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1.
Rinsho Ketsueki ; 60(6): 702-707, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31281163

RESUMO

Inherited bone marrow failure syndromes (IBMFS) are caused by mutations in genes associated with DNA repair and telomere maintenance. In addition, mutations in ribosome-related genes cause defective hematopoiesis. Patients with IBMFS exhibit a predisposition to developing hematological malignancy or solid tumor because of the defect in cellular and molecular hemostasis. The SAMD9 mutation causes the multisystem disorder, MIRAGE syndrome, characterized by congenital adrenal hypoplasia and loss of chromosome 7, providing a novel insight into the correlation between the germline and somatic mutations of SAMD9/SAMD9L and myelodysplastic syndrome (MDS) with monosomy 7. Primary immunodeficiency diseases (PID) are caused by inborn errors of the immune system. PID patients with inadequate tumor immunity are at an elevated risk of developing malignancies such as lymphoma, leukemia, and gastrointestinal cancer. Recently, monocytopenia and mycobacterial infection (MonoMAC) syndrome with the GATA2 gene mutation have been reported as PID related to bone marrow failure. Patients with MonoMAC syndrome often develop MDS and acute myeloid leukemia. Here, we present the pediatric-onset IBMFS and/or PID with cancer predisposition and briefly discuss the tumorigenesis in each monogenic disease.


Assuntos
Anemia Aplástica/complicações , Doenças da Medula Óssea/complicações , Predisposição Genética para Doença , Hemoglobinúria Paroxística/complicações , Síndromes de Imunodeficiência/complicações , Neoplasias/genética , Anemia Aplástica/genética , Doenças da Medula Óssea/genética , Criança , Hemoglobinúria Paroxística/genética , Humanos , Síndromes de Imunodeficiência/genética , Síndromes Mielodisplásicas
2.
Rinsho Ketsueki ; 60(6): 708-715, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31281164

RESUMO

Lymphoproliferative disorders (LPDs) are caused by dysregulated lymphocyte proliferation and include polyclonal benign and monoclonal malignant diseases. LPDs frequently occur in immunocompromized patients, particularly those with primary immunodeficiency disease (PID), a monogenic disease. PID-associated LPD corresponds to inherited LPD. Here, we describe inherited LPD and focus on IKZF1-associated diseases and Epstein-Barr virus-associated LPD, such as ZAP70 deficiency and X-linked lymphoproliferative syndrome type 1 with somatic reversion mosaicism. Disclosing the pathogenesis of inherited LPDs would lead to a broad understanding of LPDs and development of new treatment strategies.


Assuntos
Síndromes de Imunodeficiência/complicações , Transtornos Linfoproliferativos/genética , Infecções por Vírus Epstein-Barr , Herpesvirus Humano 4 , Humanos , Fator de Transcrição Ikaros/genética
3.
BMC Infect Dis ; 19(1): 522, 2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-31200658

RESUMO

BACKGROUND: To describe patients with inherited and acquired complement deficiency who developed invasive meningococcal disease (IMD) in England over the last decade. METHODS: Public Health England conducts enhanced surveillance of IMD in England. We retrospectively identified patients with complement deficiency who developed IMD in England during 2008-2017 and retrieved information on their clinical presentation, vaccination status, medication history, recurrence of infection and outcomes, as well as characteristics of the infecting meningococcal strain. RESULTS: A total of 16 patients with 20 IMD episodes were identified, including four with two episodes. Six patients had inherited complement deficiencies, two had immune-mediated conditions associated with complement deficiency (glomerulonephritis and vasculitis), and eight others were on Eculizumab therapy, five for paroxysmal nocturnal haemoglobinuria and three for atypical haemolytic uraemic syndrome. Cultures were available for 7 of 11 episodes among those with inherited complement deficiencies/immune-mediated conditions and the predominant capsular group was Y (7/11), followed by B (3/11) and non-groupable (1/11) strains. Among patients receiving Eculizumab therapy, 3 of the 9 episodes were due to group B (3/9), three others were NG but genotypically group B, and one case each of groups E, W and Y. CONCLUSIONS: In England, complement deficiency is rare among IMD cases and includes inherited disorders of the late complement pathway, immune-mediated disorders associated with low complement levels and patients on Eculizumab therapy. IMD due to capsular group Y predominates in patient with inherited complement deficiency, whilst those on Eculizumab therapy develop IMD due to more diverse capsular groups including non-encapsulated strains.


