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1.
Medicine (Baltimore) ; 100(13): e20866, 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33787566

RESUMO

INTRODUCTION: DOCK8 deficiency is a primary immunodeficiency characterized by recurrent infections, severe allergic disease, and autoimmunity. Here, we report a patient with DOCK8 deficiency that was initially presented as systemic lupus erythematosus (SLE) without recurrent infections and treated with hematopoietic stem cell transplantation (HSCT). PATIENT CONCERNS: A 16-month-old boy with a previous history of eczema developed high fever and hand and foot swelling. Over time, multiple purpura, oral ulcers, and oliguria developed with a persistent fever. His laboratory findings showed anemia, thrombocytopenia, and coagulopathy with a high level of C-reactive protein (CRP). No definite pathogens were identified. The complement fractions C3, C4, and CH50 were low. Autoantibodies including antinuclear antibody (ANA) and anti-ds DNA antibody were positive. He definitively satisfied the 2015 ACR/SLICC revised criteria for the diagnosis of SLE (7 points out of 16); therefore, he was treated with a steroid. Lupus nephritis was confirmed by renal biopsy later. Considering the early-onset SLE, partial exome sequencing was performed. DIAGNOSIS: One heterozygous missense variant, c.5536A>G (p.Lys1846Glu), which was inherited from his father, and heterozygous deletion of exon 1 to 8 inherited from his mother were found. Through the results of the genetic testing, the patient was confirmed to have DOCK8 deficiency. INTERVENTIONS: At the age of 28 months, he received haploidentical HSCT from his mother as a donor. OUTCOMES: Laboratory findings including complement fractions C3, C4, CH50, anti-ds DNA antibody, and the ANA became normal after HSCT. Currently, at 12 months post-HSCT, he is doing well, without any autoimmune features or infections. CONCLUSIONS: DOCK8 deficiency can be presented as autoimmune disease such as SLE. Encountering a child diagnosed with SLE at a very young age, pediatricians should consider immunodeficiency syndrome including DOCK8 deficiency.


Assuntos
Fatores de Troca do Nucleotídeo Guanina/deficiência , Transplante de Células-Tronco Hematopoéticas/métodos , Lúpus Eritematoso Sistêmico/terapia , Doenças da Imunodeficiência Primária/terapia , Humanos , Lactente , Lúpus Eritematoso Sistêmico/congênito , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Doenças da Imunodeficiência Primária/genética , Doenças da Imunodeficiência Primária/imunologia
3.
Expert Rev Clin Immunol ; 17(2): 163-168, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33412960

RESUMO

Introduction: Patients affected by Inborn Errors of Immunity (IEI) represent a potential group-at-risk in the current COVID-19 pandemic. Studies on large and small cohorts of IEI reported a huge variability clinical manifestations associated to SARS-Cov-2, ranging from asymptomatic, mild, moderate/severe to death. A great impulse to improve remote assistance programs and to switch to home-based treatment to reduce mobility and face to face contacts has been implemented.Areas covered: The authors completed a comprehensive review of the literature by searching the PubMed database for studies on large and small cohorts and case reports of IEI patients with COVID-19, with the aim to provide useful information for their clinical management during the COVID-19 pandemic.Expert opinion: Surprisingly, a low number of IEI patients affected by SARS-Cov-2 were reported with a risk to die for COVID-19 overlapping that of the general population. The low number might be explained by the choice of most physicians to inform early in the pandemic about safety measures, to switch most of the IEI patients to home therapy and to remote assistance. The guidelines issued by the scientific societies and periodically updated, represent the best tool for the clinical management of IEI patients.


