cytokine-rich environment of the MCD lesions.

Antiviral Agents↗