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1.
Clin Nucl Med ; 44(12): 949-955, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31689275

RESUMO

INTRODUCTION: Autoimmune lymphoproliferative syndrome (ALPS) is a rare immune dysregulatory condition, usually presenting in childhood with massive lymphadenopathy, splenomegaly, and an increased incidence of lymphoma. Methods to differentiate between benign ALPS adenopathy and lymphoma are needed. To this end, we evaluated the usefulness of FDG PET. METHODS: We prospectively evaluated 76 ALPS/ALPS-like patients including FS-7-associated surface antigen (FAS) germline mutation with (n = 4) and without lymphoma (n = 50), FAS-somatic (n = 6), ALPS-unknown (n = 6), and others (n = 10) who underwent FDG PET. Uptakes in 14 nodal sites, liver, and spleen were determined. RESULTS: In 76 ALPS patients, FDG PET showed uptake in multiple nodal sites in all but 1 patient. The highest SUVmax values in FAS mutation without lymphoma, FAS mutation with lymphoma, FAS somatic, ALPS-unknown, and other genetic mutations were a median (range) 9.2 (4.3-25), 16.2 (10.7-37.2), 7.6 (4.6-18.1), 11.5 (4.8-17.2), and 5.5 (0-15.3), respectively. Differences between uptake in the FAS group with and without lymphoma were statistically significant, but overlapped, making discrimination between individuals with/without lymphoma impossible. The spleen:liver uptake ratio was greater than 1 in 82% of patients. CONCLUSIONS: While statistically significant differences were observed in FAS mutation ALPS with and without lymphoma, the significant overlap in FDG uptake and visual appearance in many patients prevents discrimination between patients with and without lymphoma. Similar patterns of FDG biodistribution were noted between the various ALPS subgroups.


Assuntos
Síndrome Linfoproliferativa Autoimune/diagnóstico por imagem , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons , Adolescente , Adulto , Síndrome Linfoproliferativa Autoimune/complicações , Síndrome Linfoproliferativa Autoimune/genética , Síndrome Linfoproliferativa Autoimune/metabolismo , Criança , Pré-Escolar , Feminino , Fluordesoxiglucose F18/farmacocinética , Humanos , Linfoma/complicações , Masculino , Mutação , Esplenomegalia/complicações , Distribuição Tecidual , Adulto Jovem , Receptor fas/genética
2.
Clin Exp Dermatol ; 43(8): 913-916, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29908030

RESUMO

Ras-associated autoimmune leucoproliferative disorder (RALD) is a nonmalignant syndrome associated with somatic KRAS mutations. We report a patient with RALD and cutaneous lesions, the first such case reported, to our knowledge. An 8-year-old boy presented with erythematous plaques on his face and body, along with lymphadenopathies and spleen enlargement without systemic symptoms. An increased number of monocytes were found in skin biopsy, peripheral blood and bone marrow (BM). Juvenile myelomonocytic leukaemia (JMML) was suspected. Genetic study using peripheral blood showed no mutations in the KRAS, PTPN11, NRAS, CBL or BCR-ABL genes, but bone marrow analysis revealed a mutation (p-G12S/c.34 G>A) in the KRAS gene. The karyotype was normal. No KRAS mutations were found using molecular analysis of saliva. The diagnosis of RALD was proposed. The differential diagnosis between RALD and JMML is challenging because there are no established criteria to differentiate between them. The clinical course of RALD is uncertain, so long-term follow-up is recommended.


Assuntos
Síndrome Linfoproliferativa Autoimune/diagnóstico , Proteínas Proto-Oncogênicas p21(ras) , Dermatopatias/etiologia , Pele/patologia , Síndrome Linfoproliferativa Autoimune/complicações , Síndrome Linfoproliferativa Autoimune/genética , Síndrome Linfoproliferativa Autoimune/patologia , Biópsia , Criança , Análise Mutacional de DNA , Diagnóstico Diferencial , Genes ras , Humanos , Leucemia Mielomonocítica Juvenil/diagnóstico , Masculino , Mutação , Proteínas Proto-Oncogênicas p21(ras)/genética
6.
Ocul Immunol Inflamm ; 25(5): 703-709, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27229379

