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1.
Transplant Proc ; 51(9): 3163-3166, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31619339

RESUMO

Posttransplant lymphoproliferative disorder (PTLD) is caused by uncontrolled proliferation of lymphoid cells after a hematopoietic stem cell or solid organ transplant procedure related to the Epstein-Barr virus (EBV) infection. A primary central nervous system (CNS) PTLD (CNS-PTLD) is rare and important to distinguish from an intracranial lesion after transplantation. A 66-year-old man with pulmonary arterial hypertension who underwent living-donor lung transplantation 9 years prior noticed disorientation regarding route and dates. Brain magnetic resonance imaging revealed multiple white matter lesions and fluorodeoxyglucose (FDG) positron emission tomography showed FDG uptake in the brain and skin. CNS-PTLD was diagnosed by craniotomy biopsy and EBV-encoded RNA was positive in in situ hybridization findings and elevated in brain tissue. The treatment was started with immunosuppressant reduction and whole brain radiotherapy. But the condition progressed rapidly over 2 months after the first symptom and the patient was passed away 25 days after hospitalization. CNS-PTLD can occur several years after transplantation and it is necessary to keep in mind to distinguish brain disease because early diagnosis and treatment are important.


Assuntos
Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Transplante de Pulmão , Transtornos Linfoproliferativos/imunologia , Complicações Pós-Operatórias/imunologia , Idoso , Encéfalo/patologia , Infecções por Vírus Epstein-Barr/imunologia , Humanos , Masculino
2.
Isr Med Assoc J ; 21(7): 480-486, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31507125

RESUMO

BACKGROUND: Serum rheumatoid factors are autoantibodies of different isotypes directed against the Fc fraction of immunoglobulin G (IgG) and represent paradigmatic autoantibodies that have been largely used in clinical practice for decades. Traditionally IgG has been associated with rheumatoid arthritis and more recently included also in the classification criteria for SjÓ§gren's syndrome. Researchers have established that rheumatoid factors are positive in a variety of infectious, autoimmune, and neoplastic disorders, thus requiring a comprehensive evaluation of seropositive patients. Of note, hepatitis B and C viruses represent a crossroad that includes the high rheumatoid factor seroprevalence and chronic inflammatory disease, as well as progression to non-Hodgkin's lymphomas. Chronic antigen stimulation is the likely common ground of these processes and rheumatoid factors may represent mere bystanders or drivers of pathology. Mixed cryoglobulinemia and lymphoproliferative disease are prime examples of the deleterious effects of rheumatoid factor-B cell activity, possibly associated with hepatitis B and C. More importantly, they show a clear association in a physiological host response to infection, chronic inflammation, and the slide toward autoimmunity and malignancy. The association between hepatitis B and C infections and the appearance of serum rheumatoid factors is further supported by prevalence data, which support a coexistence of these markers in a significant proportion of cases, with viral infections being frequent causes of rheumatoid factors in patients without a rheumatic condition. We provide a comprehensive overview of the known connections between hepatitis B and C infections and rheumatoid factors.


Assuntos
Hepatite B/imunologia , Hepatite C/imunologia , Fator Reumatoide/imunologia , Autoanticorpos/imunologia , Doenças Autoimunes/imunologia , Autoimunidade/imunologia , Crioglobulinemia/imunologia , Humanos , Transtornos Linfoproliferativos/imunologia , Neoplasias/imunologia , Fator Reumatoide/sangue
3.
Int J Infect Dis ; 88: 31-33, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31398454

