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1.
Hemasphere ; 8(9): e150, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39233903

RESUMO

This EHA-ESMO Clinical Practice Guideline provides key recommendations for managing HIV-associated lymphomas.The guideline covers clinical, imaging and pathological diagnosis; staging and risk assessment; treatment and follow-up.The author group encompasses a multidisciplinary group of experts from different institutions and countries in Europe.Recommendations are based on available scientific data and the authors' collective expert opinion.

2.
Blood Adv ; 8(18): 4924-4935, 2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-38985311

RESUMO

ABSTRACT: Castleman disease (CD) encompasses a spectrum of rare disorders, including unicentric CD (UCD), idiopathic multicentric CD (iMCD), and human herpesvirus 8-associated MCD (HHV8+ MCD). We performed a systematic review of publications reporting ≥5 cases of CD between 1995 and 2021, following preferred reporting items for systematic reviews and meta-analyses guidelines, to describe and compare subtypes. We extracted data on clinical symptoms and laboratory parameters as stated in international consensus diagnostic criteria for iMCD and estimated the frequency of each criterion using meta-analyses. We analyzed 32 studies describing 559 UCD, 1023 iMCD, and 416 HHV8+ MCD cases. Although many symptoms and laboratory abnormalities occurred at similar rates in patients with iMCD and HHV8+ MCD, patients with HHV8+ MCD had significantly higher rates of constitutional symptoms (46.6% vs 98.6%; P = .038) and splenomegaly (48.2% vs 89.2%; P = .031). Renal dysfunction was significantly more common in patients with iMCD than in patients with HHV8+ MCD before adjustment (36.9% vs 17.4%; P = .04; adjusted P = .1). Patients with UCD had lower rates of symptoms and laboratory abnormalities, although these were present in 20% of patients and were particularly pronounced in pediatric UCD. There are many similarities in the symptomatology of iMCD and HHV8+ MCD; many patients experience constitutional symptoms and organ dysfunction. Differences between these subtypes likely reflect differences in pathophysiology and/or comorbidity burdens.


Assuntos
Hiperplasia do Linfonodo Gigante , Hiperplasia do Linfonodo Gigante/diagnóstico , Humanos , Herpesvirus Humano 8/isolamento & purificação , Infecções por Herpesviridae/complicações , Infecções por Herpesviridae/diagnóstico
3.
J Med Virol ; 96(8): e29836, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39078052

RESUMO

Primary effusion lymphoma (PEL) is a rare B-cell non-Hodgkin lymphoma associated with Kaposi Sarcoma-associated herpesvirus (KSHV/HHV8) infection. Lymphoma cells are coinfected with Epstein-Barr virus (EBV) in 60-80% of cases. Tools allowing a reliable PEL diagnosis are lacking. This study reports PEL diagnosis in 4 patients using a Flow-Fluorescence in situ hybridization (FlowFISH) technique that allowed detection of differentially expressed EBV and HHV8 transcripts within the same sample, revealing viral heterogeneity of the disease. Moreover, infected cells exhibited variable expressions of CD19, CD38, CD40, and CD138. Therefore, FlowFISH is a promising tool to diagnose and characterize complex viral lymphoproliferations.


Assuntos
Herpesvirus Humano 4 , Herpesvirus Humano 8 , Hibridização in Situ Fluorescente , Linfoma de Efusão Primária , Humanos , Herpesvirus Humano 8/genética , Herpesvirus Humano 8/isolamento & purificação , Hibridização in Situ Fluorescente/métodos , Linfoma de Efusão Primária/virologia , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/isolamento & purificação , Masculino , Idoso , Pessoa de Meia-Idade , Feminino , Infecções por Herpesviridae/virologia , Infecções por Herpesviridae/diagnóstico , Infecções por Vírus Epstein-Barr/virologia , Infecções por Vírus Epstein-Barr/complicações , Idoso de 80 Anos ou mais
4.
Int J Infect Dis ; 142: 106994, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38447753

