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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.
BMC Neurol ; 20(1): 323, 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32867717

RESUMO

BACKGROUND: Listeria monocytogenes is an opportunistic pathogen of the central nervous system commonly associated with impaired cell-mediated immunity. We hereby present a case of adult neurolisteriosis where the only immunological feature persistently present was serum IgM deficiency, suggesting that non-specific humoral immunity may also play a central role in the control of neuroinvasion by Listeria monocytogenes. CASE PRESENTATION: A 62-year-old male who had never experienced severe infections presented with headache, nuchal rigidity and confusion. Neuroimaging was normal and lumbar puncture revealed pleiocytosis (760 leukocytes/mm3) and hypoglycorrhachia (34 mg/dL). The patient was treated empirically for bacterial meningitis. Indeed, further analysis of the CSF showed infection by Listeria monocytogenes, which was accompanied by reduced serum IgM levels that persisted well beyond the period of acute bacterial infection. Levels of IgG and IgA isotypes, along with peripheral blood counts of major leukocyte subsets, were at the same time largely preserved. Intriguingly, the absence of membrane-bound IgM on B cells was essentially complete in the acute post-infection period leading to a remarkable recovery after 12 months, suggesting that mechanisms other than defective membrane expression are underlying serum deficiency. CONCLUSIONS: As far as we know, this is the first reported case of neurolisteriosis associated with IgM deficiency in an adult individual without a history of severe infections or other underlying conditions. A possible role of circulating IgM against invasive disease caused by Listeria monocytogenes, particularly in the early course of host-pathogen interaction, is discussed.


Assuntos
Hospedeiro Imunocomprometido , Imunoglobulina M/deficiência , Meningite por Listeria/imunologia , Humanos , Síndromes de Imunodeficiência/complicações , Masculino , Pessoa de Meia-Idade
4.
MMWR Morb Mortal Wkly Rep ; 69(28): 913-917, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32673297

RESUMO

Since establishment of the Global Polio Eradication Initiative* in 1988, polio cases have declined >99.9% worldwide; extensive use of live, attenuated oral poliovirus vaccine (OPV) in routine childhood immunization programs and mass campaigns has led to eradication of two of the three wild poliovirus (WPV) serotypes (types 2 and 3) (1). Despite its safety record, OPV can lead to rare emergence of vaccine-derived polioviruses (VDPVs) when there is prolonged circulation or replication of the vaccine virus. In areas with inadequate OPV coverage, circulating VDPVs (cVDPVs) that have reverted to neurovirulence can cause outbreaks of paralytic polio (2). Immunodeficiency-associated VDPVs (iVDPVs) are isolated from persons with primary immunodeficiency (PID). Infection with iVDPV can progress to paralysis or death of patients with PID, and excretion risks seeding cVDPV outbreaks; both risks might be reduced through antiviral treatment, which is currently under development. This report updates previous reports and includes details of iVDPV cases detected during July 2018-December 2019 (3). During this time, 16 new iVDPV cases were reported from five countries (Argentina, Egypt, Iran, Philippines, and Tunisia). Alongside acute flaccid paralysis (AFP) surveillance (4), surveillance for poliovirus infections among patients with PID has identified an increased number of persons excreting iVDPVs (5). Expansion of PID surveillance will facilitate early detection and follow-up of iVDPV excretion among patients with PID to mitigate the risk for iVDPV spread. This will be critical to help identify all poliovirus excretors and thus achieve and maintain eradication of all polioviruses.


