Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 569
Filtrar
1.
Allergol. immunopatol ; 47(4): 372-327, jul.-ago. 2019. graf, tab
Artigo em Inglês | IBECS | ID: ibc-186509

RESUMO

Introduction: Chronic granulomatous disease (CGD) is a disorder of phagocyte function, characterized by pyogenic infections and granuloma formation caused by defects in NADPH oxidase complex activity. Although the effect of CGD mainly reflects the phagocytic compartment, B cell responses are also impaired in patients with CGD. Materials and methods: Flow cytometric analysis was performed on peripheral blood samples from 35 CGD patients age-matched with healthy controls (HC). The target cells of our study were the naive (IgD+/CD27-), memory (IgD-/CD27+), and B1a (CD5+) cells. Immunoglobulins (Igs) were also measured. This study was performed in a Latin American cohort. Results: We found significantly higher levels of naive B cells and B1a cells, but lower levels of memory B cells were found in CGD patients compared to HC. There was no significant difference of cell percentages per inheritance type. Discussion: Our findings suggest that the deficiency of NADPH oxidase components can affect the differentiation of naive B cells to memory B cells. Consequently, memory cells will be low, which also influenced the expression of CD27 in memory B cells and as a result, the percentage of naive cells increases. An altered phenotype of B lymphocytes in CGD patients may contribute to the opportunistic infections and autoimmune disorders that are seen in this disease


No disponible


Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Adulto , Linfócitos B/imunologia , Subpopulações de Linfócitos B/imunologia , Doença Granulomatosa Crônica/imunologia , NADPH Oxidase 2/genética , Separação Celular , Estudos de Coortes , Citometria de Fluxo , Doença Granulomatosa Crônica/genética , Memória Imunológica , México , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/metabolismo
2.
Allergol Immunopathol (Madr) ; 47(4): 372-377, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31176517

RESUMO

INTRODUCTION: Chronic granulomatous disease (CGD) is a disorder of phagocyte function, characterized by pyogenic infections and granuloma formation caused by defects in NADPH oxidase complex activity. Although the effect of CGD mainly reflects the phagocytic compartment, B cell responses are also impaired in patients with CGD. MATERIALS AND METHODS: Flow cytometric analysis was performed on peripheral blood samples from 35 CGD patients age-matched with healthy controls (HC). The target cells of our study were the naive (IgD+/CD27-), memory (IgD-/CD27+), and B1a (CD5+) cells. Immunoglobulins (Igs) were also measured. This study was performed in a Latin American cohort. RESULTS: We found significantly higher levels of naive B cells and B1a cells, but lower levels of memory B cells were found in CGD patients compared to HC. There was no significant difference of cell percentages per inheritance type. DISCUSSION: Our findings suggest that the deficiency of NADPH oxidase components can affect the differentiation of naive B cells to memory B cells. Consequently, memory cells will be low, which also influenced the expression of CD27 in memory B cells and as a result, the percentage of naive cells increases. An altered phenotype of B lymphocytes in CGD patients may contribute to the opportunistic infections and autoimmune disorders that are seen in this disease.


Assuntos
Subpopulações de Linfócitos B/imunologia , Linfócitos B/imunologia , Doença Granulomatosa Crônica/imunologia , NADPH Oxidase 2/genética , Adolescente , Adulto , Separação Celular , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Citometria de Fluxo , Doença Granulomatosa Crônica/genética , Humanos , Memória Imunológica , Imunofenotipagem , Lactente , Masculino , México , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/metabolismo , Adulto Jovem
4.
Blood ; 133(20): 2130-2139, 2019 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-30898864

RESUMO

Primary immunodeficiencies affecting the function of neutrophils and other phagocytic leukocytes are notable for an increased susceptibility to bacterial and fungal infections as a result of impaired leukocyte recruitment, ingestion, and/or killing of microbes. The underlying molecular defects can also impact other innate immune responses to infectious and inflammatory stimuli, leading to inflammatory and autoimmune complications that are not always directly related to infection. This review will provide an update on congenital disorders affecting neutrophil function in which a combination of host defense and inflammatory complications are prominent, including nicotinamide dinucleotide phosphate oxidase defects in chronic granulomatous disease and ß2 integrin defects in leukocyte adhesion deficiency.