RESUMO

OBJECTIVES: Despite successful human immunodeficiency virus (HIV) control with combination antiretroviral therapy (cART), individuals with HIV still face health risks, including cancers, cardiovascular and neurocognitive diseases. An HIV protein, Tat, is potentially involved in these HIV-related diseases. Previous studies demonstrated circulating Tat in the blood of untreated people with HIV. Here, we measured Tat levels in the serum of cART-treated people with HIV to examine the effect of cART on Tat production. METHODS: Serum samples from 63 HIV-positive and 20 HIV-seronegative individuals were analyzed using an ELISA assay that detected Tat concentrations above 2.5 ng/mL. RESULTS: Among HIV-positive individuals, the Tat level ranged from 0 to 14 ng/mL. 25.4% (16 out of 63) exceeded the 2.5 ng/mL cut-off, with a median HIV Tat level of 4.518 [3.329-8.120] ng/mL. No correlation was revealed between Tat levels and CD4+ T cell counts, serum HIV RNA, p24 antigen, or anti-Tat levels. CONCLUSIONS: Despite cART, circulating HIV Tat persists and may contribute to HIV-related diseases. This emphasizes the need for further research on the mechanisms of Tat action in non-infected cells where it can penetrate upon circulation in the blood.


Assuntos
Infecções por HIV , Soropositividade para HIV , HIV-1 , Humanos , HIV-1/genética , Linfócitos T CD4-Positivos , Contagem de Linfócito CD4
5.
J Clin Immunol ; 44(2): 46, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38231432

RESUMO

PURPOSE: About 25% of patients with common variable immunodeficiency disease (CVID) have splenomegaly, necessitating sometimes splenectomy whom consequences on the immunological profile of CVID patients have never been studied. We analyzed 11 CVID patients' comprehensive blood immune cell phenotypes pre- and post-splenectomy. METHODS: Flow cytometry analyses of immune cell populations. RESULTS: Among 89 CVID cohort patients, 41 with splenomegaly, splenomegaly was strongly associated with granulomatous disease, autoimmune disorders, lymphoid hyperplasia, and/or portal hypertension. CVID patients with splenomegaly have significant peripheral lymphopenia (p = 0.001), and significantly fewer peripheral class-switched memory B cells (smBs) (p = 0.001), CD4+ T lymphocytes (p = 0.001), NK (p = 0.0001) and dendritic cells (p ≤ 0.01), and significantly more circulating CD4+ and CD8+ (p = 0.00001) T cell subset activation (p = 0.00005), than CVID patients without splenomegaly. Examination of splenectomy impact on circulating lymphocyte subset distributions demonstrated the drastically enhanced total circulating lymphocyte count post-splenectomy, predominantly B lymphocytes and CD8+ T cells. However, splenectomy did not change B cell distribution, with smBs remaining persistently low, in contrast to complete inversion of the circulating T cell composition, with reversal of the CD4+/CD8+ ratio suggesting that amplification of the CD8+ T cell compartment is a CVID characteristic in patients with splenomegaly. Our results highlight this CD8+ amplification in CVID-splenomegaly patients that might be explained by a homing effect to the spleen and/or possible chronic virus replication, which in turn could induce T cell expansions. CONCLUSION: Splenectomizing CVID patients with splenomegaly restores the absolute circulating lymphocyte count, suggesting that the decreased T cell count in the presence of splenomegaly cannot be used as an exclusive criterion for combined immunodeficiency.


Assuntos
Imunodeficiência de Variável Comum , Esplenomegalia , Humanos , Esplenomegalia/cirurgia , Esplenectomia , Imunodeficiência de Variável Comum/diagnóstico , Linfócitos T CD8-Positivos , Baço
6.
J Med Virol ; 96(2): e29423, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38285479