Assuntos
Saúde Global/estatística & dados numéricos , Síndromes de Imunodeficiência/complicações , Poliomielite/epidemiologia , Vacina Antipólio Oral/efeitos adversos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Poliomielite/prevenção & controle , Poliovirus/genética , Poliovirus/isolamento & purificação , Vacina Antipólio Oral/administração & dosagem , Sorogrupo
5.
J Allergy Clin Immunol Pract ; 8(7): 2125-2134, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32450236

RESUMO

In early 2020, the first US and Canadian cases of the novel severe acute respiratory syndrome coronavirus 2 infection were detected. In the ensuing months, there has been rapid spread of the infection. In March 2020, in response to the virus, state/provincial and local governments instituted shelter-in-place orders, and nonessential ambulatory care was significantly curtailed, including allergy/immunology services. With rates of new infections and fatalities potentially reaching a plateau and/or declining, restrictions on provision of routine ambulatory care are lifting, and there is a need to help guide the allergy/immunology clinician on how to reinitiate services. Given the fact that coronavirus disease 2019 will circulate within our communities for months or longer, we present a flexible, algorithmic best-practices planning approach on how to prioritize services, in 4 stratified phases of reopening according to community risk level, as well as highlight key considerations for how to safely do so. The decisions on what services to offer and how fast to proceed are left to the discretion of the individual clinician and practice, operating in accordance with state and local ordinances with respect to the level of nonessential ambulatory care that can be provided. Clear communication with staff and patients before and after all changes should be incorporated into this new paradigm on continual change, given the movement may be forward and even backward through the phases because this is an evolving situation.


Assuntos
Alergia e Imunologia , Betacoronavirus , Infecções por Coronavirus/prevenção & controle , Assistência à Saúde , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Humanos , Síndromes de Imunodeficiência/complicações , Telemedicina
6.
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
7.
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
8.
BMC Infect Dis ; 20(1): 232, 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32188404

RESUMO

BACKGROUND: The most common infection in patients positive for anti-interferon-gamma autoantibodies (anti-IFN-γ AAbs) is disseminated nontuberculous mycobacterial (dNTM) infection. Here, we report a rare case of triple infection caused by Cryptococcus, varicella-zoster virus (VZV), and nontuberculous mycobacterium in a patient with anti-IFN-γ AAbs. CASE PRESENTATION: A 53-year-old Thai man presented with a progressively enlarging right cervical mass with low-grade fever and significant weight loss for 4 months. He also developed a lesion at his left index finger. A biopsy of that lesion showed granulomatous inflammation with yeast-like organisms morphologically consistent with cryptococcosis. Serum cryptococcal antigen was positive. Histopathology of a right cervical lymph node revealed chronic granulomatous lymphadenitis, and the lymph node culture grew Mycobacterium abscessus. One month later, he complained of vision loss in his left eye and subsequently developed a group of painful vesicles at the right popliteal area of S1 dermatome. Lumbar puncture was performed and his cerebrospinal fluid was positive for VZV DNA. His blood test for anti-HIV antibody was negative. Anti-IFN-γ AAbs was positive, but test for anti-granulocyte-macrophage colony-stimulating factor autoantibodies (anti-GM-CSF AAbs) was negative. He was treated with amphotericin B plus fluconazole for cryptococcosis; a combination of amikacin, imipenem, azithromycin, and levofloxacin for dNTM infection; and, intravenous acyclovir for disseminated VZV infection. After treatment, our patient's fever and cervical lymphadenopathy were subsided, and his vision and visual acuity were both improved. CONCLUSIONS: This is the first case of triple infection with cryptococcosis, VZV, and dNTM in a patient who tested positive for anti-IFN-γ AAbs and negative for anti-GM-CSF AAbs. This case will increase awareness and heighten suspicion of these infections in patients with the described presentations and clinical characteristics, and this will accelerate diagnosis and treatment.


