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2.
Nat Immunol ; 20(3): 350-361, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30718914

RESUMO

Despite the known importance of zinc for human immunity, molecular insights into its roles have remained limited. Here we report a novel autosomal recessive disease characterized by absent B cells, agammaglobulinemia and early onset infections in five unrelated families. The immunodeficiency results from hypomorphic mutations of SLC39A7, which encodes the endoplasmic reticulum-to-cytoplasm zinc transporter ZIP7. Using CRISPR-Cas9 mutagenesis we have precisely modeled ZIP7 deficiency in mice. Homozygosity for a null allele caused embryonic death, but hypomorphic alleles reproduced the block in B cell development seen in patients. B cells from mutant mice exhibited a diminished concentration of cytoplasmic free zinc, increased phosphatase activity and decreased phosphorylation of signaling molecules downstream of the pre-B cell and B cell receptors. Our findings highlight a specific role for cytosolic Zn2+ in modulating B cell receptor signal strength and positive selection.


Assuntos
Agamaglobulinemia/imunologia , Linfócitos B/imunologia , Proteínas de Transporte de Cátions/imunologia , Zinco/imunologia , Agamaglobulinemia/genética , Agamaglobulinemia/metabolismo , Animais , Linfócitos B/metabolismo , Proteínas de Transporte de Cátions/deficiência , Proteínas de Transporte de Cátions/genética , Pré-Escolar , Citosol/imunologia , Citosol/metabolismo , Modelos Animais de Doenças , Retículo Endoplasmático/imunologia , Retículo Endoplasmático/metabolismo , Feminino , Perfilação da Expressão Gênica , Humanos , Lactente , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mutação , Linhagem , Zinco/metabolismo
3.
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
4.
Scand J Immunol ; 88(4): e12709, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30152873

RESUMO

PURPOSE: Transient hypogammaglobulinemia of infancy (THI) is a common immunodeficiency, but definitive diagnosis can only be made retrospectively. While the pathogenesis is still unknown, abnormalities have been reported in the B cell compartment. In this study, we analysed the B cell subsets of patients with an initial THI diagnosis (n = 20) and compared them with those of healthy age-matched Turkish children (n = 72). METHODS: Flow cytometric analyses of the B subsets were performed by staining with anti-CD27-PE, anti-CD19-PerCP, anti-IgD-FITC and anti-IgM-APC antibodies. RESULTS: During a median follow-up of 6.6 years, 13 patients whose IgG levels had normalized before they reached four years of age were diagnosed with definitive THI. The memory subsets of these patients were lower but not statistically different from the healthy controls (HC). The remaining seven patients had prolonged hypogammaglobulinemia after the age of four and had significantly lower memory B cell subsets compared to the HC. On follow-up, these patients had not experienced recurrent infections or autoimmunity. Re-evaluation of patients' B cell subsets six years later showed that the memory B cell ratios had increased to levels comparable to HC, despite the patients still having mildly low IgG levels. CONCLUSION: Patients with prolonged hypogammaglobulinemia had lower levels of memory B cells despite having a similar clinical course to patients who had been diagnosed with definitive THI. This subgroup of putative THI patients poses a diagnostic and classification dilemma. Our results suggested that these patients' memory B cells and IgG levels may recover over time.


Assuntos
Agamaglobulinemia/imunologia , Subpopulações de Linfócitos B/imunologia , Linfócitos B/imunologia , Doenças do Recém-Nascido/imunologia , Infecção/imunologia , Agamaglobulinemia/diagnóstico , Autoimunidade , Separação Celular , Criança , Pré-Escolar , Feminino , Citometria de Fluxo , Seguimentos , Humanos , Imunoglobulina G/sangue , Memória Imunológica , Lactente , Recém-Nascido , Doenças do Recém-Nascido/diagnóstico , Infecção/diagnóstico , Masculino , Avaliação de Resultados da Assistência ao Paciente , Turquia
5.
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
6.
Allergol. immunopatol ; 46(1): 58-66, ene.-feb. 2018. tab, graf
Artigo em Inglês | IBECS | ID: ibc-170788