RESUMO

PURPOSE: To describe inflammatory ocular findings in patients with autoimmune lymphoproliferative syndrome (ALPS). METHODS: A retrospective review of medical records for ALPS patients seen at the National Eye Institute between 2003 and 2013. RESULTS: A total of 29 ALPS patients previously referred for ocular or visual symptoms or with a history of prolonged corticosteroid use, were identified. Mean age was 20 years (range: 4-66 years). The majority were male (n = 21, 72.4%) and Caucasian (n = 24, 82.8%). Ten (34.5%) had abnormal ocular findings, the most common of which was an ocular inflammatory disorder (n = 4, 13.8%). Uveitis was seen in two patients with ALPS-FAS and one with ALPS-U, all of whom required long-term systemic immunosuppression. One patient with ALPS-FAS had a history of optic neuritis. CONCLUSIONS: ALPS can have intraocular inflammatory manifestations that require routine follow-up to ensure appropriate and timely treatment of intraocular disease. Long-term immunosuppression may be needed for patients with ALPS-associated uveitis.


Assuntos
Síndrome Linfoproliferativa Autoimune/complicações , Neurite Óptica/etiologia , Uveíte/etiologia , Adolescente , Adulto , Idoso , Síndrome Linfoproliferativa Autoimune/diagnóstico , Criança , Pré-Escolar , Feminino , Humanos , Inflamação/diagnóstico , Inflamação/etiologia , Masculino , Pessoa de Meia-Idade , Neurite Óptica/diagnóstico , Estudos Retrospectivos , Uveíte/diagnóstico , Acuidade Visual/fisiologia , Adulto Jovem
7.
Ann Am Thorac Soc ; 13(8): 1279-88, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27268092

RESUMO

RATIONALE: Patients with autoimmune lymphoproliferative syndrome (ALPS), a disorder of impaired lymphocyte apoptosis, often undergo radiographic chest imaging to evaluate the presence and progression of lymphadenopathy. These images often lead to parenchymal and interstitial lung findings of unclear clinical significance. OBJECTIVES: To characterize the pulmonary findings associated with ALPS and to determine if lung abnormalities present on computed tomographic (CT) imaging of the chest correlate with infection or functional status. METHODS: Patients with lung abnormalities observed on chest CT scans were retrospectively identified from the largest known ALPS cohort. Lung computed tomography findings were characterized and correlated with medical records, bronchoalveolar lavage, biopsy, and lung function. MEASUREMENTS AND MAIN RESULTS: CT images of the chest were available for 234 (92%) of 255 of the patients with ALPS. Among patients with a chest CT scan, 18 (8%) had lung abnormalities on at least one CT scan. Fourteen (78%) of those 18 were classified as having ALPS with undetermined genetic defect. Most patients (n = 16 [89%]) with lung lesions were asymptomatic. However, two (11%) of them had associated dyspnea and/or desaturation on room air. Immunosuppressive treatment was administered for lung disease in nine (50%) cases, and all were followed for clinical outcomes. CONCLUSIONS: Patients with ALPS can develop chest radiographic findings with protean manifestations that may mimic pulmonary infection. Management of patients with ALPS with incidental lung lesions identified by CT imaging should be guided by clinical correlation. Symptomatic patients may benefit from chest CT imaging and lesion biopsy to exclude infection and guide administration of immunosuppressive therapy.


Assuntos
Síndrome Linfoproliferativa Autoimune/complicações , Pneumopatias/diagnóstico por imagem , Pneumopatias/epidemiologia , Pulmão/patologia , Adolescente , Adulto , Doenças Assintomáticas , Criança , Pré-Escolar , Bases de Dados Factuais , Feminino , Humanos , Imunossupressores/uso terapêutico , Lactente , Pneumopatias/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Testes de Função Respiratória , Estudos Retrospectivos , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X , Estados Unidos , Adulto Jovem
8.
Indian J Pediatr ; 82(12): 1172-4, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25972287

RESUMO

Autoimmune Lymphoproliferative Syndrome (ALPS) is a rare inherited disorder of abnormal lymphocyte apoptosis, leading to chronic lymphoproliferation. It presents as lymphadenopathy, hepatosplenomegaly and autoimmune phenomena. Pure red cell aplasia is characterized by normochromic normocytic anemia, reticulocytopenia, and absence of erythroblasts from a normal bone marrow. Only few lymphoproliferative disorders have been associated with erythroid aplasia. The authors are reporting a case of ALPS associated with red cell aplasia in a 7-y-old girl.