RESUMO

A 69-year-old man who underwent cord blood transplantation seven years ago was admitted because of fever, elevated liver enzymes and thrombocytopenia. Bone marrow aspirate revealed hemophagocytic lymphohistiocytosis. Viral capsid antigen (VCA)-immunoglobulin (Ig) G, VCA-IgM, VCA-IgA, Epstein-Barr virus nuclear antigen-IgG, early antigen-diffuse-type and restricted-type (EA-DR) IgG, and EA-DR IgA titers were 2560, <10, 10, 40, 40, and <10, respectively. Real-time polymerase chain reaction assay of peripheral whole blood for Epstein-Barr virus-deoxyribonucleic acid (EBV-DNA) revealed 240,000 copies/µg DNA. Flow cytometric in situ hybridization assay confirmed that EBV-infected cells were NK-cells. Clonality evaluation by Southern blot assay of EBV-DNA terminal repeats proved to be bi-clonal. Accordingly, we made a diagnosis of NK-cell post-transplant lymphoproliferative disease with chronic active EBV infection-like clinical findings (CAEBV-like NK-cell PTLD). Although CAEBV-like PTLD is extremely rare, its prognosis seems to be very poor. The disease should be considered in such patients who present persistent or recurrent infectious mononucleosis-like symptoms after transplantation.


Assuntos
Anticorpos Antivirais/imunologia , Infecções por Vírus Epstein-Barr/diagnóstico , Herpesvirus Humano 4/imunologia , Linfo-Histiocitose Hemofagocítica/diagnóstico , Transtornos Linfoproliferativos/diagnóstico , Idoso , Doença Crônica , DNA Viral/sangue , Infecções por Vírus Epstein-Barr/imunologia , Infecções por Vírus Epstein-Barr/virologia , Humanos , Linfo-Histiocitose Hemofagocítica/imunologia , Linfo-Histiocitose Hemofagocítica/virologia , Transtornos Linfoproliferativos/imunologia , Transtornos Linfoproliferativos/virologia , Masculino , Prognóstico
4.
J Med Case Rep ; 13(1): 223, 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31327318

RESUMO

INTRODUCTION: Post-transplant lymphoproliferative disorder is a serious disorder which occurs post hematopoietic stem cell transplant or solid organ transplantation. T-prolymphocytic leukemia is a T cell type monomorphic post-transplant lymphoproliferative disorder which accounts for only 2% of all mature lymphocytic leukemias in adults over the age of 30. CASE PRESENTATION: A 59-year-old man of Chinese ethnicity presented to our hematology unit with headache, lethargy, and exertional dyspnea for the past 1 month. He underwent an uneventful cadaveric renal transplant 20 years ago for chronic glomerulonephritis-induced end-stage renal disease. He had been on long-term immunosuppressants since then consisting of orally administered prednisolone 10 mg daily and orally administered cyclosporine A 50 mg twice daily. On examination, he was pale with a palpable liver and spleen. He had a functioning renal graft. Marrow flow cytometry confirmed T-prolymphocytic leukemia with lymphocytes expressing CD2, CD3, CD7, CD52, and TCL-1. His human T-cell lymphotropic virus and Epstein-Barr virus serology and deoxyribonucleic acid (DNA) were negative. He was treated with one cycle of cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy to which he failed to respond. In view of his renal allograft, he was not suitable for alemtuzumab due to the risk of nephrotoxicity. He was given orally administered venetoclax but he died on day 17 due to severe auto tumor lysis syndrome. CONCLUSION: The place of immunophenotyping in the diagnosis and treatment of this disorder is of significant importance. More research needs to be carried out to further comprehend the pathophysiology and treatment modalities for this disorder.


Assuntos
Transplante de Rim/efeitos adversos , Transtornos Linfoproliferativos/diagnóstico , Erros de Diagnóstico , Evolução Fatal , Humanos , Imunofenotipagem/métodos , Leucemia Prolinfocítica/diagnóstico , Transtornos Linfoproliferativos/imunologia , Masculino , Pessoa de Meia-Idade
5.
World J Gastroenterol ; 25(26): 3299-3312, 2019 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-31341357