RESUMO

Background: X-linked agammaglobulinaemia (XLA) is a genetic disorder affecting B cell maturation, which is characterised by a low number of B cells, agammaglobulinaemia and increased susceptibility to a variety of bacterial infections. This study was performed to assess T cell subpopulations in a group of children with XLA in association with chronic respiratory disease (CRD). Methods: Numbers of T cell subpopulations (CD3+, CD4+, CD8+, CD3+DR+, naïve, memory, recent thymic emigrants (RTE), regulatory T cells, follicular T helpers) were measured by eight-colour flow cytometry in 22 XLA patients and 50 controls. BAFF level was measured by ELISA. Results: XLA patients with CRD had a significantly lower percentage of RTE numbers and Tregs, while significantly higher absolute counts of lymphocytes, CD3+, CD8+, CD3+DR+ and CD4+CD45RO+ T cells were detected as compared with healthy controls. In patients with XLA without CRD, the number of follicular T helper cells was altered significantly (percentage and absolute), as compared with healthy controls. Additionally, they had significantly higher counts (percentage and absolute) of CD4+CD45RA+ cells and lower percentage of CD4+CD45RO+ cells in comparison with healthy controls. Conclusions: Our study affords new information concerning CRD and T cell subsets that differentiate or are maintained in the absence of B cells in children with XLA. T cell's homeostasis depends on the presence of chronic respiratory disease that may be caused by the delay in diagnosis (AU)


No disponible


Assuntos
Humanos , Agamaglobulinemia/imunologia , Infecções Respiratórias/imunologia , Doenças Genéticas Ligadas ao Cromossomo X/imunologia , Doença Crônica , Linfócitos T Reguladores/imunologia , Fator Tímico Circulante/imunologia , Fator Ativador de Células B/imunologia , Sinusite/imunologia
7.
Ann Saudi Med ; 38(1): 65-68, 2018 Jan-Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29313528

RESUMO

Levetiracetam (LEV) is a second-generation antiepileptic drug approved for the treatment of several types of epilepsy. We report a 45-year-old female who developed hypogammaglobulinemia and B cell aplasia during LEV treatment. The Naranjo probability score for an adverse drug reaction was 6. After LEV discontinuation, the number of B cells gradually increased and reached normal levels within two months. This case suggests that monitoring of immunoglobulin levels and lymphocyte subsets analysis is important in patients treated with LEV, especially in cases of prolonged infections. SIMILAR CASES PUBLISHED: 1.


Assuntos
Agamaglobulinemia , Linfócitos B , Epilepsia/tratamento farmacológico , Linfopenia , Piracetam/análogos & derivados , Agamaglobulinemia/induzido quimicamente , Agamaglobulinemia/diagnóstico , Agamaglobulinemia/imunologia , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/efeitos adversos , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Linfócitos B/patologia , Relação Dose-Resposta a Droga , Epilepsia/etiologia , Feminino , Humanos , Levetiracetam , Linfopenia/induzido quimicamente , Linfopenia/imunologia , Linfopenia/patologia , Pessoa de Meia-Idade , Piracetam/administração & dosagem , Piracetam/efeitos adversos , Resultado do Tratamento , Suspensão de Tratamento
8.
Allergol Immunopathol (Madr) ; 46(1): 58-66, 2018 Jan - Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28477853

RESUMO

BACKGROUND: X-linked agammaglobulinaemia (XLA) is a genetic disorder affecting B cell maturation, which is characterised by a low number of B cells, agammaglobulinaemia and increased susceptibility to a variety of bacterial infections. This study was performed to assess T cell subpopulations in a group of children with XLA in association with chronic respiratory disease (CRD). METHODS: Numbers of T cell subpopulations (CD3+, CD4+, CD8+, CD3+DR+, naïve, memory, recent thymic emigrants (RTE), regulatory T cells, follicular T helpers) were measured by eight-colour flow cytometry in 22 XLA patients and 50 controls. BAFF level was measured by ELISA. RESULTS: XLA patients with CRD had a significantly lower percentage of RTE numbers and Tregs, while significantly higher absolute counts of lymphocytes, CD3+, CD8+, CD3+DR+ and CD4+CD45RO+ T cells were detected as compared with healthy controls. In patients with XLA without CRD, the number of follicular T helper cells was altered significantly (percentage and absolute), as compared with healthy controls. Additionally, they had significantly higher counts (percentage and absolute) of CD4+CD45RA+ cells and lower percentage of CD4+CD45RO+ cells in comparison with healthy controls. CONCLUSIONS: Our study affords new information concerning CRD and T cell subsets that differentiate or are maintained in the absence of B cells in children with XLA. T cell's homeostasis depends on the presence of chronic respiratory disease that may be caused by the delay in diagnosis.