Assuntos
Criptococose/tratamento farmacológico , Síndromes de Imunodeficiência/complicações , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Aciclovir/uso terapêutico , Anfotericina B/uso terapêutico , Autoanticorpos , Coinfecção , Criptococose/microbiologia , Fluconazol/uso terapêutico , Herpesvirus Humano 3/imunologia , Humanos , Interferon gama/imunologia , Linfadenopatia , Masculino , Pessoa de Meia-Idade , Infecções por Mycobacterium não Tuberculosas/microbiologia , Mycobacterium abscessus , Infecção pelo Vírus da Varicela-Zoster/tratamento farmacológico
9.
Hum Genet ; 139(6-7): 885-901, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32152698

RESUMO

Epstein-Barr virus (EBV) is a ubiquitous human pathogen, infecting > 90% of the adult population. In the vast majority of healthy individuals, infection with EBV runs a relatively benign course. However, EBV is by no means a benign pathogen. Indeed, apart from being associated with at least seven different types of malignancies, EBV infection can cause severe and often fatal diseases-hemophagocytic lymphohistiocytosis, lymphoproliferative disease, B-cell lymphoma-in rare individuals with specific monogenic inborn errors of immunity. The discovery and detailed investigation of inborn errors of immunity characterized by heightened susceptibility to, or increased frequency of, EBV-induced disease have elegantly revealed cell types and signaling pathways that play critical and non-redundant roles in host-defense against EBV. These analyses have revealed not only mechanisms underlying EBV-induced disease in rare genetic conditions, but also identified molecules and pathways that could be targeted to treat severe EBV infection and pathological consequences in immunodeficient hosts, or even potentially enhance the efficacy of an EBV-specific vaccine.


Assuntos
Infecções por Vírus Epstein-Barr/complicações , Predisposição Genética para Doença , Herpesvirus Humano 4/imunologia , Interações Hospedeiro-Patógeno/genética , Síndromes de Imunodeficiência/complicações , Transtornos Linfoproliferativos/etiologia , Infecções por Vírus Epstein-Barr/imunologia , Infecções por Vírus Epstein-Barr/virologia , Herpesvirus Humano 4/genética , Humanos , Síndromes de Imunodeficiência/imunologia , Síndromes de Imunodeficiência/virologia , Transtornos Linfoproliferativos/patologia , Transdução de Sinais
10.
Ann Biol Clin (Paris) ; 78(1): 7-16, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32108583

RESUMO

Immunosuppression is a well known risk factor for the development of lymphoid pathologies. The classification of these neoplasias is becoming more precise and complex, some features being common to all immunocompromised patients, primarily the important influence of Epstein-Barr virus. Whatever the origin of the immunodepression, these lymphoid proliferations are very heterogeneous, constituting a wide range between polymorphic aspects and clearly lymphomatous morphologies indistinguishable from those observed in immunocompetent subjects. It is important to detect precisely these different categories of proliferation within each group of immunosuppression, to better individualize the prognosis and the management of patients.


Assuntos
Hospedeiro Imunocomprometido , Linfoma/etiologia , Transformação Celular Viral/fisiologia , HIV/fisiologia , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Infecções por HIV/imunologia , Infecções por HIV/patologia , Humanos , Hospedeiro Imunocomprometido/imunologia , Síndromes de Imunodeficiência/complicações , Síndromes de Imunodeficiência/epidemiologia , Imunossupressores/efeitos adversos , Linfoma/epidemiologia , Linfoma/imunologia , Transtornos Linfoproliferativos/induzido quimicamente , Transtornos Linfoproliferativos/epidemiologia , Transtornos Linfoproliferativos/imunologia , Transplante de Órgãos/efeitos adversos , Transplante de Órgãos/estatística & dados numéricos , Condicionamento Pré-Transplante/efeitos adversos , Condicionamento Pré-Transplante/estatística & dados numéricos
11.
Allergol. immunopatol ; 48(1): 8-17, ene.-feb. 2020. ilus
Artigo em Inglês | IBECS | ID: ibc-186586