Assuntos
Doença Granulomatosa Crônica/patologia , Neutrófilos/patologia , Animais , Doenças Autoimunes/etiologia , Doenças Autoimunes/genética , Doenças Autoimunes/imunologia , Doenças Autoimunes/patologia , Variação Genética , Doença Granulomatosa Crônica/complicações , Doença Granulomatosa Crônica/genética , Doença Granulomatosa Crônica/imunologia , Humanos , Imunidade Inata , Inflamação/etiologia , Inflamação/genética , Inflamação/imunologia , Inflamação/patologia , NADPH Oxidases/genética , NADPH Oxidases/imunologia , Neutrófilos/imunologia
5.
Int Arch Allergy Immunol ; 179(1): 62-73, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30904913

RESUMO

Recurrent severe bacterial and fungal infections are characteristic features of the rare genetic immunodeficiency disorder chronic granulomatous disease (CGD). The disease usually manifests within the first years of life with an incidence of 1 in approximately 200,000 live births. The incidence is higher in Iran and Morocco where it reaches 1.5 per 100,000 live births. Mutations have been described in the 5 subunits of NADPH oxidase, mostly in gp91phox and p47phox, with fewer mutations reported in p67phox, p22phox, and p40phox. These mutations cause loss of superoxide production in phagocytic cells. CYBB, the gene encoding the large gp91phox subunit of the transmembrane component cytochrome b558 of the NADPH oxidase complex, is localized on the X-chromosome. Genetic defects in CYBB are responsible for the disease in the majority of male CGD patients. CGD is associated with the development of granulomatous reactions in the skin, lungs, bones, and lymph nodes, and chronic infections may be seen in the liver, gastrointestinal tract, brain, and eyes. There is usually a history of repeated infections, including inflammation of the lymph glands, skin infections, and pneumonia. There may also be a persistent runny nose, inflammation of the skin, and inflammation of the mucous membranes of the mouth. Gastrointestinal problems can also occur, including diarrhea, abdominal pain, and perianal abscesses. Infection of the bones, brain abscesses, obstruction of the genitourinary tract and/or gastrointestinal tract due to the formation of granulomatous tissue, and delayed growth are also symptomatic of CGD. The prevention of infectious complications in patients with CGD involves targeted prophylaxis against opportunistic microorganisms such as Staphylococcus aureus, Klebsiella spp., Salmonella spp. and Aspergillus spp. In this review, we provide an update on organ involvement and the association with specific isolated microorganisms in CGD patients.


Assuntos
Infecções Bacterianas/etiologia , Doença Granulomatosa Crônica/complicações , Micoses/etiologia , Autoimunidade , Criança , Pré-Escolar , Feminino , Doença Granulomatosa Crônica/genética , Doença Granulomatosa Crônica/imunologia , Humanos , Lactente , Abscesso Hepático/etiologia , Pneumopatias/etiologia , Masculino , NADPH Oxidases/genética , Dermatopatias/etiologia
6.
Laryngoscope ; 129(11): 2447-2450, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-30851064

RESUMO

A review of the treatment of allergic and invasive fungal sinusitis, as well as a presentation of the first recorded case of a conversion from allergic fungal sinusitis (AFS) to chronic granulomatous invasive sinusitis and the fourth case of invasive fungal sinusitis associated with Curvularia. This immunocompetent patient suffering from chronic AFS converted after repeated high-dose steroid tapers and noncompliance. AFS may present atypically and should be suspected even in immunocompetent patients with sinus disease who report new onset pain and neurologic symptoms. Clinicians should consider the potential complications associated with repeated systemic steroid administration. Laryngoscope, 129:2447-2450, 2019.