Assuntos
Agamaglobulinemia/imunologia , Fator Ativador de Células B/metabolismo , Bronquite/imunologia , Doenças Genéticas Ligadas ao Cromossomo X/imunologia , Sinusite/imunologia , Subpopulações de Linfócitos T/imunologia , Linfócitos T Reguladores/imunologia , Timócitos/imunologia , Adolescente , Agamaglobulinemia/complicações , Bronquite/complicações , Separação Celular , Criança , Pré-Escolar , Doença Crônica , Feminino , Citometria de Fluxo , Doenças Genéticas Ligadas ao Cromossomo X/complicações , Humanos , Memória Imunológica , Imunofenotipagem , Masculino , Sinusite/complicações
9.
Bull Cancer ; 105 Suppl 2: S158-S167, 2018 Dec.
Artigo em Francês | MEDLINE | ID: mdl-30686354

RESUMO

CAR-T TREATMENT OF ACUTE LEUKEMIA IN ADULTS: The prognosis for acute lymphoblastic leukemia (ALL) in adults remains poor in refractory or relapsed (R/R) situations. Among the immunotherapy strategies that have recently been developed, CAR-T cells (chimeric antigen receptor modified T-cells) represent a major technological and therapeutic advance in the management of adult and pediatric patients with such resistant diseases. The first CAR-T trials targeting the ubiquitous B-cell antigen CD19 showed very encouraging results with complete remission rates of approximately 80%. Cytokine release syndrome (CRS) and neurotoxicity are two major and potentially life-threatening adverse events, that require coordinated management with intensive care units and graduated use of IL-6 pathway blocking antibodies and steroids. In addition to immediate toxicity, many clinical issues arise such as ALL treatment from apheresis to CAR-T infusion, the role of allogeneic hematopoietic stem cell transplant (HSCT) before or after CAR-T therapy, or the reduction of escape mechanisms mostly driven by the loss of target expression. The development of these strategies in other subtypes of acute leukemias, including myeloid acute leukemia, is confronted with the expression of antigenic targets by healthy tissues and the potential risk of prolonged cytopenias. This review adopts a clinical perspective to detail the main results of CD19 CAR-T in ALL and the challenges raised by this new therapeutic approach. Cet article fait partie du numéro supplément Les cellules CAR-T : une révolution thérapeutique ? réalisé avec le soutien institutionnel des partenaires Gilead : Kite et Celgene.


Assuntos
Antígenos CD19/imunologia , Imunoterapia Adotiva/métodos , Leucemia Mieloide Aguda/terapia , Receptores de Antígenos Quiméricos , Adulto , Agamaglobulinemia/imunologia , Remoção de Componentes Sanguíneos , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Fase II como Assunto , Doença Enxerto-Hospedeiro/imunologia , Humanos , Imunoterapia Adotiva/efeitos adversos , Infecção/etiologia , Leucemia Mieloide Aguda/imunologia , Indução de Remissão , Linfócitos T/imunologia , Evasão Tumoral/imunologia
10.
Front Immunol ; 9: 2984, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30619340