RESUMO

Reactivation of hepatitis B virus (HBV) replication is characterized by increased HBV-DNA serum values of about 1 log or by HBV DNA turning positive if previously undetectable in serum, possibly associated with liver damage and seldom life-threatening. Due to HBV reactivation, hepatitis B surface antigen (HBsAg)-negative/anti-HBc-positive subjects may revert to HBsAg-positive. In patients with hemo-lymphoproliferative disease, the frequency of HBV reactivation depends on the type of lymphoproliferative disorder, the individual's HBV serological status and the potency and duration of immunosuppression. In particular, it occurs in 10%-50% of the HBsAg-positive and in 2%-25% of the HBsAg- negative/anti-HBc-positive, the highest incidences being registered in patients receiving rituximab-based therapy. HBV reactivation can be prevented by accurate screening of patients at risk and by a pharmacological prophylaxis with anti-HBV nucleo(t)sides starting 2-3 wk before the beginning of immunosuppressive treatment and covering the entire period of administration of immunosuppressive drugs and a long subsequent period, the duration of which depends substantially on the degree of immunodepression achieved. Patients with significant HBV replication before immunosuppressive therapy should receive anti-HBV nucleo(t)sides as a long-term (may be life-long) treatment. This review article is mainly directed to doctors engaged every day in the treatment of patients with onco-lymphoproliferative diseases, so that they can broaden their knowledge on HBV infection and on its reactivation induced by the drugs with high immunosuppressive potential that they use in the care of their patients.


Assuntos
Antibioticoprofilaxia/métodos , Antivirais/uso terapêutico , Vírus da Hepatite B/isolamento & purificação , Hepatite B/prevenção & controle , Imunossupressores/efeitos adversos , Transtornos Linfoproliferativos/tratamento farmacológico , DNA Viral/sangue , Hepatite B/imunologia , Hepatite B/virologia , Anticorpos Anti-Hepatite B/sangue , Anticorpos Anti-Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/sangue , Antígenos de Superfície da Hepatite B/imunologia , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Humanos , Transtornos Linfoproliferativos/imunologia , Fatores de Tempo , Ativação Viral/efeitos dos fármacos , Ativação Viral/imunologia
6.
Front Biosci (Landmark Ed) ; 24: 1284-1315, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31136980

RESUMO

Cellular therapies are a rapidly evolving approach to treat cancer in the light of their unique mechanism of action that potentially overcomes drug resistance and induces durable remissions. Modalities of adoptive cell therapy include gene-modified T cells expressing novel T cell receptors or chimeric antigen receptors (CAR) that modify the immune system to recognize tumor cells and carry out potent anti-tumor effector functions. CAR T cells have shown very promising clinical results and several trials are being conducted worldwide to establish their role in cancer treatment. Most successful results have been observed in lymphoproliferative disorders with the use of CD19-directed CAR T cells, which led to their commercial approval by FDA. In this review, we provide a comprehensive overview of the current role of CAR T cell therapies in hematological malignancies and solid tumors, their associated toxicities and potential future developments in the armamentarium for cancer treatment.


Assuntos
Imunoterapia Adotiva/métodos , Neoplasias/terapia , Receptores de Antígenos Quiméricos/imunologia , Linfócitos T/imunologia , Antígenos CD19/imunologia , Antígenos CD19/metabolismo , Neoplasias Hematológicas/imunologia , Neoplasias Hematológicas/patologia , Neoplasias Hematológicas/terapia , Humanos , Imunoterapia Adotiva/tendências , Transtornos Linfoproliferativos/imunologia , Transtornos Linfoproliferativos/patologia , Transtornos Linfoproliferativos/terapia , Neoplasias/imunologia , Neoplasias/patologia , Medicina de Precisão/métodos , Medicina de Precisão/tendências , Receptores de Antígenos Quiméricos/metabolismo , Linfócitos T/metabolismo , Resultado do Tratamento
7.
Eur J Dermatol ; 29(1): 21-28, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30998212

