Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 72
Filtrar
3.
Open Forum Infect Dis ; 7(11): ofaa175, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33204743

RESUMO

We report a case of chronic hepatosplenic aspergillosis following immune reconstitution complicating colic aspergillosis in an AIDS patient with multicentric Castleman disease. Symptoms mimicked the clinical presentation of chronic disseminated candidiasis and responded to corticosteroid. This emerging entity enlarges the spectrum of fungal immune reconstitution inflammatory syndrome in the HIV setting.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33007500

RESUMO

BACKGROUND: Primary immune deficiencies (PIDs) are a heterogeneous group of disorders resulting from defects in immune system. They lead to increased susceptibility to infections and immune dysregulation. The resulting chronic inflammation can induce long-term complications, including AA amyloidosis (AAA). OBJECTIVES: To present the French cases of PID-related AAA and perform a systematic literature review to determine its main features and predisposing factors. METHODS: A systematic literature review was performed by searching MEDLINE up until 2019. New French cases were identified with the help of the Reference Center for Auto-Inflammatory Diseases and AA Amyloidosis and the Reference Center for Hereditary Immune Deficiencies. RESULTS: Forty patients were identified including 2 new French cases. PIDs were varied: immunoglobulin deficits (n = 30), chronic granulomatous disease (n = 3), hyper-IgM syndrome (n = 3), hereditary complete C4 deficiency (n = 1), leucocyte adhesion deficiency type 1 (n = 1), hyper-IgE syndrome (n = 1), and Chediak-Higashi syndrome (n = 1). The mean age at PID diagnosis was 22.2 ± 16.02 years. Renal involvement was the most common manifestation of AAA (80%). Infections were extremely heterogeneous; bacterial infection with pulmonary involvement was the most frequent. Bronchiectasis was particularly common (52.5%). The delay between the first symptoms of PID and AAA diagnosis was 16.18 ± 7 years. Thirteen concomitant diagnoses were made. Twenty patients died during follow-up. CONCLUSION: AAA is a rare life-threatening complication of PID, especially in cases of long diagnostic and therapeutic delays. Bronchiectasis should be considered as a warning sign of chronic inflammation and increased risk of AAA.

5.
Hematol Oncol ; 2020 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-33099794

RESUMO

Reactive hemophagocytic lymphohistiocytosis (rHLH) management requires early recognition, trigger identification, and adequate treatment in order to reduce mortality. We assessed the diagnostic yield of tissue biopsies to identify trigger in severe rHLH. We included all consecutive patients presenting an rHLH diagnosis (HLH-2004 criteria) admitted to the intensive care unit (ICU) of a tertiary hospital. This retrospective diagnostic accuracy study was conducted according to the Standards for Reporting Diagnostic Accuracy Statement. Among the 134 included patients (median age 47 years [IQR 47-56]), an underlying immunodeficiency was previously known in 61.2%. rHLH trigger was identified in 127 patients (94.8%) (hematological disorder 75%, infection 16%, systemic disease 4%). Diagnostic yield of tissue biopsies was as follows: lymph node 75% (95% confidence interval [CI], 61-85), skin 50% (95% CI, 27-73), bone marrow 44% (95% CI, 34-55), liver 30% (95% CI, 15-49). Splenectomy (yield 77%; 95% CI, 46-95) was reserved to cases of diagnostic deadlock. Procedural severe adverse events included two cases of reversible hemorrhagic shock. Seventy-eight percent of patients received etoposide regarding to the rHLH severity, and 68% could receive trigger-specific treatment in the ICU. A comprehensive diagnostic workup led to an rHLH trigger identification in 95% of patients, allowing prompt initiation of appropriate therapy. Prospective studies to validate a standardized diagnostic approach are warranted.

6.
Blood ; 136(20): 2290-2295, 2020 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-32959052

RESUMO

Anti-CD20 monoclonal antibodies are widely used for the treatment of hematological malignancies or autoimmune disease but may be responsible for a secondary humoral deficiency. In the context of COVID-19 infection, this may prevent the elicitation of a specific SARS-CoV-2 antibody response. We report a series of 17 consecutive patients with profound B-cell lymphopenia and prolonged COVID-19 symptoms, negative immunoglobulin G (IgG)-IgM SARS-CoV-2 serology, and positive RNAemia measured by digital polymerase chain reaction who were treated with 4 units of COVID-19 convalescent plasma. Within 48 hours of transfusion, all but 1 patient experienced an improvement of clinical symptoms. The inflammatory syndrome abated within a week. Only 1 patient who needed mechanical ventilation for severe COVID-19 disease died of bacterial pneumonia. SARS-CoV-2 RNAemia decreased to below the sensitivity threshold in all 9 evaluated patients. In 3 patients, virus-specific T-cell responses were analyzed using T-cell enzyme-linked immunospot assay before convalescent plasma transfusion. All showed a maintained SARS-CoV-2 T-cell response and poor cross-response to other coronaviruses. No adverse event was reported. Convalescent plasma with anti-SARS-CoV-2 antibodies appears to be a very promising approach in the context of protracted COVID-19 symptoms in patients unable to mount a specific humoral response to SARS-CoV-2.