Assuntos
Síndrome Linfoproliferativa Autoimune , Hepatomegalia , Imunoglobulinas Intravenosas/administração & dosagem , Linfadenopatia , Prednisolona/administração & dosagem , Aplasia Pura de Série Vermelha , Esplenomegalia , Síndrome Linfoproliferativa Autoimune/sangue , Síndrome Linfoproliferativa Autoimune/complicações , Síndrome Linfoproliferativa Autoimune/diagnóstico , Síndrome Linfoproliferativa Autoimune/tratamento farmacológico , Síndrome Linfoproliferativa Autoimune/fisiopatologia , Biópsia por Agulha Fina/métodos , Criança , Diagnóstico Diferencial , Esquema de Medicação , Feminino , Glucocorticoides/administração & dosagem , Testes Hematológicos/métodos , Hepatomegalia/diagnóstico por imagem , Hepatomegalia/etiologia , Humanos , Fatores Imunológicos/administração & dosagem , Testes Imunológicos/métodos , Linfadenopatia/diagnóstico por imagem , Linfadenopatia/etiologia , Aplasia Pura de Série Vermelha/diagnóstico , Aplasia Pura de Série Vermelha/etiologia , Esplenomegalia/diagnóstico por imagem , Esplenomegalia/etiologia , Resultado do Tratamento
9.
J Clin Immunol ; 35(4): 348-55, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25814141

RESUMO

Caspase-8 deficiency (CED) was originally described in 2002 in two pediatric patients presenting with clinical manifestations resembling autoimmune lymphoproliferative syndrome (ALPS) accompanied by infections, and T, B and NK cell defects. Since then, no new CED patients were published. Here we report two adult siblings (Pt1 and Pt2) presenting in their late thirties with pulmonary hypertension leading to lung transplant (Pt1), and a complex neurological disease leading to multiple cranial nerves palsies (Pt2) as their main manifestations. A thorough clinical and immunological evaluation was performed at the Primary Immunodeficiency Clinic at NIH, followed by whole exome sequencing. The patients had multiorgan lymphocytic infiltration and granulomas, as well as clinical signs of immune deficiency/ immune dysregulation. Both siblings carried homozygous mutations in CASP8, c.1096C > T, p.248R > W. This was the same mutation described on the previously published CED patients, to whom these new patients were likely distantly related. We report two new CED patients presenting during adulthood with life-threatening end-organ lymphocyte infiltrates affecting the lungs, liver, spleen, bone marrow and central nervous system. This phenotype broadens the clinical spectrum of manifestations associated with this disease and warrants the search of CASP8 mutations in other cohorts of patients.


Assuntos
Síndrome Linfoproliferativa Autoimune/diagnóstico , Síndrome Linfoproliferativa Autoimune/genética , Caspase 8/genética , Granuloma/patologia , Mutação , Irmãos , Adulto , Síndrome Linfoproliferativa Autoimune/complicações , Biópsia , Citocinas/biossíntese , Exoma , Feminino , Hepatomegalia/diagnóstico , Sequenciamento de Nucleotídeos em Larga Escala , Homozigoto , Humanos , Imunofenotipagem , Pulmão/patologia , Linfócitos/imunologia , Linfócitos/metabolismo , Masculino , Esplenomegalia/diagnóstico , Tomografia Computadorizada por Raios X
10.
Curr Allergy Asthma Rep ; 14(9): 462, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25086580

RESUMO

Autoimmune lymphoproliferative syndrome (ALPS) is characterized by immune dysregulation due to a defect in lymphocyte apoptosis. The clinical manifestations may be noted in multiple family members and include lymphadenopathy, splenomegaly, increased risk of lymphoma, and autoimmune disease, which typically involves hematopoietic cell lines manifesting as multilineage cytopenias. Since the disease was first characterized in the early 1990s, there have been many advances in the diagnosis and management of this syndrome. The inherited genetic defect of many ALPS patients has involved (FAS) pathway signaling proteins, but there remain those patients who carry undefined genetic defects. Despite ALPS having historically been considered a primary immune defect presenting in early childhood, adult onset presentation is increasingly becoming recognized and more so in genetically undefined patients and those with somatic FAS mutations. Thus, future research may identify novel pathways and/or regulatory proteins important in lymphocyte activation and apoptosis.