RESUMO

Hydroa vacciniforme (HV) is a cutaneous subset of Epstein-Barr virus (EBV)-associated T/NK lymphoproliferative disorders (LPDs). Our previous case series study clearly showed a clinical spectrum of EBV-associated T/NK LPDs including HV, hypersensitivity to mosquito bites (HMB), chronic active EBV infection (CAEBV), and hemophagocytic lymphohistiocytosis (HLH). Patients with HV are divided into two groups: a benign subtype designated "classic HV" (cHV) and more serious systemic HV (sHV), also called "HV-like LPD" in the 2017 World Health Organization (WHO) classification. Patients with cHV usually have an increased number of EBV-infected γδT cells and patients with sHV without HMB are further classified into two groups: γδT-cell- and αßT-cell-dominant types. Patients with HMB, with or without HV-like eruptions, have an increased number of EBV-infected NK cells in the blood. Patients with cHV and γδT-cell-dominant sHV show a favourable prognosis, but the other subtypes such as αßT-cell-dominant sHV and HMB have a poor prognosis with mortality rates of 11.5 and 3.51 per 100 person-years, respectively. In addition to the clinical subtypes and the dominant lymphocyte subsets, the poor prognostic indicators include onset age over nine years and expression of the reactivation marker, BZLF1 mRNA. No prognostic correlation has been reported for anti-EBV antibody titres or EBV DNA load. The clinical subtypes and their prognostic factors should be considered for therapeutic interventions.


Assuntos
Infecções por Vírus Epstein-Barr/imunologia , Hidroa Vaciniforme/imunologia , Hidroa Vaciniforme/virologia , Transtornos Linfoproliferativos/imunologia , Transtornos Linfoproliferativos/virologia , Dermatopatias Virais/imunologia , Dermatopatias Virais/virologia , Humanos
8.
Int J Mol Sci ; 20(7)2019 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-30970593

RESUMO

The crosstalk between gut microbiota (GM) and the immune system is intense and complex. When dysbiosis occurs, the resulting pro-inflammatory environment can lead to bacterial translocation, systemic immune activation, tissue damage, and cancerogenesis. GM composition seems to impact both the therapeutic activity and the side effects of anticancer treatment; in particular, robust evidence has shown that the GM modulates the response to immunotherapy in patients affected by metastatic melanoma. Despite accumulating knowledge supporting the role of GM composition in lymphomagenesis, unexplored areas still remain. No studies have been designed to investigate GM alteration in patients diagnosed with lymphoproliferative disorders and treated with chemo-free therapies, and the potential association between GM, therapy outcome, and immune-related adverse events has never been analyzed. Additional studies should be considered to create opportunities for a more tailored approach in this set of patients. In this review, we describe the possible role of the GM during chemo-free treatment of lymphoid malignancies.


Assuntos
Disbiose/imunologia , Transtornos Linfoproliferativos/microbiologia , Animais , Disbiose/complicações , Microbioma Gastrointestinal/imunologia , Humanos , Transtornos Linfoproliferativos/imunologia , Microbiota , Medicina de Precisão
10.
J Immunol ; 202(9): 2616-2627, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30910863

RESUMO

Appropriate T cell responses are controlled by strict balance between activatory and inhibitory pathways downstream of TCR. Although mice or humans with impaired TCR signaling develop autoimmunity, the precise molecular mechanisms linking reduced TCR signaling to autoimmunity are not fully understood. Engagement of TCR activates Ca2+ signaling mainly through store-operated Ca2+ entry activated by stromal interaction molecule (Stim) 1 and Stim2. Despite defective T cell activation, mice deficient in both Stim1 and Stim2 in T cells (conditional double knockout [cDKO]) developed lymphoproliferative disorders and skin inflammation with a concomitant increase in serum IgG1 and IgE levels. In cDKO mice, follicular helper T (Tfh) cells were dramatically increased in number, and they produced IL-4 spontaneously. These inflammatory symptoms were abolished by the deletion of IL-4 in cDKO mice. Tfh development and inflammatory symptoms in cDKO mice were abrogated by further deletion of NFAT2 in T cells. These findings suggest that Tfh cells spontaneously developed in the absence of Ca2+ signaling and caused unregulated type 2 responses.