Assuntos
Doença Granulomatosa Crônica/microbiologia , Infecções Fúngicas Invasivas/microbiologia , Doenças dos Seios Paranasais/microbiologia , Rinite Alérgica/microbiologia , Sinusite/microbiologia , Adulto , Doença Crônica , Doença Granulomatosa Crônica/imunologia , Humanos , Imunocompetência , Infecções Fúngicas Invasivas/imunologia , Masculino , Doenças dos Seios Paranasais/imunologia , Rinite Alérgica/imunologia , Sinusite/imunologia
7.
Mol Oral Microbiol ; 34(2): 27-38, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30632295

RESUMO

Neutrophils are phagocytic innate immune cells essential for killing bacteria via activation of a wide variety of effector responses and generation of large amounts of reactive oxygen species (ROS). Majority of the ROS in neutrophils is generated by activation of the superoxide-generating enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Independent of their anti-microbial function, NADPH oxidase-derived ROS have emerged as key regulators of host immune responses and neutrophilic inflammation. Data from patients with inherited defects in the NADPH oxidase subunit alleles that ablate its enzyme function as well as mouse models demonstrate profound dysregulation of host inflammatory responses, neutrophil hyper-activation and tissue damage in response to microbial ligands or tissue trauma. A large body of literature now demonstrates how oxidants function as essential signaling molecules that are essential for the regulation of neutrophil responses during priming, degranulation, neutrophil extracellular trap formation, and apoptosis, independent of their role in microbial killing. In this review we summarize how NADPH oxidase-derived oxidants modulate neutrophil function in a cell intrinsic manner and regulate host inflammatory responses. In addition, we summarize studies that have elucidated possible roles of oxidants in neutrophilic responses within the oral mucosa and periodontal disease.


Assuntos
NADPH Oxidases/imunologia , NADPH Oxidases/metabolismo , Neutrófilos/enzimologia , Neutrófilos/imunologia , Neutrófilos/metabolismo , Animais , Anti-Infecciosos/metabolismo , Anti-Infecciosos/farmacologia , Apoptose , Bactérias/imunologia , Bactérias/patogenicidade , Armadilhas Extracelulares , Doença Granulomatosa Crônica/imunologia , Humanos , Imunidade Inata , Inflamação/imunologia , Camundongos , Mucosa Bucal/imunologia , NADPH Oxidase 2 , Estresse Oxidativo , Doenças Periodontais/imunologia , Espécies Reativas de Oxigênio/metabolismo , Espécies Reativas de Oxigênio/farmacologia , Explosão Respiratória/imunologia
8.
J Infect Chemother ; 25(5): 365-367, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30642769

RESUMO

Chronic granulomatous disease (CGD) is a primary immunodeficiency disease characterized by severe recurrent infections such as pneumonia, liver and skin infections. However, prostatic abscesses are rare as only two cases have been reported thus far. We present the case of a 41-year-old patient with CGD who was admitted to the hospital with fever and subsequently, Klebsiella pneumoniae was identified on blood culture. Abdominal computed tomography revealed a prostatic abscess. He improved with intravenous antibiotics and drainage of the abscess. After he was taken off the intravenous antibiotics and started on an oral agent, he was discharged from the hospital. We confirmed a reduction in the prostatic abscess size and continued the antibiotic therapy for 52 days. A prostatic abscess is an uncommon disease being diagnosed at a median age of 49 years. Sometimes it is discovered in patients with fever of unknown origin and might be considered as an infection site of CGD patients.


Assuntos
Abscesso Abdominal/microbiologia , Bacteriemia/microbiologia , Doença Granulomatosa Crônica/imunologia , Infecções por Klebsiella/microbiologia , Doenças Prostáticas/microbiologia , Abscesso Abdominal/imunologia , Abscesso Abdominal/terapia , Adulto , Antibacterianos/uso terapêutico , Bacteriemia/imunologia , Bacteriemia/terapia , Drenagem , Humanos , Infecções por Klebsiella/imunologia , Klebsiella pneumoniae/isolamento & purificação , Klebsiella pneumoniae/patogenicidade , Masculino , Próstata/diagnóstico por imagem , Próstata/microbiologia , Próstata/cirurgia , Doenças Prostáticas/imunologia , Tomografia Computadorizada por Raios X , Resultado do Tratamento
9.
Scand J Immunol ; 89(2): e12737, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30506560