Assuntos
Síndrome Linfoproliferativa Autoimune , Imunossupressores/uso terapêutico , Receptor fas/genética , Anti-Inflamatórios/uso terapêutico , Apoptose , Síndrome Linfoproliferativa Autoimune/complicações , Síndrome Linfoproliferativa Autoimune/diagnóstico , Síndrome Linfoproliferativa Autoimune/tratamento farmacológico , Síndrome Linfoproliferativa Autoimune/genética , Diagnóstico Diferencial , Humanos , Ativação Linfocitária/imunologia , Transdução de Sinais , Esplenomegalia/etiologia , Linfócitos T/imunologia , Receptor fas/fisiologia
11.
Pediatrics ; 132(5): e1440-4, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24101757

RESUMO

Autoimmune lymphoproliferative syndrome (ALPS) is a rare inherited disorder of apoptosis, most commonly due to mutations in the FAS (TNFRSF6) gene. It presents with chronic lymphadenopathy, splenomegaly, and symptomatic multilineage cytopenias in an otherwise healthy child. Unfortunately, these clinical findings are also noted in other childhood lymphoproliferative conditions, such as leukemia, lymphoma, and hemophagocytic lymphohistiocytosis, which can confound the diagnosis. This report describes a 6-year-old girl with symptoms misdiagnosed as hemophagocytic lymphohistiocytosis and treated with chemotherapy before the recognition that her symptoms and laboratory values were consistent with a somatic FAS mutation leading to ALPS. This case should alert pediatricians to include ALPS in the differential diagnosis of a child with lymphadenopathy, splenomegaly, and cytopenias; obtain discriminating screening laboratory biomarkers, such as serum vitamin B-12 and ferritin levels; and, in the setting of a highly suspicious clinical scenario for ALPS, pursue testing for somatic FAS mutations when germ-line mutation testing is negative.


Assuntos
Síndrome Linfoproliferativa Autoimune/diagnóstico , Erros de Diagnóstico , Linfo-Histiocitose Hemofagocítica/diagnóstico , Síndrome Linfoproliferativa Autoimune/complicações , Feminino , Humanos , Lactente , Linfo-Histiocitose Hemofagocítica/complicações
13.
J Pediatr Hematol Oncol ; 35(5): e187-9, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23588339

RESUMO

Autoimmune lymphoproliferative syndrome (ALPS) is caused by a nonmalignant defective Fas-mediated apoptosis. The main clinical manifestations are chronic lymphadenopathy, splenomegaly, and autoimmune cytopenia. Most patients with ALPS have a FAS germline mutation. ALPS has occasionally been associated with glomerulonephritis and we present the first report of tubulointerstitial nephritis associated with probable ALPS. A 5-year-old girl presented with fever, vomiting, hypertension, and azotemia. No autoantibodies, viral, or streptococcal antibodies were detected. A renal biopsy showed small-vessel vasculitis with normal glomeruli and inflammation in the interstitium. The patient responded to prednisolone treatment and obtained a full renal recovery. Symptoms of connective tissue disorder supervened and after the development of more pronounced splenomegaly, a diagnosis of ALPS was confirmed.


Assuntos
Síndrome Linfoproliferativa Autoimune/complicações , Nefrite Intersticial/etiologia , Anti-Inflamatórios/uso terapêutico , Síndrome Linfoproliferativa Autoimune/patologia , Pré-Escolar , Feminino , Humanos , Nefrite Intersticial/tratamento farmacológico , Nefrite Intersticial/patologia , Prednisona/uso terapêutico
14.
Blood ; 121(16): 3117-25, 2013 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-23430113

