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1.
BMJ Case Rep ; 12(8)2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31434669

RESUMO

Good's syndrome (GS) is a rare, adult-onset combined B cell and T cell immunodeficiency with an associated thymoma. These patients have an increased risk of bacterial, fungal, viral and opportunistic infections. This report describes a 75-year-old female patient who presented with a full body rash and an anterior mediastinal mass. She underwent a biopsy of her rash and mass, which revealed erythema multiforme and WHO Type A thymoma, respectively. During her hospitalisation, she was also found to have oropharyngeal candidiasis, methicillin-susceptible Staphylococcus aureus bacteraemia and herpes simplex virus type 2 (HSV-2) skin lesions. Based on the number of infections and severity of her rash, an immunocompromised state was suspected. Immunological testing revealed a B cell and T cell deficiency as well as low serum immunoglobulins. This combination of hypogammaglobulinaemia and thymoma led to a diagnosis of GS. While there have been many case reports of GS, this is the first report of the immunodeficiency presenting with erythema multiforme.


Assuntos
Antibacterianos/uso terapêutico , Reabilitação Cardíaca , Eritema Multiforme/diagnóstico , Síndromes de Imunodeficiência/diagnóstico , Infecções Estafilocócicas/diagnóstico , Timoma/diagnóstico , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Idoso , Eritema Multiforme/complicações , Eritema Multiforme/tratamento farmacológico , Eritema Multiforme/imunologia , Evolução Fatal , Feminino , Hidratação , Humanos , Hospedeiro Imunocomprometido , Síndromes de Imunodeficiência/complicações , Síndromes de Imunodeficiência/tratamento farmacológico , Síndromes de Imunodeficiência/imunologia , Pneumonia , Choque Séptico , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/imunologia , Timoma/imunologia
3.
Biologicals ; 60: 60-67, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31160148

RESUMO

Octanorm (marketed as cutaquig® in Canada and US [2018] and registered in several European countries [2019]) is a new immunoglobulin subcutaneous 16.5% liquid for the treatment of patients with primary immune deficiency (PID) and secondary immune deficiency (SID) depending on country's specific indications. Octanorm contains ≥96% human IgG and is characterized by especially low concentrations of polymers and aggregates, IgA and IgM, a physiological osmolality along with a low isoagglutinin titer. The Octanorm manufacturing process is based on the well-established IVIG octagam® 5% and 10% process, but yields a higher immunoglobulin concentration of 16.5% in the final product. Octanorm shows a distribution of immunoglobulin G subclasses closely proportional to native human plasma and comprises a broad spectrum of antibodies against infectious agents. Potential procoagulant activity is not detectable. IgG functionality and physico-chemical integrity have been demonstrated by state-of-the-art-methods. The virus safety of Octanorm is ensured via a combination of three validated independent methods as part of the manufacturing process. Substantial prion depletion during the manufacturing process has also been demonstrated. Compared with other commercially available subcutaneous immunoglobulin (SCIG) 20% products, Octanorm 16.5% shows a lower viscosity, which is a valuable feature that allows for a more comfortable infusion experience.


Assuntos
Biomarcadores Farmacológicos , Imunoglobulina G/química , Adulto , Estabilidade de Medicamentos , Feminino , Humanos , Imunoglobulina G/uso terapêutico , Síndromes de Imunodeficiência/tratamento farmacológico , Infusões Subcutâneas
4.
Biologicals ; 59: 20-28, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30992162

RESUMO

Patients with primary immunodeficiency disorders are vulnerable to infectious diseases. Intravenous immunoglobulin (IVIG) therapeutic products manufactured from human plasma are employed widely to protect patients from pathogens such as measles virus, which causes a potentially fatal and contagious disease. Therefore, health authorities stipulate a minimum titer of measles neutralizing antibodies (mnAbs) in IVIG products to ensure efficient protection. In general, mnAb titers are measured in a cell-based neutralization assay; however, this assay is labor intensive and time consuming, and the results are variable. Here, we compared a cell-based neutralizing assay with several ELISA tests to evaluate whether ELISAs can overcome the limitations of cell-based assays. The mnAb concentrations measured by the ELISAs showed a strong and significant positive correlation with those measured in a cell-based assay. Also, strong positive correlations were identified for measurement of individual source plasmas, which are used as raw materials for manufacturing IVIG products. Measurement by ELISA revealed that about 80% of 198 source plasmas had mnAb concentrations of <500 mIU/mL. These results suggest that quantitative ELISAs based on relevant antigens allow reliable and comprehensive measurement of mnAb concentrations in source plasmas and drug product; these ELISAs are also faster and more accurate than cell-based assay.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Imunoglobulinas Intravenosas/imunologia , Síndromes de Imunodeficiência/imunologia , Vírus do Sarampo/imunologia , Testes de Neutralização/métodos , Contaminação de Medicamentos/prevenção & controle , Ensaio de Imunoadsorção Enzimática/métodos , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Síndromes de Imunodeficiência/tratamento farmacológico , Reprodutibilidade dos Testes
5.
Int Immunopharmacol ; 71: 404-410, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30952104

RESUMO

BACKGROUND: Immunoglobulin (IG) replacement therapy in patients with primary immunodeficiency diseases (PID) can be administered daily to every 2 weeks subcutaneously (SCIG) or every 3 or 4 weeks intravenously (IVIG). OBJECTIVES: Develop a population pharmacokinetic (PK) model simulating IG exposure with Ig20Gly, a 20% SCIG; determine the dose adjustment factor for Ig20Gly relative to IVIG. METHODS: Data from patients with PID treated with Ig20Gly and IVIG 10% were used to characterize IG population PK by nonlinear mixed-effects modeling and validated using data splitting and a visual predictive check. IG profiles were simulated for 1000 patients/interval treated with Ig20Gly (daily, every 2 days, every 3 days, twice weekly, weekly, every 2 weeks). An Ig20Gly adjustment factor of 130% was used to simulate Ig20Gly to IVIG AUC ratios for weekly or every 2 weeks Ig20Gly dosing intervals and a monthly IVIG dosing interval. RESULTS: A 1-compartment model, using weight as a covariate on clearance, derived from an index modeling dataset (n = 81) demonstrated predictability for a validation dataset (n = 21). The model estimate of bioavailability was 73.9%. Simulations for 6 dosing intervals showed similar mean profiles with overlapping prediction intervals. Mean AUC ratios of Ig20Gly to IVIG with a dose adjustment factor of 1.30:1 were 98.7% for weekly and 97.7% for twice-weekly administration demonstrating comparable exposure. CONCLUSION: Ig20Gly exposures from daily to up to every 2 weeks appeared equivalent. A 1.30 conversion factor provided coverage comparable to IVIG when Ig20Gly is administered daily to every 2 weeks.


Assuntos
Simulação por Computador , Imunoglobulinas Intravenosas/farmacocinética , Síndromes de Imunodeficiência/tratamento farmacológico , Administração Intravenosa , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Protocolos Clínicos , Cálculos da Dosagem de Medicamento , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Grupos Populacionais , Software , Adulto Jovem
6.
BMJ Case Rep ; 12(3)2019 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-30898962

RESUMO

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


Assuntos
Síndromes de Imunodeficiência/complicações , Timoma/etiologia , Neoplasias do Timo/etiologia , Administração Intravenosa , Idoso , Humanos , Imunoglobulina G/administração & dosagem , Síndromes de Imunodeficiência/tratamento farmacológico , Fatores Imunológicos/administração & dosagem , Masculino , Timoma/patologia , Neoplasias do Timo/patologia
7.
Front Immunol ; 10: 58, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30740107

RESUMO

Mendelian susceptibility to mycobacterial diseases (MSMD) is a rare condition of primary immunodeficiency disorder. Interleukin-12 receptor ß1 (IL12RB1) deficiency, is the most common genetic etiology of MSMD, which is characterized by the selective predisposition to clinical disease caused by weakly-virulent mycobacteria, such as Bacillus Calmette-Guérin (BCG) vaccines, and environmental non-tuberculous mycobacteria (NTM). To the best of our knowledge, this is the first case of IL12RB1 deficiency to be reported from Iraq. Our case is an 8-year-old Syrian girl, for first-cousin parents, with a refugee-status in the North of Iraq. She had a history of disseminated BCG infection 2 months after receiving BCG vaccine, in addition to repeated episodes of mild or severe illnesses, such as maculopapular skin rash, lymphadenopathy, gastroenteritis, meningitis, and clinically diagnosed tuberculosis (TB) based on local TB-prevalence setting. Because of limited medical facilities in the war-torn countries; in Syria and Iraq, no diagnosis could be reached. We used Flinders Technology Associates (FTA) cards to transfer her bone marrow aspirate to Japan. A homozygous IL12RB1 mutation was detected by whole exome sequencing in Japan, using genomic-DNA extracted from dried bone marrow sample spots on FTA filter paper. In conclusion, diagnosis of MSMD due to IL12RB1 deficiency was possible by transferring the FTA sample of the patient for genetic evaluation in Japan. Our report recalls the need of pediatricians in countries with TB-prevalence and high parental consanguinity, to consider IL12RB1 deficiency in the differential diagnosis of a child with clinical evidence of TB, especially with the history of disseminated BCG disease.


Assuntos
Teste em Amostras de Sangue Seco , Síndromes de Imunodeficiência/diagnóstico , Infecções por Micobactéria não Tuberculosa/diagnóstico , Receptores de Interleucina-12/deficiência , Refugiados , Tuberculose/diagnóstico , Antibacterianos/uso terapêutico , Vacina BCG/efeitos adversos , Criança , Consanguinidade , Diagnóstico Diferencial , Feminino , Predisposição Genética para Doença , Humanos , Síndromes de Imunodeficiência/tratamento farmacológico , Iraque , Japão , Mutação , Infecções por Micobactéria não Tuberculosa/tratamento farmacológico , Síria , Resultado do Tratamento , Sequenciamento Completo do Exoma
8.
Pneumologie ; 73(2): 94-107, 2019 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-30759496

RESUMO

Clinical manifestations of primary immunodeficiency are heterogeneous, and early diagnosis is challenging. Leading symptoms are recurrent upper and lower respiratory tract infections. Response to antibiotic therapy is often reduced. Beside infectious complications autoimmunity, autoinflammation and malignant diseases occur frequently. About 50 % of all PID patients are diagnosed after childhood, and the main group are patients with primary antibody deficiencies. Treatment of choice is the immunoglobulin substitution and the prophylactic or therapeutic use of antibiotics. In patients presenting with immunodysregulation, immunosuppression is additionally indicated. Especially due to recurrent lower airway infection and/or interstitial lung diseases PID patients have a decreased live expectancy. Hence, both early diagnosis and sufficient therapy are mandatory.


Assuntos
Imunoglobulinas/uso terapêutico , Síndromes de Imunodeficiência/tratamento farmacológico , Inflamação/imunologia , Autoimunidade , Criança , Humanos , Síndromes de Imunodeficiência/imunologia , Neoplasias , Pneumologia , Infecções Respiratórias/etiologia
9.
Antivir Chem Chemother ; 27: 2040206619829382, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30776910

RESUMO

AMD3100 (plerixafor, Mozobil®) was first identified as an anti-HIV agent specifically active against the T4-lymphotropic HIV strains, as it selectively blocked the CXCR4 receptor. Through interference with the interaction of CXCR4 with its natural ligand, SDF-1 (also named CXCL12), it also mobilized the CD34+stem cells from the bone marrow into the peripheral blood stream. In December 2008, AMD3100 was formally approved by the US FDA for autologous transplantation in patients with Non-Hodgkin's Lymphoma or multiple myeloma. It may be beneficially used in various other malignant diseases as well as hereditary immunological disorders such as WHIM syndrome, and physiopathological processes such as hepatopulmonary syndrome.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Aprovação de Drogas/legislação & jurisprudência , Compostos Heterocíclicos/uso terapêutico , Animais , Fármacos Anti-HIV/farmacologia , Antineoplásicos/uso terapêutico , Reposicionamento de Medicamentos , Infecções por HIV/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas/métodos , Síndrome Hepatopulmonar/tratamento farmacológico , Compostos Heterocíclicos/farmacologia , Humanos , Síndromes de Imunodeficiência/tratamento farmacológico , Camundongos , Receptores CXCR4/antagonistas & inibidores , Fatores de Tempo , Estados Unidos , United States Food and Drug Administration , Verrugas/tratamento farmacológico
10.
Curr Pharm Biotechnol ; 20(3): 245-253, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30806311

RESUMO

BACKGROUND: The modern immunology is targeted to the detailed study of various immunopathological conditions at the molecular and cellular level, development of new methods for the prevention, diagnostics and treatment of contagious and non-contagious diseases of humans and animals. METHODS: In the present work we took the rats with model of cyclophosphamide-induced immunodeficiency and studied the features of gender impact of the complex extract of immunocompetent organs (thymus, spleen and mesenteric lymph nodes) Sus scrofa and its separate fraction with molecular weight less than 30 kDa administered to male and female rats. RESULTS: The impact of gender differences and tissue-specific biomolecules (30 kDa fraction) on hematological parameters (leukocytes, erythrocytes, platelets), functional activity of immune system (IL-2, IL-4, IL-6, complement system, IgG, IgM), biochemical parameters of hepatocytes functioning (activity of ALP and LDG), carbohydrate metabolism (glucose) and lipid metabolism (triglycerides). CONCLUSION: Decrease of ALP activity is caused by inhibition of bile formation in a liver after introduction of cytostatic agent, and in contrast to complex extract, the administration of fraction 30 kDa allows improving bile production in male rats.