RESUMO

Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by susceptibility to bacterial and fungal infections resulting from the inadequacy of phagocytic leucocytes to produce reactive oxygen radicals. CGD is a genetically heterogeneous disease with an X-linked recessive (XR-CGD) form caused by mutations in the CYBB (OMIM #300481) gene encoding the gp91(phox) protein, and an autosomal recessive (AR-CGD) form caused by mutations in the CYBA (OMIM #608508), NCF1 (OMIM #608512), NCF2 (OMIM #608515) and NCF4 (OMIM #601488) genes encoding p22(phox), p47(phox), p67(phox) and p40(phox), respectively. The genetic mutation of one of the cytosolic p47phox/p67phox proteins and membrane-bound gp91phox/p22phox proteins, which constitutes the NADPH oxidase enzyme complex, causes the disease. In this study, we evaluated the clinical, laboratory and genetic findings and the prognostic effects of molecular inheritance of our 24 CGD cases (14 XR, 10 autosomal recessive-AR). Consanguinity (three XR and all AR cases) showed statistically significant relationship with the type of hereditary inheritance (P < 0.001). 83% patients had an infection since early infancy. The mean age of initiation of symptoms was earlier in XR cases, and 78% patients had respiratory tract infections. Bone marrow transplantation was performed in five XR cases (two ex) and four AR (one ex) cases. Three of nine XR and two of six AR cases deceased on medical follow-up. In countries especially with high consanguinity rates, the early diagnosis for appropriate prophylactic treatment of CGD is quietly important to avoid from recurrent severe infections, early death and fatal complications of late transplantation.


Assuntos
Consanguinidade , Doença Granulomatosa Crônica/imunologia , NADPH Oxidases/metabolismo , Adolescente , Idade de Início , Transplante de Medula Óssea , Criança , Pré-Escolar , Feminino , Seguimentos , Genes Recessivos/genética , Genes Ligados ao Cromossomo X/genética , Doença Granulomatosa Crônica/epidemiologia , Doença Granulomatosa Crônica/genética , Humanos , Masculino , Mutação/genética , NADPH Oxidase 2/genética , Espécies Reativas de Oxigênio/metabolismo , Estudos Retrospectivos , Resultado do Tratamento , Turquia/epidemiologia
12.
Microbiol Immunol ; 62(4): 269-280, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29573449

RESUMO

Human phagocyte flavocytochrome b558 (Cyt b), the catalytic center of nicotinamide adenine dinucleotide phosphate oxidase, consists of a heavily glycosylated large subunit (gp91phox ; Nox2) and a small subunit (p22phox ). Cyt b is a membrane-spanning complex enzyme. Chronic granulomatous disease (CGD) is predominantly caused by a mutation in the CYBB gene encoding gp91phox on the X-chromosome. Because the phagocytes of patients with CGD are not able to generate the superoxide anion, these patients are susceptible to severe infections that can be fatal. It has been suggested that the extracellular region of gp91phox is necessary for and critical to forming the epitope of mAb 7D5 and that 7D5 provides a useful tool for rapid screening of X-linked CGD by FACS. To further elucidate the mAb 7D5 epitope on human gp91phox , chimeric DNA expressed human and mouse gp91phox recombinant protein were constructed. The fusion proteins were immunostained for mAb 7D5 and analyzed by FACS and western blot analysis. The 143 ELGDRQNES151 region was found to reside at the extracellular surface on human gp91phox and to be an important epitope for the interaction with mAb 7D5, as analyzed by FACS analysis. In particular, amino acid R147 is a unique epitope on the membrane-associated Cyt b for mAb 7D5. In conclusion, it is proposed that FACS analysis using mAb 7D5 is a valuable tool for early diagnosis of CGD.