Assuntos
Diabetes Mellitus Experimental/imunologia , Diabetes Mellitus Tipo 2/imunologia , Doenças do Sistema Imunitário/imunologia , Molécula 1 de Interação Estromal/deficiência , Molécula 2 de Interação Estromal/deficiência , Linfócitos T Auxiliares-Indutores/imunologia , Animais , Sinalização do Cálcio/genética , Sinalização do Cálcio/imunologia , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patologia , Doenças do Sistema Imunitário/genética , Doenças do Sistema Imunitário/patologia , Imunoglobulina E/genética , Imunoglobulina E/imunologia , Imunoglobulina G/genética , Imunoglobulina G/imunologia , Interleucina-4/genética , Interleucina-4/imunologia , Transtornos Linfoproliferativos/genética , Transtornos Linfoproliferativos/imunologia , Transtornos Linfoproliferativos/patologia , Camundongos , Camundongos Knockout , Fatores de Transcrição NFATC/genética , Fatores de Transcrição NFATC/imunologia , Dermatopatias/genética , Dermatopatias/imunologia , Dermatopatias/patologia , Linfócitos T Auxiliares-Indutores/patologia
11.
Immunol Rev ; 288(1): 198-213, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30874349

RESUMO

Surface expression of a functional B cell antigen receptor (BCR) is essential for the survival and proliferation of mature B cells. Most types of B-cell lymphoproliferative disorders retain surface BCR expression, including B-cell non-Hodgkin lymphomas (B-NHL) and chronic lymphocytic leukemia (CLL). Targeting BCR effectors in B-NHL cell lines in vitro has indicated that this signaling axis is crucial for malignant B cell growth. This has led to the development of inhibitors of BCR signaling, which are currently used for the treatment of CLL and several B-NHL subtypes. Recent studies based on conditional BCR inactivation in a MYC-driven mouse B-cell lymphoma model have revisited the role of the BCR in MYC-expressing tumor B cells. Indeed, lymphoma cells losing BCR expression continue to grow unless subjected to competition with their BCR-expressing counterparts, which causes their elimination. Here, we discuss the molecular nature of the fitness signal delivered by the BCR to MYC-expressing malignant B cells, ensuring their preferential persistence within a rapidly expanding tumor population. We also review growing evidence of Ig-negative cases belonging to several B-NHL subtypes and CLL, and discuss the clinical implications of these findings in relation to an emerging picture of clinical resistances to anti-BCR therapies.


Assuntos
Linfócitos B/imunologia , Neoplasias Hematológicas/imunologia , Transtornos Linfoproliferativos/imunologia , Receptores de Antígenos de Linfócitos B/metabolismo , Microambiente Tumoral/imunologia , Animais , Humanos , Camundongos , Fenótipo , Receptores de Antígenos de Linfócitos B/genética , Transdução de Sinais
12.
Cancer Treat Res ; 176: 249-268, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30596222

RESUMO

Primary cutaneous CD30-positive lymphoproliferative disorders (CD30+ LPD) encompass lymphomatoid papulosis (LyP), primary cutaneous anaplastic large cell lymphoma (pcALCL), and borderline lesions [1]. CD30+ LPD are the second most common cutaneous T-cell lymphomas (CTCL) after mycosis fungoides (MF) and represent approximately 25% of all CTCL cases [2]. Their common phenotypic hallmark is an expression of the CD30 antigen, a cytokine receptor belonging to the tumor necrosis factor (TNF) receptor superfamily. Both LyP and pcALCL show numerous clinical, histological and immunophenotypic variants, and generally have an indolent course with a favorable prognosis. Overlapping features of LyP and pcALCL with other CD30+ T-cell lymphomas, inflammatory, and/or infectious conditions emphasize the importance of careful clinicopathologic correlation and staging.


Assuntos
Papulose Linfomatoide , Transtornos Linfoproliferativos , Micose Fungoide , Neoplasias Cutâneas , Adulto , Humanos , Imunofenotipagem , Antígeno Ki-1 , Papulose Linfomatoide/diagnóstico , Papulose Linfomatoide/terapia , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/imunologia , Transtornos Linfoproliferativos/terapia , Micose Fungoide/diagnóstico , Micose Fungoide/terapia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/terapia
13.
Eur J Dermatol ; 29(1): 39-44, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30670369

RESUMO

BACKGROUND: CD8+ CD30+ primary cutaneous T-cell lymphomas (PCTCL) are rare entities with overlapping pathological features and variable outcome. OBJECTIVES: We sought to highlight the importance of correlation between pathological findings and clinical presentation for correct classification of the disease. MATERIALS & METHODS: Two cases of CD8+ CD30+ PCTCL were investigated. The first patient presented with a multiple necro-erythematous lesion of the limb and the second with a papulo-necrotic lesion of the eyelid. RESULTS: Despite a different clinical presentation, pathological findings were similar in both cases. Clinico-pathological correlation led to a diagnosis of primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma in the first case and primary cutaneous anaplastic large-cell lymphoma in the second. The first patient died shortly after diagnosis and the second is alive without recurrence. CONCLUSIONS: Clinico-pathological correlation is essential for the correct identification of these rare diseases.