Assuntos
Fatores Biológicos/metabolismo , Fatores Biológicos/uso terapêutico , Ciclofosfamida/toxicidade , Síndromes de Imunodeficiência/induzido quimicamente , Síndromes de Imunodeficiência/metabolismo , Imunossupressores/toxicidade , Caracteres Sexuais , Animais , Fatores Biológicos/isolamento & purificação , Feminino , Humanos , Síndromes de Imunodeficiência/tratamento farmacológico , Leucócitos/metabolismo , Fígado/metabolismo , Masculino , Ratos , Ratos Wistar , Baço/metabolismo , Sus scrofa , Resultado do Tratamento
11.
Front Immunol ; 10: 40, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30778345

RESUMO

Introduction: Subcutaneously administered immunoglobulin (SCIG) is increasingly used to treat patients with primary immunodeficiencies (PIDs). Octanorm (marketed as cutaquig® in USA and Canada) is a new 16.5% solution of human SCIG, manufactured by a process based on that of the intravenous preparation (IVIG) octagam®. Objectives: To investigate the efficacy, safety and tolerability of octanorm in a prospective, open-label, single-arm phase 3 study involving adult and pediatric patients with PIDs (NCT01888484; clinicaltrials.gov/ct2/show/NCT01888484). Methods: Patients who were previously treated with IVIG received a total of 64 weekly SCIG infusions, including 12 weekly infusions during the wash-in/wash-out period, followed by 52 weekly infusions during the evaluation period. Results: A total of 61 patients aged 2-73 years received 3,497 infusions of octanorm. The mean dose per patient was 0.175 g/kg/infusion. The mean calculated dose conversion factor from the patients' previous IVIG dose for octanorm was 1.37. No serious bacterial infections developed during the study. The rate of other infections per person-year during the primary observation period was 3.43 (upper 95% CI 4.57). All but one non-bacterial infection were mild or moderate in intensity. IgG trough levels were constant during the course of the study. Eleven patients (18.0%) experienced 14 mild or moderate systemic adverse events (AEs) related to octanorm. The rate of related AEs per infusion was 0.004. In 76.7% of infusions, no infusion site reactions were observed and only two (0.3%) reactions were deemed severe. The incidence of site reactions decreased with successive infusions. Conclusion: The new 16.5% SCIG octanorm was shown to be efficacious in preventing infections in PIDs, and was well tolerated.


Assuntos
Imunização Passiva , Síndromes de Imunodeficiência/tratamento farmacológico , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Imunização Passiva/métodos , Imunoglobulina G/administração & dosagem , Imunoglobulina G/sangue , Imunoglobulinas Intravenosas/administração & dosagem , Imunoglobulinas Intravenosas/farmacocinética , Imunoglobulinas Intravenosas/uso terapêutico , Infusões Subcutâneas , Masculino , Pessoa de Meia-Idade , Adulto Jovem
12.
N Engl J Med ; 380(2): 163-170, 2019 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-30625055

RESUMO

WHIM syndrome (warts, hypogammaglobulinemia, infections, and myelokathexis), a primary immunodeficiency disorder involving panleukopenia, is caused by autosomal dominant gain-of-function mutations in CXC chemokine receptor 4 (CXCR4). Myelokathexis is neutropenia caused by neutrophil retention in bone marrow. Patients with WHIM syndrome are often treated with granulocyte colony-stimulating factor (G-CSF), which can increase neutrophil counts but does not affect cytopenias other than neutropenia. In this investigator-initiated, open-label study, three severely affected patients with WHIM syndrome who could not receive G-CSF were treated with low-dose plerixafor, a CXCR4 antagonist, for 19 to 52 months. Myelofibrosis, panleukopenia, anemia, and thrombocytopenia were ameliorated, the wart burden and frequency of infection declined, human papillomavirus-associated oropharyngeal squamous-cell carcinoma stabilized, and quality of life improved markedly. Adverse events were mainly infections attributable to the underlying immunodeficiency. One patient died from complications of elective reconstructive surgery. (Funded by the National Institutes of Health.).