Assuntos
Proteínas do Sistema Complemento/deficiência , Síndromes de Imunodeficiência/complicações , Infecções Meningocócicas/complicações , Infecções Meningocócicas/microbiologia , Neisseria meningitidis/genética , Adolescente , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Criança , Pré-Escolar , Inglaterra/epidemiologia , Genótipo , Humanos , Síndromes de Imunodeficiência/etiologia , Infecções Meningocócicas/epidemiologia , Programas Nacionais de Saúde/estatística & dados numéricos , Polissacarídeos Bacterianos/genética , Estudos Retrospectivos , Adulto Jovem
4.
Tohoku J Exp Med ; 247(4): 265-269, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31006737

RESUMO

Chronic granulomatous disease (CGD) is a type of primary immunodeficiency disease, which increases susceptibility to recurrent bacterial and fungal infections. Sputum and bronchoalveolar lavage fluid are often obtained using bronchoscopy from adult patients for pathogenic diagnosis, although this approach is much more invasive for infants. We report the case of a 2-month-old boy with CGD, in which gastric aspirate culture was used to diagnose fungal pneumonia. Rasamsonia piperina was isolated from the gastric aspirate, and the patient was successfully treated with micafungin based on the drug susceptibility test results for the fungal isolate. The acid tolerance test revealed that R. piperina could grow at pH 2, indicating high acid resistance. Although we can only report our experience with a single case, gastric aspirate culture may be a useful tool for detecting fungal respiratory pathogens in children with primary immunodeficiency. Detecting these pathogens may help improve outcomes, as early diagnosis and appropriate treatment are extremely important for immunocompromised patients with respiratory infections.


Assuntos
Ascomicetos/fisiologia , Síndromes de Imunodeficiência/congênito , Síndromes de Imunodeficiência/diagnóstico , Micoses/microbiologia , Pneumonia/complicações , Pneumonia/microbiologia , Estômago/patologia , Humanos , Concentração de Íons de Hidrogênio , Síndromes de Imunodeficiência/complicações , Lactente , Pneumonia/diagnóstico por imagem , Sucção , Tomografia Computadorizada por Raios X
5.
BMJ Case Rep ; 12(3)2019 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-30898962

RESUMO

The Good's syndrome (GS) is a low prevalence entity where thymoma often is associated with immunodeficiency. Patients may start presenting recurrent rhinosinusal infections, bronchopulmonary infections, haematological alterations and diarrhoea, secondary to immunodeficiency. They can also present respiratory symptoms and parathymic syndromes derived from the existence of thymoma, a slow-growing neoplasm located in the anterior mediastinum. We present the case of a 76-year-old man diagnosed with thymoma by image analysis, which had presented multiple episodes of pneumonia and two admissions to the hospital for diarrhoea of weeks of evolution. After finishing the study, the patient is diagnosed of GS. In this case, thymectomy prevented the appearance of parathymic syndrome, but without any effect on immunodeficiency symptoms. To decrease repeat infections, substitution therapy with immunoglobulins was started. The prognosis will depend mainly on the recurrent infectious and to a lesser extent on the thymic neoplasm.


Assuntos
Síndromes de Imunodeficiência/complicações , Timoma/etiologia , Neoplasias do Timo/etiologia , Administração Intravenosa , Idoso , Humanos , Imunoglobulina G/administração & dosagem , Síndromes de Imunodeficiência/tratamento farmacológico , Fatores Imunológicos/administração & dosagem , Masculino , Timoma/patologia , Neoplasias do Timo/patologia
6.
Orphanet J Rare Dis ; 14(1): 61, 2019 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-30819232