Assuntos
Anticorpos Monoclonais/imunologia , Grupo dos Citocromos b/imunologia , Epitopos/imunologia , NADPH Oxidase 2/imunologia , NADPH Oxidases/imunologia , Fagócitos/imunologia , Sequência de Aminoácidos , Animais , Anticorpos Monoclonais/química , Linhagem Celular , Epitopos/análise , Epitopos/química , Doença Granulomatosa Crônica/imunologia , Células HL-60 , Humanos , Glicoproteínas de Membrana/química , Glicoproteínas de Membrana/genética , Camundongos , Mutação , NADPH Oxidase 2/biossíntese , NADPH Oxidase 2/química , NADPH Oxidase 2/genética , Domínios Proteicos , Células RAW 264.7 , Proteínas Recombinantes de Fusão/genética , Análise de Sequência de Proteína , Homologia de Sequência de Aminoácidos , Superóxidos/metabolismo
13.
mBio ; 9(2)2018 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-29588403

RESUMO

Invasive aspergillosis (IA) remains the primary cause of morbidity and mortality in chronic granulomatous disease (CGD) patients, often due to infection by Aspergillus species refractory to antifungals. This motivates the search for alternative treatments, including immunotherapy. We investigated the effect of exogenous type I interferon (IFN) activation on the outcome of IA caused by three Aspergillus species, A. fumigatus, A. nidulans, and A. tanneri, in CGD mice. The animals were treated with poly(I):poly(C) carboxymethyl cellulose poly-l-lysine (PICLC), a mimetic of double-stranded RNA, 24 h preinfection and postinfection. The survival rates and lung fungal burdens were markedly improved by PICLC immunotherapy in animals infected with any one of the three Aspergillus species. While protection from IA was remarkable, PICLC induction of type I IFN in the lungs surged 24 h posttreatment and returned to baseline levels by 48 h, suggesting that PICLC altered early events in protection against IA. Immunophenotyping of recruited leukocytes and histopathological examination of tissue sections showed that PICLC induced similar cellular infiltrates as those in untreated-infected mice, in both cases dominated by monocytic cells and neutrophils. However, the PICLC immunotherapy resulted in a marked earlier recruitment of the leukocytes. Unlike with conidia, infection with A. nidulans germlings reduced the protective effect of PICLC immunotherapy. Additionally, antibody depletion of neutrophils totally reversed the protection, suggesting that neutrophils are crucial for PICLC-mediated protection. Together, these data show that prophylactic PICLC immunotherapy prerecruits these cells, enabling them to attack the conidia and thus resulting in a profound protection from IA.IMPORTANCE Patients with chronic granulomatous disease (CGD) are highly susceptible to invasive aspergillosis (IA). While Aspergillus fumigatus is the most-studied Aspergillus species, CGD patients often suffer IA caused by A. nidulans, A. tanneri, and other rare species. These non-fumigatus Aspergillus species are more resistant to antifungal drugs and cause higher fatality rates than A. fumigatus Therefore, alternative therapies are needed to protect CGD patients. We report an effective immunotherapy of mice infected with three Aspergillus species via PICLC dosing. While protection from IA was long lasting, PICLC induction of type I IFN surged but quickly returned to baseline levels, suggesting that PICLC was altering early events in IA. Interestingly, we found responding immune cells to be similar between PICLC-treated and untreated-infected mice. However, PICLC immunotherapy resulted in an earlier recruitment of the leukocytes and suppressed fungal growth. This study highlights the value of type I IFN induction in CGD patients.


Assuntos
Antifúngicos/uso terapêutico , Aspergilose/tratamento farmacológico , Aspergillus/patogenicidade , Doença Granulomatosa Crônica/tratamento farmacológico , Doença Granulomatosa Crônica/microbiologia , Interferon Tipo I/uso terapêutico , Pulmão/metabolismo , Pulmão/microbiologia , Neutrófilos/citologia , Animais , Aspergilose/imunologia , Aspergilose/microbiologia , Citometria de Fluxo , Doença Granulomatosa Crônica/imunologia , Pulmão/imunologia , Masculino , Camundongos , Camundongos Knockout , Neutrófilos/efeitos dos fármacos
14.
Clin Immunol ; 193: 52-59, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29410324