Assuntos
/epidemiologia , Doenças da Imunodeficiência Primária/epidemiologia , Doenças da Imunodeficiência Primária/terapia , /diagnóstico , Humanos , Imunização Passiva , Guias de Prática Clínica como Assunto , Consulta Remota , /isolamento & purificação
5.
Nucleic Acids Res ; 49(3): 1619-1630, 2021 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-33444456

RESUMO

Human DNA ligase I (LIG1) is the main replicative ligase and it also seals DNA breaks to complete DNA repair and recombination pathways. Immune compromised patients harbor hypomorphic LIG1 alleles encoding substitutions of conserved arginine residues, R771W and R641L, that compromise LIG1 activity through poorly defined mechanisms. To understand the molecular basis of LIG1 syndrome mutations, we determined high resolution X-ray structures and performed systematic biochemical characterization of LIG1 mutants using steady-state and pre-steady state kinetic approaches. Our results unveil a cooperative network of plastic DNA-LIG1 interactions that connect DNA substrate engagement with productive binding of Mg2+ cofactors for catalysis. LIG1 syndrome mutations destabilize this network, compromising Mg2+ binding affinity, decreasing ligation efficiency, and leading to elevated abortive ligation that may underlie the disease pathology. These findings provide novel insights into the fundamental mechanism by which DNA ligases engage with a nicked DNA substrate, and they suggest that disease pathology of LIG1 syndrome could be modulated by Mg2+ levels.


Assuntos
DNA Ligase Dependente de ATP/química , DNA Ligase Dependente de ATP/genética , Mutação , Doenças da Imunodeficiência Primária/genética , Sítios de Ligação , DNA/metabolismo , DNA Ligase Dependente de ATP/metabolismo , Humanos , Ligantes , Magnésio/química , Modelos Moleculares , Dobramento de Proteína , Síndrome
6.
J Allergy Clin Immunol ; 147(3): 870-875.e1, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33338534

RESUMO

BACKGROUND: As of November 2020, severe acute respiratory syndrome coronavirus 2 has resulted in 55 million infections worldwide and more than 1.3 million deaths from coronavirus disease 2019 (COVID-19). Outcomes following severe acute respiratory syndrome coronavirus 2 infection in individuals with primary immunodeficiency (PID) or symptomatic secondary immunodeficiency (SID) remain uncertain. OBJECTIVES: We sought to document the outcomes of individuals with PID or symptomatic SID following COVID-19 in the United Kingdom. METHODS: At the start of the COVID-19 pandemic, the United Kingdom Primary Immunodeficiency Network established a registry of cases to collate the nationwide outcomes of COVID-19 in individuals with PID or symptomatic SID and determine risk factors associated with morbidity and mortality from COVID-19 in these patient groups. RESULTS: A total of 100 patients had been enrolled by July 1, 2020, 60 with PID, 7 with other inborn errors of immunity including autoinflammatory diseases and C1 inhibitor deficiency, and 33 with symptomatic SID. In individuals with PID, 53.3% (32 of 60) were hospitalized, the infection-fatality ratio was 20.0% (12 of 60), the case-fatality ratio was 31.6% (12 of 38), and the inpatient mortality was 37.5% (12 of 32). Individuals with SID had worse outcomes than those with PID; 75.8% (25 of 33) were hospitalized, the infection-fatality ratio was 33.3% (11 of 33), the case-fatality ratio was 39.2% (11 of 28), and inpatient mortality was 44.0% (11 of 25). CONCLUSIONS: In comparison to the general population, adult patients with PID and symptomatic SID display greater morbidity and mortality from COVID-19. This increased risk must be reflected in public health guidelines to adequately protect vulnerable patients from exposure to the virus.


