RESUMO
Propionate defects (PDs) mainly include methylmalonic (MMA) and propionic acidemia (PA) defects. Lifelong PD patients progress from the compensated to the decompensated stages, the latter of which are characterized by life-threatening acidemia and hyperammonemia crises. PD patients can suffer immunocompromise, especially during the decompensation stage. There is a significant gap in the research regarding the humoral immune response in PD patients. Here, we analyzed serum immunoglobulin concentrations and hemograms across compensated and decompensated stages in PD patients. Nutritional status and crisis triggers of decompensation were also explored. Twenty patients were studied, and 25 decompensation events (DE) and 8 compensation events (CE) were recorded. Compared with those in the CE group, the IgG levels in the DE group (513.4 ± 244.5 mg/dL) were significantly lower than those in the CE group (860.8 ± 456.5 mg/dL) (p < 0.0087). The mean hemoglobin concentration was significantly lower in the DE group (11.8 g/dL) than in the CE group (13.4 g/dL) (p < 0.05). The most frequent (48%) possible decompensation trigger factor was infection. Most of the events were registered in eutrophic patients (87.9%), despite which 65.2% and 50% of patients who experienced decompensated and compensated events, respectively, presented with hypogammaglobulinemia G. These findings provide evidence of the immunodeficiency of PD patients, independent of their nutritional status. We suggest that PD patients be managed as immunocompromised independently of their nutritional status or metabolic state (compensated or decompensated).
Assuntos
Agamaglobulinemia , Estado Nutricional , Humanos , Masculino , Feminino , Agamaglobulinemia/sangue , Agamaglobulinemia/imunologia , Agamaglobulinemia/complicações , Pessoa de Meia-Idade , Idoso , Imunoglobulina G/sangue , Adulto , Propionatos/sangue , Acidemia PropiônicaRESUMO
INTRODUCTION: Common variable immunodeficiency and X-linked agammaglobulinaemia are primary immunodeficiencies classified as antibody deficiencies, and they both result in hypogammaglobulinaemia. OBJECTIVE: Evaluate the lipid profile and other cardiovascular risk biomarkers in CVID and XLA patients. METHODS: In total, 24 patients and 12 healthy controls matched by age and gender were included in the study. We evaluated anthropometric measurements, and seric total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), triglycerides (TG), apo A-I, small dense LDL (sdLDL), C-reactive protein (CRP), and tumour necrosis factor alpha (TNF-alpha), myeloperoxidase (MPO), cholesteryl ester transfer protein (CETP), and lecithin cholesterol acyltransferase (LCAT) were assessed. RESULTS: CRP (p = 0.008) and TNF-alpha (p < 0.001) concentrations were significantly higher, whereas HDL-c (p = 0.025) and apo A-I (p = 0.013) levels were significantly lower in patients than in the controls. In the patient group, a negative and significant correlation was observed between HDL-c and TNF-alpha (r = -0.406; p = 0.049) and between HDL-c and TG (r = -0.641; p = 0.001). CONCLUSION: Common variable immunodeficiency and X-linked agammaglobulinaemia patients presented themselves with increased inflammatory markers associated with a decreased HDL-c and apo A-I levels, which can predispose to a high cardiovascular risk.
Assuntos
Agamaglobulinemia/fisiopatologia , Doenças Cardiovasculares/etiologia , Imunodeficiência de Variável Comum/fisiopatologia , Doenças Genéticas Ligadas ao Cromossomo X/fisiopatologia , Mediadores da Inflamação/sangue , Lipídeos/sangue , Regulação para Cima , Adolescente , Adulto , Agamaglobulinemia/sangue , Agamaglobulinemia/imunologia , Apolipoproteína A-I/sangue , Biomarcadores/sangue , Índice de Massa Corporal , Brasil/epidemiologia , Doenças Cardiovasculares/epidemiologia , Criança , HDL-Colesterol/sangue , Imunodeficiência de Variável Comum/sangue , Imunodeficiência de Variável Comum/imunologia , Estudos Transversais , Regulação para Baixo , Feminino , Doenças Genéticas Ligadas ao Cromossomo X/sangue , Doenças Genéticas Ligadas ao Cromossomo X/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Risco , Adulto JovemRESUMO
Autosomal-Recessive Osteopetrosis (ARO) comprises a heterogeneous group of bone diseases for which mutations in five genes are known as causative. Most ARO are classified as osteoclast-rich, but recently a subset of osteoclast-poor ARO has been recognized as due to a defect in TNFSF11 (also called RANKL or TRANCE, coding for the RANKL protein), a master gene driving osteoclast differentiation along the RANKL-RANK axis. RANKL and RANK (coded for by the TNFRSF11A gene) also play a role in the immune system, which raises the possibility that defects in this pathway might cause osteopetrosis with immunodeficiency. From a large series of ARO patients we selected a Turkish consanguineous family with two siblings affected by ARO and hypogammaglobulinemia with no defects in known osteopetrosis genes. Sequencing of genes involved in the RANKL downstream pathway identified a homozygous mutation in the TNFRSF11A gene in both siblings. Their monocytes failed to differentiate in vitro into osteoclasts upon exposure to M-CSF and RANKL, in keeping with an osteoclast-intrinsic defect. Immunological analysis showed that their hypogammaglobulinemia was associated with impairment in immunoglobulin-secreting B cells. Investigation of other patients revealed a defect in both TNFRSF11A alleles in six additional, unrelated families. Our results indicate that TNFRSF11A mutations can cause a clinical condition in which severe ARO is associated with an immunoglobulin-production defect.
Assuntos
Agamaglobulinemia/sangue , Osteoclastos/patologia , Osteopetrose/genética , Receptor Ativador de Fator Nuclear kappa-B/genética , Fosfatase Ácida/metabolismo , Actinas/metabolismo , Sequência de Aminoácidos , Substituição de Aminoácidos , Argentina , Arginina/metabolismo , Biópsia , Estudos de Casos e Controles , Linhagem Celular Transformada , Proliferação de Células , Transformação Celular Viral , Células Cultivadas , Estudos de Coortes , Consanguinidade , Cisteína/metabolismo , Análise Mutacional de DNA , Dendritos/fisiologia , Feminino , Genes Recessivos , Herpesvirus Humano 4/fisiologia , Heterozigoto , Homozigoto , Humanos , Ílio/cirurgia , Isoenzimas/metabolismo , Antígenos Comuns de Leucócito/metabolismo , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/patologia , Lipopolissacarídeos/farmacologia , Fator Estimulador de Colônias de Macrófagos/farmacologia , Masculino , Modelos Imunológicos , Dados de Sequência Molecular , Mutação de Sentido Incorreto , Osteoclastos/metabolismo , Osteoclastos/ultraestrutura , Osteopetrose/diagnóstico , Osteopetrose/diagnóstico por imagem , Osteopetrose/patologia , Osteopetrose/fisiopatologia , Osteoprotegerina/metabolismo , Paquistão , Linhagem , Polimorfismo Genético , Estrutura Terciária de Proteína , Ligante RANK/metabolismo , Radiografia Torácica/métodos , Receptor Ativador de Fator Nuclear kappa-B/química , Receptor Ativador de Fator Nuclear kappa-B/imunologia , Receptores de Vitronectina/metabolismoRESUMO
A hipogamaglobulinemia com imunoglobulina M (IgM) normal ou elevada é uma imunodeficiência raramente observada, sendo também conhecida com o nome de síndrome de Hiper IgM. Esta síndrome é diagnosticada em pacientes portadores de níveis séricos de imunoglobulinas (IgG e IgA) diminuídos, com níveis de imunoglobulina M (IgM) normais ou elevados. O objetivo do presente relato é descrever as características clínico-laboratoriais e a evoluçäo de dois pacientes portadores desta síndrome, com idades de 2 anos e 10 meses e 10 anos, acompanhados na Unidade de Alergia e Imunologia do ICr HCFMUSP. As manifestaçöes clínicas foram precoces, com infecçöes recorrentes de vias aéreas e trato gastrointestinal. A avaliaçäo imunológica encontramos diminuiçäo dos níveis de IgG e IgA, com níveis de IgM normais no primeiro paciente e elevados (acima do percentil 97,5) no segundo paciente. Após o diagnóstico, os pacientes receberam gamaglobulina, antibióticos e orientaçäo quanto à nutriçäo e ambiente físico, com melhora evidente dos sintomas apresentados e sem o desenvolvimento de complicaçöes. Os autores ressaltam a importância do diagnóstico precoce da síndrome de Hiper IgM para tratamento adequado e controle dos processos infecciosos.