RESUMO

Chronic granulomatous disease (CGD) is a phagocytic disorder characterized by a defective production of reactive oxygen species (ROSs). Although infections and granuloma formation are the most common manifestations in CGD patients, a significant number of patients experienced autoimmunity and inflammatory diseases suggesting that adaptive immune abnormalities might be involved. Here we investigated T-cell compartment and showed that CGD patients had a skewed TCRV-beta distribution in CD8+ T cells, particularly in older patients, and a reduced proliferative responses toward mitogens compared to healthy donors (HD). Afterwards we studied the role of gp91phox protein in causing these alterations and demonstrated that human T cells do not express gp91phox and TCR-stimulated ROS generation is gp91phox-NADPH oxidase independent. Finally, we proved that the NADPH oxidase is not active in the T cell compartment even when forcing gp91phox expression transducing T cells from X-CGD and HD with a SIN lentiviral vector (LVV) encoding the gp91phox cDNA.


Assuntos
Linfócitos T CD8-Positivos/fisiologia , Doença Granulomatosa Crônica/imunologia , NADPH Oxidase 2/metabolismo , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Adolescente , Adulto , Proliferação de Células , Células Cultivadas , Criança , Pré-Escolar , Humanos , Lentivirus/genética , Ativação Linfocitária , Masculino , NADPH Oxidase 2/genética , NADPH Oxidases/metabolismo , Fagocitose , Espécies Reativas de Oxigênio/metabolismo , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Adulto Jovem
15.
J Allergy Clin Immunol ; 141(1): 365-371, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28528201

RESUMO

BACKGROUND: Chronic granulomatous disease (CGD) is characterized by recurrent life-threatening bacterial and fungal infections and aberrant inflammation. Mutations in CYBB cause X-linked CGD and account for 65% to 70% of cases in Western countries. OBJECTIVE: We sought to understand the clinical manifestations associated with the X-linked CGD carrier state. METHODS: We undertook a comprehensive retrospective study of 162 affected female subjects. We examined dihydrorhodamine 123 (DHR) oxidation data for percentage of X-chromosome inactivation. We correlated lyonization (%DHR+) with clinical features. Where possible, we followed %DHR+ values over time. RESULTS: Clinical data were available for 93 female subjects: %DHR+ values were 46% (mean) and 47% (median; SD, 24). Using the %DHR+ value as the criterion for X inactivation, 78% of patients had levels of inactivation of 20% to 80%, suggesting random inactivation that was independent of age. In contrast, carriers with CGD-type infections had median %DHR+ values of 8% (n = 14; range, 0.06% to 48%), and those with only autoimmune or inflammatory manifestations had median %DHR+ values of 39% (n = 31; range, 7.4% to 74%). Those with both infections and autoimmunity had low %DHR+ values (n = 6; range, 3% to 14%). A %DHR+ value of less than 10% was strongly associated with infections (odds ratio, 99). Strong association persisted when %DHR+ values were less than 20% (odds ratio, 12). Autoimmunity was not associated with %DHR+ values. In 2 sets of identical twins, the %DHR+ populations tracked closely over time. Although the %DHR+ populations were very similar between sisters, those between mothers and daughters were unrelated. CONCLUSIONS: A low %DHR+ value strongly predicts infection risk in X-linked CGD carriers, and the carrier state itself is associated with autoimmunity.