RESUMO

Defective lymphocyte apoptosis results in chronic lymphadenopathy and/or splenomegaly associated with autoimmune phenomena. The prototype for human apoptosis disorders is the autoimmune lymphoproliferative syndrome (ALPS), which is caused by mutations in the FAS apoptotic pathway. Recently, patients with an ALPS-like disease called RAS-associated autoimmune leukoproliferative disorder, in which somatic mutations in NRAS or KRAS are found, also were described. Despite this progress, many patients with ALPS-like disease remain undefined genetically. We identified a homozygous, loss-of-function mutation in PRKCD (PKCδ) in a patient who presented with chronic lymphadenopathy, splenomegaly, autoantibodies, elevated immunoglobulins and natural killer dysfunction associated with chronic, low-grade Epstein-Barr virus infection. This mutation markedly decreased protein expression and resulted in ex vivo B-cell hyperproliferation, a phenotype similar to that of the PKCδ knockout mouse. Lymph nodes showed intense follicular hyperplasia, also mirroring the mouse model. Immunophenotyping of circulating lymphocytes demonstrated expansion of CD5+CD20+ B cells. Knockdown of PKCδ in normal mononuclear cells recapitulated the B-cell hyperproliferative phenotype in vitro. Reconstitution of PKCδ in patient-derived EBV-transformed B-cell lines partially restored phorbol-12-myristate-13-acetate-induced cell death. In summary, homozygous PRKCD mutation results in B-cell hyperproliferation and defective apoptosis with consequent lymphocyte accumulation and autoantibody production in humans, and disrupts natural killer cell function.


Assuntos
Síndrome Linfoproliferativa Autoimune/genética , Linfócitos B/patologia , Mutação , Proteína Quinase C-delta/genética , Animais , Apoptose , Síndrome Linfoproliferativa Autoimune/complicações , Síndrome Linfoproliferativa Autoimune/imunologia , Síndrome Linfoproliferativa Autoimune/patologia , Linfócitos B/imunologia , Linfócitos B/metabolismo , Linhagem Celular , Proliferação de Células , Criança , Citocinas/imunologia , Infecções por Vírus Epstein-Barr/complicações , Expressão Gênica , Técnicas de Silenciamento de Genes , Herpesvirus Humano 4/isolamento & purificação , Homozigoto , Humanos , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/patologia , Linfonodos/imunologia , Linfonodos/patologia , Doenças Linfáticas/complicações , Masculino , Camundongos , Proteína Quinase C-delta/imunologia , Esplenomegalia/complicações
15.
Rev Med Interne ; 34(3): 148-53, 2013 Mar.
Artigo em Francês | MEDLINE | ID: mdl-22703729

RESUMO

Although primary immunodeficiencies (PID) are typically marked by increased susceptibility to infections, autoimmune manifestations have increasingly been recognized as an important component of several forms of PID. Here, we discuss two forms of PID in which autoimmune cytopenias are particularly common and may be the first manifestation of the disease in adults: autoimmune lymphoproliferative syndrome (ALPS) and common variable immunodeficiency (CVID). Approximately one fifth of patients with CVID develop autoimmune diseases, and immune thrombocytopenic purpura (ITP) and autoimmune hemolytic anemia (AHA) are the most common. Since autoimmune cytopenias frequently precede the diagnosis of CVID, testing for immunoglobulin levels should be performed in patients diagnosed with AITP and AHA. Patients with CVID in association with autoimmune cytopenias have a "particular phenotype" with lower susceptibility to infection and higher susceptibility to autoimmune manifestations and, for patients with AHA, a more frequent development of splenomegaly and lymphoma. Corticosteroids and high doses of intravenous immunoglobulins (IVIg) seem to have the same efficacy as in idiopathic AITP and AHA. Splenectomy and rituximab are as effective as in idiopathic autoimmune cytopenias but are associated with an increased risk of severe infection and should, in our opinion, be considered only for those rare patients with "refractory diseases". The course and outcome of autoimmune cytopenias is not affected by supportive IVIg therapy. Autoimmune destruction of blood cells affects over 70% of ALPS patients. The median age of first presentation is 24 months of age, but with increasing awareness of this condition, adults with autoimmune cytopenias are now being diagnosed more frequently. Testing for ALPS should therefore be considered in young adults with unexplained Evan's syndrome. Patients usually respond to immunosuppressive medications, including corticosteroids. Unlike many patients with idiopathic autoimmune cytopenias, the cytopenias in patients with ALPS typically do not respond to IVIg. After corticosteroids, the immunosuppressive drug that is the most studied in ALPS patients is mycophenolate mofetyl. Rituximab and splenectomy are relatively contraindicated in ALPS because of an increase risk of severe infection and should be reserved for patients who fail all other therapies.


