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1.
Int Arch Allergy Immunol ; 180(2): 150-158, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31284281

RESUMO

INTRODUCTION: Regulatory lymphocytes (CD4+ T regulatory cells [Treg], CD8+ Treg, and B regulatory cells [Breg]) play a critical role in immune homeostasis and tolerance. Common variable immunodeficiency (CVID) is associated with increased susceptibility to infections and increased frequency of inflammatory and autoimmune diseases. CD4+ Treg cell abnormalities have been reported in CVID; however, CD8+ Treg cells have not been reported in CVID. The objective of this study was to evaluate CD4+ Treg and CD8+ Treg cells in CVID patients. METHODS: In 25 patients with CVID and age-matched healthy controls, Treg cells, evaluated in freshly isolated peripheral blood mononuclear cells (natural; nCD4+ Treg and nCD8+ Treg) and following in vitro activation with anti-CD3/CD28 monoclonal antibodies (induced; iCD4+ Treg and iCD8+ Treg) as well as Breg cells were analyzed with specific monoclonal antibodies and isotype controls using flow cytometry. RESULTS: The proportions of nCD4+ Treg (CD4+ CD127low CD25high FoxP3+), iCD4+ Treg (CD4+ CD127low CD25high FoxP3+), iCD8+ Treg (CD8+ CD25high CD183+ FoxP3+), and Breg (CD19+ CD24high CD38high) lymphocytes were significantly lower in patients with CVID than in controls. CONCLUSIONS: Altered regulatory lymphocytes may play a role in the pathogenesis and autoimmunity and inflammation associated with CVID.


Assuntos
Linfócitos B Reguladores/imunologia , Linfócitos T CD8-Positivos/imunologia , Imunodeficiência de Variável Comum/imunologia , Linfócitos T Reguladores/imunologia , Adolescente , Adulto , Idoso , Envelhecimento/imunologia , Autoimunidade/imunologia , Feminino , Humanos , Inflamação/imunologia , Ativação Linfocitária/imunologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
2.
Turk J Med Sci ; 49(2): 497-505, 2019 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-30997788

RESUMO

Background/aim: The serum immunoglobulin levels are used routinely in clinical practice because they provide key information on the humoral immune status. This study aimed to determine the age-related reference values of serum immunoglobulin levels in healthy children. Materials and methods: A total of 330 healthy children, aged between 0 and 18 years, were included in this study. The serum immunoglobulin levels were measured using a nephelometric method in a total of 11 groups, each group consisting of 30 individuals, and IgG subclasses in 6 groups of children aged more than 2 years. Results: The serum IgG levels were high during the newborn period, decreased until the sixth month, and again increased to a maximum level at the age of 18 years. The level of IgA was found to be extremely low in the newborn period and then increased with age. While the lowest value was in the newborn period for serum IgM level, the highest value was in the 16- to 18-year-old period. The IgG subclasses varied depending on the age groups. Conclusion: The updated reference intervals of immunoglobulin levels in children may be used for the accurate diagnosis of immune deficiencies.


Assuntos
Imunodeficiência de Variável Comum/sangue , Imunidade Humoral/imunologia , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Adolescente , Criança , Pré-Escolar , Imunodeficiência de Variável Comum/imunologia , Voluntários Saudáveis , Humanos , Lactente , Recém-Nascido , Masculino , Nefelometria e Turbidimetria , Valores de Referência , Reprodutibilidade dos Testes
3.
J Biol Regul Homeost Agents ; 33(2): 315-319, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30942065

RESUMO

In recent years, gut microbiota (GM) has emerged as a key factor in shaping the pathogenesis of a vast array of immune-mediated diseases, as well as in the response to immune-based treatments such as anti PD-1 and anti-CTLA4 therapy or influenza vaccination. In addition, GM has a significant role in the immune system development and is fundamental in developing mucosal immunity. Recent data suggest that GM plays an important role in the immune system of immune deficient patients. GM status has a remarkable impact on the immune system and in immune deficient patients; this can lead to important consequences. Prebiotics are indeed a promising candidate in restoring GM homeostasis and improving immunity. Antibiotics are also capable of altering the microbial equilibrium.


Assuntos
Imunodeficiência de Variável Comum/imunologia , Imunodeficiência de Variável Comum/microbiologia , Microbioma Gastrointestinal , Imunidade nas Mucosas , Citocinas/imunologia , Humanos , Sistema Imunitário
4.
Allergol. immunopatol ; 47(1): 52-59, ene.-feb. 2019. tab, graf
Artigo em Inglês | IBECS | ID: ibc-180772

RESUMO

Background: Common variable immunodeficiency (CVID) is a heterogeneous disorder characterized by low serum levels of immunoglobulins (Igs) and recurrent infection. In most CVID patients, a defect in the differentiation of B cells into plasma cells has been observed. Several factors play an important role in the proliferation and differentiation of B cells, including IRF4 and XBP1 transcription factors. Methods: In the present study we investigated the expression of IRF4 and XBP1 in the B-cells of CVID and healthy controls (HCs). For this purpose, we assessed the expression of IRF4 and XBP1 at both mRNA and protein levels by real time-PCR and flow cytometry, respectively. Results: We found that IRF4 expression was significantly increased in CVID patients compared with controls. Although the XBP1 protein level was lower in patients in comparison to controls, this difference was not significant. Conclusion: Taken together, increased IRF4 expression could be involved in defective functions of B cells in CVID patients


No disponible


Assuntos
Humanos , Masculino , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Linfócitos B/imunologia , Imunodeficiência de Variável Comum/imunologia , Fatores Reguladores de Interferon/metabolismo , Citometria de Fluxo , Fatores Reguladores de Interferon/genética , RNA Mensageiro/genética , Regulação para Cima , Proteína 1 de Ligação a X-Box/genética , Proteína 1 de Ligação a X-Box/metabolismo
6.
Front Immunol ; 9: 2545, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30532750

RESUMO

Common variable immune deficiency disorder (CVID) is the most clinically relevant cause of antibody failure. It is a highly heterogeneous disease with different underlying etiologies. CVID has been associated with a quantitative B cell defect, however, little is known about the quality of B cells present. Here, we studied the naïve and antigen selected B-cell receptor (BCR) repertoire in 33 CVID patients using next generation sequencing, to investigate B cells quality. Analysis for each individual patient revealed whether they have a defect in immune repertoire formation [V(D)J recombination] or specification (somatic hypermutation, subclass distribution, or selection). The naïve BCR repertoire was normal in most of the patients, although alterations in repertoire diversity and the junctions were found in a limited number of patients indicating possible defects in early B-cell development or V(D)J recombination in these patients. In contrast, major differences were found in the antigen selected BCR repertoire. Here, most patients (15/17) showed a reduced frequency of somatic hypermutation (SHM), changes in subclass distribution and/or minor alterations in antigen selection. Together these data show that in our CVID cohort only a small number of patients have a defect in formation of the naïve BCR repertoire, whereas the clear majority of patients have disturbances in their antigen selected repertoire, suggesting a defect in repertoire specification in the germinal centers of these patients. This highlights that CVID patients not only have a quantitative B cell defect, but that also the quality of, especially post germinal center B cells, is impaired.


Assuntos
Linfócitos B/imunologia , Imunodeficiência de Variável Comum/imunologia , Centro Germinativo/imunologia , Receptores de Antígenos de Linfócitos B/genética , Adolescente , Adulto , Idoso , Diferenciação Celular , Criança , Seleção Clonal Mediada por Antígeno , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Hipermutação Somática de Imunoglobulina/genética , Adulto Jovem
7.
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
8.
Int J Immunopathol Pharmacol ; 32: 2058738418779458, 2018 Jan-Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29978731

RESUMO

Common variable immunodeficiency (CVID) and immunoglobulin A deficiency (IgAD) are the most prevalent primary immunodeficiency disorders. High rates of familial inheritance have been described in CVID and IgAD, but it is unknown in different ethnic populations. We aimed to determine the prevalence of familial cases and whether they showed more severe clinical characteristics than sporadic ones in Turkish patients. A total of 40 CVID and 70 IgAD patients and their 251 first-degree relatives (FDRs) were evaluated. Demographic, clinical, and laboratory data were reviewed. A familial case was defined as a patient with at least one affected FDR (A-FDR). The rate of parental consanguinity was 19.1%. There were 37 familial cases (37/110) (33.6%) with at least one A-FDR. There were 48 A-FDRs who had immunoglobulins lower than age-related normals (48/251) (19.1%). Pulmonary infections were significantly higher in familial cases. To our knowledge, this study includes the highest number of CVID/IgAD patients and their FDRs in literature. Familial cases are at least 30% of the IgAD and CVID patients, and they have more frequent lower respiratory tract infections than sporadic ones, so these patients have to be evaluated depending on their being familial or sporadic for better management. The risk of carrying any immunologic alterations in relatives of patients with IgAD and CVID is approximately 20%. Although most A-FDRs are asymptomatic, considering the risk of progression to CVID by age, we highly recommend routine screening for FDRs.


Assuntos
Imunodeficiência de Variável Comum/epidemiologia , Consanguinidade , Deficiência de IgA/epidemiologia , Imunoglobulina A/sangue , Adulto , Imunodeficiência de Variável Comum/genética , Imunodeficiência de Variável Comum/imunologia , Feminino , Hereditariedade , Humanos , Deficiência de IgA/genética , Deficiência de IgA/imunologia , Masculino , Pessoa de Meia-Idade , Linhagem , Turquia
9.
Allergol. immunopatol ; 46(2): 127-135, mar.-abr. 2018. tab, graf
Artigo em Inglês | IBECS | ID: ibc-172170

RESUMO

Background: Common variable immunodeficiency (CVID) is one of the most prevalent symptomatic primary immunodeficiencies (PIDs), which manifests a wide clinical variability such as autoimmunity, as well as T cell and B cell abnormalities. Methods: A total of 72 patients with CVID were enrolled in this study. Patients were evaluated for clinical manifestations and classified according to the presence or absence of autoimmune disease. We measured regulatory T cells (Tregs) and B-cell subsets using flow cytometry, as well as specific antibody response (SAR) to pneumococcal vaccine, autoantibodies and anti-IgA in patients. Results: Twenty-nine patients (40.3%) have shown at least one autoimmune manifestation. Autoimmune cytopenias and autoimmune gastrointestinal diseases were the most common. A significant association was detected between autoimmunity and presence of hepatomegaly and splenomegaly. Among CVID patients, 38.5% and 79.3% presented a defect in Tregs and switched memory B-cells, respectively, whereas 69.0% presented CD21low B cell expansion. Among patients with a defect in Treg, switched memory and CD21low B cell, the frequency of autoimmunity was 80.0%, 52.2% and 55.0%, respectively. A negative correlation was observed between the frequency of Tregs and CD21low B cell population. 82.2% of patients had a defective SAR which was associated with the lack of autoantibodies. Conclusions: Autoimmunity may be the first clinical manifestation of CVID, thus routine screening of immunoglobulins is suggested for patients with autoimmunity. Lack of SAR in CVID is associated with the lack of specific autoantibodies in patients with autoimmunity. It is suggested that physicians use alternative diagnostic procedures (AU)


No disponible


Assuntos
Humanos , Imunodeficiência de Variável Comum/complicações , Doenças Autoimunes/epidemiologia , Subpopulações de Linfócitos B/imunologia , Linfócitos T Reguladores/imunologia , Vacinas Pneumocócicas/imunologia , Autoanticorpos/imunologia , Imunodeficiência de Variável Comum/imunologia
10.
Iran J Immunol ; 15(1): 1-13, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29549228

RESUMO

BACKGROUND: Patients with unclassified hypogammaglobulinemia (UCH) constitute a diagnostic and therapeutic dilemma, because information concerning the clinical and immunological characteristics of these patients is insufficient. OBJECTIVE: To evaluate B-cell subsets in cases with UCH and common variable immunodeficiency (CVID) and their association with treatment requirement in UCH patients. METHODS: The study included 41 UCH, 25 CVID, and 36 healthy individuals between the ages of 4-18 years. RESULTS: The absolute count of total memory and switched memory B-cells were lower in the CVID cases in comparison to the control group. Additionally, the absolute count of marginal zone-like B cells in the 4-10 year age group, and the absolute count of switched plasmablasts in the 10-18 year age group were lower in CVID cases when compared to both the control and UCH groups. The UCH group was categorized based on IVIG replacement therapy. Therefore, the percentage of switched memory B cells was significantly lower in the IVIG-receiving group (10.6% ± 3.10%) compared to the control group (14.0% ± 5.60%). However, there was no significant difference between the IVIG-receiving group and the CVID group. Regarding the comparison of the non-IVIG replacement group and the CVID group, the absolute count of total memory B cells, marginal zone-like B cells, and switched memory B cells were significantly higher in the UCH group. CONCLUSION: B-lymphocyte subsets in UCH cases that did not require IVIG replacement were similar to the control group. On the other hand, the percentage of switched memory B-cells in the UCH cases that required IVIG replacement was not different from that of the CVID cases.


Assuntos
Agamaglobulinemia/imunologia , Subpopulações de Linfócitos B/imunologia , Linfócitos B/imunologia , Imunodeficiência de Variável Comum/imunologia , Adolescente , Agamaglobulinemia/terapia , Criança , Pré-Escolar , Imunodeficiência de Variável Comum/terapia , Feminino , Citometria de Fluxo , Humanos , Switching de Imunoglobulina , Imunoglobulinas Intravenosas/uso terapêutico , Memória Imunológica , Contagem de Linfócitos , Masculino
11.
Scand J Immunol ; 87(5): e12663, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29574865

RESUMO

Common variable immunodeficiency (CVID) is the most prevalent symptomatic type of human primary immunodeficiency diseases (PID). Clinically, CVID is characterized by increased susceptibility to infections and a wide variety of autoimmune and rheumatologic disorders. All patients with CVID registered in Iranian PID Registry (IPIDR) were enrolled in this retrospective cohort study. We investigated the frequency of rheumatologic diseases and its association with immunological and clinical phenotypes in patients with CVID. A total of 227 patients with CVID were enrolled in this study. The prevalence of rheumatologic disorders was 10.1% with a higher frequency in women than men. Most common rheumatologic manifestations were juvenile idiopathic arthritis (JIA) and adult rheumatoid arthritis (RA) followed by juvenile spondyloarthritis (JSpA) and undifferentiated inflammatory arthritis (UIA). Septic arthritis in patients with CVID with a history of RA and JIA was higher than patients without rheumatologic complication. Patients with CVID with a history of autoimmunity (both rheumatologic and non-rheumatologic autoimmunity) had lower regulatory T cells counts in comparison with patients without autoimmune disorders. There was an association between defect in specific antibody responses and negative serologic test results in patients with rheumatologic manifestations. JIA, RA, JSpA and UIA are the most frequent rheumatologic disorders in patients with CVID. Due to antibody deficiency, serologic tests may be negative in these patients. Therefore, these conditions pose significant diagnostic and therapeutic challenges for immunologists and rheumatologists in charge of the care for these patients.


Assuntos
Artrite Juvenil/epidemiologia , Artrite Reumatoide/epidemiologia , Artrite/epidemiologia , Imunodeficiência de Variável Comum/imunologia , Imunodeficiência de Variável Comum/patologia , Espondilite Anquilosante/epidemiologia , Adolescente , Adulto , Anticorpos/sangue , Artrite/complicações , Artrite Juvenil/complicações , Artrite Reumatoide/complicações , Autoimunidade/imunologia , Imunodeficiência de Variável Comum/complicações , Feminino , Humanos , Irã (Geográfico)/epidemiologia , Contagem de Linfócitos , Masculino , Estudos Retrospectivos , Espondilite Anquilosante/complicações , Adulto Jovem
12.
Int J Mol Sci ; 19(2)2018 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-29393912

RESUMO

Common variable immunodeficiency (CVID) is an immunodeficiency disorder with a high incidence of gastrointestinal manifestations and an increased risk of gastric carcinoma and lymphoma. This review discusses the latest advancements into the immunological, clinical and diagnostic aspects of gastric malignancies in patients with CVID. The exact molecular pathways underlying the relationships between CVID and gastric malignancies remain poorly understood. These include genetics, immune dysregulation and chronic infections by Helicobacter pylori. Further studies are needed to better stratify the risk for cancer in these patients, to elaborate surveillance programs aimed at preventing these complications, and to develop new and more effective therapeutic approaches.


Assuntos
Adenocarcinoma/patologia , Imunodeficiência de Variável Comum/patologia , Imunoglobulinas/deficiência , Linfoma/patologia , Neoplasias Gástricas/patologia , Adenocarcinoma/diagnóstico , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/imunologia , Corticosteroides/uso terapêutico , Antineoplásicos/uso terapêutico , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Linfócitos B/patologia , Imunodeficiência de Variável Comum/diagnóstico , Imunodeficiência de Variável Comum/tratamento farmacológico , Imunodeficiência de Variável Comum/imunologia , Árvores de Decisões , Gerenciamento Clínico , Detecção Precoce de Câncer , Helicobacter pylori/patogenicidade , Helicobacter pylori/fisiologia , Humanos , Imunoglobulinas/uso terapêutico , Linfoma/diagnóstico , Linfoma/tratamento farmacológico , Linfoma/imunologia , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/imunologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Linfócitos T/patologia
13.
Liver Transpl ; 24(2): 171-181, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29156507

RESUMO

Common variable immunodeficiency (CVID) is the most common form of primary immunodeficiency characterized by antibody deficiency, recurrent bacterial infections, and autoimmunity. Advanced chronic liver disease occurs in a subset of patients with CVID and manifests with various histological features, such as nodular regenerative hyperplasia, inflammation, fibrosis, and cholangiopathy. We present a case series characterizing the outcomes in adult patients transplanted for primary CVID-related liver disease. We discuss the unique transplantation challenges faced in this primary immunodeficiency group including susceptibility to infections and early disease recurrence. There is a statistically significant decrease in 3-year and 5-year survival after liver transplantation in those with CVID-related liver disease (55% at 3 and 5 years) compared with all-comers (89% at 3 years, 81% at 5 years), prompting a need for discussion of suitability of transplantation in this group of patients as well as methods for reducing posttransplantation risk such as scrupulous search for infectious agents and reduction of immunosuppression. Liver Transplantation 24 171-181 2018 AASLD.


Assuntos
Imunodeficiência de Variável Comum/imunologia , Hepatopatias/cirurgia , Transplante de Fígado/efeitos adversos , Adulto , Doença Crônica , Imunodeficiência de Variável Comum/complicações , Imunodeficiência de Variável Comum/diagnóstico , Evolução Fatal , Feminino , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Hepatopatias/diagnóstico , Hepatopatias/imunologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Recidiva , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
14.
Allergol Immunopathol (Madr) ; 46(2): 127-135, 2018 Mar - Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28735808

RESUMO

BACKGROUND: Common variable immunodeficiency (CVID) is one of the most prevalent symptomatic primary immunodeficiencies (PIDs), which manifests a wide clinical variability such as autoimmunity, as well as T cell and B cell abnormalities. METHODS: A total of 72 patients with CVID were enrolled in this study. Patients were evaluated for clinical manifestations and classified according to the presence or absence of autoimmune disease. We measured regulatory T cells (Tregs) and B-cell subsets using flow cytometry, as well as specific antibody response (SAR) to pneumococcal vaccine, autoantibodies and anti-IgA in patients. RESULTS: Twenty-nine patients (40.3%) have shown at least one autoimmune manifestation. Autoimmune cytopenias and autoimmune gastrointestinal diseases were the most common. A significant association was detected between autoimmunity and presence of hepatomegaly and splenomegaly. Among CVID patients, 38.5% and 79.3% presented a defect in Tregs and switched memory B-cells, respectively, whereas 69.0% presented CD21low B cell expansion. Among patients with a defect in Treg, switched memory and CD21low B cell, the frequency of autoimmunity was 80.0%, 52.2% and 55.0%, respectively. A negative correlation was observed between the frequency of Tregs and CD21low B cell population. 82.2% of patients had a defective SAR which was associated with the lack of autoantibodies. CONCLUSIONS: Autoimmunity may be the first clinical manifestation of CVID, thus routine screening of immunoglobulins is suggested for patients with autoimmunity. Lack of SAR in CVID is associated with the lack of specific autoantibodies in patients with autoimmunity. It is suggested that physicians use alternative diagnostic procedures.


Assuntos
Doenças Autoimunes/imunologia , Linfócitos B Reguladores/imunologia , Imunodeficiência de Variável Comum/imunologia , Gastroenteropatias/imunologia , Linfócitos T Reguladores/imunologia , Adolescente , Adulto , Anticorpos Antibacterianos/sangue , Autoanticorpos/sangue , Doenças Autoimunes/epidemiologia , Autoimunidade , Separação Celular , Imunodeficiência de Variável Comum/epidemiologia , Feminino , Citometria de Fluxo , Gastroenteropatias/epidemiologia , Humanos , Irã (Geográfico)/epidemiologia , Masculino , Vacinas Pneumocócicas/imunologia , Adulto Jovem
15.
Artigo em Espanhol | CUMED | ID: cum-74636

RESUMO

La inmunodeficiencia variable común (IDVC) es una inmunodeficiencia primaria por déficit de anticuerpos, relativamente frecuente. Es considerada un trastorno genético debido a la presencia de mutaciones en genes que codifican para determinado componente del sistema inmune adaptativo. Se caracteriza por disminución de los niveles séricos de IgG, IgA y, en ocasiones, de IgM. El cuadro clínico es muy variable y se describen cuatro fenotipos clínicos. Presentación del caso: Paciente de 16 años de edad, que desde el primer año de vida presentó múltiples cuadros infecciosos respiratorios altos y bajos, complicados y no complicados, principalmente de etiología bacteriana, los cuales requirieron ingresos y tratamientos antimicrobianos de amplio espectro. Se reportaron antecedentes personales y familiares de asma, dermatitis atópica y eczemas recurrentes. Además, presentó trastornos gastrointestinales de diferentes causas e intolerancia a la leche. En una ocasión fue ingresado por un síndrome adénico, que se interpretó como una mononucleosis infecciosa. Se le realizaron estudios inmunológicos a raíz de una neumonía complicada encontrando disminución de los niveles séricos de IgG y se corroboró por citometría de flujo disminución de la población linfocitaria CD19 positiva. Recibió tratamiento con inmunoglobulinas por vía intravenosa con una buena respuesta. Ante cuadros infecciosos que se repiten, principalmente de origen bacterianos, es importante pensar en esta enfermedad, pues el diagnóstico y el tratamiento oportuno mejoran la calidad de vida del paciente …(AU)


Assuntos
Humanos , Masculino , Feminino , Imunodeficiência de Variável Comum/genética , Imunodeficiência de Variável Comum/imunologia , Linfócitos T , Linfócitos B , Infecções Respiratórias/genética
16.
J. investig. allergol. clin. immunol ; 28(3): 172-181, 2018. tab, graf
Artigo em Inglês | IBECS | ID: ibc-174451

RESUMO

Background: Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency (PID). It is characterized by heterogeneous clinical manifestations and defects in B cells and T cells. In the present study, we investigated helper T (TH) cell subsets and regulatory T (Treg) cells and their related cytokines and transcription factors in CVID patients with no definitive genetic diagnosis. Methods: The study population comprised 13 CVID patients and 13 healthy controls. Mutation analysis was performed using whole exome sequencing in CVID patients to rule out monogenic PIDs. TH subsets and Treg were analyzed using flow cytometry. The expression of determinant cytokines (IFN-gamma, IL-17, IL-22, and IL-10) and cell subset specific transcription factors was evaluated before and after stimulation. Results: The main clinical presentations of these patients were infections only and lymphoproliferative phenotypes. No autoimmune or allergy phenotypes were recorded. The frequencies of CD4+ T cells, TH17, and Treg cells were significantly reduced in CVID patients; however, TH1, TH1-like TH17, and TH22 subsets were normal. After stimulation, expression of retinoic-acid-orphan-receptor-C (RORC), runtrelated transcription factor 1 (RUNX1), IL17, and IL10 was significantly lower in CVID patients than in the healthy controls. Moreover, the concentration of IL-17 and IL-10 in the cell culture supernatants of stimulated CD4+ T cells was lower in CVID patients than in healthy controls. Conclusions: Our findings demonstrate that the imbalance of TH17 and Tregs could be associated with infection and the lymphoproliferative phenotype in CVID patients without monogenic disorders


Antecedentes: La inmunodeficiencia variable común (CVID) es la inmunodeficiencia primaria (PID) sintomática más frecuente, caracterizada por manifestaciones clínicas heterogéneas y alteraciones de los linfocitos B y T. En este trabajo, investigamos las poblaciones de linfocitos T cooperadores (Th) y linfocitos T reguladores (Treg), así como sus citocinas y factores de transcripción, en pacientes con CVID sin un diagnóstico genético definitivo. Métodos: Se estudiaron 13 pacientes con CVID y 13 controles sanos (HC). El análisis de las mutaciones se realizó mediante secuenciación del exoma completo en los pacientes con CVID para descartar PID monogénicas. Las poblaciones de linfocitos Th y Treg se examinaron mediante citometría de flujo. Se cuantificaron las citocinas características (IFN-gamma, IL-17, IL-22 e IL-10) y los factores de transcripción específicos de estas subpoblaciones linfocitarias, tanto antes como después de la estimulación. Resultados: Las principales manifestaciones clínicas de estos pacientes fueron las infecciones y los fenotipos linfoproliferativos, pero no se encontraron fenotipos autoinmunes ni de enfermedad alérgica. Los porcentajes de linfocitos T CD4+, Th17 y linfocitos Treg se redujo significativamente en los pacientes con CVID; sin embargo, las poblaciones de Th1, Th1similares a Th17 y Th 22 fueron normales. Después de la estimulación, la expresión de los genes receptor huérfano tipo C del ácido retinoico (RORC) y del factor de transcripción 1 relacionado con Runt (RUNX1), IL-17 e IL-10 fue significativamente menor en los pacientes con IDCV en comparación con los controles sanos. También se objetivó una menor concentración de IL-17 e IL-10 en los sobrenadantes del cultivo de linfocitos T CD4 + estimulados de los pacientes con CVID, respecto a los HC. Conclusiones: Nuestros hallazgos demuestran que en los pacientes con CVID sin un diagnóstico genético definitivo y sin trastornos monogénicos, el desequilibrio de Th17 y Treg podría estar asociado con infecciones y fenotipos linfoproliferativos


Assuntos
Humanos , Imunodeficiência de Variável Comum/imunologia , Linfócitos T Reguladores/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Autoimunidade/imunologia , Transtornos Linfoproliferativos/imunologia , Infecção/imunologia , Estudos de Casos e Controles , Exoma/genética , T-Linfocitopenia Idiopática CD4-Positiva/genética
17.
Pan Afr Med J ; 28: 48, 2017.
Artigo em Francês | MEDLINE | ID: mdl-29184600

RESUMO

Common Variable Immune Deficiency (CVID) is rare. It is a constitutional deficit of humoral immunity characterized by recurrent bacterial infections and by increased frequency of tumors, autoimmune or granulomatous diseases. Gastrointestinal manifestations are very variable and sometimes reveal common variable immune deficiency. We report the case of a 31-year old patient with a history of childhood recurrent respiratory infections complicated by bronchiectasis and with a 3-year history of recurrent glairy diarrhea. Etiological balance was in favor of CVID with autoimmune manifestation (vitiligo). Patient's treatment was based on monthly immunoglobulin (Ig) infusions with favorable outcome at 2-year follow-up.


Assuntos
Imunodeficiência de Variável Comum/diagnóstico , Gastroenteropatias/etiologia , Vitiligo/etiologia , Adulto , Infecções Bacterianas/etiologia , Imunodeficiência de Variável Comum/imunologia , Imunodeficiência de Variável Comum/fisiopatologia , Diarreia/etiologia , Seguimentos , Humanos , Imunoglobulinas/administração & dosagem , Masculino
18.
Scand J Immunol ; 86(3): 171-178, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29083052

RESUMO

Common variable immunodeficiency (CVID) is a syndrome with predominantly defective B cell function. However, abnormalities in the number and function of other lymphocyte subpopulations in peripheral blood (PB) have been described in most patients. We have analysed the distribution of iNKT cell subpopulations in the PB of CVID patients and the ability of these cells to provide in vitro cognate B cell help. The total of iNKT cells was reduced in the PB of CVID patients, especially CD4+, CD4-/CD8- and CCR5+/CXCR3+. These findings were associated with an enrichment of memory-like and a tendency towards a reduction in TNF-α-expressing effector iNKT cells in the peripheral blood mononuclear cells (PBMC) of CVID patients. Moreover, an accumulation of follicular helper iNKT cells in the PB of CVID patients was demonstrated. CVID αGalCer-pulsed iNKT cells are not able to induce autologous B cell proliferation although they do induce proliferation to healthy donor B cells. Interestingly, autologous and heterologous co-cultures did not differ in the amount of immunoglobulin secreted by B cells in vitro. Finally, reduced intracellular SAP expression in iNKT cells and other lymphocytes in the blood from CVID patients was observed. These results provide further insights into the immunological mechanisms underlying the iNKT cell defects and the potential targets to improve B cell help in CVID.