Assuntos
Doenças da Imunodeficiência Primária , Sistema de Registros , /imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , /mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças da Imunodeficiência Primária/imunologia , Doenças da Imunodeficiência Primária/mortalidade , Doenças da Imunodeficiência Primária/virologia , Fatores de Risco , Reino Unido/epidemiologia
7.
Ann Pharmacother ; 55(1): 117-122, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32567360

RESUMO

OBJECTIVE: To assess the clinical use and determine the place in therapy for immune globulin intravenous (IV), human-slra, a recently approved IV immune globulin for the treatment of primary immune deficiency diseases (PIDD). DATA SOURCES: A PubMed and MEDLINE search (2010 to April 2020) was conducted for relevant articles. Data were also obtained from the package insert. STUDY SELECTION AND DATA EXTRACTION: English language publications regarding the clinical efficacy and safety of immune globulin-slra were analyzed. Publications focused on use of immune globulin products were also included. DATA SYNTHESIS: Immune globulin-slra is indicated for patients with PIDD and was specifically developed to include donor plasma with high respiratory syncytial virus (RSV) antibody titers. Efficacy was demonstrated through favorable incidence of infections and infection-related complications. Patients treated with immune globulin-slra had increases in anti-RSV neutralizing antibody titers compared with baseline. Adverse events occurred at rates similar to or less than other available immune globulin products. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This review describes a new immune globulin product available for use in patients with PIDD. A novel approach to managing patients at risk of serious infections may be to utilize products with formulations proven to not only boost IgG levels, but also antibodies to specific pathogens. CONCLUSIONS: The choice of which immune globulin product to select for a patient or formulary is complex. Each product is unique, and differences between products should be taken into consideration, along with cost and availability.


Assuntos
Imunoglobulinas Intravenosas/uso terapêutico , Doenças da Imunodeficiência Primária/tratamento farmacológico , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Anticorpos Antivirais/análise , Anticorpos Antivirais/imunologia , Ensaios Clínicos como Assunto , Ensaios Clínicos Fase III como Assunto , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Imunoglobulinas Intravenosas/sangue , Imunoglobulinas Intravenosas/imunologia , Infecções por Vírus Respiratório Sincicial/imunologia , Resultado do Tratamento
8.
Blood ; 136(26): 2968-2969, 2020 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-33367549
9.
J Interferon Cytokine Res ; 40(12): 549-554, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33337932

RESUMO

Coronavirus disease 2019 (COVID-19) has spread rapidly and become a pandemic. Caused by a novel human coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), severe COVID-19 is characterized by cytokine storm syndromes due to innate immune activation. Primary immunodeficiency (PID) cases represent a special patient population whose impaired immune system might make them susceptible to severe infections, posing a higher risk to COVID-19, but this could also lead to suppressed inflammatory responses and cytokine storm. It remains an open question as to whether the impaired immune system constitutes a predisposing or protective factor for PID patients when facing SARS-CoV-2 infection. After literature review, it was found that, similar to other patient populations with different comorbidities, PID patients may be susceptible to SARS-CoV-2 infection. Their varied immune status, however, may lead to different disease severity and outcomes after SARS-CoV-2 infection. PID patients with deficiency in antiviral innate immune signaling [eg, Toll-like receptor (TLR)3, TLR7, or interferon regulatory factor 7 (IRF7)] or interferon signaling (IFNAR2) may be linked to severe COVID-19. Because of its anti-infection, anti-inflammatory, and immunomodulatory effects, routine intravenous immunoglobulin therapy may provide some protective effects to the PID patients.


Assuntos
/complicações , Sistema Imunitário , Inflamação , Doenças da Imunodeficiência Primária/complicações , Doenças da Imunodeficiência Primária/imunologia , Comorbidade , Suscetibilidade a Doenças , Humanos , Imunidade Inata , Imunoglobulinas Intravenosas/metabolismo , Fator Regulador 7 de Interferon/metabolismo , Pandemias , Receptor de Interferon alfa e beta/metabolismo , Risco , Receptor 3 Toll-Like/metabolismo , Receptor 7 Toll-Like/metabolismo
10.
Int J Med Sci ; 17(18): 2974-2986, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33173418