RESUMO

Despite the success of combination antiretroviral therapy, people living with human immunodeficiency virus (HIV) still have an increased risk of Epstein-Barr virus (EBV)-associated B cell malignancies. In the HIV setting, B cell physiology is altered by coexistence with HIV-infected cells and the chronic action of secreted viral proteins, for example, HIV-1 Tat that, once released, efficiently penetrates noninfected cells. We modeled the chronic action of HIV-1 Tat on B cells by ectopically expressing Tat or TatC22G mutant in two lymphoblastoid B cell lines. The RNA-sequencing analysis revealed that Tat deregulated the expression of hundreds of genes in B cells, including the downregulation of a subset of major histocompatibility complex (MHC) class II-related genes. Tat-induced downregulation of HLA-DRB1 and HLA-DRB5 genes led to a decrease in HLA-DR surface expression; this effect was reproduced by coculturing B cells with Tat-expressing T cells. Chronic Tat presence decreased the NF-ᴋB pathway activity in B cells; this downregulated NF-ᴋB-dependent transcriptional targets, including MHC class II genes. Notably, HLA-DRB1 and surface HLA-DR expression was also decreased in B cells from people with HIV. Tat-induced HLA-DR downregulation in B cells impaired EBV-specific CD4+ T cell response, which contributed to the escape from immune surveillance and could eventually promote B cell lymphomagenesis in people with HIV.


Assuntos
Linfócitos B , Infecções por Vírus Epstein-Barr , Infecções por HIV , Linfoma , Produtos do Gene tat do Vírus da Imunodeficiência Humana , Humanos , Regulação para Baixo , Herpesvirus Humano 4/genética , Infecções por HIV/genética , HIV-1/genética , Cadeias HLA-DRB1 , Produtos do Gene tat do Vírus da Imunodeficiência Humana/genética
7.
Virchows Arch ; 484(3): 481-490, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37924346

RESUMO

Granulomatous disease is a serious complication of common variable immunodeficiency (CVID-GD) that occurs in 8-22% of these patients and can mimic sarcoidosis, with which it shares certain clinical, biological, and radiological features. However, few studies to date have compared the two pathologies immunologically and histologically. Therefore, we analyzed the immunological-histological findings for different tissue samples from ten patients with CVID-GD and compared them to those of biopsy-proven sarcoidosis. Specifically, we wanted to know whether or not the signaling abnormalities observed in sarcoidosis granulomas are also present in CVID-GD. Morphological differences were found between CVID-GD histology and classical sarcoidosis: mainly, the former's notable lymphoid hyperplasia associated with granulomas not observed in the latter. All CVID-GD involved organs contained several follicular helper-T (TFH) cells within the granulomatosis, while those cells were inconstantly and more weakly expressed in sarcoidosis. Moreover, CVID and sarcoidosis granulomas expressed the phosphorylated-signal transducer and activator of transcription (pSTAT)1 and pSTAT3 factors, regardless of the organ studied and without any significant difference between entities. Our results suggest that the macrophage-activation mechanism in CVID resembles that of sarcoidosis, thereby suggesting that Janus kinase (JAK)-STAT-pathway blockade might be useful in currently difficult-to-treat CVID-GD.


Assuntos
Imunodeficiência de Variável Comum , Sarcoidose , Humanos , Imunodeficiência de Variável Comum/complicações , Sarcoidose/complicações , Granuloma/etiologia , Biópsia , Transdução de Sinais
8.
Intern Med ; 63(7): 993-998, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37558474

RESUMO

Hodgkin lymphoma (HL) and idiopathic multicentric Castleman disease (iMCD) are markedly different conditions. However, in some cases, histological similarities caused by elevated cytokines, including interleukin-6, can lead to a misdiagnosis of HL as Castleman disease (CD). We herein report a patient with HL who had been diagnosed with CD by an expert panel and for whom an additional biopsy was useful for determining the correct diagnosis. Furthermore, we analyzed the positron emission tomography/computed tomography findings at the diagnosis and found that the maximum standardized uptake value was useful for distinguishing HL from iMCD.


Assuntos
Hiperplasia do Linfonodo Gigante , Doença de Hodgkin , Humanos , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/patologia , Hiperplasia do Linfonodo Gigante/diagnóstico por imagem , Hiperplasia do Linfonodo Gigante/patologia , Diagnóstico Diferencial , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons/métodos
9.
Ann Hematol ; 102(8): 2059-2068, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37386347