RESUMO

B cell activation via the B cell receptor (BCR) signalosome involves participation of signaling molecules such as BTK and BLNK. Genetic defects in these molecules are known to impair B cell differentiation and subsequently lead to agammaglobulinemia. Here we identified novel mutations in BTK and BLNK in two unrelated patients that perturb the intrinsic B-cell receptor signaling pathway and lead to selective IgM deficiency, whereas production of other immunoglobulin isotypes and IgG antibody response remain intact. Currently it is unknown how BCR signaling strength affects mature B cell development in humans. Both patients show reduced levels of BCR signalosome phosphorylation as well as impaired BCR-dependent Ca2+ influx, which was accompanied by a marked decrease in IgD+IgM+CD27+ MZ-like B-cells. We further describe reduced expression of essential B cell differentiation factors such as BAFF-R and T-Bet in the patients' B-cells, which might contribute to the observed deficiency of MZ-like B cells. MZ-like B cells are known to produce natural IgM antibodies that play an essential role in immune homeostasis. By using surface plasmon resonance (SPR) technology and a synthetic blood group A trisaccharide as antigen we were able to show that both patients lack the presence of anti-blood group A IgM considered to be prototypical natural antibodies whereas IgG levels were normal. Antibody binding dynamics and binding affinity of anti-blood group A IgG were comparable between patients and healthy controls. These results indicate that human IgM deficiency can be associated with signaling defects in the BCR signalosome, defective production of natural IgM antibodies in the blood group A/B/0 system and abnormalities in B cell development.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Tirosina Quinase da Agamaglobulinemia/genética , Agamaglobulinemia/genética , Linfócitos B/imunologia , Imunoglobulina M/deficiência , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adolescente , Adulto , Tirosina Quinase da Agamaglobulinemia/metabolismo , Agamaglobulinemia/imunologia , Linfócitos B/metabolismo , Humanos , Imunoglobulina M/imunologia , Masculino , Receptores de Antígenos de Linfócitos B/imunologia , Receptores de Antígenos de Linfócitos B/metabolismo , Transdução de Sinais/genética , Transdução de Sinais/imunologia
12.
Rev Med Suisse ; 13(557): 739-742, 2017 Apr 05.
Artigo em Francês | MEDLINE | ID: mdl-28722362

RESUMO

Transient hypogammaglobulinemia of infancy is characterized as a reduction of one or more classes of immunoglobulins with a response to vaccines and normal subpopulations of lymphocytes B presenting in the first years of life. The diagnosis is made a posteriori, once the levels of immunoglobulins are normalized, in general between 2 and 4 years of age. Clinical presentation varies : the child may be either asymptomatic or present with recurrent infections, atopy and / or auto-immunity. There are no clinical or immunological features that distinguish this condition from a common variable immunodeficiency (CVID). Because of the risk of severe infections, it is necessary a follow up by a paediatric immunologist. Depending on the presentation and evolution, a prophylaxis with antibiotics or a substitution with immunoglobulins might be indicated.


Assuntos
Agamaglobulinemia/diagnóstico , Imunodeficiência de Variável Comum/diagnóstico , Imunoglobulinas/imunologia , Agamaglobulinemia/imunologia , Agamaglobulinemia/terapia , Linfócitos B/imunologia , Pré-Escolar , Humanos , Lactente
13.
Clin Immunol ; 183: 41-45, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28705765

RESUMO

Over the past decades, a pleiotropic spectrum of B-cell intrinsic defects leading to early onset agammaglobulinemia and absent B cells has been described. Herein we report terminal 14q32.33 deletion as a novel cause of agammaglobulinemia. We describe a 20-year old man with a 1MB terminal 14q32.33 deletion resulting in a loss of the entire Immunoglobulin heavy chain gene region of chromosome 14. The patient presented with absent serum immunoglobulin levels and absent circulating B cells since age 2. The clinical picture was dominated by severe episodes of recurrent upper respiratory tract infections. In the literature, the most prevalent features of terminal 14q32.33 deletions include mental disability, facial malformation, hypotonia, seizures, and visual problems with retinal abnormalities. Neither increased susceptibility to infections nor agammaglobulinemia have been described as a manifestation of terminal 14q32.33 deletion. Thus, our findings expand the known clinical spectrum of terminal 14q32.33 deletion to include susceptibility to infections.


Assuntos
Agamaglobulinemia/genética , Deleção Cromossômica , Cromossomos Humanos Par 14/genética , Agamaglobulinemia/imunologia , Humanos , Cadeias Pesadas de Imunoglobulinas/genética , Masculino , Adulto Jovem
14.
J Clin Immunol ; 37(6): 539-547, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28711959

RESUMO

This multicentre, open-label, prospective, single-arm study was designed to evaluate the efficacy, pharmacokinetics, and safety of IqYmune®, a highly purified 10% polyvalent immunoglobulin preparation for intravenous administration in patients with primary immunodeficiency. IqYmune® was administered to 62 patients (aged 2-61 years) with X-linked agammaglobulinemia or common variable immune deficiency at a dose from 0.22 to 0.97 g/kg every 3 to 4 weeks for 12 months with an infusion rate up to 8 mL/kg/h. A pharmacokinetic study was performed at steady state between the 8th and the 9th infusion. A single case of serious bacterial infection was observed, leading to an annualized rate of serious bacterial infections/patient (primary endpoint) of 0.017 (98% CI: 0.000, 0.115). Overall, 228 infections were reported, most frequently bronchitis, chronic sinusitis, nasopharyngitis and upper respiratory tract infection. The mean annualized rate of infections was 3.79/patient. A lower risk of infections was associated with an IgG trough level > 8 g/L (p = 0.01). The mean annualized durations of absence from work or school and of hospitalization due to infections were 1.01 and 0.89 days/patient, respectively. The mean serum IgG trough level before the 6th infusion was 7.73 g/L after a mean dose of IqYmune® of 0.57 g/kg. The pharmacokinetic profile of IqYmune® was consistent with that of other intravenous immunoglobulins. Overall, 15.5% of infusions were associated with an adverse event occurring within 72 h post infusion. Headache was the most common adverse event. In conclusion, IqYmune® was shown to be effective and well tolerated in patients with primary immunodeficiency.


Assuntos
Agamaglobulinemia/terapia , Imunodeficiência de Variável Comum/terapia , Doenças Genéticas Ligadas ao Cromossomo X/terapia , Imunoglobulinas Intravenosas/uso terapêutico , Imunoterapia/métodos , Adolescente , Adulto , Agamaglobulinemia/imunologia , Criança , Pré-Escolar , Ensaios Clínicos como Assunto , Imunodeficiência de Variável Comum/imunologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Europa (Continente) , Feminino , Doenças Genéticas Ligadas ao Cromossomo X/imunologia , Cefaleia/diagnóstico , Cefaleia/etiologia , Humanos , Imunoglobulinas Intravenosas/efeitos adversos , Imunoglobulinas Intravenosas/farmacocinética , Imunoterapia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
15.
J Clin Immunol ; 37(5): 427-433, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28589420

RESUMO

PURPOSE: The specific antibody response to the unconjugated 23-valent pneumococcal polysaccharide vaccine is one of the most common tests used to assess for possible humoral immunodeficiency. The results can be difficult to interpret because most people have been immunized with one or more of the pneumococcal vaccines and there is controversy regarding what constitutes a normal response. To circumvent this problem, we developed an ELISA to measure IgG-specific antibodies to the Salmonella Vi Typhim (S. Typhim) vaccine, a pure polysaccharide vaccine, which is a neoantigen for the vast majority of people in the USA. METHODS: We compared the pre- and post-vaccination serum titers to the Vi Typhim vaccine in healthy controls (n = 22), patients previously diagnosed with a primary immunodeficiency (n = 30), and patients referred for possible humoral immune deficiency (n = 29). We also determined if the S. Typhim vaccine could be used to assess specific antibody responses in people on antibody replacement therapy. RESULTS: Following immunization with the S. Typhim vaccine, we found that a 2-fold increase in titers is 100% sensitive and specific in detecting known humoral immune deficiencies as determined by ROC curve analysis. This cut-off value was successfully applied to possible immune deficiency patients (n = 29), resulting in the diagnosis of seven subjects with humoral immunodeficiency. The use of immunoglobulin replacement therapy did not affect the median response ratios compared to subjects not receiving gammaglobulin. CONCLUSION: This study suggests that measurement of the specific antibody response to the S. Typhim vaccine may have advantages over pneumococcal vaccination in the evaluation of the humoral immune response.