RESUMO

In the ongoing COVID-19 pandemic, all COVID-19 patients are naïve patients as it is the first-time humans have been exposed to the SARS-CoV-2 virus. As with exposure to many viruses, individuals with pre-existing, compromised immune systems may be at increased risk of developing severe symptoms and/or dying because of (SARS-CoV-2) infection. To learn more about such individuals, we conducted a search and review of published reports on the clinical characteristics and outcomes of COVID-19 patients with pre-existing, compromised immune systems. Here we present our review of patients who possess pre-existing primary antibody deficiency (PAD) and those who are organ transplant recipients on maintenance immunosuppressants. Our review indicates different clinical outcomes for the patients with pre-existing PAD, depending on the underlying causes. For organ transplant recipients, drug-induced immune suppression alone does not appear to enhance COVID-19 mortality risk - rather, advanced age, comorbidities, and the development of secondary complications appears required.


Assuntos
Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Doenças do Sistema Imunitário/complicações , Doenças do Sistema Imunitário/diagnóstico , Hospedeiro Imunocomprometido , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Betacoronavirus/imunologia , Betacoronavirus/fisiologia , Comorbidade , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Humanos , Hospedeiro Imunocomprometido/imunologia , Imunossupressores/uso terapêutico , Mortalidade , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Doenças da Imunodeficiência Primária/complicações , Doenças da Imunodeficiência Primária/diagnóstico , Doenças da Imunodeficiência Primária/imunologia , Doenças da Imunodeficiência Primária/mortalidade , Prognóstico , Transplantados/estatística & dados numéricos
11.
S Afr Med J ; 110(7): 594-598, 2020 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-32880327

RESUMO

Chronic rhinitis is a troublesome condition for sufferers. It is tempting to label all patients with chronic nasal symptoms as having allergic rhinitis (AR), but many such patients have other causes of chronic rhinitis that need a specific diagnosis and management strategy. Even when the patient fully fits the definition of AR, their condition will be best served by combining medication with ongoing patient education.


Assuntos
Doença Crônica , Rinite/diagnóstico , Doença Crônica/terapia , Transtornos da Motilidade Ciliar/diagnóstico , Fibrose Cística/diagnóstico , Diagnóstico Diferencial , Humanos , Educação de Pacientes como Assunto , Doenças da Imunodeficiência Primária/diagnóstico , Rinite/etiologia , Rinite/terapia , África do Sul
12.
Adv Exp Med Biol ; 1274: 203-222, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32894512

RESUMO

The lipid kinases that generate the lipid signalling phosphoinositides have been established as fundamental signalling enzymes that control numerous aspects of how cells respond to their extracellular environment. In addition, they play critical roles in regulating membrane trafficking and lipid transport within the cell. The class I phosphoinositide kinases which generate the critical lipid signal PIP3 are hyperactivated in numerous human pathologies including cancer, overgrowth syndromes, and primary immunodeficiencies. The type III phosphatidylinositol 4-kinase beta isoform (PI4KB), which are evolutionarily similar to the class I PI3Ks, have been found to be essential host factors mediating the replication of numerous devastating pathogenic viruses. Finally, targeting the parasite variant of PI4KB has been established as one of the most promising strategies for the development of anti-malarial and anti-cryptosporidium strategies. Therefore, the development of targeted isoform selective inhibitors for these enzymes are of paramount importance. The first generation of PI3K inhibitors have recently been clinically approved for a number of different cancers, highlighting their therapeutic value. This review will examine the history of the class I PI3Ks, and the type III PI4Ks, their relevance to human disease, and the structural basis for their regulation and inhibition by potent and selective inhibitors.