Assuntos
Anticorpos Antivirais/imunologia , Linfócitos B/patologia , Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Soros Imunes/administração & dosagem , Linfopenia/terapia , Pneumonia Viral/imunologia , Adulto , Idoso , Linfócitos B/imunologia , Transfusão de Componentes Sanguíneos , Infecções por Coronavirus/sangue , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , Feminino , França , Neoplasias Hematológicas/complicações , Humanos , Imunização Passiva , Linfopenia/etiologia , Linfopenia/patologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/terapia , Pneumonia Viral/virologia
7.
J Exp Med ; 217(11)2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-32812031

RESUMO

Epstein-Barr virus (EBV) preferentially infects epithelial cells and B lymphocytes and sometimes T and NK lymphocytes. Persistence of EBV-infected cells results in severe lymphoproliferative disorders (LPDs). Diagnosis of EBV-driven T or NK cell LPD and chronic active EBV diseases (CAEBV) is difficult, often requiring biopsies. Herein, we report a flow-FISH cytometry assay that detects cells expressing EBV-encoded small RNAs (EBERs), allowing rapid identification of EBV-infected cells among PBMCs. EBV-infected B, T, and/or NK cells were detectable in various LPD conditions. Diagnosis of CAEBV in 22 patients of Caucasian and African origins was established. All exhibited circulating EBV-infected T and/or NK cells, highlighting that CAEBV is not restricted to native American and Asian populations. Proportions of EBV-infected cells correlated with blood EBV loads. We showed that EBV-infected T cells had an effector memory activated phenotype, whereas EBV-infected B cells expressed plasma cell differentiation markers. Thus, this method achieves accurate and unambiguous diagnoses of different forms of EBV-driven LPD and represents a powerful tool to study their pathophysiological mechanisms.

11.
J Exp Med ; 217(6)2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32207811

RESUMO

Autosomal dominant hyper-IgE syndrome (AD-HIES) is typically caused by dominant-negative (DN) STAT3 mutations. Patients suffer from cold staphylococcal lesions and mucocutaneous candidiasis, severe allergy, and skeletal abnormalities. We report 12 patients from 8 unrelated kindreds with AD-HIES due to DN IL6ST mutations. We identified seven different truncating mutations, one of which was recurrent. The mutant alleles encode GP130 receptors bearing the transmembrane domain but lacking both the recycling motif and all four STAT3-recruiting tyrosine residues. Upon overexpression, the mutant proteins accumulate at the cell surface and are loss of function and DN for cellular responses to IL-6, IL-11, LIF, and OSM. Moreover, the patients' heterozygous leukocytes and fibroblasts respond poorly to IL-6 and IL-11. Consistently, patients with STAT3 and IL6ST mutations display infectious and allergic manifestations of IL-6R deficiency, and some of the skeletal abnormalities of IL-11R deficiency. DN STAT3 and IL6ST mutations thus appear to underlie clinical phenocopies through impairment of the IL-6 and IL-11 response pathways.

12.
J Exp Med ; 216(12): 2800-2818, 2019 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-31537641

RESUMO

Infection of T cells by Epstein-Barr virus (EBV) causes chronic active EBV infection (CAEBV) characterized by T cell lymphoproliferative disorders (T-LPD) of unclear etiology. Here, we identified two homozygous biallelic loss-of-function mutations in PIK3CD and TNFRSF9 in a patient who developed a fatal CAEBV. The mutation in TNFRSF9 gene coding CD137/4-1BB, a costimulatory molecule expressed by antigen-specific activated T cells, resulted in a complete loss of CD137 expression and impaired T cell expansion toward CD137 ligand-expressing cells. Isolated as observed in one sibling, CD137 deficiency resulted in persistent EBV-infected T cells but without clinical manifestations. The mutation in PIK3CD gene that encodes the catalytic subunit p110δ of the PI3K significantly reduced its kinase activity. Deficient T cells for PIK3CD exhibited reduced AKT signaling, while calcium flux, RAS-MAPK activation, and proliferation were increased, suggestive of an imbalance between the PLCγ1 and PI3K pathways. These skewed signals in T cells may sustain accumulation of EBV-infected T cells, a process controlled by the CD137-CD137L pathway, highlighting its critical role in immunity to EBV.