RESUMO

BACKGROUND: Warts Hypogammaglobulinemia Immunodeficiency Myelokathexis (WHIM) syndrome is a primary immunodeficiency characterized by recurrent bacterial infections, severe chronic neutropenia, with lymphopenia, monocytopenia and myelokathexis which is caused by heterozygous gain of functions mutations of the CXC chemokine receptor 4 (CXCR4). WHIM patients display an increased incidence of non-hematopoietic conditions, such as congenital heart disease suggesting that abnormal CXCR4 may put these patients at increased risk of congenital anomalies. Studies conducted on CXCR4 and SDF-1-deficient mice have demonstrated the role of CXCR4 signaling in neuronal cell migration and brain development. In particular, CXCR4 conditional knockout mice display abnormal cerebellar morphology and poor coordination and balance on motor testing. RESULTS: In order to evaluate a possible neurological involvement in WHIM syndrome subjects, we performed neurological examination, including International Cooperative Ataxia Rating Scale, cognitive and psychopathological assessment and brain Magnetic Resonance Imaging (MRI) in 6 WHIM patients (age range 8-51 years) with typical gain of functions mutations of CXCR4 (R334X or G336X). In three cases (P3, P5, P6) neurological evaluation revealed fine and global motor coordination disorders, balance disturbances, mild limb ataxia and excessive talkativeness. Brain MRI showed an abnormal orientation of the cerebellar folia involving bilaterally the gracilis and biventer lobules together with the tonsils in four subjects (P3, P4, P5, P6). The neuropsychiatric evaluation showed increased risk of internalizing and/or externalizing problems in four patients (P2, P3, P4, P6). CONCLUSIONS: Taken together, these observations suggest CXCR4 gain of function mutations can be associated with cerebellar malformation, mild neuromotor and psychopathological dysfunction in WHIM patients.


Assuntos
Cerebelo/anormalidades , Síndromes de Imunodeficiência/complicações , Síndromes de Imunodeficiência/diagnóstico por imagem , Imagem por Ressonância Magnética , Transtornos Mentais/etiologia , Malformações do Sistema Nervoso/etiologia , Verrugas/complicações , Verrugas/diagnóstico por imagem , Adolescente , Adulto , Cerebelo/diagnóstico por imagem , Criança , Feminino , Mutação com Ganho de Função , Humanos , Síndromes de Imunodeficiência/genética , Síndromes de Imunodeficiência/patologia , Pessoa de Meia-Idade , Receptores CXCR4/genética , Verrugas/genética , Verrugas/patologia , Adulto Jovem
7.
Asian Pac J Cancer Prev ; 20(2): 495-501, 2019 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-30803212

RESUMO

Background: Intestinal parasitic infection in immunodeficient patients especially those with impaired cellular immunity, like neoplasia, renal or heart transplant needs careful consideration. The objective of this study is to evaluate the prevalence of intestinal parasites in different group of patients including cancer patients; organ transplants recipients, and primary immunodeficiency patients. Methods: Stool samples from 190 patients including 80 patients with Primary Immunodeficiency, 85 cancer patients and 25 organ transplant recipients were collected; a direct examination with Phosphate buffered saline (PBS) and formalin ether concentration was performed. The DNA was extracted from parasitologically confirmed patients and nested PCR and sequencing was performed and new obtained sequences of Cryptosporidium parvum and Enterocytozoon bieneusi were compared with deposited ones. Results: In general, the prevalence of parasites was 26/80 (32.5%) in primary immunodeficiency, 22/85(25.9%) in cancer group, and 7/25 (28%) in organ transplant. The prevalence of intestinal parasitic infections in primary immunodeficiency patients were Blastocystis hominis 13 (16.2%), Giardia lamblia 10 (12.5%), Cryptosporidium 1(1.2%), Chilomastix mesnilii 1 (1.2%), Dientamoeba fragilis 1(1.2%). Of 25 organ transplants, 6 (24%) Cryptosporidium sp were found, all of which were confirmed as Cryptosporidium parvum and one case of Microspora in a heart transplant recipient was confirmed as Enterocytozoon bieneusi by PCR sequencing. The predominant intestinal parasitic infection in cancer patients was 19 (22.3%) Blastocystis hominis followed by two (2.3%) Giardia lamblia and one Dientamoeba fragilis 1 (1.1%). Conclusion: The high rate of infection with Blastocystis hominis was found in cancer patients especially colorectal cancer patients, so careful consideration should be given by physicians. Cryptosporidium sp was found to be the major cause of parasitic intestinal infection in patients with organ transplant compared to primary immunodeficiency patients; so transplant recipients undergoing immunosuppressive therapy should be considered as a risk group for acquiring microsporidiosis and Cryptosporidium infection.