RESUMO

Data on mTOR inhibitors (mTORi) in autoimmune cytopenia (AIC), in adults are scarce. We retrospectively analysed 30 cases of refractory or relapsing AIC treated with an mTORi-based therapy. Eleven warm autoimmune hemolytic anaemia, 10 autoimmune thrombocytopenia, 6 acquired pure red cell aplasia, 3 autoimmune neutropenia were included. Twenty were multilineage AIC (67%) and 21 were secondary AIC (70%). mTORi were associated with other therapies in 23 AIC (77%). Twenty-two AIC (73%) responded to mTORi-based therapy: 5 reached a partial response (17%) and 17 a complete response (57%). Survival without unfavourable outcome (failure, requirement of a new therapy, or death) was longer in multilineage AIC compared to single-lineage AIC (p = 0.049) with a median event-free survival of 48 versus 12 months. Median event-free survival was 48 months in secondary AIC and 33 months in primary AIC (p = 0.79). mTORi were discontinued in 4 patients (15%) for safety reasons and in 3 patients for patient's choice (12%). In conclusion, mTORi could be considered as an alternative or an add-on therapy in refractory or relapsing AIC in adult patients, especially in multilineage AIC.


Assuntos
Anemia Hemolítica Autoimune , Trombocitopenia , Humanos , Adulto , Inibidores de MTOR , Estudos Retrospectivos , Recidiva Local de Neoplasia , Anemia Hemolítica Autoimune/tratamento farmacológico , Trombocitopenia/tratamento farmacológico
10.
Blood Adv ; 7(18): 5663-5669, 2023 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-37288720

RESUMO

Rituximab has revolutionized the treatment of Kaposi sarcoma-associated herpesvirus/human herpesvirus 8-associated multicentric Castleman disease (HHV8+ MCD), converting a rapidly fatal illness into a relapsing disease. HHV8+ MCD mainly affects patients with HIV infection but can also be observed in patients without HIV infection. We retrospectively analyzed a cohort of 99 patients (73 who tested HIV+ and 26 who tested HIV-), with HHV8+ MCD treated with rituximab-based therapy. Baseline characteristics were similar in patients who had HIV- and HIV+ results, although those who tested HIV- were older (65 vs 42 years) and presented less frequently with Kaposi sarcoma (15% vs 40%). Ninety-five patients (70 HIV+ and 25 HIV-) achieved complete remission (CR) after rituximab-based therapy. After a median follow-up of 51 months, 36 patients (12 HIV- and 24 HIV+) experienced disease progression. The 5-year progression-free survival (PFS) was 54%. The 5-year PFS was lower in HIV- patients than in HIV+ patients : 26% and 62%, respectively (P = .02). A multivariate prognostic factors analysis including time-dependent covariates revealed that HIV- status, reoccurrence of HHV8 DNA >3 log copies per mL, and serum C-reactive protein (CRP) >20 mg/mL were independently associated with an increased risk of progression after rituximab-induced CR (P = .001; P = .01; and P = .01, respectively). The lower rate of progression observed in the population with HIV+ results despite a longer follow-up period might have resulted from the possible immune restoration upon antiretroviral therapy. HHV8 viral load and serum CRP monitoring after rituximab therapy provide information on the progression risk and may help in the decision to resume specific therapy.


Assuntos
Hiperplasia do Linfonodo Gigante , Infecções por HIV , Herpesvirus Humano 8 , Sarcoma de Kaposi , Humanos , Rituximab/efeitos adversos , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Estudos Retrospectivos , Hiperplasia do Linfonodo Gigante/tratamento farmacológico , Hiperplasia do Linfonodo Gigante/complicações , Recidiva Local de Neoplasia , Sarcoma de Kaposi/complicações , Herpesvirus Humano 8/genética
11.
Br J Haematol ; 202(2): 267-278, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37221131