RESUMO

Introduction and objectives: LRBA deficiency is caused by loss of LRBA protein expression, due to either homozygous or compounds heterozygous mutations in LRBA. LRBA deficiency has been shown to affect vesicular trafficking and autophagy. To date, LRBA has been observed in the cytosol, Golgi apparatus and some lysosomes in LPS-stimulated murine macrophages. The objectives of the present study were to study the LRBA localization in organelles involved in vesicular traffic, phagocytosis, and autophagy in mononuclear phagocytes (MP). Materials and methods: We analyzed LRBA colocalization with different endosomes markets using confocal microscopy in MP. We used the autophagy inhibitors to determine the role of LRBA in formation, maturation or degradation of the autophagosome. Results: LRBA intracellular trafficking depends on the activity of the GTPase ADP ribosylation factor-1 (ARF) in MP. LRBA was identified in early, late endosomes but did not colocalize strongly with lysosomal markers. Although LRBA appears not to be recruited during the phagocytic cargo uptake, it greatly colocalized with the microtubule-associated protein 1A/1B-light chain 3 (LC3) under a steady state and this decreased after the induction of autophagy flux. Although the use of inhibitors of lysosome fusion did not restore the LRBA/LC3 colocalization, inhibitors of either early to late endosomes trafficking or PI3K pathway did. Conclusions: Taken together, our results show that LRBA is located in endomembrane system vesicles, mainly in the early and late endosomes. Although LRBA appears not to be involved in the phagocytic uptake, it is recruited in the early steps of the autophagy flux


No disponible


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Membrana Celular/metabolismo , Lipopolissacarídeos/farmacologia , Síndromes de Imunodeficiência/complicações , Diferenciação Celular , Endossomos , Microscopia Confocal/métodos , Autofagossomos , Fatores de Ribosilação do ADP , Fagocitose , Western Blotting , Sistema Fagocitário Mononuclear
12.
Int J Hematol ; 111(6): 897-902, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31993940

RESUMO

Regulatory T-cells (Tregs) are major mediators of mammalian self-tolerance via cytotoxic T-lymphocyte antigen 4 (CTLA4) signaling pathways. An immune dysregulation syndrome associated with heterozygous germline mutations in CTLA4 was recently reported. Clinical features include recurrent infections, systemic lymphadenopathy, various autoimmune conditions, hypogammaglobulinemia, and autosomal dominant inheritance, characteristic of primary immunodeficient disease (PID). PID symptoms are variable and few patients with sporadic de novo CTLA4 germline mutations have been described. Here, we report the case of a 26-year-old man with an immune dysregulation syndrome and a de novo CTLA4 germline mutation. The patient exhibited several clinical features associated with PID. Next-generation sequencing revealed a CTLA4 germline mutation, c.436G>A; p.G146R, in exon 2 of CTLA4. Sanger sequencing confirmed the patient was the only member of his family with this germline mutation. The patient was diagnosed with an immune dysregulation syndrome associated with de novo germline CTLA4 mutation, complicated by steroid-refractory rheumatoid arthritis. Treatment with abatacept, a CTLA4-immunoglobulin fusion molecule, was initiated, resulting in dramatic resolution of the patient's clinical symptoms. As PID with CTLA4 germline mutation is rare and patients may be under-diagnosed, physicians should be aware of the features of PID.


Assuntos
Abatacepte/uso terapêutico , Antígeno CTLA-4/genética , Mutação em Linhagem Germinativa , Síndromes de Imunodeficiência/tratamento farmacológico , Síndromes de Imunodeficiência/genética , Adulto , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/etiologia , Autoimunidade , Heterozigoto , Humanos , Tolerância Imunológica , Síndromes de Imunodeficiência/complicações , Síndromes de Imunodeficiência/imunologia , Masculino , Linfócitos T Reguladores/imunologia , Resultado do Tratamento
13.
Pediatr Infect Dis J ; 39(2): e25-e27, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31929435

RESUMO

We present a case of herpes zoster ophthalmicus in an otherwise healthy 14-month-old male associated with vaccine-strain varicella-zoster virus 11 weeks after monovalent varicella vaccine administration. Herpes zoster ophthalmicus, especially in the setting of familial immunoglobulin A deficiency, prompted further immunologic workup. A high index of suspicion is necessary for timely diagnosis and treatment of vaccine-strain herpes zoster.