Assuntos
Classe I de Fosfatidilinositol 3-Quinases/deficiência , Infecções por Vírus Epstein-Barr/etiologia , Herpesvirus Humano 4/imunologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/deficiência , Ativação Viral/genética , Ativação Viral/imunologia , Classe I de Fosfatidilinositol 3-Quinases/química , Suscetibilidade a Doenças , Infecções por Vírus Epstein-Barr/diagnóstico , Mutação em Linhagem Germinativa , Histocitoquímica , Homozigoto , Humanos , Imunofenotipagem , Mutação com Perda de Função , Ativação Linfocitária , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/etiologia , Transtornos Linfoproliferativos/metabolismo , Modelos Moleculares , Linhagem , Fosfolipase C gama/metabolismo , Conformação Proteica , Proteínas Proto-Oncogênicas c-akt , Proteínas Quinases S6 Ribossômicas/metabolismo , Análise de Sequência de DNA , Transdução de Sinais , Relação Estrutura-Atividade , Linfócitos T/virologia , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/química
13.
Amyloid ; 26(4): 197-202, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31364863

RESUMO

Introduction: HHV8-negative Castleman disease (CD) is classified as hyaline vascular (HV) type, or mixed or plasma cell (PC) types. It may present as multicentric CD (MCD) or unicentric CD (UCD). CD is a rare cause of AA amyloidosis (AAA). We aimed to report the main features of CD with secondary AAA through a description of new cases and a systematic literature review. Patients and methods: New cases were identified from the French National Reference Center for AAA. A systematic literature review was performed to identify HHV8-negative CD cases associated with AAA. Results: Thirty-seven patients were analysed, consisting of two new cases and 35 from literature. Twenty-three had UCD and 14 had MCD. PC was the main histologic subtype (n = 25; 68%) in both UCD and MCD patients. Surgical excision of UCD was performed in 21 patients (91%) with a favourable outcome, except for four patients (19%). Clinical and biologic remission was achieved in six patients with MCD (43%), all of whom were treated with anti-interleukin-6 (IL-6) therapy. Conclusions: AAA is a rare complication of CD, namely idiopathic MCD and UCD presenting with the PC histologic subtype. Surgical excision of UCD should be the first-line treatment whenever possible, while anti-IL-6 therapies seem effective for MCD.


Assuntos
Amiloidose/epidemiologia , Hiperplasia do Linfonodo Gigante/epidemiologia , Adulto , Amiloidose/etiologia , Amiloidose/terapia , Hiperplasia do Linfonodo Gigante/complicações , Hiperplasia do Linfonodo Gigante/imunologia , Hiperplasia do Linfonodo Gigante/terapia , Bases de Dados Factuais , Feminino , França/epidemiologia , Humanos , Imunoterapia , Interleucina-6/antagonistas & inibidores , Masculino , Pessoa de Meia-Idade
14.
J Clin Med ; 8(5)2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-31052269

RESUMO

Epidemiology of opportunistic infections (OI) after kidney allograft transplantation in the modern era of immunosuppression and the use of OI prevention strategies are poorly described. We retrospectively analyzed a single-center cohort on kidney allograft adult recipients transplanted between January 2008 and December 2013. The control group included all kidney recipients transplanted in the same period, but with no OI. We analyzed 538 kidney transplantations (538 patients). The proportion of OI was 15% (80 and 72 patients). OI occurred 12.8 (6.0-31.2) months after transplantation. Viruses were the leading cause (n = 54, (10%)), followed by fungal (n = 15 (3%)), parasitic (n = 6 (1%)), and bacterial (n = 5 (0.9%)) infections. Independent risk factors for OI were extended criteria donor (2.53 (1.48-4.31), p = 0.0007) and BK viremia (6.38 (3.62-11.23), p < 0.0001). High blood lymphocyte count at the time of transplantation was an independent protective factor (0.60 (0.38-0.94), p = 0.026). OI was an independent risk factor for allograft loss (2.53 (1.29-4.95), p = 0.007) but not for patient survival. Post-kidney transplantation OIs were mostly viral and occurred beyond one year after transplantation. Pre-transplantation lymphopenia and extended criteria donor are independent risk factors for OI, unlike induction therapy, hence the need to adjust immunosuppressive regimens to such transplant candidates.

16.
Br J Haematol ; 186(2): 269-273, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31016730

RESUMO

We retrospectively analysed 71 cases of Unicentric Castleman disease, a rare, usually asymptomatic, benign lymphoproliferative disorder presenting as a unique nodal mass. Although surgery is considered as the gold standard therapy, only 38 patients (54%) underwent initial surgical resection and 95% were cured. An additional 9 patients had surgery after an attempt at medical reduction. Reduction therapy was used in 21 patients with a 55% response rate, but without evidence for an optimal regimen. Radiotherapy was limited to 8 patients because of associated toxicity. Watch and wait was considered in 13 asymptomatic patients and 11 of these remained stable for up to 17 years.


Assuntos
Hiperplasia do Linfonodo Gigante/mortalidade , Hiperplasia do Linfonodo Gigante/patologia , Hiperplasia do Linfonodo Gigante/terapia , Adulto , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida
17.
J Rheumatol ; 46(11): 1535-1539, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-30877203

RESUMO

OBJECTIVE: To describe a new autoinflammatory syndrome with recurrent fever and monoclonal gammopathy that differs from Schnitzler syndrome. METHODS: We conducted a retrospective study of patients with monoclonal gammopathy and recurrent fever of unknown origin. RESULTS: Five patients were studied; median age at onset of symptoms was 44 years. Median frequency of fever attacks was 6 episodes per year. In the absence of treatment, the median duration of fevers was 3 days. CONCLUSION: This new autoinflammatory syndrome is defined by an association among monoclonal gammopathy, arthralgias, and recurrent fever.

18.
Blood ; 133(11): 1186-1190, 2019 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-30610029

RESUMO

Kaposi sarcoma-associated herpesvirus/human herpesvirus 8 is associated with multicentric Castleman disease (MCD) and primary effusion lymphoma (PEL). In MCD, infected B cells, although polyclonal, express a monotypic immunoglobulin Mλ phenotype, probably through editing toward λ light chain in mature B cells. They are considered to originate from pre-germinal center (GC) naive B cells. Both viral and human interleukin-6 contribute to the plasmacytic differentiation of these cells, and viral replication can be observed in some infected cells. PEL cells are clonal B cells considered as GC/post-GC B cells. One can also hypothesize that they originate from the same infected naive B cells and that additional factors could be responsible for their peculiar phenotype.


Assuntos
Herpesvirus Humano 8/patogenicidade , Transtornos Linfoproliferativos/etiologia , Sarcoma de Kaposi/complicações , Humanos , Transtornos Linfoproliferativos/patologia , Prognóstico , Sarcoma de Kaposi/virologia
19.
J Allergy Clin Immunol ; 143(4): 1575-1585.e4, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30554723

RESUMO

BACKGROUND: Commensals induce local IgA responses essential to the induction of tolerance to gut microbiota, but it remains unclear whether antimicrobiota responses remain confined to the gut. OBJECTIVE: The aim of this study was to investigate systemic and intestinal responses against the whole microbiota under homeostatic conditions and in the absence of IgA. METHODS: We analyzed blood and feces from healthy donors, patients with selective IgA deficiency (SIgAd), and patients with common variable immunodeficiency (CVID). Immunoglobulin-coated bacterial repertoires were analyzed by using combined bacterial fluorescence-activated cell sorting and 16S rRNA sequencing. Bacterial lysates were probed by using Western blot analysis with healthy donor sera. RESULTS: Although absent from the healthy gut, serum antimicrobiota IgG are present in healthy subjects and increased in patients with SIgAd. IgG converges with nonoverlapping secretory IgA specificities to target the same bacteria. Each individual subject targets a diverse microbiota repertoire with a proportion that correlates inversely with systemic inflammation. Finally, intravenous immunoglobulin preparations target CVID gut microbiota much less efficiently than healthy microbiota. CONCLUSION: Secretory IgA and systemic IgG converge to target gut microbiota at the cellular level. SIgAd-associated inflammation is inversely correlated with systemic anticommensal IgG responses, which might serve as a second line of defense. We speculate that patients with SIgAd could benefit from oral IgA supplementation. Our data also suggest that intravenous immunoglobulin preparations can be supplemented with IgG from IgA-deficient patient pools to offer better protection against gut bacterial translocations in patients with CVID.


Assuntos
Microbioma Gastrointestinal/imunologia , Imunoglobulina A Secretora/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Anticorpos Antibacterianos/imunologia , Imunodeficiência de Variável Comum/imunologia , Fezes/química , Humanos , Deficiência de IgA/imunologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...