Assuntos
Medula Óssea/patologia , Compostos Heterocíclicos/uso terapêutico , Síndromes de Imunodeficiência/tratamento farmacológico , Receptores CXCR4/antagonistas & inibidores , Verrugas/tratamento farmacológico , Exame de Medula Óssea , Evolução Fatal , Humanos , Síndromes de Imunodeficiência/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias de Células Escamosas/tratamento farmacológico , Neoplasias de Células Escamosas/genética , Fenótipo , Mielofibrose Primária/tratamento farmacológico , Mielofibrose Primária/patologia , Receptores CXCR4/genética , Verrugas/patologia
14.
Hematology ; 24(1): 173-182, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30458690

RESUMO

OBJECTIVE: Immunoglobulin replacement therapy (IgRT) is increasingly used in secondary immunodeficiency (SID) related to hematological malignancies (HM) to prevent infections. Study's objective was to document prospectively the efficacy and safety of IgRT in patients with HM-associated SID. METHODS: Non-interventional, prospective French longitudinal study. RESULTS: One-hundred and sixty patients starting IgRT for HM-associated SID (myeloma: 54 cases, chronic lymphoid leukemia: 54, aggressive non-Hodgkin B-cell lymphoma: 19, indolent non-Hodgkin B-cell lymphoma: 29, and Hodgkin disease: 4. entered an observational, prospective, longitudinal study and were followed-up for 8.7 ± 4.0 months. Seventeen patients died (five within the context of sepsis). Compared to baseline, IgRT increased serum immunoglobulin levels by 3.4 ± 2.4 g/L and decreased frequency and severity of infections. Treatment was discontinued in 9% of patients, stopped for futility in 31%, temporally interrupted in 8%, suspended during summertime in 14% and pursued without interruption in 38% of patients. CONCLUSION: Our data confirm the efficacy of IgRT in reducing the risk of infections in HM-associated SID therefore fulfilling physicians' main expectations. They also illustrate the heterogeneity of management policies within the community setting.


Assuntos
Neoplasias Hematológicas/tratamento farmacológico , Imunoglobulinas Intravenosas/administração & dosagem , Síndromes de Imunodeficiência/tratamento farmacológico , Idoso , Feminino , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/mortalidade , Humanos , Síndromes de Imunodeficiência/sangue , Síndromes de Imunodeficiência/etiologia , Síndromes de Imunodeficiência/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
15.
Int Immunopharmacol ; 66: 119-126, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30447530

RESUMO

PURPOSE: Primary (PID) and secondary immune deficiencies (SID) represent diverse groups of diagnoses, yet both can be effectively treated with intravenous immunoglobulin (IVIG) replacement therapy. Guidelines for the use of IVIG in SID vary due to the paucity of data. The objective was to analyze available IVIG Privigen® (IgPro10, CSL Behring, Bern, Switzerland) data on Efficiency Index (EI) and pharmacokinetic (PK) parameters in patients with PID and SID. METHODS: Three Privigen® studies (NCT00168025, NCT00322556, and the observational study IgPro10_5001) were used to identify patients with PID and SID meeting the qualifying criteria for the PK analysis. PK properties of IVIG were estimated using a population PK model based on a standard two-compartment PK model. Immunoglobulin G (IgG) EI was calculated as the gain in serum IgG level per unit external IgG dose. RESULTS: A similar IVIG dose-serum IgG concentration relationship was observed in patients with PID (N = 90) and SID (N = 91). IgG EI was inversely proportional to the endogenous IgG concentration and comparable in PID (slope = -1.079) and SID (slope = -2.12). CONCLUSIONS: These findings indicate that the disposition of Privigen® is similar during IgG replacement therapy in PID and SID. The results contribute to the understanding of IVIG treatment of SID and may support an evidence-based approach for the use of IVIG in SID in the future.


Assuntos
Imunoglobulinas Intravenosas/farmacocinética , Síndromes de Imunodeficiência/tratamento farmacológico , Fatores Imunológicos/farmacocinética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Adulto Jovem
16.
Pediatr Pulmonol ; 54(2): 194-199, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30575324

RESUMO

BACKGROUND: The role of viruses in children with respiratory tract infections and humoral immunodeficiencies has hardly been studied. We have evaluated these infections in children with humoral immunodeficiencies who required immunoglobulin replacement therapy, considering their relationship with symptoms, lung function, bacterial co-infection, and outcomes. METHODS: We conducted a prospective case-control study during a 1-year period, including children with humoral immunodeficiencies receiving immunoglobulin replacement therapy. For each patient, at least one healthy family member was included. Respiratory samples for viral detection were taken every 1-3 months, and in case of respiratory tract infections. Symptoms questionnaires were filled biweekly. Spirometry and sputum culture were performed in every episode. RESULTS: Sixty-six episodes were analyzed in 14 patients (median age 12 years; IQR 7-17), identifying 18 respiratory viruses (27.3%), being rhinovirus the most frequently isolated one (12/18; 66%). Positive viral episodes were associated with clinical symptoms (89% vs 43%), more frequent antibiotic treatment (44% vs 15%) or hospital admission (22% vs 0%) than negative ones. Patients with positive viral detection showed impaired lung function, with lower FEV1 and FVC values. CONCLUSIONS: In our experience, viral respiratory tract infections can cause significant respiratory symptoms and impaired lung function, in children with HID, despite immunoglobulin replacement therapy. These patients could benefit from the monitoring of viral infections, as these may be a gateway for ongoing lung damage.


Assuntos
Imunoglobulinas/uso terapêutico , Síndromes de Imunodeficiência , Infecções Respiratórias , Viroses , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Síndromes de Imunodeficiência/tratamento farmacológico , Síndromes de Imunodeficiência/epidemiologia , Síndromes de Imunodeficiência/fisiopatologia , Masculino , Testes de Função Respiratória , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/fisiopatologia , Espanha/epidemiologia , Viroses/tratamento farmacológico , Viroses/epidemiologia , Viroses/fisiopatologia
17.
J Clin Immunol ; 38(8): 854-863, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30499059

RESUMO

PURPOSE: We aimed to report the clinical manifestations and immunological features of activated phosphatidylinositol 3-kinase δ syndrome 1 (APDS1) in a Chinese cohort. Moreover, we investigated the efficacy and safety of rapamycin therapy for Chinese patients with APDS1. METHODS: Fifteen Chinese patients with APDS1 from 14 unrelated families were enrolled in this study. These patients were diagnosed based on clinical features, immunological phenotype, and whole-exome sequencing. Four patients were treated with rapamycin, and the clinical efficacy and safety of rapamycin were observed. The changes of phosphorylation of Akt and mammalian target of rapamycin (mTOR) signaling pathway after rapamycin treatment were detected by flow cytometry and real-time PCR. RESULTS: The common clinical manifestations of the patients included lymphadenopathy (93%), recurrent sinopulmonary infections (93%), hepatosplenomegaly (93%), and diarrhea (78%). Epstein-Barr virus (EBV) (80%) and fungus (Aspergillus) (47%) were the most common pathogens. Immunological phenotype included elevated Immunoglobulin (Ig) M levels (100%), decreased naive T cells, increased senescent T cells, and expanded transitional B cells. Whole-exome sequencing indicated that 13 patients had heterogeneous PIK3CD E1021K mutations, 1 patient had heterogeneous E1025G mutation and 1 patient had heterogeneous Y524N mutation. Gain-of-function (GOF) PIK3CD mutations increased the phosphorylation of the Akt-mTOR signaling pathway. Four patients underwent rapamycin therapy, experiencing substantial improvement in clinical symptoms and immunological phenotype. Rapamycin inhibited the activated Akt-mTOR signaling pathway. CONCLUSIONS: We described 15 Chinese patients with APDS1. Treatment with the mTOR inhibitor rapamycin improved patient outcomes.


Assuntos
Classe Ia de Fosfatidilinositol 3-Quinase/metabolismo , Síndromes de Imunodeficiência/imunologia , Células Precursoras de Linfócitos B/imunologia , Sirolimo/uso terapêutico , Linfócitos T/imunologia , Adolescente , Criança , Pré-Escolar , Classe I de Fosfatidilinositol 3-Quinases/genética , Classe I de Fosfatidilinositol 3-Quinases/imunologia , Estudos de Coortes , Feminino , Hepatomegalia , Humanos , Imunoglobulina M/sangue , Síndromes de Imunodeficiência/tratamento farmacológico , Lactente , Linfadenopatia , Masculino , Mutação/genética , Proteína Oncogênica v-akt/metabolismo , Fosforilação , Infecções Respiratórias , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo
18.
Lima; Perú. Ministerio de Salud. Instituto Nacional de Salud; dic. 2018.
Não convencional em Espanhol | BRISA/RedTESA | ID: biblio-979664