Assuntos
1-Fosfatidilinositol 4-Quinase/antagonistas & inibidores , Doenças do Sistema Imunitário/tratamento farmacológico , Neoplasias/tratamento farmacológico , Doenças Parasitárias/tratamento farmacológico , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase/uso terapêutico , Doenças da Imunodeficiência Primária/tratamento farmacológico , Viroses/tratamento farmacológico , 1-Fosfatidilinositol 4-Quinase/metabolismo , Animais , Humanos , Doenças do Sistema Imunitário/enzimologia , Neoplasias/enzimologia , Doenças Parasitárias/enzimologia , Inibidores de Fosfoinositídeo-3 Quinase/farmacologia , Doenças da Imunodeficiência Primária/enzimologia , Viroses/enzimologia
13.
S Afr Med J ; 110(3): 197-203, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32657696

RESUMO

BACKGROUND: The primary immunodeficiency diseases (PIDs) constitute a diverse and ever-expanding group of inborn errors affecting a wide range of immune functions. They are not well documented in sub-Saharan Africa. OBJECTIVES: To describe the spectrum of PIDs at a tertiary paediatric hospital. METHODS: A retrospective descriptive study of PIDs diagnosed at Red Cross War Memorial Children's Hospital, Cape Town, South Africa (SA), between 1975 and 2017 was undertaken. RESULTS: We identified 252 children with PIDs, spanning eight of the nine categories listed in the 2017 classification of the International Union of Immunological Societies. Predominantly antibody deficiencies, combined immunodeficiencies with associated syndromic features, and immunodeficiencies affecting cellular and humoral immunity accounted for most children with PIDs (n=199, 79.0%). The mean age (standard deviation) at diagnosis was 46 (50) months, and the male/female ratio was 1.5:1. There was a history of parental consanguinity in 3 cases (1.2%). Recurrent infection was the most prevalent presenting phenotype, manifesting in 177 patients (70.2%). Genetic or chromosomal confirmation was obtained in 42/252 cases (16.7%). Common interventions used to prevent infection were antimicrobial prophylaxis and immunoglobulin replacement therapy, administered to 95 (37.7%) and 93 (36.9%) of the patients, respectively. Six of 7 children who underwent haematopoietic stem cell transplantation (HSCT) had successful outcomes. The 7th patient died 2 months after HSCT from overwhelming infection. Although we could not account for the children lost to follow-up during the study period, 53 deaths were confirmed (21.0%). CONCLUSIONS: Several challenges exist in the recognition and treatment of children with PIDs in our setting. These include limited access to genetic diagnostics and HSCT. Suboptimal treatment options contribute to the overall mortality of PIDs in SA.


Assuntos
Doenças da Imunodeficiência Primária/terapia , Adolescente , Criança , Pré-Escolar , Feminino , Hospitais Pediátricos , Humanos , Lactente , Recém-Nascido , Masculino , Doenças da Imunodeficiência Primária/epidemiologia , Doenças da Imunodeficiência Primária/genética , Doenças da Imunodeficiência Primária/mortalidade , Cruz Vermelha , Estudos Retrospectivos , África do Sul/epidemiologia , Fatores de Tempo
14.
Int J Infect Dis ; 98: 486-493, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32663603

RESUMO

OBJECTIVES: We aimed to determine the incidence and relative risk (RR) of invasive pneumococcal disease (IPD) in patients with asplenia/hyposplenism, using a nationwide population-based database. METHODS: From 2009 to 2018, all claimed cases of newly diagnosed asplenia/hyposplenism in the National Health Insurance Service in South Korea were included. The incidence and RR of IPD in asplenia/hyposplenism patients were investigated using the Korean Center for Disease Control criteria. RESULTS: Fifty-seven IPD cases were identified among 21,376 patients with 82,748 person-years of exposure. The cumulative 8-year IPD incidence was 0.5%; 45.6% of the infections occurred within two years after an asplenia/hyposplenism diagnosis. The age-standardised incidence rate was 104.5 per 100,000 person-years (95% confidence interval [CI], 103.6-105.4). Patients aged <5 years had a 15.1-times higher risk of IPD than those aged ≥60 years (95% CI: 5.8-39.5, p < 0.0001). The RR of IPD was 32.0 times higher in patients with asplenia/hyposplenism than in the general population (95% CI, 21.7-47.0); the standardized incidence ratio was 17.9(95% CI, 11.8-26.0). CONCLUSIONS: This large population-based study highlights the high IPD incidence rate and RR in Korean patients with asplenia/hyposplenism. Increased awareness and effective prevention strategies are needed for these high-risk populations, especially children aged <5 years.