Assuntos
Síndrome Linfoproliferativa Autoimune/complicações , Imunodeficiência de Variável Comum/complicações , Corticosteroides/uso terapêutico , Anemia Hemolítica Autoimune/complicações , Anemia Hemolítica Autoimune/tratamento farmacológico , Síndrome Linfoproliferativa Autoimune/tratamento farmacológico , Imunodeficiência de Variável Comum/tratamento farmacológico , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Imunossupressores/uso terapêutico , Púrpura Trombocitopênica Idiopática/complicações , Púrpura Trombocitopênica Idiopática/tratamento farmacológico
18.
Blood ; 119(15): 3495-502, 2012 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-22343728

RESUMO

In addition to its proapoptotic function, caspase-8 is also important for several other processes, including suppressing necroptosis, cell migration, and immune cell survival. In the present study, we report that the loss of caspase-8 in B lymphocytes leads to B-cell malignancies and that the risk for these tumors is further enhanced in the absence of p53. We also report that deficiency of caspase-8 results in impaired cytokinesis and that casp8(-/-) lymphomas display remarkably elevated levels of chromosomal aberrations. Our data support an important role for caspase-8 in the maintenance of genomic integrity and highlight its tumor-suppressive function.


Assuntos
Caspase 8/fisiologia , Instabilidade Cromossômica/genética , Linfoma de Células B/genética , Células 3T3 , Animais , Síndrome Linfoproliferativa Autoimune/complicações , Síndrome Linfoproliferativa Autoimune/genética , Síndrome Linfoproliferativa Autoimune/imunologia , Síndrome Linfoproliferativa Autoimune/patologia , Linfócitos B/imunologia , Linfócitos B/metabolismo , Linfócitos B/fisiologia , Caspase 8/genética , Células Cultivadas , Regulação para Baixo/genética , Regulação para Baixo/imunologia , Genes p53/fisiologia , Predisposição Genética para Doença , Linfoma de Células B/etiologia , Linfoma de Células B/mortalidade , Linfoma de Células B/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Análise de Sobrevida
20.
Blood ; 118(18): 4798-807, 2011 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-21885602

RESUMO

Autoimmune lymphoproliferative syndrome (ALPS) is a genetic disorder characterized by early-onset, chronic, nonmalignant lymphoproliferation, autoimmune manifestations, and susceptibility to lymphoma. The majority of ALPS patients carry heterozygous germline (ALPS-FAS) or somatic mutations (ALPS-sFAS) of the TNFRSF6 gene coding for FAS. Although the clinical features of ALPS have been described previously, long-term follow-up data on morbidity and mortality are scarce. We performed a retrospective analysis of clinical and genetic features of 90 ALPS-FAS and ALPS-sFAS patients monitored over a median period of 20.5 years. Heterozygous germline mutations of TNFRSF6 were identified in 83% of probands. Somatic TNFRSF6 mutations were found in 17% of index cases (all located within the intracellular domain of FAS). Sixty percent of the ALPS-FAS patients with mutations in the extracellular domain had a somatic mutation affecting the second allele of TNFRSF6; age at onset was later in these patients. No other genotype-phenotype correlations could be found. Long-term analysis confirmed a trend toward spontaneous remission of lymphoproliferation in adulthood but mixed outcomes for autoimmune manifestations. We observed significant and potentially life-threatening disease and treatment-related morbidity, including a high risk of sepsis after splenectomy that calls for careful long-term monitoring of ALPS patients. We also noted a significantly greater occurrence of disease-related symptoms in male than in female patients.


Assuntos
Síndrome Linfoproliferativa Autoimune/genética , Mutação , Receptor fas/genética , Adolescente , Adulto , Idoso , Síndrome Linfoproliferativa Autoimune/sangue , Síndrome Linfoproliferativa Autoimune/complicações , Síndrome Linfoproliferativa Autoimune/epidemiologia , Criança , Pré-Escolar , Estudos de Coortes , Coleta de Dados , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Mutação/fisiologia , Adulto Jovem
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