Assuntos
Agamaglobulinemia/diagnóstico , Agamaglobulinemia/imunologia , Anticorpos Antibacterianos/imunologia , Vacinas Tíficas-Paratíficas/imunologia , Adolescente , Adulto , Agamaglobulinemia/sangue , Idoso , Anticorpos Antibacterianos/sangue , Área Sob a Curva , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Síndromes de Imunodeficiência/sangue , Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/imunologia , Masculino , Pessoa de Meia-Idade , Polissacarídeos Bacterianos/administração & dosagem , Polissacarídeos Bacterianos/imunologia , Curva ROC , Vacinas Tíficas-Paratíficas/administração & dosagem , Vacinação , Adulto Jovem
16.
PLoS One ; 12(4): e0175961, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28422989

RESUMO

The lack of BTK in X-linked agammaglobulinemia (XLA) patients does not affect monocytes and polymorphonuclear cells (PMN) phenotype and functions. In this study, we show that XLA patients had an increased frequency of the intermediate monocytes subset and that BTK-deficient monocytes and PMN had a normal expression of receptors involved in the activation and cellular responses. We demonstrate that BTK is not required for migration, phagocytosis and the production of reactive oxygen species (ROS) following engagement of FC gamma receptors (FcγR). XLA monocytes and PMN showed an efficient calcium (Ca2+)-independent activation of oxidative burst, suggesting that oxidative burst is less dependent by Ca2+ mobilization. The phagocytosis was functional and it remained unaltered also after Ca2+ chelation, confirming the independence of phagocytosis on Ca2+ mobilization. Intravenous immunoglobulin (IVIg) infusion exerted an anti-inflammatory effect by reducing the frequency of pro-inflammatory monocytes. In monocytes, the IVIg reduce the oxidative burst and phagocytosis even if these functions remained efficient.


Assuntos
Agamaglobulinemia/tratamento farmacológico , Doenças Genéticas Ligadas ao Cromossomo X/tratamento farmacológico , Imunoglobulinas Intravenosas/uso terapêutico , Leucócitos Mononucleares/efeitos dos fármacos , Monócitos/efeitos dos fármacos , Proteínas Tirosina Quinases/deficiência , Adulto , Tirosina Quinase da Agamaglobulinemia , Agamaglobulinemia/genética , Agamaglobulinemia/imunologia , Agamaglobulinemia/patologia , Cálcio/metabolismo , Quelantes de Cálcio/farmacologia , Estudos de Casos e Controles , Movimento Celular/efeitos dos fármacos , Esquema de Medicação , Regulação da Expressão Gênica , Doenças Genéticas Ligadas ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/imunologia , Doenças Genéticas Ligadas ao Cromossomo X/patologia , Humanos , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/patologia , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Monócitos/patologia , Fagocitose/efeitos dos fármacos , Fenótipo , Proteínas Tirosina Quinases/genética , Proteínas Tirosina Quinases/imunologia , Espécies Reativas de Oxigênio/imunologia , Espécies Reativas de Oxigênio/metabolismo , Receptores de IgG/genética , Receptores de IgG/imunologia , Explosão Respiratória/efeitos dos fármacos , Explosão Respiratória/imunologia , Transdução de Sinais
17.
J Investig Allergol Clin Immunol ; 27(2): 129-131, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28398200
18.
Rev Chil Pediatr ; 88(1): 136-141, 2017 02.
Artigo em Espanhol | MEDLINE | ID: mdl-28288231

RESUMO

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


Assuntos
Agamaglobulinemia/diagnóstico , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico , Doença Granulomatosa Crônica/diagnóstico , Síndromes de Imunodeficiência/diagnóstico , Agamaglobulinemia/imunologia , Agamaglobulinemia/fisiopatologia , Doenças Genéticas Ligadas ao Cromossomo X/imunologia , Doenças Genéticas Ligadas ao Cromossomo X/fisiopatologia , Doença Granulomatosa Crônica/imunologia , Doença Granulomatosa Crônica/fisiopatologia , Humanos , Síndromes de Imunodeficiência/imunologia , Síndromes de Imunodeficiência/fisiopatologia , Lactente , Unidades de Terapia Intensiva Pediátrica , Masculino , Índice de Gravidade de Doença
19.
Curr Opin Rheumatol ; 29(3): 228-233, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28240614

RESUMO

PURPOSE OF REVIEW: There are no established guidelines for evaluating and treating hypogammaglobulinemia in patients with rheumatic disease who receive B-cell depleting agents. The purpose of this article is to review findings in the work-up and treatment of common variable immunodeficiency (CVID) that can guide our evaluation of patients with autoimmune disease who develop hypogammaglobulinemia after rituximab/B-cell depleting therapy. RECENT FINDINGS: Infection rates are higher in rheumatic disease patients who develop hypogammaglobulinemia than those who do not. However, not all patients who develop hypogammaglobulinemia are at increased risk of developing infection after B-cell depleting therapy. Recent consensus statements have helped refine the diagnosis of impaired immune responses in patients with CVID, and can provide guidance for the diagnostic work-up and therapeutic decision making for patients with secondary drug induced hypogammaglobulinemia. SUMMARY: Based on findings in studies of CVID, assessment of vaccine response in patients with hypogammglogulinemia after rituximab therapy in the setting of recurrent infections can help predict propensity for infection and thus guide decision making with regards to intravenous immunoglobulin supplementation and retreatment with rituximab.


Assuntos
Agamaglobulinemia , Linfócitos B/imunologia , Imunidade Celular , Rituximab/administração & dosagem , Agamaglobulinemia/diagnóstico , Agamaglobulinemia/tratamento farmacológico , Agamaglobulinemia/imunologia , Humanos , Fatores Imunológicos/administração & dosagem
20.
Allergol. immunopatol ; 45(1): 55-62, ene.-feb. 2017. tab, graf
Artigo em Inglês | IBECS | ID: ibc-158975

RESUMO

Background: This is a prospective study that assessed pneumococcal antibody levels in PID patients under intravenous immunoglobulin (IVIG) treatment using different brands. Methods: Twenty-one patients receiving regular IVIG every 28 days were invited to participate: 12 with common variable immunodeficiency, six with X-linked agammaglobulinaemia and three with hyper-IgM syndrome. One blood sample was collected from each patient just prior to IVIG administration at a threemonth time interval during one year. A questionnaire was filled in with patient’s demographic data and history of infections during the study period. Streptococcus pneumoniae antibodies against six serotypes (1, 5, 6B, 9V, 14 and 19F) were assessed by ELISA both in patients’ serum (trough levels) and in IVIG samples. Results: Median total IgG trough serum levels were 7.91 g/L (range, 4.59-12.20). All patients had antibody levels above 0.35 g/mL to the six serotypes on all four measurements. However, only 28.6% of patients had pneumococcal antibodies for the six analysed serotypes above 1.3 g/mL on all four evaluations during the one-year period. No correlation was found between IgG trough levels and pneumococcal specific antibodies. Eighteen of the 21 patients (85.7%) had infections at some point during the 12-month follow-up, 62/64 (96.9%) clinically classified in respiratory tract infections, four of which were pneumonia. Conclusions: Pneumococcal antibodies are present in a high range of concentrations in sera from PID patients and also in IVIG preparations. Even maintaining a recommended IgG trough level, these patients can be susceptible to these bacteria and that may contribute to recurrent respiratory infections (AU)


No disponible


Assuntos
Humanos , Síndromes de Imunodeficiência/imunologia , Streptococcus pneumoniae/patogenicidade , Infecções Pneumocócicas/imunologia , Infecções Respiratórias/imunologia , Imunodeficiência de Variável Comum/imunologia , Agamaglobulinemia/imunologia , Síndrome de Imunodeficiência com Hiper-IgM/imunologia , Estudos Prospectivos , Anticorpos/imunologia
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