Assuntos
Síndrome de Heterotaxia/complicações , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/etiologia , Esplenopatias/complicações , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Masculino , Pessoa de Meia-Idade , Infecções Pneumocócicas/microbiologia , Doenças da Imunodeficiência Primária , República da Coreia/epidemiologia , Fatores de Risco , Baço/anormalidades , Adulto Jovem
15.
Nat Commun ; 11(1): 3355, 2020 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-32620778

RESUMO

Mammalian DNA methylation patterns are established by two de novo DNA methyltransferases, DNMT3A and DNMT3B, which exhibit both redundant and distinctive methylation activities. However, the related molecular basis remains undetermined. Through comprehensive structural, enzymology and cellular characterization of DNMT3A and DNMT3B, we here report a multi-layered substrate-recognition mechanism underpinning their divergent genomic methylation activities. A hydrogen bond in the catalytic loop of DNMT3B causes a lower CpG specificity than DNMT3A, while the interplay of target recognition domain and homodimeric interface fine-tunes the distinct target selection between the two enzymes, with Lysine 777 of DNMT3B acting as a unique sensor of the +1 flanking base. The divergent substrate preference between DNMT3A and DNMT3B provides an explanation for site-specific epigenomic alterations seen in ICF syndrome with DNMT3B mutations. Together, this study reveals distinctive substrate-readout mechanisms of the two DNMT3 enzymes, implicative of their differential roles during development and pathogenesis.


Assuntos
Ilhas de CpG/genética , DNA (Citosina-5-)-Metiltransferases/metabolismo , Metilação de DNA , Animais , Domínio Catalítico , Linhagem Celular , DNA (Citosina-5-)-Metiltransferases/genética , DNA (Citosina-5-)-Metiltransferases/ultraestrutura , Células-Tronco Embrionárias , Ensaios Enzimáticos , Epigênese Genética , Face/anormalidades , Humanos , Camundongos , Mutação , Doenças da Imunodeficiência Primária/genética , Relação Estrutura-Atividade , Especificidade por Substrato/genética , Difração de Raios X
16.
J Cardiothorac Surg ; 15(1): 141, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32539831

RESUMO

BACKGROUND: Good syndrome is a rare condition, manifesting as immunodeficiency due to hypogammaglobulinemia associated with thymoma. Herein, we present a patient with Good syndrome whose thymoma was resected after treatment of cytomegalovirus hepatitis. CASE PRESENTATION: The patient was a 45-year-old woman presenting with fever, cough, and nasal discharge, and was diagnosed with thymoma and hypogammaglobulinemia. She subsequently developed cytomegalovirus hepatitis that was treated by immunoglobulin. After resolution of the hepatitis, she underwent thymectomy through a left anterior thoracotomy. Her postoperative course was uneventful, and while receiving ongoing immunoglobulin therapy, she has been doing well without signs of infection. CONCLUSIONS: Management of infections is important for patients with Good syndrome. To minimize the risk of perioperative infection, we should take care while planning the surgical approach and procedure.


Assuntos
Agamaglobulinemia/complicações , Infecções por Citomegalovirus/complicações , Doenças da Imunodeficiência Primária/complicações , Timoma/complicações , Timoma/cirurgia , Neoplasias do Timo/complicações , Neoplasias do Timo/cirurgia , Agamaglobulinemia/terapia , Comorbidade , Citomegalovirus , Feminino , Hepatite/complicações , Hepatite/cirurgia , Humanos , Pessoa de Meia-Idade , Doenças da Imunodeficiência Primária/terapia , Timectomia
17.
BMC Infect Dis ; 20(1): 431, 2020 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-32563248