RESUMO

INTRODUCCIÓN: Este documento técnico se realiza a solicitud del Instituto Nacional de Salud del Niño-Breña. a) Cuadro clínico: Las inmunodeficiencias primarias (IDP) son un grupo heterogéneo de trastornos caracterizados por una función deficiente o ausente en uno o más componentes del sistema inmunitario que predispone a una mayor frecuencia y severidad de infecciones, autoinmunidad, inflamación aberrante y malignidad. Su prevalencia a nivel global se estima en 1 caso por cada 2 000 recién nacidos vivos. En Perú, se reporta 1 caso por cada 516 mil habitantes. La IDP de anticuerpos constituye el grupo más común con alrededor del 50% a 60% de casos. El reemplazo de inmunoglobulina G (IgG) mediante su administración intravenosa (IVIg) o subcutánea (SCIg), permite limitar las complicaciones infecciosas y lesiones pulmonares crónicas. b) Tecnología sanitaria: La inmunoglobulina humana al 20% (Hizentra® 20%) es una solución de IgG humana polivalente para administración subcutánea que suministra un amplio espectro de anticuerpos IgG opsonizantes y neutralizantes, contra una amplia variedad de agentes bacterianos y virales. Su mecanismo de acción podría incluir efectos inmunomoduladores. Se indica para el tratamiento de IDP en adultos y pacientes pediátricos mayores de dos años. Los eventos adversos (EA) más frecuentes (5% o más de sujetos) son reacciones locales (hinchazón, enrojecimiento, calor, dolor, hematoma y picazón en el lugar de la infusión), dolor de cabeza, diarrea, fatiga, dolor de espalda, náuseas, dolor en extremidades, tos, infección del tracto respiratorio superior, erupción cutánea, prurito, vómitos, dolor abdominal superior, migraña, artralgia, dolor, caídas y nasofaringitis. Hizentra® 20% cuenta con aprobación de la Food and Drug Administration (FDA) desde el año 2010 y de la European Medicines Agency (EMA) desde el año 2011. En Perú, cuenta con un registro sanitario vigente (BE01010). OBJETIVO: Describir la evidencia científica disponible sobre la eficacia y seguridad de inmunoglobulina humana al 20% de aplicación sub-cutánea para el tratamiento de inmunodeficiencia primaria de anticuerpos en población menor de 18 años de edad. METODOLOGÍA: Se formuló la pregunta PICO por parte de médicos y especialistas de la siguiente manera, P: pacientes menores de 18 años con IDP de anticuerpos; I: SCIg al 20%; C: IVIg al 5% o 10%; O: infecciones y mortalidad asociada a infecciones, prevención de complicaciones, sobrevida y eventos adversos. Se realizó una búsqueda sistemática en MEDLINE (Pubmed), EMBASE (OVID), The Cochrane Library y LILACS. Ésta se complementó con la búsqueda de evidencia en páginas institucionales de agencias gubernamentales y buscadores genéricos. Se priorizó la identificación y selección de ensayos clínicos aleatorizados controlados (ECAs), revisiones sistemáticas (RS) con o sin meta-análisis (MA), guías de práctica clínica (GPC), evaluaciones de tecnología sanitaria (ETS) y evaluaciones económicas (EE) de América Latina. La calidad de la evidencia se valoró usando las siguientes herramientas: la herramienta propuesta por la colaboración Cochrane para la valoración de la calidad de ECAs, AMSTAR 2 para RS, y AGREE II para valorar el rigor metodológico de las GPC. RESULTADOS: No se identificaron estudios que comparen la eficacia y seguridad del uso de SCIg al 20%, respecto a IgIV al 5% o 10%. La GPC incluida recomienda el uso de inmunoglobulina para todos los trastornos con producción de anticuerpos significativamente afectada, sin especificar preferencia por algún tipo de formulación (intravenosa o subcutánea) o concentración. CONCLUSIONES: La evidencia sobre la eficacia y seguridad de la SCIg al 20% se basa en ensayos clínicos no controlados y pacientes tratados previamente con una formulación o concentración distinta de inmunoglobulina. No se hallaron estudios que compraran SCIg al 20% con IVIg al 5% o 10%. Las GPC incluida no específica preferencia por algún tipo de formulación (intravenosa o subcutánea) o concentración de inmunoglobulina. La ETS incluida analizó de manera conjunta el uso de inmunoglobulina en diferentes formulaciones y concentraciones concluyendo que su uso es una terapia efectiva y esencial en personas con inmunodeficiencia primaria con predominio en alteración de anticuerpos. La GPC incluida obtuvo un puntaje de 71,2% en la valoración global de calidad, y de 75% en el dominio de rigor en la elaboración.


Assuntos
Humanos , Imunoglobulinas/uso terapêutico , Síndromes de Imunodeficiência/tratamento farmacológico , Avaliação da Tecnologia Biomédica , Análise Custo-Eficiência , Injeções Subcutâneas
19.
J Clin Immunol ; 38(8): 886-897, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30465179

RESUMO

PURPOSE: Primary immunodeficiency diseases (PIDDs) are a heterogenous group of disorders characterized by intrinsic impairment in the immune system. Most patients with PIDD require life-long immunoglobulin G replacement therapy, which has been shown to reduce the rate of infections and, related hospitalizations and reduce health-related quality of life (HRQOL). Here, treatment satisfaction and HRQOL in patients with PIDD was evaluated upon switching from intravenous (IVIG) or subcutaneous immunoglobulins (SCIGs) to 20% SCIG (Hizentra®), and during long-term steady-state Hizentra® treatment. METHODS: Analyses were based on two pivotal (switch) and four extension/follow-up (maintenance) Phase III studies of Hizentra® conducted in Europe (EU), Japan (JP), and the United States (US). Two validated questionnaires were used: Life Quality Index (LQI) for assessment of IgG-specific perceptions of HRQOL and Short Form 36 version 2 (SF-36v2). RESULTS: In the EU and JP switch studies, there was significant and meaningful improvement from Screening in LQI domain scores at all time points, largely driven by patients switching from IVIG to SCIG. In the EU switch study, there were also significant increases in mean SF-36v2 domain scores for Physical Function and General Health from Screening to Week 12. These improvements were observed also at Week 24. Overall, LQI and SF-36v2 domain scores were generally sustained in the maintenance studies. CONCLUSIONS: These results showed that switching patients from IVIG to SCIG improves patient self-reported health status and IgG-specific HRQOL perception. The maintenance studies generally showed no deterioration of this improved health status over a long follow-up period.


Assuntos
Imunoglobulina G/uso terapêutico , Imunoglobulinas Intravenosas/uso terapêutico , Síndromes de Imunodeficiência/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Adolescente , Adulto , Criança , Ensaios Clínicos Fase III como Assunto , Substituição de Medicamentos , Europa (Continente) , Feminino , Humanos , Infusões Subcutâneas , Japão , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Percepção , Qualidade de Vida , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
20.
Clin Med (Lond) ; 18(5): 364-370, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30287427

RESUMO

Supply of immunoglobulin in the UK faces pressures due to increasing demand, cost and variable supply. This paper describes immunoglobulin replacement therapy (IGRT) in primary immunodeficiency (PID) and secondary immunodeficiency (SID) to assist in the ongoing planning of UK immunoglobulin provision. A retrospective analysis of the National Immunoglobulin Database and the UKPID registry was carried out. In total, 3,222 patients are registered as receiving IGRT for immunodeficiencies. Predominately antibody disorders made up the largest diagnostic category (61% of patients). The total cost of IGRT for immunodeficiency for 2015/16 was £40,673,350; an average annual cost of £1,099,254 per centre and £12,124 per PID patient. SCIg accounted for 43.8% and 50.1% of IGRT, with home therapy accounting for 42.7% and 57.5% of place of therapy in the National Immunoglobulin Database and UKPID registry respectively. In 2015/16 use of immunoglobulin in SID increased by 24% over the previous financial year. The overall trends of increasing demand in immunology are mirrored in other specialties, most notably neurology and haematology. These data are the first national overview of IGRT for immunodeficiencies, providing a valuable resource for clinicians and policy makers in the ongoing management of UK immunoglobulin supply.


Assuntos
Imunoglobulinas Intravenosas/uso terapêutico , Síndromes de Imunodeficiência/tratamento farmacológico , Síndromes de Imunodeficiência/epidemiologia , Bases de Dados Factuais , Humanos , Síndromes de Imunodeficiência/diagnóstico , Estudos Retrospectivos , Reino Unido/epidemiologia
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