RESUMO

Unicentric Castleman disease (UCD) is a lymphoproliferative disease of unknown cause. Paraneoplastic pemphigus (PNP) is a major complication shown to be associated with a poor prognosis, with particular severity in patients with bronchiolitis obliterans (BO). This study describes the clinical and biological characteristics of UCD-PNP patients in a large Western cohort. A total of 148 patients diagnosed with UCD were identified, including 14 patients with a defined PNP. PNP was significantly associated with myasthenia gravis (MG) and FDC sarcoma during follow-up (FDCS). PNP was also significantly associated with reduced survival. These data, together with a multivariate analysis by principal components, led to the identification of UCD-PNP as a group at risk of MG, FDCS and death. PDGFRB sequencing performed on UCD lesions from six patients found the gain-of-function p.N666S variant in two. Interestingly, both patients had hyaline-vascular UCD subtype, were in the UCD-PNP subgroup and had FDCS. Sera from 25 UCD-PNP patients and 6 PNP patients without UCD were tested for PNP-associated autoantibodies. Sera from UCD-PNP patients had a strong reactivity against the N-terminal domain of recombinant periplakin (rPPL, 82%) and showed reactivity against at least two domains of rPPL. These features were not found in patients with UCD alone or in the PNP group without UCD. These data indicate that UCD-PNP patients belong to a subgroup sharing strong clinical and biological identity that might help to decipher the different dynamics of UCD natural history.


Assuntos
Hiperplasia do Linfonodo Gigante , Miastenia Gravis , Síndromes Paraneoplásicas , Pênfigo , Humanos , Pênfigo/diagnóstico , Pênfigo/etiologia , Hiperplasia do Linfonodo Gigante/patologia , Autoanticorpos , Miastenia Gravis/diagnóstico , Síndromes Paraneoplásicas/etiologia , Síndromes Paraneoplásicas/diagnóstico
12.
J Med Virol ; 95(3): e28633, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36866703

RESUMO

Burkitt lymphoma (BL) is a B cell malignancy associated with the Epstein-Barr virus (EBV). Most BL cases are characterized by a t(8;14) chromosomal translocation involving the MYC oncogene and the immunoglobulin heavy chain gene (IGH). The role of EBV in promoting this translocation remains largely unknown. Here we provide the experimental evidence that EBV reactivation from latency leads to an increase in the proximity between the MYC and IGH loci, otherwise located far away in the nuclear space both in B-lymphoblastoid cell lines and in patients' B-cells. Specific DNA damage within the MYC locus, followed by the MRE11-dependent DNA repair plays a role in this process. Using a CRISPR/Cas9-based B cell model to induce specific DNA double strand breaks in MYC and IGH loci, we have shown that the MYC-IGH proximity induced by EBV reactivation leads to an increased t(8;14) translocation frequency.


Assuntos
Linfoma de Burkitt , Infecções por Vírus Epstein-Barr , Humanos , Herpesvirus Humano 4/genética , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Linfoma de Burkitt/genética , Linfoma de Burkitt/metabolismo , Linfoma de Burkitt/patologia , Genes de Cadeia Pesada de Imunoglobulina
14.
J Allergy Clin Immunol ; 152(2): 528-537, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36587851

RESUMO

BACKGROUND: Granulomatous and lymphocytic interstitial lung disease (gl-ILD) is a major cause of morbidity and mortality among patients with common variable immunodeficiency. Corticosteroids are recommended as first-line treatment for gl-ILD, but evidence for their efficacy is lacking. OBJECTIVES: This study analyzed the effect of high-dose corticosteroids (≥0.3 mg/kg prednisone equivalent) on gl-ILD, measured by high-resolution computed tomography (HRCT) scans, and pulmonary function test (PFT) results. METHODS: Patients who had received high-dose corticosteroids but no other immunosuppressive therapy at the time (n = 56) and who underwent repeated HRCT scanning or PFT (n = 39) during the retrospective and/or prospective phase of the Study of Interstitial Lung Disease in Primary Antibody Deficiency (STILPAD) were included in the analysis. Patients without any immunosuppressive treatment were selected as controls (n = 23). HRCT scans were blinded, randomized, and scored using the Hartman score. Differences between the baseline and follow-up HRCT scans and PFT were analyzed. RESULTS: Treatment with high-dose corticosteroids significantly improved HRCT scores and forced vital capacity. Carbon monoxide diffusion capacity significantly improved in both groups. Of 18 patients, for whom extended follow-up data was available, 13 achieved a long-term, maintenance therapy independent remission. All patients with relapse were retreated with corticosteroids, but only one-fifth of them responded. Two opportunistic infections were found in the corticosteroid treatment group, while overall infection rate was similar between cohorts. CONCLUSIONS: Induction therapy with high-dose corticosteroids improved HRCT scans and PFT results of patients with gl-ILD and achieved long-term remission in 42% of patients. It was not associated with major side effects. Low-dose maintenance therapy provided no benefit and efficacy was poor in relapsing disease.