RESUMO

BACKGROUND: Good's syndrome (GS) is characterized by immunodeficiency, and can lead to severe infection, which is the most significant complication. Although Mycobacterium rarely causes infection in patients with GS, disseminated nontuberculous mycobacterial (NTM) infection frequently occurs in GS patients that are also positive for the human immunodeficiency virus (HIV) or anti-interferon (IFN)-γ autoantibodies. Here, we report a rare case of GS with NTM without HIV or IFN-γ autoantibodies. CASE PRESENTATION: A 57-year-old Japanese male with GS and myasthenia gravis (treated with prednisolone and tacrolimus) was diagnosed with disseminated NTM infection caused by Mycobacterium abscessus subsp. massiliense. He presented with fever and back pain. Blood, lumbar tissue, urine, stool, and sputum cultures tested positive for M. abscessus. Bacteremia, spondylitis, intestinal lumber abscess, and lung infection were confirmed by bacteriological examination and diagnostic imaging; urinary and intestinal tract infections were suspected by bacteriological examination but not confirmed by imaging. Despite multidrug combination therapy, including azithromycin, imipenem/cilastatin, levofloxacin, minocycline, linezolid, and sitafloxacin, the patient ultimately died of the infection. The patient tested negative for HIV and anti-IFN-γ autoantibodies. CONCLUSIONS: Since myasthenia gravis symptoms interfere with therapy, patients with GS and their physicians should carefully consider the antibacterial treatment options against disseminated NTM.


Assuntos
Pneumopatias/microbiologia , Infecções por Mycobacterium não Tuberculosas/microbiologia , Mycobacterium abscessus , Doenças da Imunodeficiência Primária/complicações , Antibacterianos/uso terapêutico , Autoanticorpos/sangue , Quimioterapia Combinada , Evolução Fatal , Fluoroquinolonas/uso terapêutico , Soronegatividade para HIV , Humanos , Interferon gama/imunologia , Pneumopatias/complicações , Pneumopatias/imunologia , Masculino , Pessoa de Meia-Idade , Miastenia Gravis/complicações , Infecções por Mycobacterium não Tuberculosas/complicações , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/imunologia , Síndrome
18.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(3): 1025-1031, 2020 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-32552976

RESUMO

OBJECTIVE: To investigate the prevalence of respiratory viral infections in patients with primary immunodeficiency disease (PID) during hematopoietic stem cell transplantation. METHODS: 108 specimens of nasopharyngeal aspirate were collected from 22 PID patients before and after hematopoietic stem cell transplantation from July 2016 to July 2018 in the Department of Hematology. The TR-PCR was used to detect for respiratory viruses including respiratory syncytial virus(RSV),human metapneumoviros(hMPV),coronavirus(CoV) and parainfluenza 1-3 (PIV1-3). And the clinical characteristics and co-infection were analyzed. RESULTS: Among the total 108 specimens, viral pathogens were identified in 41 (37.96%) specimens. Among which the pathogens of highest detection rate was RSV (25.9%). Different types of PID showed different virus infection rates, among which the highest infection rate was severe combined immunodeficiency disease (SCID) patients, with the virus detection rate was 57.9%. The incidence of co-infection with two or more than two viruses was 19.5%. CONCLUSION: Patients with PID who undergo hematopoietic stem cell transplantation are more susceptible to respiratory viruses. RSV is an important respiratory tract virus pathogen after hematopoietic stem cell transplantation.


Assuntos
Metapneumovirus , Doenças da Imunodeficiência Primária , Vírus Sincicial Respiratório Humano , Infecções Respiratórias , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas , Humanos , Doenças da Imunodeficiência Primária/terapia
19.
Scand J Immunol ; 92(4): e12913, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32506568