Assuntos
Genes Ligados ao Cromossomo X , Estudos de Associação Genética , Doença Granulomatosa Crônica/diagnóstico , Doença Granulomatosa Crônica/genética , Heterozigoto , Fenótipo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Criança , Pré-Escolar , Feminino , Doença Granulomatosa Crônica/complicações , Doença Granulomatosa Crônica/imunologia , Humanos , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Lactente , Pessoa de Meia-Idade , Mutação , Razão de Chances , Avaliação de Sintomas , Inativação do Cromossomo X , Adulto Jovem
16.
J Clin Pathol ; 71(5): 425-435, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-28970295

RESUMO

BACKGROUND: Primary immunodeficiency disorders (PID) include a wide spectrum of inherited disorders characterised by functional abnormalities of one or more components of the immune system. Recent updates from the genomic data have contributed significantly to its better understanding with identification of new entities. Diagnosis is always challenging due to their variable clinical presentation. With the evolution of molecular diagnosis, many of these children are being diagnosed early and offered appropriate therapy. However, in developing countries, early diagnosis is still not being made: as a result these patients succumb to their disease. Autopsy data on PID is notably lacking in the literature with histopathological evaluation of PID being limited to rare case reports. OBJECTIVE: To analyse the clinical, immunologic (including mutational) and morphologic features at autopsy in 10 proven and suspected cases of primary immunodeficiency disorders diagnosed at our Institute over the past decade. METHODS: Study includes a detailed clinico-pathological analysis of 10 proven and suspected cases of primary immunodeficiency disorders. RESULTS: A varied spectrum of infectious and non-infectious complications were identified in these cases of which fungal infections were found to be more frequent compared with viral or bacterial infections. Rare and novel morphological findings, like granulomatous involvement of the heart in a patient with chronic granulomatous disease, systemic amyloidosis in a teenage girl with X-linked agammaglobulinemia, are highlighted which is distinctly lacking in the literature. CONCLUSIONS: The present study is perhaps the first autopsy series on PID. Even in the molecular era, such analysis is still important, as correlation of pathological features with clinical symptoms provides clues for a timely diagnosis and appropriate therapeutic intervention.


Assuntos
Amiloidose/patologia , Doença Granulomatosa Crônica/patologia , Hospedeiro Imunocomprometido , Síndromes de Imunodeficiência/patologia , Infecções Oportunistas/patologia , Amiloidose/genética , Amiloidose/imunologia , Amiloidose/mortalidade , Autopsia , Biópsia , Causas de Morte , Criança , Pré-Escolar , Análise Mutacional de DNA , Países em Desenvolvimento , Diagnóstico Precoce , Feminino , Marcadores Genéticos , Predisposição Genética para Doença , Doença Granulomatosa Crônica/genética , Doença Granulomatosa Crônica/imunologia , Doença Granulomatosa Crônica/mortalidade , Humanos , Imuno-Histoquímica , Síndromes de Imunodeficiência/genética , Síndromes de Imunodeficiência/imunologia , Síndromes de Imunodeficiência/mortalidade , Índia , Lactente , Recém-Nascido , Masculino , Mutação , Infecções Oportunistas/genética , Infecções Oportunistas/imunologia , Infecções Oportunistas/mortalidade , Fenótipo , Valor Preditivo dos Testes , Prognóstico
17.
Curr Opin Hematol ; 25(1): 7-12, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29135572

RESUMO

PURPOSE OF REVIEW: Chronic granulomatous disease (CGD) is a primary immunodeficiency, with a defect of phagocytes in killing specific pathogens. CGD is characterized by severe recurrent bacterial and fungal infections and dysregulated inflammatory response. Since its first description as fatal disease about 60 years ago, a significant improvement in outcome has been achieved in the last 20 years. The purpose of this review is to framework recent advances in CGD immunopathogenesis, management of disease manifestation and cure of CGD patients. RECENT FINDINGS: For years, CGD is a known cause of life-threatening infections and excessive inflammation. The cause and the management of inflammatory reactions, however, have not been clarified, and the range of clinical presentation is growing with corresponding novel therapeutic interventions. Recent work focuses on the best outcome of hematopoietic stem cell transplantation (HSCT) and gene therapy for the cure of CGD patients, more specifically, those with X-linked and p47 mutations. SUMMARY: The genetics and phenotype of CGD is well characterized; however, the underlying mechanisms, the treatment of its inflammatory manifestations and the cure of CGD is under further investigation.


