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1.
BMC Infect Dis ; 20(1): 828, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33176707

RESUMO

BACKGROUND: Severe and disseminated non-tuberculous mycobacterial (NTM) infections are frequently linked to a genetic predisposition but acquired defects of the interferon gamma (IFNγ) / interleukin 12 (IL-12) pathway need to be considered in adult patients with persistent or recurrent infections. Neutralizing anti-IFNγ autoantibodies disrupting IFNγ signalling have been identified as the cause of a severe and unique acquired immunodeficiency syndrome with increased susceptibility to NTM and other intracellular pathogens. CASE PRESENTATION: An adult Asian female with a previous history of recurrent NTM infections presented with persistent diarrhea, abdominal pain, night sweats and weight loss. Severe colitis due to a simultaneous infection with cytomegalovirus (CMV) and Salmonella typhimurium was diagnosed, with both pathogens also detectable in blood samples. Imaging studies further revealed thoracic as well as abdominal lymphadenopathy and a disseminated Mycobacterium intracellulare infection was diagnosed after a lymph node biopsy. Further diagnostics revealed the presence of high-titer neutralizing anti-IFNγ autoantibodies, allowing for the diagnosis of adult-onset immunodeficiency with anti-IFNγ autoantibodies (AIIA). CONCLUSIONS: We here present a severe case of acquired immunodeficiency with anti-IFNγ autoantibodies with simultaneous, disseminated infections with both viral and microbial pathogens. The case illustrates how the diagnosis can cause considerable difficulties and is often delayed due to unusual presentations. Histological studies in our patient give further insight into the pathophysiological significance of impaired IFNγ signalling. B-cell-depleting therapy with rituximab offers a targeted treatment approach in AIIA.


Assuntos
Autoanticorpos/imunologia , Infecções por Citomegalovirus/diagnóstico , Citomegalovirus/isolamento & purificação , Síndromes de Imunodeficiência/diagnóstico , Interferon gama/imunologia , Linfadenopatia/diagnóstico , Complexo Mycobacterium avium/isolamento & purificação , Infecção por Mycobacterium avium-intracellulare/diagnóstico , Infecções por Salmonella/diagnóstico , Salmonella typhimurium/isolamento & purificação , Adulto , Antibacterianos/uso terapêutico , Antivirais/uso terapêutico , Autoanticorpos/sangue , Biópsia , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/virologia , Diagnóstico Tardio , Feminino , Seguimentos , Humanos , Síndromes de Imunodeficiência/complicações , Síndromes de Imunodeficiência/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Interferon gama/metabolismo , Interleucina-12/metabolismo , Linfadenopatia/complicações , Linfadenopatia/tratamento farmacológico , Linfadenopatia/patologia , Infecção por Mycobacterium avium-intracellulare/complicações , Infecção por Mycobacterium avium-intracellulare/tratamento farmacológico , Infecção por Mycobacterium avium-intracellulare/microbiologia , Infecções por Salmonella/complicações , Infecções por Salmonella/tratamento farmacológico , Infecções por Salmonella/microbiologia , Resultado do Tratamento
2.
Medicine (Baltimore) ; 99(36): e21738, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899003

RESUMO

INTRODUCTION: Anti-interferon-gamma (anti-IFN-γ) autoantibody increases susceptibility to lower-virulence pathogens and causes immunodeficiency syndrome in HIV-negative patients. PATIENT CONCERNS: A 69-year-old Chinese man presented with a 2-month history of pruritic skin lesions on his forearms, trunk, and legs. He was diagnosed with 5 opportunistic infections without conventional immunosuppression-associated factors in past. The most conspicuous characteristics were recurrent pulmonary infection, persistent immunoglobulin E elevation and eosinophilia during the whole disease course. DIAGNOSIS: Enzyme-linked immunosorbent assay showed anti-IFN-γ autoantibody positive. The final diagnosis for the patient was adult-onset immunodeficiency due to anti-IFN-γ autoantibody, non-tuberculous mycobacterial (NTM) infection and reactive dermatosis. INTERVENTIONS: The patient underwent long-term anti-NTM and corticosteroid maintenance treatment. OUTCOMES: The patient was followed for 2 years during which opportunistic infection no longer happened, the immunoglobulin E level and eosinophil count reduced, the autoantibody levels remained largely steady and lung lesions absorbed. CONCLUSION: Clinicians should be vigilant for NTM infection in patients with anti-IFN-γ autoantibodies, even when culture results are negative. Long-term anti-non-tuberculous mycobacteria and glucocorticoid regimens were effective.


Assuntos
Autoanticorpos/imunologia , Síndromes de Imunodeficiência/complicações , Interferon gama/imunologia , Infecções por Mycobacterium não Tuberculosas/complicações , Idoso , Humanos , Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/imunologia , Masculino , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/imunologia , Infecções Oportunistas/complicações , Dermatopatias/complicações , Dermatopatias/imunologia
3.
Ann Hematol ; 99(6): 1231-1239, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32382770

RESUMO

Parainfluenza virus (PIV) infection is a significant cause of morbidity and mortality, especially in hematologic malignancy patients including hematopoietic stem cell transplantation (HCT) recipients. However, limited information is available for risk stratification in PIV-infected patients with hematologic malignancy with or without HCT. Patients with hematologic malignancy diagnosed with PIV from January 2009 to December 2018 were retrospectively included in a tertiary care hospital in Seoul, South Korea. Upper respiratory tract infection (URTI) was defined as the detection of PIV in a nasopharyngeal sample with URTI symptoms without new pulmonary infiltrates. Lower respiratory tract infection (LRTI) was defined as detection of PIV in either upper or lower respiratory tract samples with new pulmonary infiltrates, with or without hypoxia. PIV-associated mortality was defined as death with respiratory failure and persistent LRTI within 90 days after diagnosis. The study included 143 adult patients. Of these, 55 (38%) progressed to or initially presented with LRTI. Among these, 22 (40%) died from PIV-associated mortality. An immunodeficiency risk score was developed from associated risk factors using a multivariable Cox regression model. Patients were stratified into low (0-2), moderate (3-5), and high risk (6-8) groups with PIV-associated mortalities of 0%, 9%, and 67%, respectively (p < 0.005, Harrell's C-index = 0.84). PIV infection can result in substantial mortality in patients with hematologic malignancy if it progresses to LRTI. The immunodeficiency risk score presented here may be useful for distinguishing moderate and high risk groups that might benefit from antiviral therapy.


Assuntos
Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/mortalidade , Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/mortalidade , Infecções por Paramyxoviridae/diagnóstico , Infecções por Paramyxoviridae/mortalidade , Adulto , Estudos de Coortes , Feminino , Neoplasias Hematológicas/imunologia , Humanos , Síndromes de Imunodeficiência/imunologia , Masculino , Pessoa de Meia-Idade , Mortalidade/tendências , Infecções por Paramyxoviridae/imunologia , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco
4.
Ann Hematol ; 99(7): 1565-1573, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32436013

RESUMO

The number of patients who are administered immunosuppressive agents has been increasing. Accordingly, more patients face higher risks for developing immunodeficiency-associated lymphoproliferative disorders (LPD). Although immunodeficiency-associated LPD are distinct from other lymphoid neoplasms in terms of their immunocompromised backgrounds, little is known about the impact of lymphopenia at diagnosis on survival in patients with these LPD. Seventy-one immunodeficiency-associated LPD in Kyoto University Hospital (post-transplant LPD (PTLD), n = 26; other iatrogenic immunodeficiency-associated LPD, n = 45) were reviewed and analyzed. The median age at diagnosis was 63 years (range, 3-83). Diffuse large B cell lymphoma was the most common subtype (n = 33), followed by Hodgkin lymphoma (n = 12), B cell monomorphic LPD not specified (n = 11), and polymorphic LPD or early-phase diseases (n = 15). The median follow-up period for survivors was 2.5 years and overall survival (OS) and progression-free survival (PFS) at 2.5 years were 75% and 67%, respectively. Multivariate analysis showed that lymphopenia (≤ 800/µL) at diagnosis predicted inferior OS (HR, 3.72; P = 0.043) and PFS (HR, 3.82; P = 0.012). Serum albumin values also strongly affected OS (> 3.18 g/dL vs. ≤ 3.18 g/dL; HR, 0.21; P = 0.010) and PFS (HR, 0.26; P = 0.013). Lymphopenia at diagnosis is suggested to predict inferior OS and PFS in patients with immunodeficiency-associated LPDs. Immunocompromised status might affect disease progression in these distinct lymphoid neoplasms growing under immunocompromised backgrounds.


Assuntos
Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/mortalidade , Linfopenia/diagnóstico , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Hospitais Universitários , Humanos , Síndromes de Imunodeficiência/complicações , Síndromes de Imunodeficiência/terapia , Japão/epidemiologia , Linfopenia/complicações , Linfopenia/mortalidade , Transtornos Linfoproliferativos/complicações , Transtornos Linfoproliferativos/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Adulto Jovem
5.
Zhonghua Er Ke Za Zhi ; 58(3): 228-232, 2020 Mar 02.
Artigo em Chinês | MEDLINE | ID: mdl-32135596

RESUMO

Objective: To summarize the clinical features of immunodeficiency diseases with interstitial lung disease (ILD) as major clinical manifestations and to improve understanding etiology of ILD. Methods: The clinical features and clinical clues for diagnosis of six cases with immunodeficiency presented with ILD in Shenzhen Children's Hospital from January 2014 to December 2016 were retrospectively analyzed. Results: The patients' age ranged from 3 months to 5 years and 9 months, 5 cases were male. All cases had cough and tachypnea, 3 cases had lung infection and respiratory failure, 2 cases had chronic hypoxia and one had clubbing. Three cases had skin rashes; 5 cases had failure to thrive. Chest CT scan showed diffuse ground glass opacity in all the 6 cases, and 2 cases had cystic changes and one had "crazy-paving" pattern. Five patients were suspected to have surfactant dysfunction and genetic testing was performed before diagnosis of immunodeficiency, of which the results were negative. With human immunodeficiency virus antibody test or immunologic laboratory testing and/or immune genetic panel, acquired immune deficiency syndrome was confirmed in one case, hyper-IgM syndrome was confirmed in two cases and hyper-IgE syndrome in one case, Wiskott-Aldrich syndrome in one and STAT3 gain of function genetic mutation in another. All cases had clinical clues indicative of underlying immunocompromise. Conclusions: The clinical features of immunodeficiency diseases with ILD are cough, tachypnea or hypoxia, respiratory failure with infection, diffuse ground glass opacity in Chest CT imaging. With thorough medical history and immunology screening, there would be clinical clues indicative of underlying immunocompromise. Screening for immunodeficiency disease should be emphasized in the differential diagnosis of ILD, otherwise it may lead to misdiagnosis or unnecessary testing.


Assuntos
Síndromes de Imunodeficiência , Doenças Pulmonares Intersticiais , Pré-Escolar , Tosse , Diagnóstico Diferencial , Feminino , Humanos , Síndromes de Imunodeficiência/complicações , Síndromes de Imunodeficiência/diagnóstico , Lactente , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/etiologia , Masculino , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
6.
Allergy Asthma Proc ; 41(2): 141-143, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-32122450

RESUMO

The newborn screen for severe combined immunodeficiency (SCID) uses real-time quantitative polymerase chain reaction for T-cell receptor excision circles and is highly sensitive for SCID. However, T-cell lymphopenia from other primary and secondary causes, such as DiGeorge syndrome, prematurity, thymic involution from stress, and thymectomy during cardiac surgery, is also detected. We present a newborn girl with T-cell lymphopenia of unknown etiology detected via abnormal newborn screen.


Assuntos
Síndromes de Imunodeficiência/diagnóstico , Recém-Nascido Prematuro , Linfopenia/diagnóstico , Linfócitos T/patologia , Anti-Inflamatórios/efeitos adversos , Betametasona/efeitos adversos , Células Cultivadas , Feminino , Humanos , Imunofenotipagem , Imunossupressão , Lactente , Recém-Nascido , Triagem Neonatal , Receptores de Antígenos de Linfócitos T/genética
7.
Curr Opin Hematol ; 27(3): 163-171, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32205587

RESUMO

PURPOSE OF REVIEW: By establishing mechanisms that deliver oxygen to sustain cells and tissues, fight life-threatening pathogens and harness the immune system to eradicate cancer cells, hematopoietic stem and progenitor cells (HSPCs) are vital in health and disease. The cell biological framework for HSPC generation has been rigorously developed, yet recent single-cell transcriptomic analyses have unveiled permutations of the hematopoietic hierarchy that differ considerably from the traditional roadmap. Deploying mutants that disrupt specific steps in hematopoiesis constitutes a powerful strategy for deconvoluting the complex cell biology. It is striking that a single transcription factor, GATA2, is so crucial for HSPC generation and function, and therefore it is instructive to consider mechanisms governing GATA2 expression and activity. The present review focuses on an essential GATA2 enhancer (+9.5) and how +9.5 mutants inform basic and clinical/translational science. RECENT FINDINGS: +9.5 is essential for HSPC generation and function during development and hematopoietic regeneration. Human +9.5 mutations cause immunodeficiency, myelodysplastic syndrome, and acute myeloid leukemia. Qualitatively and quantitatively distinct contributions of +9.5 cis-regulatory elements confer context-dependent enhancer activity. The discovery of +9.5 and its mutant alleles spawned fundamental insights into hematopoiesis, and given its role to suppress blood disease emergence, clinical centers test for mutations in this sequence to diagnose the cause of enigmatic cytopenias. SUMMARY: Multidisciplinary approaches to discover and understand cis-regulatory elements governing expression of key regulators of hematopoiesis unveil biological and mechanistic insights that provide the logic for innovating clinical applications.


Assuntos
Elementos Facilitadores Genéticos , Fator de Transcrição GATA2 , Células-Tronco Hematopoéticas , Síndromes de Imunodeficiência , Leucemia Mieloide Aguda , Mutação , Síndromes Mielodisplásicas , Animais , Fator de Transcrição GATA2/biossíntese , Fator de Transcrição GATA2/genética , Células-Tronco Hematopoéticas/metabolismo , Células-Tronco Hematopoéticas/patologia , Humanos , Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/genética , Síndromes de Imunodeficiência/metabolismo , Síndromes de Imunodeficiência/patologia , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/metabolismo , Síndromes Mielodisplásicas/patologia , Medicina de Precisão
8.
J Clin Pathol ; 73(9): 587-592, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32094276

RESUMO

AIMS: An association between antibody deficiency and clozapine use in individuals with schizophrenia has recently been reported. We hypothesised that if clozapine-associated hypogammaglobulinaemia was clinically relevant this would manifest in referral patterns. METHODS: Retrospective case note review of patients referred and assessed by Immunology Centre for Wales (ICW) between January 2005 and July 2018 with extraction of clinical and immunological features for individuals with diagnosis of schizophrenia-like illness. RESULTS: 1791 adult patients were assessed at ICW during this period; 23 patients had a psychiatric diagnosis of schizophrenia or schizoaffective disorder. Principal indications for referral were findings of low calculated globulin and immunoglobulins. Clozapine was the single most commonly prescribed antipsychotic (17/23), disproportionately increased relative to reported use in the general schizophrenia population (OR 6.48, 95% CI: 1.79 to 23.5). Clozapine therapy was noted in 6/7 (86%) of patients subsequently requiring immunoglobulin replacement therapy (IgRT). Marked reduction of class-switched memory B cells (CSMB) and plasmablasts were observed in clozapine-treated individuals relative to healthy age-matched controls. Clozapine duration is associated with CSMB decline. One patient discontinued clozapine, with gradual recovery of IgG levels without use of IgRT. CONCLUSIONS: Our findings are consistent with enrichment of clozapine-treatment within schizophrenic individuals referred for ICW assessment over the last 13 years. These individuals displayed clinical patterns closely resembling the primary immunodeficiency common variable immunodeficiency, however appears reversible on drug cessation. This has diagnostic, monitoring and treatment implications for psychiatry and immunology teams and directs prospective studies to address causality and the wider implications for this patient group.


Assuntos
Antipsicóticos/uso terapêutico , Clozapina/uso terapêutico , Síndromes de Imunodeficiência/patologia , Esquizofrenia/patologia , Linfócitos B/patologia , Imunodeficiência de Variável Comum , Humanos , Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/tratamento farmacológico , Estudos Retrospectivos , Esquizofrenia/diagnóstico , Esquizofrenia/tratamento farmacológico
9.
Pediatr Allergy Immunol ; 31 Suppl 24: 19-21, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32017215

RESUMO

Recurrent respiratory infections (RRIs) are frequent in children and are characterized by more than 6 airway infections in 1 year or more than 1 upper airway infection per month in the period between September and April or more than 3 lower airway infections in 1 year. Often pediatric RRIs are related to predisposing factors, such as reduced airway size, poor tussive reflex, and immaturity of the immune system. RRIs due to immature immune system are a transient condition, with spontaneous resolution in the school age. However, some RRIs are expression of more complex diseases. Red flags are the onset of symptoms in the first year of life, the involvement of other systems, unusual pathogens, slowing of growth, severe infections of the lower airways, and recurrence of the infection site. To help the pediatrician in the RRI differential diagnosis, we have created a roadmap based on scientific literature data and clinical practice that identifies 6 macro areas: immunodeficiencies, simple minimal genetic immunodeficiency, atopy, obesity, nutritional deficiencies, autoinflammatory diseases, and complex diseases.


Assuntos
Hipersensibilidade Imediata/diagnóstico , Síndromes de Imunodeficiência/diagnóstico , Obesidade/diagnóstico , Infecções Respiratórias/diagnóstico , Autoimunidade , Criança , Pré-Escolar , Diagnóstico Diferencial , Humanos , Lactente , Guias de Prática Clínica como Assunto , Recidiva
10.
BMJ Case Rep ; 13(1)2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31969413

RESUMO

Live vaccine-acquired infection should attest for the occurrence of inborn errors of immunity. Autosomal recessive immunodeficiency 31B, a result of a signal transducer and activator of transcription 1 genetic mutation, results in defected interferon pathways: interferon alpha/beta and interferon gamma. These interferons are crucial for the defence against viral and mycobacterial infections. Recognition is important for preventive and therapeutic approaches. Herein, we report the presentation of a newly diagnosed 13-month-old child with immunodeficiency 31B after presenting with disseminated measles and varicella infection after Measles, Mumps, Rubella and Varicella vaccination.


Assuntos
Vacina contra Varicela/efeitos adversos , Varicela/tratamento farmacológico , Varicela/etiologia , Síndromes de Imunodeficiência/diagnóstico , Vacina contra Sarampo-Caxumba-Rubéola/efeitos adversos , Sarampo/tratamento farmacológico , Sarampo/etiologia , Quimioterapia Combinada , Humanos , Síndromes de Imunodeficiência/congênito , Lactente , Vacinas Combinadas/efeitos adversos
11.
Pediatr Ann ; 49(1): e17-e26, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31930419

RESUMO

Leukocytes, or white blood cells, are part of the innate immune system that defends against infectious and foreign agents. In pediatrics, it is important to use age-specific laboratory values when interpreting results. Infections are the most common cause of leukocytosis or leukopenia in children. Symptoms suggestive of more serious etiologies include persistent fevers, weight loss, bruising, fatigue, and adenopathy. Neutropenia is of special importance in pediatrics due to associations of severe neutropenia with genetic syndromes and overlapping presentations with primary immunodeficiencies. Although the discovery of novel genetic mutations has aided the hematologist/oncologist and the immunologist in managing these conditions, the relationship between clinical phenotype and mutation is still not well known. [Pediatr Ann. 2020;49(1):e17-e26.].


Assuntos
Transtornos Leucocíticos/diagnóstico , Transtornos Leucocíticos/terapia , Pediatras , Criança , Humanos , Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/terapia , Leucócitos
12.
J Clin Pathol ; 73(5): 250-256, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31831575

RESUMO

Post-anaphylaxis mast cell anergy (PAMA), commonly referred to as 'empty mast cell (MC) syndrome', is a state of temporary loss of cutaneous MC reactivity in the immediate aftermath of anaphylaxis. Data relating to this condition are sparse and the incidence rate is currently unknown. PAMA has been described only in a few published case reports in the context of hymenoptera venom allergy and perioperative anaphylaxis. Best practice guidelines regarding optimal timing for performing skin tests postanaphylaxis are largely based on expert opinion, and allergy work-up has been recommended after 4-6 weeks postanaphylaxis to avoid false-negative results.This article provides a review of clinical literature surrounding PAMA, critically evaluates intracellular events in MCs from in vitro data and hypothesises regarding plausible immune mechanisms. There are no published data to directly explain molecular mechanisms underlying this phenomenon. Although not evidence based, PAMA has been attributed to depletion of MC granules following anaphylaxis. It is also plausible that exposure to high allergen concentrations in anaphylaxis can induce a temporary shift in MCs towards dominance of inhibitory signalling pathways, thus contributing to a state of transient hyporesponsiveness observed in some patients. Other potential contributory factors for reduced MC reactivity include downregulation of FcεRI expression, cross-linking of FcεRI to the inhibitory, low-affinity IgG receptors and administration of pharmacotherapeutic agents for anaphylaxis treatment. It is likely that this interesting phenomenon can be explained by a combination of these proposed mechanisms in addition to other genetic/host factors that have not yet been identified.


Assuntos
Anafilaxia/fisiopatologia , Síndromes de Imunodeficiência/etiologia , Mastócitos/imunologia , Anafilaxia/diagnóstico , Anafilaxia/imunologia , Reações Falso-Negativas , Humanos , Síndromes de Imunodeficiência/diagnóstico , Testes Cutâneos
14.
Clin Immunol ; 210: 108269, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31683054

RESUMO

Genetic studies have led to identification of an increasing number of monogenic primary immunodeficiency disorders. Monoallelic pathogenic gain-of-function (GOF) variants in NFKBIA, the gene encoding IκBα, result in an immunodeficiency disorder, typically accompanied by anhidrotic ectodermal dysplasia (EDA). So far, 14 patients with immunodeficiency due to NFKBIA GOF mutations have been reported. In this study we report three patients from the same family with immunodeficiency, presenting with recurrent respiratory tract infections, bronchiectasis and viral skin conditions due to a novel pathogenic NFKBIA variant (c.106 T > G, p.Ser36Ala), which results in reduced IκBα degradation. Immunological investigations revealed inadequate antibody responses against vaccine antigens, despite hypergammaglobulinemia. Interestingly, none of the studied patients displayed features of EDA. Therefore, missense NFKBIA variants substituting serine 36 of IκBα, differ from the rest of pathogenic GOF NFKBIA variants in that they cause combined immunodeficiency, even in the absence of EDA.


Assuntos
Mutação com Ganho de Função/genética , Síndromes de Imunodeficiência/diagnóstico , Leucócitos Mononucleares/imunologia , Meningites Bacterianas/diagnóstico , Inibidor de NF-kappaB alfa/genética , Neisseria meningitidis/fisiologia , Papillomaviridae/fisiologia , Infecções por Pseudomonas/diagnóstico , Pseudomonas aeruginosa/fisiologia , Viroses/imunologia , Adulto , Artrite Juvenil , Azitromicina/uso terapêutico , Bronquiectasia , Proliferação de Células , Células Cultivadas , Criança , Displasia Ectodérmica , Gentamicinas/uso terapêutico , Humanos , Síndromes de Imunodeficiência/genética , Masculino , Meningites Bacterianas/tratamento farmacológico , Linhagem , Infecções por Pseudomonas/tratamento farmacológico , Viroses/diagnóstico , Verrugas , Adulto Jovem
15.
Clin Immunol ; 210: 108307, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31760095

RESUMO

An increasing healthcare challenge in the management of haematological malignancy (HM) is secondary immunodeficiency. From January 2019, the EMA included the evaluation of specific antibody (Ab) responses to better select patients for immunoglobulin replacement therapy (IgRT). We evaluated Ab responses to pneumococcal and Salmonella typhi pure polysaccharide immunization in a cohort of 42 HM patients and 24 healthy-controls. Pre-post specific Ab concentrations were measured by ELISA at 4 weeks. Globally, significantly lower Typhim Vi (TV) seroprevalence (9%) compared to 23-valent pneumococcal polysaccharide vaccine (PPV) (76%) (p <0.001) was observed. TV non responders (88%) were higher than PPV non responders (62%) (p <0.0001) and correlated better to infectious history. By ROC analysis, pre-post 5-fold TV increase was the best cut-off to discriminate HM with recurrent infections and controls (sensitivity 91%, specificity 100%). Despite the small sample cohort, our results suggest that specific anti-S typhi Ab response is a useful complementary assay in the diagnosis and management decision of SID to HM.


Assuntos
Neoplasias Hematológicas/diagnóstico , Síndromes de Imunodeficiência/diagnóstico , Polissacarídeos Bacterianos/imunologia , Salmonella typhi/fisiologia , Febre Tifoide/imunologia , Vacinas Tíficas-Paratíficas/imunologia , Adulto , Idoso , Anticorpos Antibacterianos/sangue , Formação de Anticorpos , Estudos de Coortes , Feminino , Neoplasias Hematológicas/epidemiologia , Neoplasias Hematológicas/imunologia , Humanos , Síndromes de Imunodeficiência/epidemiologia , Síndromes de Imunodeficiência/imunologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Estudos Soroepidemiológicos , Espanha/epidemiologia
17.
J Med Case Rep ; 13(1): 348, 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31779680

RESUMO

BACKGROUND: Thymomas are known to be associated with myasthenia gravis and Good syndrome. Good syndrome is the association of thymoma with combined B cell and T cell immunodeficiency. The combination of all three diseases has not been reported. We discuss the therapeutic dilemma of immunosuppression in such a case. CASE PRESENTATION: A 27-year-old Sinhalese man was evaluated for persistent cough which was associated with pleuritic chest pain and was found to have pleural-based lesions in his left hemithorax. Further evaluation confirmed these lesions to be implants from a thymoma. He subsequently developed myasthenia gravis and impending myasthenic crisis precipitated by pneumonia. He was found to have hypogammaglobulinemia with low B cell counts, confirming a diagnosis of Good syndrome. Treatment with intravenously administered broad-spectrum antibiotics, acetylcholinesterase inhibitors, orally administered glucocorticoids, plasma exchange, and intravenous immunoglobulin led to clinical improvement. He subsequently underwent thymectomy and debulking of the tumor and was maintained on regular intravenous immunoglobulins combined with low-dose prednisolone. CONCLUSIONS: Regular intravenous immunoglobulins combined with low-dose immunosuppression in addition to thymectomy appear to be safe when myasthenia gravis occurs in association with Good syndrome.


Assuntos
Síndromes de Imunodeficiência/complicações , Miastenia Gravis/complicações , Timoma/complicações , Neoplasias do Timo/complicações , Adulto , Terapia Combinada , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/terapia , Masculino , Miastenia Gravis/diagnóstico , Miastenia Gravis/terapia , Prednisolona/uso terapêutico , Síndrome , Timectomia , Timoma/diagnóstico , Timoma/terapia , Neoplasias do Timo/diagnóstico , Neoplasias do Timo/terapia
19.
Rev Prat ; 69(6): 659-665, 2019 Jun.
Artigo em Francês | MEDLINE | ID: mdl-31626429

RESUMO

Primary immune deficiencies (PIDs) include rare and heterogeneous syndromes due to genetic abnormalities involving the immune system. In the registry of the French National Reference Center for Primary Immune Deficiencies (CEREDIH), the median age of clinical onset is 2 years, but 25% of patients develop the first symptoms after 15 years. A diagnosis of PID should be considered in the presence of an unusual association of infections, autoimmune pathologies, granulomatous disease, polyclonal lymphoproliferation or atypical lymphoma. PID management currently benefits from new antibiotic prophylaxis, the improvement of allogeneic hematopoietic stem cell transplantation procedure and the development of gene therapy. In addition, the understanding of the pathophysi ological mechanisms led to new treatments targeting the pathways implicated by the genetic defects. In this review, we briefly recall the classification of PID. We illustrate the problem of PID in adults with clinical cases and then summarize the main principles of management in adults PID patients.


Assuntos
Síndromes de Imunodeficiência , Adulto , Criança , Pré-Escolar , Terapia Genética , Humanos , Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/imunologia , Síndromes de Imunodeficiência/terapia , Sistema de Registros
20.
Adv Respir Med ; 87(4): 239-242, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31476012

RESUMO

INTRODUCTION: Immunodeficient children are at a high risk of disseminated Bacillus Calmette-Guérin [BCG] infection. We assessed the literature on clinical manifestations of BCGosis in children with specific primary immunodeficiencies. MATERIAL AND METHODS: We conducted a systematic review of clinical practice articles by searching Medline, PubMed, Embase, Scopus, Web of Science and Google Scholar from their inception to date. RESULTS: Thirty-seven articles were included regarding BCG vaccination and its dissemination in children with primary immunodeficiencies. Articles on dissemination after intravesicular BCG were excluded from the study. CONCLUSIONS: Since disseminated BCG vaccination may be the first manifestation of a primary immunodeficiency disease, a comprehensive search for immunological defects in children developing these problems after BCG vaccination seems rational.


Assuntos
Vacina BCG/efeitos adversos , Síndromes de Imunodeficiência/diagnóstico , Mycobacterium bovis/patogenicidade , Tuberculose/prevenção & controle , Adjuvantes Imunológicos/efeitos adversos , Vacina BCG/administração & dosagem , Humanos , Síndromes de Imunodeficiência/imunologia , Vacinação/efeitos adversos
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