Assuntos
Antígenos CD8/imunologia , Antígeno Ki-1/imunologia , Linfoma/patologia , Transtornos Linfoproliferativos/patologia , Neoplasias Cutâneas/patologia , Idoso , Evolução Fatal , Feminino , Humanos , Linfoma/imunologia , Transtornos Linfoproliferativos/imunologia , Pessoa de Meia-Idade , Prognóstico , Neoplasias Cutâneas/imunologia
14.
Transplant Proc ; 51(1): 194-197, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30655153

RESUMO

BACKGROUND: Solid organ transplantation is associated with a higher risk of Epstein-Barr virus (EBV)-related lymphoproliferative disease due to immunosuppressive regimen. Little evidence is currently available on post-transplant lymphoproliferative disorders (PTLDs) in the lung transplant (LuTx) setting, particularly in cystic fibrosis (CF) recipients. METHODS: We retrospectively analyzed all the cases of PTLDs that occurred in our LuTx center between January 2015 and December 2017. We reviewed clinical and radiologic data, donor and recipient EBV serostatus, immunosuppressive therapy, histologic data, and follow-up of these patients. RESULTS: A total of 77 LuTxs were performed at our center in the study period; 39 (50.6%) patients had CF; 4 developed EBV-related PTLDs. They were all young (17-26 years) CF patients with high serum EBV DNA load. Disease onset was within the first 3 months after LuTx. In 3 cases presentation was associated with fever and infection-like symptoms, whereas in 1 case radiologic suspicion arose unexpectedly from a CT scan performed for different clinical reasons. Diagnosis was reached through lung biopsy in all cases. All patients received rituximab, cyclophosphamide, doxorubicin hydrochloride (hydroxydaunomycin), vincristine sulfate (Oncovin), and prednisone with variable response and complications. CONCLUSION: In our experience, the early development of EBV-related PTLD was a highly aggressive, life-threatening condition, which exclusively affected young CF patients in the early post-transplant period. The rate of this complication was relatively high in our population. Diagnosis with lung biopsy is crucial in all suspected cases and regular monitoring of EBV DNA levels is of utmost importance given the high correlation with PTLDs in patients at increased risk.


Assuntos
Fibrose Cística , Infecções por Vírus Epstein-Barr , Transplante de Pulmão/efeitos adversos , Transtornos Linfoproliferativos/virologia , Adolescente , Adulto , Fibrose Cística/cirurgia , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/imunologia , Feminino , Herpesvirus Humano 4 , Humanos , Imunossupressão/efeitos adversos , Imunossupressores/uso terapêutico , Transtornos Linfoproliferativos/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Transplantados
15.
J Allergy Clin Immunol ; 143(1): 266-275, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29778502