Assuntos
Doença Granulomatosa Crônica , Terapia Genética , Doença Granulomatosa Crônica/imunologia , Doença Granulomatosa Crônica/terapia , Transplante de Células-Tronco Hematopoéticas , Humanos , Inflamação/imunologia , Inflamação/terapia
18.
J Innate Immun ; 10(2): 145-160, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29248928

RESUMO

Invasive aspergillosis mainly occurs in immunocompromised patients and is commonly caused by Aspergillus fumigatus, while A.nidulans is rarely the causative agent. However, in chronic granulomatous disease (CGD) patients, A. nidulans is a frequent cause of invasive aspergillosis and is associated with higher mortality. Immune recognition of A. nidulans was compared to A. fumigatus to offer an insight into why A. nidulans infections are prevalent in CGD. Live cell imaging with J774A.1 macrophage-like cells and LC3-GFP-mCherry bone marrow-derived macrophages (BMDMs) revealed that phagocytosis of A. nidulans was slower compared to A. fumigatus. This difference could be attributed to slower migration of J774A.1 cells and a lower percentage of migrating BMDMs. In addition, delayed phagosome acidification and LC3-associated phagocytosis was observed with A. nidulans. Cytokine and oxidative burst measurements in human peripheral blood mononuclear cells revealed a lower oxidative burst upon challenge with A. nidulans. In contrast, A. nidulans induced significantly higher concentrations of cytokines. Collectively, our data demonstrate that A. nidulans is phagocytosed and processed at a slower rate compared to A. fumigatus, resulting in reduced fungal killing and increased germination of conidia. This slower rate of A. nidulans clearance may be permissive for overgrowth within certain immune settings.


Assuntos
Aspergillus fumigatus/imunologia , Aspergillus nidulans/imunologia , Fagocitose , Animais , Aspergilose/imunologia , Aspergilose/microbiologia , Linhagem Celular , Movimento Celular , Citocinas/metabolismo , Doença Granulomatosa Crônica/imunologia , Doença Granulomatosa Crônica/microbiologia , Humanos , Cinética , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/microbiologia , Macrófagos/metabolismo , Macrófagos/microbiologia , Camundongos , Fagossomos/metabolismo , Fagossomos/microbiologia , Espécies Reativas de Oxigênio/metabolismo , Especificidade da Espécie
20.
Rev Chil Pediatr ; 88(1): 136-141, 2017 02.
Artigo em Espanhol | MEDLINE | ID: mdl-28288231

RESUMO

Primary immunodeficiency diseases (PID) are congenital disorders secondary to an impaired immune response. Infections, autoimmune disorders, atopy, and lymphoproliferative syndromes are commonly associated with this disorder. OBJECTIVE: To present and discuss 3 infants diagnosed with PID. CLINICAL CASES: The cases are presented of three patients with PID diagnosed during their first admission to a Paediatric Intensive Critical Care Unit. The first patient, a 4-month-old infant affected by a severe pneumonia, and was diagnosed as a Severe Combined Immunodeficiency Disease. The second patient was an 8-month-old infant with Candida lusitaniae mesenteric adenitis, and diagnosed with a Chronic Granulomatous Disease. The last patient, a 6-month-old infant presented with ecthyma gangrenosum and X-linked agammaglobulinaemia. CONCLUSION: PID should be suspected when an infectious disease does not responde to the appropriate therapy within the expected period. An update of each disease is presented.


Assuntos
Agamaglobulinemia/diagnóstico , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico , Doença Granulomatosa Crônica/diagnóstico , Síndromes de Imunodeficiência/diagnóstico , Agamaglobulinemia/imunologia , Agamaglobulinemia/fisiopatologia , Doenças Genéticas Ligadas ao Cromossomo X/imunologia , Doenças Genéticas Ligadas ao Cromossomo X/fisiopatologia , Doença Granulomatosa Crônica/imunologia , Doença Granulomatosa Crônica/fisiopatologia , Humanos , Síndromes de Imunodeficiência/imunologia , Síndromes de Imunodeficiência/fisiopatologia , Lactente , Unidades de Terapia Intensiva Pediátrica , Masculino , Índice de Gravidade de Doença
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA