RESUMO
INTRODUCTION: We report a case of an exceptional syndromic association of apparently congenital rhinobronchial dystrophy associated with congenital anosmia and common variable immunodeficiency in a twelve-year-old girl. CASE SUMMARY: This young girl, born in 2000, consulted for the first time in 2012 for recurrent respiratory tract infections, refractory to all forms of treatment, starting in early childhood, associated with congenital anosmia and severe atrophic rhinitis as well as common variable immunodeficiency. The laboratory work-up essentially revealed IgG4 deficiency and imaging demonstrated bronchiectasis (lingula), multiple tracheobronchial diverticula, atrophic rhinitis and congenital anosmia with agenesis of the olfactory bulbs and sulci. DISCUSSION: After eliminating a number of differential diagnoses, we were left with the problem of the aetiology, the possible links between these various symptoms and the genetic basis for this apparently congenital complex rhinobronchial disease associated with common variable immunodeficiency. Do these various symptoms correspond to a chance association or an exceptional congenital syndrome that has not yet been identified in the literature? CONCLUSION: A review of the clinical and genetic literature did not enable us to propose a single diagnosis for these symptoms or this complex syndrome.
Assuntos
Broncopatias/congênito , Imunodeficiência de Variável Comum/congênito , Doenças Nasais/congênito , Transtornos do Olfato/congênito , Broncopatias/diagnóstico , Criança , Imunodeficiência de Variável Comum/diagnóstico , Feminino , Humanos , Doenças Nasais/diagnóstico , Transtornos do Olfato/diagnóstico , SíndromeRESUMO
We used whole exome sequencing to determine the genetic background of CVID in two non-consanguineous German families. We identified IFNK (interferon-kappa) as the only candidate gene that harbored truncating mutations in affected members from both families. One family segregated c.30_31insTGTT, a known frameshift variant, while the other family segregated the novel IFNK mutation p.K199X that creates a premature stop codon. We sequenced the whole coding region of IFNK in a further series of 167 CVID patients and 192 healthy controls. Frameshift mutation c.30_31insTGTT was identified in 12 cases and 17 controls (OR 0.79, 95% CI 0.33-1.81, p=0.79), whereas the p.K199X mutation remained restricted to the original family. No additional truncating variants were found. We conclude that, given their frequent occurrence in non-diseased family members and controls, it is unlikely that truncating variants in IFNK constitute a major factor in the development of CVID.
Assuntos
Imunodeficiência de Variável Comum/genética , Imunodeficiência de Variável Comum/imunologia , Mutação da Fase de Leitura , Interferon Tipo I/genética , Adulto , Idoso , Imunodeficiência de Variável Comum/congênito , Feminino , Genoma Humano , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Análise de Sequência de DNA , Sequenciamento do ExomaRESUMO
Smooth muscle tumours (SMT) after transplantation (PTSMT) or associated with congenital immunodeficiency syndromes (CI-SMT) and human immunodeficiency virus (HIV-SMT) are rare. The majority of PTSMT and CI-SMT are associated with Epstein-Barr virus (EBV), while some HIV-SMT can be EBV-negative. SMT in immunodeficient states may present with unspecific symptoms which are mainly related to tumour localisation. In PTSMT, >50% of tumours manifest in the liver/transplant liver, but in general PTSMT, HIV-SMT and CI-SMT can occur at any site as single or multiple tumours. Multiple tumour manifestations do not define metastatic disease as PTSMT can occur synchronously and/or metachronously. PTSMT can originate from the recipient as well as from the donor. Morphologically, most tumours, in particular PTSMT, lack marked histological atypia or tumour necrosis, while some HIV-SMT and CI-SMT can present as sarcoma-like variants, but histomorphology does not predict clinical aggressiveness or tumourbiological behaviour. In PTSMT, surgery and reduced immunosuppression show comparable overall survival rates, while poor prognosis is mainly associated with intracranial manifestation and non-resectable tumours. In HIV-SMT and CI-SMT, surgery should be performed. In all 3 tumour types, adverse prognosis is mainly related to comorbidities associated with immunosuppression but not with the extent of histological atypia or tumour size.
Assuntos
Imunodeficiência de Variável Comum/complicações , Infecções por Vírus Epstein-Barr/complicações , Infecções por HIV/complicações , Herpesvirus Humano 4/isolamento & purificação , Neoplasias Musculares/complicações , Músculo Liso/patologia , Adolescente , Imunodeficiência de Variável Comum/congênito , Imunodeficiência de Variável Comum/virologia , Infecções por Vírus Epstein-Barr/virologia , Feminino , Infecções por HIV/virologia , Humanos , Terapia de Imunossupressão , Neoplasias Musculares/patologia , Neoplasias Musculares/terapia , Neoplasias Musculares/virologia , Transplante de Órgãos , Prognóstico , Fatores de RiscoAssuntos
Imunodeficiência de Variável Comum/imunologia , Imunoterapia , Síndrome da Deleção Distal 11q de Jacobsen/imunologia , Complicações Pós-Operatórias , Síndrome do Desconforto Respiratório/imunologia , Antibacterianos/administração & dosagem , Pré-Escolar , Imunodeficiência de Variável Comum/congênito , Imunodeficiência de Variável Comum/diagnóstico , Imunodeficiência de Variável Comum/fisiopatologia , Imunodeficiência de Variável Comum/terapia , Comunicação Interatrial/cirurgia , Humanos , Imunoglobulinas/deficiência , Imunoglobulinas Intravenosas/administração & dosagem , Síndrome da Deleção Distal 11q de Jacobsen/diagnóstico , Síndrome da Deleção Distal 11q de Jacobsen/genética , Síndrome da Deleção Distal 11q de Jacobsen/fisiopatologia , Síndrome da Deleção Distal 11q de Jacobsen/terapia , Linfopenia , Masculino , Mediastinite/etiologia , Mediastinite/terapia , Complicações Pós-Operatórias/imunologia , Respiração Artificial , Síndrome do Desconforto Respiratório/congênito , Síndrome do Desconforto Respiratório/diagnóstico , Síndrome do Desconforto Respiratório/fisiopatologia , Síndrome do Desconforto Respiratório/terapiaRESUMO
Transfusion-associated graft-versus-host disease (TA-GvHD) is a rare complication of blood transfusion that has a fatal outcome in most patients. It is caused by the transfusion of viable T cells present in blood products that are not rejected by the transfusion recipient, either because of recipient immunodeficiency or because of a common HLA haplotype between the blood donor and recipient. Because effective treatment is not available, risk identification and prevention are of central importance. Among the potential risk factors that have been discussed to date, a definite hazard for developing TA-GvHD has been recognized for HLA-matched transfusions or transfusions from blood relatives, intrauterine and exchange transfusions, patients with congenital immunodeficiency syndromes, bone marrow transplantation, stem cell transplantation, or lymphomas. Patients at possible TA-GvHD risk who will require further evaluation include patients with hematologic malignancies, solid tumors, or solid organ transplantation. Although postulated, an increased risk for term or preterm newborns and patients with HIV/AIDS has not thus far been demonstrated.
Assuntos
Doadores de Sangue , Transfusão de Sangue , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/prevenção & controle , Doença Enxerto-Hospedeiro/terapia , Antígenos HLA , Linfócitos T , Síndrome da Imunodeficiência Adquirida/terapia , Transplante de Medula Óssea , Imunodeficiência de Variável Comum/congênito , Imunodeficiência de Variável Comum/terapia , Doença Enxerto-Hospedeiro/etiologia , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Neoplasias/terapia , Transplante de Órgãos , Transplante de Células-TroncoRESUMO
We treated a patient with meningioma suffering from a congenital immunodeficiency syndrome. The patient was diagnosed with common variable immunodeficiency (CVID) in youth, and had suffered from repeated infections, especially in the respiratory tract, requiring continuous treatment with antibiotics. Imaging revealed a tumor located in the left frontal region with a broad attachment suggesting meningioma in the convexity dura mater. Gammaglobulin was infused intravenously preceding the operation and serum gammaglobulin was controlled at over 400 mg/dl and then a Simpson grade 1 operation was performed. The patient did not show any complications in infectious susceptibility, and there was no recurrence of the tumor in the 5 years following the operation. The surgical risk for CVID patients in the neurosurgical field is still not clear, but we could maintain the condition of the patient by controlling the serum gammaglobulin level in the perioperative period.
Assuntos
Imunodeficiência de Variável Comum/congênito , Neoplasias Meníngeas/cirurgia , Meningioma/cirurgia , Imunodeficiência de Variável Comum/complicações , Feminino , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-IdadeRESUMO
We evaluated the T-cell repertoire and the thymic output in two infants, one with Omenn Syndrome (OS) and another with complete DiGeorge Syndrome (DGS), who developed generalized dermatitis. The patients shared common T-cell abnormalities, as demonstrated by the low response to mitogenic stimulation, by an unusual usage of specific T-cell receptor (TCR) segments, and by a reduction of TCR diversity in both alpha/beta and gamma/delta populations. Furthermore, they both showed an impaired thymic function, as assessed by the low number of TCR recombination excision circles, which are formed from excised DNA during the rearrangement of TCR genes. These data indicated that generalized erythrodermia may be present in different forms of T-cell immunodeficiency and may reflect intrinsic defects in either V(D)J recombination or in thymic development, leading to the peripheral expansion of T-cell clonotypes, that bear peculiar TCR chains.
Assuntos
Imunodeficiência de Variável Comum/complicações , Imunodeficiência de Variável Comum/imunologia , Dermatite/etiologia , Síndrome de DiGeorge/complicações , Síndrome de DiGeorge/imunologia , Linfócitos T/patologia , Timo/fisiopatologia , Imunodeficiência de Variável Comum/congênito , Imunodeficiência de Variável Comum/fisiopatologia , Síndrome de DiGeorge/congênito , Síndrome de DiGeorge/fisiopatologia , Feminino , Amplificação de Genes , Rearranjo Gênico do Linfócito T , Humanos , Lactente , Recém-Nascido , Masculino , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/imunologiaRESUMO
Combined immunodeficiency disorders are characterized by abnormalities in cellular and humoral immunity. This classification includes common variable immunodeficiency (CVI), a primary immunodeficiency disorder characterized by hypogammaglobulinemia, recurrent bacterial infections, and significant T-cell abnormalities. Associated autoimmune diseases include rheumatoid arthritis, pernicious anemia, idiopathic thrombocytopenic purpura, and systemic lupus erythematous. Granulomatous lesions in lymphoid tissues, solid organs, and skin have been reported. We describe a patient with CVI who developed cutaneous granulomas with perineural invasion; to our knowledge, this is a previously undescribed feature.