Assuntos
Herpes Zoster Oftálmico/etiologia , Herpes Zoster Oftálmico/prevenção & controle , Vacina contra Herpes Zoster/imunologia , Herpesvirus Humano 3/imunologia , Síndromes de Imunodeficiência/complicações , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Antivirais/uso terapêutico , Vacina contra Varicela/imunologia , Herpes Zoster Oftálmico/diagnóstico , Herpes Zoster Oftálmico/tratamento farmacológico , Vacina contra Herpes Zoster/administração & dosagem , Herpesvirus Humano 3/genética , Humanos , Imunoglobulina A/sangue , Imunoglobulina A/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Lactente , Masculino , Avaliação de Sintomas , Resultado do Tratamento
14.
Pediatr Rheumatol Online J ; 17(1): 82, 2019 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-31847838

RESUMO

BACKGROUND: Lipopolysaccharide (LPS)-responsive and beige like anchor (LRBA) deficiency is categorized as a subtype of common variable immune deficiency (CVID). A growing number of case reports and cohorts reveal a broad spectrum of clinical manifestations and variable phenotype expression, including immune dysregulation, enteropathy and recurrent infections. The association between rheumatic disease and CVID generally has been well established, arthritis has been less frequently reported and minimal data regarding its clinical features and characteristic in LRBA deficiency has been published. This case report and literature review evaluates the characteristics and features of arthritis in LRBA deficiency patients. CASE PRESENTATION AND REVIEW RESULTS: Herein, we describe a unique case of LRBA deficiency first presented with poly articular arthritis. Alongside the report, a literature review focusing on LRBA deficiency, rheumatic disease and arthritis has been conducted. We reviewed 43 publications. Among these, 7 patients were identified with arthritis. Age of first presentation was six weeks to 3 years. Male to female ratio was 4/3. Two patients were diagnosed with polyarticular Juvenile idiopathic arthritis (JIA) and three with oligoarticular JIA. Each patient was found to have different genomic mutation. The treatment was diverse and included corticosteroids, cyclosporine, methotrexate, adalidumab and abatacept. CONCLUSION: Joint involvement is variable in LRBA deficiency, hence it should always be kept in mind as a differential diagnosis for a patient with combination of juvenile arthritis and clinically atypical immune dysregulation and / or immunodeficiency.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/deficiência , Artrite/etiologia , Autoimunidade , Síndromes de Imunodeficiência/complicações , Artrite/diagnóstico , Artrite/imunologia , Biópsia , Pré-Escolar , Feminino , Humanos , Síndromes de Imunodeficiência/metabolismo , Imagem por Ressonância Magnética
15.
Rev Med Suisse ; 15(671): 2105-2108, 2019 Nov 13.
Artigo em Francês | MEDLINE | ID: mdl-31742942

RESUMO

Screening for latent tuberculosis infection (LTI) is recommended in immunosuppressed patients due to an increased risk of progression from LTI to active tuberculosis. Screening involves indirect immunological tests such as the tuberculin skin test (TST) and the interferon-y release assays (IGRAs). IGRAs seem to show superior performance compared to TST in screening for LTI. However, their use and interpretation in immunosuppressed patients is questionable, particularly because of an increased number of false negative or indeterminate results and a low agreement between tests. Presently, there are no swiss national recommendations for their use in immunosuppressed -patients, except for candidates to anti-TNF treatment.


Assuntos
Hospedeiro Imunocomprometido , Síndromes de Imunodeficiência/complicações , Síndromes de Imunodeficiência/microbiologia , Tuberculose Latente/complicações , Tuberculose Latente/diagnóstico , Humanos , Testes de Liberação de Interferon-gama , Sensibilidade e Especificidade , Teste Tuberculínico , Fator de Necrose Tumoral alfa/antagonistas & inibidores
16.
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
17.
BMC Med Genet ; 20(1): 182, 2019 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-31727123