Assuntos
Linfócitos B/imunologia , Comunicação Celular , Imunodeficiência de Variável Comum/imunologia , Células T Matadoras Naturais/imunologia , Saposinas/metabolismo , Adolescente , Adulto , Antígenos CD4/metabolismo , Antígenos CD8/metabolismo , Proliferação de Células , Células Cultivadas , Técnicas de Cocultura , Feminino , Galactosilceramidas/imunologia , Humanos , Imunoglobulinas/metabolismo , Memória Imunológica , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Receptores CCR5/metabolismo , Receptores CXCR3/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Adulto Jovem
19.
Expert Rev Clin Immunol ; 13(11): 1099-1106, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-29019451

RESUMO

OBJECTIVES: The aim of this study was to evaluate the frequency of autoimmunity in primary antibody deficiency (PAD). METHODS: A total of 471 patients with PADs enrolled in this retrospective cohort study. For all patients' demographic information, clinical records and laboratory data were collected to investigate autoimmune complications. RESULTS: Autoimmune disorders as the first presentation of immunodeficiency were recorded in 11 patients (2.5%). History of autoimmunity was recorded in 125 patients during the course of the disease (26.5%). The frequency of autoimmunity in common variable immune deficiency (32.0%) was higher than other forms of PADs. The most common autoimmune manifestations were reported to be autoimmune gastrointestinal disease and autoimmune cytopenias. Among patients with autoimmunity, 87 patients (69.6%) had a history of one autoimmune disorder, while 38 patients (30.4%) had a history of multiple autoimmunities. The immune thrombocytopenic purpura and autoimmune hemolytic anemia were the most two concomitant autoimmune disorders in 16 (42.1%) of 38 patients with multiple autoimmunities. Comparing the frequency of Tregs in PAD patients with autoimmunity showed that, patients with multiple autoimmunities had lower Tregs than those with single autoimmunity (p = 0.017). CONCLUSION: It is important that non-immunologist physicians be alert of the associated autoimmunity with PADs in order to reduce the diagnostic delay and establish timely immunoglobulin replacement therapy in these patients.


Assuntos
Anemia Hemolítica Autoimune/epidemiologia , Imunodeficiência de Variável Comum/epidemiologia , Gastroenteropatias/epidemiologia , Síndromes de Imunodeficiência/epidemiologia , Púrpura Trombocitopênica Idiopática/epidemiologia , Linfócitos T Reguladores/imunologia , Adolescente , Adulto , Anemia Hemolítica Autoimune/imunologia , Autoanticorpos/metabolismo , Autoimunidade , Criança , Estudos de Coortes , Imunodeficiência de Variável Comum/imunologia , Diagnóstico Tardio , Feminino , Gastroenteropatias/imunologia , Humanos , Síndromes de Imunodeficiência/imunologia , Masculino , Púrpura Trombocitopênica Idiopática/imunologia , Estudos Retrospectivos , Adulto Jovem
20.
Curr Allergy Asthma Rep ; 17(11): 78, 2017 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-28983790

RESUMO

PURPOSE OF REVIEW: Vaccination against influenza in patients with primary antibody deficiency is recommended. Common variable immunodeficiency (CVID) is the most frequent and clinically relevant antibody deficiency disease and is by definition characterized by an impaired vaccination response. The purpose of this review is to present the current knowledge of humoral and cellular vaccine response to influenza in CVID patients. RECENT FINDINGS: Studies conducted in CVID patients demonstrated an impaired humoral response upon influenza vaccination. Data on cellular immune response are in part conflicting, with two out of three studies showing responses similar to healthy controls. Available data suggest a benefit from influenza vaccination in CVID patients. Therefore, annual influenza vaccination in patients and their close household contacts is recommended.


Assuntos
Imunodeficiência de Variável Comum/imunologia , Hospedeiro Imunocomprometido , Influenza Humana/prevenção & controle , Vacinação , Animais , Imunodeficiência de Variável Comum/virologia , Humanos , Imunidade Celular , Vacinas contra Influenza/imunologia , Influenza Humana/imunologia , Linfócitos T/imunologia
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