Assuntos
Doenças Pulmonares Intersticiais , Humanos , Corticosteroides/uso terapêutico , Imunossupressores/uso terapêutico , Pulmão/diagnóstico por imagem , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/etiologia , Estudos Prospectivos , Estudos Retrospectivos
15.
Blood Adv ; 7(9): 1682-1691, 2023 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-36508281

RESUMO

Kaposi sarcoma-associated herpesvirus (KSHV)/human herpesvirus 8-associated multicentric Castleman disease (MCD) is a polyclonal B-cell lymphoproliferative disorder that mainly occurs in immunocompromised hosts. The diagnosis relies on lymph node biopsy demonstrating KSHV-infected cells located in the mantle zone with a marked interfollicular plasma cell infiltration. Infected cells are large cells positive for immunoglobulin M (IgM), λ light chain, and CD38, described initially as infected plasmablasts. We show that IgM+λ+CD38high cells were also detectable in the peripheral blood of 14 out of 18 (78%) patients with active KSHV-MCD and absent in 40 controls. Using immunofluorescence and flow-fluorescence in situ hybridization, we demonstrate that these cells are KSHV infected and express both latent and lytic KSHV transcripts. These KSHV-infected viroblasts (KIVs) harbor a distinct phenotype compared with conventional plasmablasts. We also identified several putative mechanisms of immune escape used by KSHV, because KIVs displayed an overall decrease of costimulatory molecules, with a remarkable lack of CD40 expression and are interleukin-10-producing cells. The identification of this specific and easily accessible KSHV+ circulating population brings new elements to the understanding of KSHV-MCD but also raises new questions that need to be clarified.


Assuntos
Hiperplasia do Linfonodo Gigante , Herpesvirus Humano 8 , Humanos , Herpesvirus Humano 8/genética , Herpesvirus Humano 8/metabolismo , Hiperplasia do Linfonodo Gigante/complicações , Hibridização in Situ Fluorescente , Imunoglobulina M
16.
Ann Pathol ; 43(1): 13-24, 2023 Jan.
Artigo em Francês | MEDLINE | ID: mdl-36192235

RESUMO

The term "Castleman disease" covers a variety of entities that have very different clinical, biological, pathological and physiopathological features. In this issue, we review the characteristics of the unicentric Castleman disease, of the HHV8 associated multicentric Castleman disease and the idiopathic multicentric Castleman disease associated or not with TAFRO syndrome ("thrombocytopenia, anasarca, fever, reticulin myelofibrosis and/or renal insufficiency, organomegaly"). We detail the differential diagnostics of these entities.


Assuntos
Hiperplasia do Linfonodo Gigante , Insuficiência Renal , Trombocitopenia , Humanos , Hiperplasia do Linfonodo Gigante/diagnóstico , Hiperplasia do Linfonodo Gigante/patologia , Trombocitopenia/complicações , Trombocitopenia/patologia , Edema/patologia
17.
J Clin Immunol ; 43(1): 181-191, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36155879

RESUMO

PURPOSE: Hypogammaglobulinemia in a context of lymphoma is usually considered as secondary and prior lymphoma remains an exclusion criterion for a common variable immunodeficiency (CVID) diagnosis. We hypothesized that lymphoma could be the revealing symptom of an underlying primary immunodeficiency (PID), challenging the distinction between primary and secondary hypogammaglobulinemia. METHODS: Within a French cohort of adult patients with hypogammaglobulinemia, patients who developed a lymphoma either during follow-up or before the diagnosis of hypogammaglobulinemia were identified. These two chronology groups were then compared. For patients without previous genetic diagnosis, a targeted next-generation sequencing of 300 PID-associated genes was performed. RESULTS: A total of forty-seven patients had developed 54 distinct lymphomas: non-Hodgkin B cell lymphoma (67%), Hodgkin lymphoma (26%), and T cell lymphoma (7%). In 25 patients, lymphoma developed prior to the diagnosis of hypogammaglobulinemia. In this group of patients, Hodgkin lymphoma was overrepresented compared to the group of patients in whom lymphoma occurred during follow-up (48% versus 9%), whereas MALT lymphoma was absent (0 versus 32%). Despite the histopathological differences, both groups presented with similar characteristics in terms of age at hypogammaglobulinemia diagnosis, consanguinity rate, or severe T cell defect. Overall, genetic analyses identified a molecular diagnosis in 10/47 patients (21%), distributed in both groups and without peculiar gene recurrence. Most of these patients presented with a late onset combined immunodeficiency (LOCID) phenotype. CONCLUSION: Prior or concomitant lymphoma should not be used as an exclusion criteria for CVID diagnosis, and these patients should be investigated accordingly.