RESUMO

BACKGROUND: Majeed syndrome is a rare, autosomal recessive autoinflammatory disorder first described in 1989. The syndrome starts during infancy with recurrent relapses of osteomyelitis typically associated with fever, congenital dyserythropoietic anemia (CDA), and often neutrophilic dermatosis. Mutations in the LPIN2 gene located on the short arm of chromosome 18 have been identified as being responsible for Majeed syndrome. CASE PRESENTATION: We report an 8-month-old boy, who presented with recurrent fever, mild to moderate anemia, and severe neutropenia. Erythrocyte sedimentation rate and C-reactive protein were elevated. Molecular testing identified a paternal splicing donor site variant c.2327 + 1G > C and a maternal frameshift variant c.1691_1694delGAGA (Arg564Lysfs*3) in LPIN2. CONCLUSIONS: Only a few cases with LPIN2 mutation have been reported, mainly in the Middle East with homozygous variants. Our patient exhibited a mild clinical phenotype and severe neutropenia, different from previous reports.


Assuntos
Anemia Diseritropoética Congênita/genética , Febre/complicações , Síndromes de Imunodeficiência/genética , Mutação , Neutropenia/complicações , Proteínas Nucleares/genética , Osteomielite/genética , Anemia Diseritropoética Congênita/complicações , Feminino , Humanos , Síndromes de Imunodeficiência/complicações , Lactente , Masculino , Osteomielite/complicações , Linhagem , Recidiva , Índice de Gravidade de Doença
18.
Kyobu Geka ; 72(12): 1031-1033, 2019 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-31701916

RESUMO

A 50-year-old man was admitted to our hospital for severe pneumonia. An anterior mediastinum tumor and the hypogammaglobulinaemia were detected during treatment of pneumonia, and Good's syndrome was diagnosed. The clinical characteristics of Good's syndrome are increased susceptibility to bacterial infections and opportunistic viral and fungal infections. We planned thymectomy with the perioperative supplementation of immunoganmmagloblin to prevent perioperative infectious complications after pneumonia recovered completely. Extended thymo-thymectomy was performed. Pathological examination revealed type AB thymoma. The hypogammaglobulinaemia did not improved following thymectomy, and the patient had to be treated by immunoglobulin supplementation to maintain adequate trough immunoglobulin G( IgG) values.


Assuntos
Agamaglobulinemia , Síndromes de Imunodeficiência , Timoma , Neoplasias do Timo , Humanos , Síndromes de Imunodeficiência/complicações , Masculino , Pessoa de Meia-Idade , Timectomia , Timoma/complicações , Timoma/cirurgia , Neoplasias do Timo/complicações , Neoplasias do Timo/cirurgia
19.
Rev. esp. quimioter ; 32(5): 410-425, oct. 2019. tab
Artigo em Inglês | IBECS | ID: ibc-188707

RESUMO

Due to the rise in the number and types of immunosuppressed patients, invasive fungal infections (IFI) are an increasing and major cause of morbidity and mortality in immunocompromised adults and children. There is a broad group of pediatric patients at risk for IFI in whom primary and/or secondary antifungal prophylaxis (AFP) should be considered despite scant evidence. Pediatric groups at risk for IFI includes extremely premature infants in some settings, while in high-risk children with cancer receiving chemotherapy or undergoing haematopoietic stem cell transplantation (HCT), AFP against yeast and moulds is usually recommended. For solid organ transplanted, children, prophylaxis depends on the type of transplant and associated risk factors. In children with primary or acquired immunodeficiency such as HIV or long-term immunosuppressive treatment, AFP depends on the type of immunodeficiency and the degree of immunosuppression. Chronic granulomatous disease is associated with a particular high-risk of IFI and anti-mould prophylaxis is always indicated. In contrast, AFP is not generally recommended in children with long stay in intensive care units. The choice of AFP is limited by the approval of antifungal agents in different age groups and by their pharmacokinetics characteristics. This document aims to review current available information on AFP in children and to provide a comprehensive proposal for each type of patient