Assuntos
Fezes/parasitologia , Síndromes de Imunodeficiência/complicações , Enteropatias Parasitárias/epidemiologia , Neoplasias/complicações , Transplante de Órgãos/efeitos adversos , Parasitos/isolamento & purificação , Adolescente , Adulto , Idoso , Animais , Criança , Pré-Escolar , Estudos Transversais , Feminino , Seguimentos , Humanos , Enteropatias Parasitárias/parasitologia , Irã (Geográfico)/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Adulto Jovem
8.
Crit Rev Oncol Hematol ; 133: 149-162, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30661651

RESUMO

Neutropenia is a dangerous and potentially fatal condition that renders patients vulnerable to recurrent infections. Its severity is commensurate with the absolute count of neutrophil granulocytes in the circulation. In paediatric patients, neutropenia can have many different aetiologies. Primary causes make up but a small portion of the whole and are relatively unknown. In the past decades, a number of genes has been discovered that are responsible for congenital neutropenia. By perturbation of mitochondrial energy metabolism, vesicle trafficking or synthesis of functional proteins, these mutations cause a maturation arrest in myeloid precursor cells in the bone marrow. Apart from these isolated forms, congenital neutropenia is associated with a multiplicity of syndromic diseases that includes among others: oculocutaneous albinism, metabolic diseases and bone marrow failure syndromes. Congenital neutropenia is a primary immunodeficiency disease that is associated with recurrent bacterial infections, auto-inflammatory and auto-immune phenomena, haematological malignancy and neuro-psychiatric manifestations. The aim of this review is to give a comprehensive overview of the most recent literature concerning the clinical, aetiological and genetic features of congenital neutropenia and the syndromes in which it might be encountered.


Assuntos
Síndromes de Imunodeficiência , Neutropenia/congênito , Criança , Humanos , Síndromes de Imunodeficiência/complicações , Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/epidemiologia , Síndromes de Imunodeficiência/genética , Neutropenia/complicações , Neutropenia/diagnóstico , Neutropenia/epidemiologia , Neutropenia/genética , Fenótipo
9.
BMJ Case Rep ; 12(1)2019 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-30610030

RESUMO

Selective immunoglobulin M deficiency (sIgMD) is an immunodeficiency with undefined pathogenesis and commonly presenting with recurrent infections. 1 The European Society for Immunodeficiencies Registry defines sIgMD as a serum IgM level repeatedly below 2 SD of normal with normal levels of serum IgA, IgG and IgG subclasses, normal vaccination responses, absence of T-cell defects and absence of causative external factors. Rarely it can also be associated with autoimmune diseases. 2-7 Here we describe a patient with primary sIgMD; who presented with multiple autoimmune diseases without a history of recurrent infections and we provide a short literature review on sIgMD and autoimmune diseases.


Assuntos
Doenças Autoimunes/diagnóstico , Imunoglobulina M/deficiência , Síndromes de Imunodeficiência/diagnóstico , Doença Mista do Tecido Conjuntivo/tratamento farmacológico , Doença Mista do Tecido Conjuntivo/imunologia , Adulto , Assistência ao Convalescente , Antirreumáticos/administração & dosagem , Antirreumáticos/uso terapêutico , Doenças Autoimunes/complicações , Doenças Autoimunes/imunologia , Humanos , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/uso terapêutico , Iloprosta/administração & dosagem , Iloprosta/uso terapêutico , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Síndromes de Imunodeficiência/complicações , Síndromes de Imunodeficiência/imunologia , Infusões Intravenosas , Masculino , Doença Mista do Tecido Conjuntivo/sangue , Doença Mista do Tecido Conjuntivo/diagnóstico , Mialgia/diagnóstico , Mialgia/etiologia , Nifedipino/administração & dosagem , Nifedipino/uso terapêutico , Sinovite/diagnóstico , Sinovite/etiologia , Resultado do Tratamento , Vasodilatadores/administração & dosagem , Vasodilatadores/uso terapêutico
10.
Zhonghua Er Ke Za Zhi ; 57(1): 55-59, 2019 Jan 02.
Artigo em Chinês | MEDLINE | ID: mdl-30630233

RESUMO

Objective: To analyze the clinical and genetic features of immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome with a case report and literature review. Methods: The clinical data and genetic test of a girl diagnosed with ICF syndrome in the Department of Nephrology and Immunology in Qingdao Women and Children's Hospital in December 2016 were extracted and analyzed. "ICF syndrome" "immunodeficiency, centromeric instability and facial anomalies syndrome" "ICF syndrome and DNMT3B" were used as key words to search Chinese databases and Pubmed for literature until March 2018, and the literature was reviewed. Results: A female patient aged 22 months old with ocular hypertelorism and low-set ears was admitted due to recurrent infection over one year. Laboratory tests showed humoral immune deficiency with IgG<1.34 g/L, IgA<0.060 g/L, and IgM<0.179 g/L, but normal cellular immunity (total T lymphocyte 0.503, hepler T lymphocyte 0.328, cytotoxic T lymphocyte 0.166, natural killer cell 0.184, total B lymphocyte 0.276). Whole-exome sequencing revealed a de novo heterozygous splice site mutation c.922-2A>G in intron 8, and a de novo heterozygous missense mutation c.2477G>A in exon 23 of DNMT3B gene. Chromosome karyotype analysis showed 46, XX, with 64 out of 100 karyotypes showing centromere instability in chromosome 1. Five papers were found which were all in English, with total of 29 patients. Forty-three mutations were reported, including 34 missense, 2 deletion, 1 insertion, 6 splice site mutations. Eleven patients had complex heterozygosis mutations. All patients had centromere instability, humoral immune deficiency and facial dysplasia which were mainly ocular hypertelorism and low-set ears. Most patients had language and motor development delay, and a few were combined with mental retardation. Conclusions: ICF syndrome is a rare autosomal recessive primary immunodeficiency with classic clinical triad manifestations. De novo mutation of DNMT3B gene is one of etiologies according to genetic test.


Assuntos
Anormalidades Múltiplas , DNA (Citosina-5-)-Metiltransferases , Face , Síndromes de Imunodeficiência , Anormalidades Múltiplas/genética , Centrômero , Instabilidade Cromossômica , DNA (Citosina-5-)-Metiltransferases/genética , Face/anormalidades , Feminino , Humanos , Síndromes de Imunodeficiência/complicações , Síndromes de Imunodeficiência/genética , Lactente , Mutação
11.
Clin Immunol ; 198: 39-45, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30572125

RESUMO

The incorporation of next generation sequencing into routine immunological practice has enabled the identification of novel inborn errors of disease, helped define new categories of immune deficiency and extended the clinical spectrum associated with many long-recognised diseases. The family of EBV (Epstein Barr Virus)-sensitive primary immune deficiencies is one such group and in this paper we describe three families: two with X-linked lymphoproliferative disease type-1 (XLP-1) and one with deficiency of Interleukin-2 Inducible T-cell Kinase (ITK). Both diseases have a wide range of clinical manifestations and are united by an exquisite predisposition to EBV, dysgammaglobulinemia, hemophagocytic lymphohistiocytosis, and lymphoma. We detail our approach to diagnosis, treatment, and risk stratification in these diseases where both clinicians and patients must grapple with constant uncertainty.


Assuntos
Síndromes de Imunodeficiência/complicações , Transtornos Linfoproliferativos/terapia , Proteínas Tirosina Quinases/deficiência , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Linfo-Histiocitose Hemofagocítica/etiologia , Transtornos Linfoproliferativos/genética , Masculino , Pessoa de Meia-Idade , Proteínas Tirosina Quinases/genética , Estudos Retrospectivos
12.
Dig Dis ; 37(1): 45-52, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30153682

RESUMO

BACKGROUND: It has been reported that 5-50% of patients with primary immune deficiencies (PID) may present with or develop gastrointestinal (GI) manifestations. OBJECTIVE: This study was aimed at analyzing GI and related endoscopic, histopathological findings in children with PID. METHODS: Children with PID who were evaluated by endoscopy between 2005 and 2016 were enrolled in this study. Demographic data, growth parameters, signs and symptoms at diagnosis were obtained. RESULTS: Of 425 children with PID, 195 had GI manifestations. Forty-seven of 195 children required endoscopic investigation, 30 (63.8%) were male, and the mean age was 7.7 ± 5 years. The rate of consanguinity was 61.7%, and the most common symptom was chronic diarrhea (57.4%). Seventy-two percent of the patients were malnourished. Giardia intestinalis was detected in 4, and Helicobacter pylori was confirmed in 8/45 (17.7%) patients. Non-celiac villous flatting was discovered in 15.5% of patients. Twelve patients were diagnosed as having immunodeficiency associated inflammatory bowel disease (IBD)-like colitis. CONCLUSIONS: PID may present with GI manifestations or develop during the course of the disease. Investigating immunodeficiency in patients with atypical GI symptoms can provide an appropriate therapeutic option, and an improved quality of life, particularly in populations with a high rate of consanguinity.


Assuntos
Gastroenteropatias/complicações , Gastroenteropatias/imunologia , Síndromes de Imunodeficiência/complicações , Adolescente , Criança , Pré-Escolar , Endoscopia , Feminino , Gastroenteropatias/patologia , Humanos , Síndromes de Imunodeficiência/patologia , Lactente , Masculino , Fenótipo , Qualidade de Vida
13.
Orv Hetil ; 159(49): 2043-2049, 2018 Dec.
Artigo em Húngaro | MEDLINE | ID: mdl-30525882

RESUMO

The respiratory infections are the most common presentations and leading cause of morbidity and mortality in primary immunodeficiencies. The pathogen or spectrum of pathogens may be characteristic for the underlying primary immunodeficiency, and that knowledge plays an important role in the empirical treatment or prevention of the infections, or, conversely, the identification of an unusual pathogen may raise the suspicion on an immunodeficiency. Apart from the acute respiratory infections, chronic lung diseases are also common complications. The recurrent infections result in bronchiectasis, an irreversible structural damage of the respiratory tract, that frequently serve as locus for subsequent infections. The other group of chronic pulmonary complications are the interstitial lung diseases, which seem to be independent from infections and can be regarded as the pulmonary manifestation of the immune dysregulation. It is important to identify those patients with immunodeficiency who are at increased risk of secondary lung complications and to regularly screen this group for the early detection of the pulmonary complications. Orv Hetil. 2018; 159(49): 2043-2049.


Assuntos
Síndromes de Imunodeficiência/complicações , Pneumopatias/imunologia , Doenças Respiratórias/etiologia , Feminino , Humanos , Doenças Pulmonares Intersticiais/etiologia , Masculino , Pneumonia/etiologia , Sinusite/etiologia
14.
Orv Hetil ; 159(49): 2065-2072, 2018 Dec.
Artigo em Húngaro | MEDLINE | ID: mdl-30525884

RESUMO

Experimental and clinical data suggest a complex interaction between the endocrine and immune systems. However, only few epidemiological studies are available dealing with endocrine complications in different types of primary immunodeficiency diseases. It is well documented that there is a close association between immunodeficiency syndromes and the development of autoimmune disorders. Most of the endocrine dysfunctions are caused mainly by immune dysregulation and autoimmunity like in APECED (autoimmune polyendocrinopathy, candidiasis, ectodermal dystrophy) and IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked) syndromes. In these disorders, an immunologically mediated destructive process by autoreactive T cells damages multiple endocrine organs like the thyroid, parathyroid, adrenal cortex and endocrine pancreas. In some other forms of immunodeficiencies, like Di George syndrome, endocrine disturbances are mainly caused by the underlying genetic disorders but autoimmunity may also take part in the process. The aim of this paper is to give an overview of the different forms of endocrine disturbances and their pathological background in APECED and IPEX syndromes, Di George syndrome and ataxia telangiectasia. Orv Hetil. 2018; 159(49): 2065-2072.


Assuntos
Doenças do Sistema Endócrino/complicações , Doenças do Sistema Endócrino/imunologia , Síndromes de Imunodeficiência/complicações , Síndromes de Imunodeficiência/imunologia , Autoanticorpos/imunologia , Humanos , Poliendocrinopatias Autoimunes
15.
Orv Hetil ; 159(49): 2079-2086, 2018 Dec.
Artigo em Húngaro | MEDLINE | ID: mdl-30525885

RESUMO

Characteristic lesions of the oral cavity in primary immunodeficiencies are commonly found in the form of periodontal disease, tooth decay and disorders of the oral mucosa. Humoral immunodeficiencies may cause tooth decay, while severe forms of plaque-induced periodontal disease are common in phagocytic deficiencies. The structural abnormalities of the teeth can occur in immunodeficiencies associated with apoptosis defect. Oral squamous cell carcinoma is a possible complication of immunodeficiencies associated with DNA repair defects. Orv Hetil. 2018; 159(49): 2079-2086.


Assuntos
Síndromes de Imunodeficiência/imunologia , Doenças Periodontais/imunologia , Humanos , Doenças do Sistema Imunitário/imunologia , Síndromes de Imunodeficiência/complicações , Doenças Periodontais/complicações
16.
mSphere ; 3(6)2018 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-30541782

RESUMO

Several immunodeficiencies are associated with high susceptibility to persistent and progressive human papillomavirus (HPV) infection leading to a wide range of cutaneous and mucosal lesions. However, the HPV types most commonly associated with such clinical manifestations in these patients have not been systematically defined. Here, we used virion enrichment, rolling circle amplification, and deep sequencing to identify circular DNA viruses present in skin swabs and/or wart biopsy samples from 48 patients with rare genetic immunodeficiencies, including patients with warts, hypogammaglobulinemia, infections, myelokathexis (WHIM) syndrome, or epidermodysplasia verruciformis (EV). Their profiles were compared with the profiles of swabs from 14 healthy adults and warts from 6 immunologically normal children. Individual patients were typically infected with multiple HPV types; up to 26 different types were isolated from a single patient (multiple anatomical sites, one time point). Among these, we identified the complete genomes of 83 previously unknown HPV types and 35 incomplete genomes representing possible additional new types. HPV types in the genus Gammapapillomavirus were common in WHIM patients, whereas EV patients mainly shed HPVs from the genus Betapapillomavirus. Preliminary evidence based on three WHIM patients treated with plerixafor, a leukocyte mobilizing agent, suggest that longer-term therapy may correlate with decreased HPV diversity and increased predominance of HPV types associated with childhood skin warts.IMPORTANCE Although some members of the viral family Papillomaviridae cause benign skin warts (papillomas), many human papillomavirus (HPV) infections are not associated with visible symptoms. For example, most healthy adults chronically shed Gammapapillomavirus (Gamma) virions from apparently healthy skin surfaces. To further explore the diversity of papillomaviruses, we performed viromic surveys on immunodeficient individuals suffering from florid skin warts. Our results nearly double the number of known Gamma HPV types and suggest that WHIM syndrome patients are uniquely susceptible to Gamma HPV-associated skin warts. Preliminary results suggest that treatment with the drug plerixafor may promote resolution of the unusual Gamma HPV skin warts observed in WHIM patients.


Assuntos
DNA Viral/genética , Síndromes de Imunodeficiência/complicações , Papillomaviridae/classificação , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/virologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , DNA Viral/química , Feminino , Genoma Viral , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Metagenômica , Pessoa de Meia-Idade , Membrana Mucosa/virologia , Técnicas de Amplificação de Ácido Nucleico , Papillomaviridae/genética , Pele/virologia , Adulto Jovem
17.
Transfusion ; 58 Suppl 3: 3056-3064, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30536429

RESUMO

Primary immunodeficiency (PID) diseases result from genetic defects of the immune system that increase a patient's susceptibility to infections. The types of infections that occur in patients with PID diseases are dictated largely by the nature of the immunodeficiency, which can be defined by dysfunction of cellular or humoral defenses. An increasing number of PID diseases, including those with both cellular and humoral defects, have antibody deficiency as a major feature, and as a result can benefit from immunoglobulin replacement therapy. In fact, the most common PID diseases worldwide are antibody deficiencies and include common variable immunodeficiency, congenital agammaglobulinemia, hyper-IgM syndrome, specific antibody deficiency, and Good syndrome. Although immunoglobulin replacement therapy is the cornerstone of treatment for the majority of these conditions, a thorough understanding of the specific infections for which these patients are at increased risk can hasten diagnosis and guide additional therapies. Moreover, the infection trends in some patients with PID disease who have profound defects of cellular immunity, such as autosomal-dominant hyper-IgE syndrome (Job/Buckley syndrome) or dedicator of cytokinesis 8 (DOCK8) deficiency, suggest that select patients might benefit from immunoglobulin replacement therapy even if their immunodeficiency is not limited to antibody defects. In this review, we provide an overview of the predisposition to infections seen in PID disease that may benefit from immunoglobulin replacement therapy.


Assuntos
Imunoglobulinas/uso terapêutico , Síndromes de Imunodeficiência/complicações , Síndromes de Imunodeficiência/terapia , Infecção/imunologia , Agamaglobulinemia/complicações , Agamaglobulinemia/imunologia , Agamaglobulinemia/terapia , Imunodeficiência de Variável Comum/imunologia , Imunodeficiência de Variável Comum/terapia , Doenças Genéticas Ligadas ao Cromossomo X/imunologia , Doenças Genéticas Ligadas ao Cromossomo X/terapia , Humanos , Síndromes de Imunodeficiência/classificação , Síndromes de Imunodeficiência/imunologia , Infecção/terapia , Fatores de Risco
19.
Orv Hetil ; 159(23): 919-928, 2018 Jun.
Artigo em Húngaro | MEDLINE | ID: mdl-29860881

RESUMO

Primary immune deficiencies (PIDs) are characterized by quantitative and/or functional abnormalities of the immune system elements. Bone and joint abnormalities are not rare in patients with immunodeficiencies. Joint manifestations, of which arthritis is the most common, occur mainly in humoral PIDs (X-linked agammaglobulinemia, common variable immunodeficiency, and IgA deficiency) and occasionally in defects of the phagocyte system (chronic granulomatous disease, glicogen storage diseases). Monoarthritis or oligoarthritis is the usual pattern, caused by Mycoplasma, Staphylococcus, Streptococcus, Pneumococcus or Haemophilus species. These bacteria can provoke not only synovial infections, but also aseptic arthritogenic inflammatory responses. Infectious arthritis or osteomyelitis must be diagnosed and treated with antimicrobial therapy at the earliest. Bone lesions are far less common and usually present as infectious complications in humoral PID. Larger bone manifestations occur in hyper-IgE syndrome and spondyloepiphyseal dysplasia. Short stature is the most common in reticular dysgenesis, in autoimmune polyendocrinopathy candidiasis ectodermal dysplasia and in DNA repair disorders. Knowledge of PID syndromes both enhances the diagnostic capabilities of physicians and provides understanding the pathophysiology of bone and joint abnormalities associated with immune dysfunction. In children and occasionally in adults, a combination of bone and/or joint manifestations and hypogammaglobulinemia may be the first sign of PID. When lymphoproliferative disease or infection can not be proved, investigations for PID should be accomplished. Orv Hetil. 2018; 159(23): 918-928.


Assuntos
Artrite Infecciosa/imunologia , Autoimunidade/imunologia , Síndromes de Imunodeficiência/complicações , Doenças Reumáticas/imunologia , Humanos , Síndromes de Imunodeficiência/imunologia
20.
Orv Hetil ; 159(23): 908-918, 2018 Jun.
Artigo em Húngaro | MEDLINE | ID: mdl-29860882

RESUMO

Primary immunodeficiencies consist of a group of genetically heterogeneous immune disorders affecting distinct elements of the innate and adaptive immune system. Patients with primary immunodeficiency are more prone to develop not only recurrent infections, but non-infectious complications, like inflammatory or granulomatous conditions, lymphoproliferative and solid malignancies, autoinflammatory disorders, and a broad spectrum of autoimmune diseases. The concomitant appearance of primary immunodeficiency and autoimmunity appears to be rather paradoxical, therefore making the diagnosis of immunodeficiency patients with autoimmune complications challenging. Mutations of one or more genes playing a fundamental role in immunoregulation and/or immune tolerance network are thought to be responsible for primary immunodeficiencies. The diverse immunological abnomalities along with the compensatory and excessive sustained inflammatory response result in tissue damage and finally in manifestation of organ-, cell-specific or systemic autoimmune diseases. Several forms of primary immunodeficiency disorders are characterized by a variety of specific autoimmune phenomena. This overview addresses the spectrum of autoimmune diseases associated with primary immunodeficiencies, and explores the molecular and cellular mechanisms underlying abnormalities of the immune system. The case presented finally highlights that both the recognition of autoimmune diseases in association with immunodeficiencies and the diagnosis of immunodefiency in those phenotypes with predominant autoimmunity could be challenging. Orv Hetil. 2018; 159(23): 908-918.


Assuntos
Doenças Autoimunes/complicações , Doenças Autoimunes/fisiopatologia , Síndromes de Imunodeficiência/complicações , Síndromes de Imunodeficiência/fisiopatologia , Autoimunidade/imunologia , Humanos
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