RESUMO

BACKGROUND: Activated phosphatidylinositol-3-OH kinase δ syndrome type 1 (APDS1) is a recently described primary immunodeficiency syndrome characterized by recurrent respiratory tract infections, lymphoid hyperplasia, and Herpesviridae infections caused by germline gain-of-function mutations of PIK3CD. Hematopoietic stem cell transplantation (HSCT) can be considered to ameliorate progressive immunodeficiency and associated malignancy, but appropriate indications, methods, and outcomes of HSCT for APDS1 remain undefined. OBJECTIVE: Our objective was to analyze the clinical manifestations, laboratory findings, prognosis, and treatment of APDS1 and explore appropriate indications and methods of HSCT. METHODS: We reviewed retrospectively the medical records of cohorts undergoing HSCT at collaborating facilities. RESULTS: Thirty-year overall survival was 86.1%, but event-free survival was 39.6%. Life-threatening events, such as severe infections or lymphoproliferation, were frequent in childhood and adolescence and were common indications for HSCT. Nine patients underwent HSCT with fludarabine-based reduced-intensity conditioning. Seven patients survived after frequent adverse complications and engraftment failure. Most symptoms improved after HSCT. CONCLUSION: Patients with APDS1 showed variable clinical manifestations. Life-threatening progressive combined immunodeficiency and massive lymphoproliferation were common indications for HSCT. Fludarabine-based reduced-intensity conditioning-HSCT ameliorated clinical symptoms, but transplantation-related complications were frequent, including graft failure.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Síndromes de Imunodeficiência , Transtornos Linfoproliferativos , Adolescente , Adulto , Aloenxertos , Criança , Pré-Escolar , Classe I de Fosfatidilinositol 3-Quinases/imunologia , Intervalo Livre de Doença , Feminino , Humanos , Síndromes de Imunodeficiência/imunologia , Síndromes de Imunodeficiência/mortalidade , Síndromes de Imunodeficiência/patologia , Síndromes de Imunodeficiência/terapia , Transtornos Linfoproliferativos/imunologia , Transtornos Linfoproliferativos/mortalidade , Transtornos Linfoproliferativos/patologia , Transtornos Linfoproliferativos/terapia , Masculino , Taxa de Sobrevida
18.
Int J Surg Pathol ; 27(1): 94-97, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29944019

RESUMO

A 56-year-old man, who received deceased kidney transplant 20 years ago, presented with an enlarged submandibular lymph node. Histologic examination revealed nodal marginal zone lymphoma in which the neoplastic lymphoid cells showed diffuse positivity for Epstein-Barr virus early RNA by in situ hybridization. Systemic lymphoma workup showed stage I disease. The tumor was managed as a posttransplant lymphoproliferative disorder and the immunosuppression was modified. There was no evidence of lymphoma at follow-up 6 years after excision alone. This case supports the inclusion of Epstein-Barr virus-positive nodal marginal zone lymphoma as a form of monomorphic B-cell lymphoproliferative disorder, in line with the status of its extranodal mucosa-associated lymphoid tissue lymphoma counterpart.


Assuntos
Infecções por Vírus Epstein-Barr/imunologia , Hospedeiro Imunocomprometido , Transplante de Rim/efeitos adversos , Linfonodos/patologia , Linfoma de Zona Marginal Tipo Células B/imunologia , Herpesvirus Humano 4 , Humanos , Linfoma de Zona Marginal Tipo Células B/virologia , Transtornos Linfoproliferativos/imunologia , Transtornos Linfoproliferativos/virologia , Masculino , Pessoa de Meia-Idade
20.
Colomb Med (Cali) ; 49(3): 236-243, 2018 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-30410199

RESUMO

Bi-allelic mutations in LRBA (from Lipopolysaccharide-responsive and beige-like anchor protein) result in a primary immunodeficiency with clinical features ranging from hypogammaglobulinemia and lymphoproliferative syndrome to inflammatory bowel disease and heterogeneous autoimmune manifestations. LRBA deficiency has been shown to affect vesicular trafficking, autophagy and apoptosis, which may lead to alterations of several molecules and processes that play key roles for immunity. In this review, we will discuss the relationship of LRBA with the endovesicular system in the context of receptor trafficking, autophagy and apoptosis. Since these mechanisms of homeostasis are inherent to all living cells and not only limited to the immune system and also, because they are involved in physiological as well as pathological processes such as embryogenesis or tumoral transformation, we envisage advancing in the identification of potential pharmacological agents to manipulate these processes.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Membrana Celular/metabolismo , Síndromes de Imunodeficiência/genética , Agamaglobulinemia/genética , Agamaglobulinemia/imunologia , Animais , Apoptose/fisiologia , Autofagia/fisiologia , Humanos , Síndromes de Imunodeficiência/imunologia , Síndromes de Imunodeficiência/fisiopatologia , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/imunologia , Transtornos Linfoproliferativos/genética , Transtornos Linfoproliferativos/imunologia , Mutação
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