Las infecciones fúngicas invasoras (IFI) constituyen un problema creciente en adultos y niños inmunodeprimidos, acompañándose de una elevada morbimortalidad. El número de niños inmunodeprimidos va en aumento. Los grupos de riesgo de IFI en pediatría incluyen a los grandes prematuros, que se benefician de profilaxis con fluconazol, pacientes hemato-oncológicos sometidos a quimioterapia o trasplante de precursores hematopoyéticos con neutropenias prolongadas, en quienes la profilaxis frente a hongos filamentosos suele recomendarse en situaciones de alto riesgo. En niños sometidos a trasplante de órgano sólido, la profilaxis depende del tipo de trasplante y factores de riesgo asociados. En pacientes con inmunodeficiencias primarias o adquiridas como la infección VIH o tratamiento inmunosupresor prolongado, la profilaxis antifúngica dependerá del tipo de inmunodeficiencia primaria y del grado de inmunosupresión. La enfermedad granulomatosa crónica tiene riesgo particularmente elevado de IFI y requiere siempre profilaxis frente a hongos filamentosos. En cambio, en niños con ingresos prolongados en cuidados intensivos la profilaxis frente a IFI habitualmente no está indicada. El tipo de profilaxis está limitado por la diferente aprobación de antifúngicos a distintas edades. Este documento pretende revisar la información actual disponible respecto a profilaxis antifúngica en niños, con propuesta para la estrategia más apropiada en cada tipo de paciente


Assuntos
Humanos , Recém-Nascido , Criança , Antifúngicos/uso terapêutico , Hospedeiro Imunocomprometido , Infecções Fúngicas Invasivas/prevenção & controle , Prevenção Primária/métodos , Prevenção Secundária/métodos , Candidíase/prevenção & controle , Monitoramento de Medicamentos , Infecções por HIV/complicações , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Síndromes de Imunodeficiência/complicações , Unidades de Terapia Intensiva Pediátrica , Lactente Extremamente Prematuro , Neoplasias/tratamento farmacológico , Pneumonia por Pneumocystis/prevenção & controle , Fatores de Risco , Transplantados
20.
Am J Pathol ; 189(12): 2440-2449, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31541646

RESUMO

Cells of the developing central nervous system are particularly susceptible to formation of double-stranded DNA breaks (DSBs) arising from physiological and/or environmental insults. Therefore, efficient repair of DSBs is especially vital for maintaining cellular health and proper functioning in the developing brain. Here, increased expression of DSB initiating and nonhomologous end joining repair machinery in newborn neurons in the developing brains of both mouse and human are demonstrated. In parallel, the first characterization is provided of the brain phenotype in the Lig4R278H/R278H (Lig4R/R) mouse model of DNA Ligase 4 (LIG4) syndrome, in which a hypomorphic Lig4 mutation, originally identified in patients, impedes nonhomologous end joining. It is shown that Lig4R/R mice develop nonprogressive microcephaly, resulting primarily from apoptotic death of newborn neurons that is both spatially and temporally specific during peak cortical neurogenesis. This apoptosis leads to a reduction in neurons throughout the postnatal cerebral cortex, but with a more prominent impact on those of the lower cortical layers. Together, these findings begin to uncover the pathogenesis of microcephaly in LIG4 syndrome and open avenues to more focused investigations on the critical roles of DSB formation and repair in vulnerable neuronal populations of the brain.


Assuntos
Apoptose , Córtex Cerebral/patologia , Anormalidades Craniofaciais/complicações , DNA Ligase Dependente de ATP/metabolismo , Modelos Animais de Doenças , Transtornos do Crescimento/complicações , Síndromes de Imunodeficiência/complicações , Microcefalia/etiologia , Neurônios/patologia , Animais , Córtex Cerebral/metabolismo , Quebras de DNA de Cadeia Dupla , DNA Ligase Dependente de ATP/genética , Feminino , Técnicas de Introdução de Genes , Masculino , Camundongos , Microcefalia/patologia , Mutação , Neurônios/metabolismo , Análise Espaço-Temporal
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