RESUMO

Cartilage-hair hypoplasia (CHH) is an autosomal recessive syndromic immunodeficiency with skeletal dysplasia, short stature, hypotrichosis, variable degree of immune dysfunction and increased incidence of anaemia, Hirschsprung disease and malignancy. CHH is caused by variants in the RMRP gene, encoding the untranslated RNA molecule of the mitochondrial RNA-processing endoribonuclease, which participates in for example cell cycle regulation and telomere maintenance. Recent studies have expanded our understanding of the complex pathogenesis of CHH. Immune dysfunction has a major impact on clinical course and prognosis. Clinical features of immune dysfunction are highly variable, progressive and include infections, lung disease, immune dysregulation and malignancy. Mortality is increased compared with the general population, due to infections, malignancy and pulmonary disease. Several risk factors for early mortality have been reported in the Finnish CHH cohort and can be used to guide management. Newborn screening for severe combined immunodeficiency can possibly be of prognostic value in CHH. Regular follow-up by a multidisciplinary team should be implemented to address immune dysfunction in all patients with CHH, also in asymptomatic cases. Haematopoietic stem cell transplantation can cure immune dysfunction, but its benefits in mildly symptomatic patients with CHH remain debatable. Further research is needed to understand the mechanisms behind the variability of clinical features, to search for potential molecular treatment targets, to examine and validate risk factors for early mortality outside the Finnish CHH cohort and to develop management guidelines. This review focuses on the pathogenesis, clinical course and management of CHH.


Assuntos
Cabelo/anormalidades , Doença de Hirschsprung/imunologia , Osteocondrodisplasias/congênito , Doenças da Imunodeficiência Primária/imunologia , Animais , Cabelo/imunologia , Cabelo/patologia , Cabelo/fisiopatologia , Doença de Hirschsprung/patologia , Doença de Hirschsprung/fisiopatologia , Humanos , Osteocondrodisplasias/imunologia , Osteocondrodisplasias/patologia , Osteocondrodisplasias/fisiopatologia , Doenças da Imunodeficiência Primária/patologia , Doenças da Imunodeficiência Primária/fisiopatologia
20.
Int J Infect Dis ; 97: 117-125, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32497805

RESUMO

BACKGROUND: Disseminated Bacillus Calmette-Guérin (BCG) disease (BCGosis) is a classical feature of children with primary immunodeficiency disorders (PIDs). METHODS: A 15-year retrospective review was conducted in KK Women's and Children's Hospital in Singapore, from January 2003 to October 2017. RESULTS: Ten patients were identified, the majority male (60.0%). The median age at presentation of symptoms of BCG infections was 3.8 (0.8 - 7.4) months. All the patients had likely underlying PIDS - four with Severe Combined Immunodeficiency (SCID), three with Mendelian Susceptibility to Mycobacterial Diseases (MSMD), one with Anhidrotic Ectodermal Dysplasia with Primary Immunodeficiency (EDA-ID), one with combined immunodeficiency (CID), and one with STAT-1 gain-of-function mutation. Definitive BCGosis was confirmed in all patients by the identification of Mycobacterium bovis subsp BCG from microbiological cultures. The susceptibility profiles of Mycobacterium bovis subsp BCG are as follows: Rifampicin (88.9%), Isoniazid (44.47%), Ethambutol (100.0%), Streptomycin (100.0%), Kanamycin (100.0%), Ethionamide (25.0%), and Ofloxacin (100.0%). Four patients (40.0%) received a three-drug regimen. Five patients (50.0%) underwent hematopoietic stem cell transplant (HSCT), of which three (60%) have recovered. Overall mortality was 50.0%. CONCLUSION: Disseminated BCG disease (BCGosis) should prompt immunology evaluation to determine the diagnosis of the immune defect. A three-drug regimen is adequate for treatment if the patient undergoes early HSCT.


Assuntos
Vacina BCG/efeitos adversos , Mycobacterium bovis , Doenças da Imunodeficiência Primária/complicações , Tuberculose/etiologia , Vacina BCG/uso terapêutico , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Doenças da Imunodeficiência Primária/terapia , Estudos Retrospectivos , Singapura , Tuberculose/tratamento farmacológico , Tuberculose/etnologia
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