Assuntos
Agamaglobulinemia , Imunodeficiência de Variável Comum , Doença de Hodgkin , Humanos , Imunodeficiência de Variável Comum/diagnóstico , Imunodeficiência de Variável Comum/genética , Imunodeficiência de Variável Comum/complicações , Agamaglobulinemia/diagnóstico , Agamaglobulinemia/complicações , Doença de Hodgkin/diagnóstico , Linfócitos T , Fenótipo
18.
Virol J ; 19(1): 172, 2022 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-36316777

RESUMO

Inborn errors of immunity (IEI) are a heterogeneous entity with an increasing number of late diagnoses. Besides infections, inflammatory manifestations are a growing part of the clinical landscape of IEI. These complications are of unknown causes and often lead to the prescription of immunosuppressive agents that worsen the underlying immune defect. We here report the case of an adult patient diagnosed with chronic Human Adenovirus C-1 arthritis in the setting of primary agammaglobulinemia. Metagenomic next-generation sequencing led to the correct diagnosis and high-dose intravenous immunoglobulins resulted in complete recovery. This observation gives new insights into adenoviral immunity and underlines the importance of metagenomics in the diagnosis of inflammatory manifestations in immunocompromised patients.


Assuntos
Adenovírus Humanos , Agamaglobulinemia , Artrite , Adulto , Humanos , Agamaglobulinemia/complicações , Agamaglobulinemia/diagnóstico , Adenoviridae/genética , Artrite/diagnóstico , Artrite/complicações , Imunoglobulinas Intravenosas/uso terapêutico
19.
Am J Cancer Res ; 12(9): 4227-4240, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36225639

RESUMO

Castleman disease (CD) has been reported as a group of poorly understood lymphoproliferative disorders, including unicentric CD (UCD) and idiopathic multicentric CD (iMCD) which are human immunodeficiency virus (HIV) negative and human herpes virus 8 (HHV-8) negative. The clinical and independent prognostic factors of CD remain poorly elucidated. We retrospectively collected the clinical information of 428 patients with HIV and HHV-8 negative CD from 12 large medical centers with 15-year follow-up. We analyzed the clinicopathologic features of 428 patients (248 with UCD and 180 with iMCD) with a median age of 41 years. The histology subtypes were hyaline-vascular (HV) histopathology for 215 patients (56.58%) and plasmacytic (PC) histopathology for 165 patients (43.42%). Most patients with UCD underwent surgical excision, whereas the treatment strategies of patients with iMCD were heterogeneous. The outcome for patients with UCD was better than that for patients with iMCD, 5-year overall survival (OS) rates were 95% and 74%, respectively. In further analysis, a multivariate analysis using a Cox regression model revealed that PC subtype, hepatomegaly and/or splenomegaly, hemoglobin ≤ 80 g/L, and albumin ≤ 30 g/L were independent prognostic factors of CD for OS. The model of iMCD revealed that age > 60 years, hepatomegaly and/or splenomegaly, and hemoglobin ≤ 80 g/L were independent risk factors. In UCD, single-factor analysis identified two significant risk factors: hemoglobin ≤ 100 g/L and albumin ≤ 30 g/L. Our study emphasizes the distinction of clinical characteristics between UCD and iMCD. The importance of poor risk factors of different clinical classifications may direct more precise and appropriate treatment strategies.

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