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2.
Scand J Immunol ; 99(2): e13338, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38981850

RESUMO

Due to the high rate of post-operative sepsis and other infectious complications, a routine immunological screening protocol has been initiated since 2015 in our paediatric surgery clinic for all patients admitted with oesophageal atresia (EA) and warrant a delayed definitive treatment. In our study, we aimed to evaluate the immunodeficiencies in EA patients, by comparing them to healthy age-matched controls. As a prospective cohort study, EA patients admitted between 2015 and 2022, who had their definitive operation after the newborn period (>28 days of age) were included. On admission, serum concentrations of IgG, IgA, IgM, lymphocyte subset levels, C3 and C4 levels, specific IgG antibody responses against hepatitis B, hepatitis A, measles, varicella zoster were evaluated. The patients were age-matched with healthy controls to compare the results and followed up until three years of age. If a humoral immunodeficiency was detected, intravenous immunoglobulin treatment was administered before major oesophageal surgery and during follow-up. 31 EA patients (18 M/13F) with a mean age of 13.3 ± 9.0 months were compared with 40 age-matched healthy controls. Mean serum IgG levels were found to be statistically lower than controls in all age groups (P < .05). Transient hypogammaglobulinemia of infancy (THI) and unclassified syndromic immunodeficiencies (USI) were found to be strikingly high, accounting for 29.0% and 22.5%, respectively, adding up to 51.5% of EA patients. This is the first study evaluating immunodeficiencies in EA patients found in the reviewed literature. More than half of EA patients that required delayed surgery had humoral immunodeficiency, so preoperative screening and immunology referral may improve patient outcomes.


Assuntos
Agamaglobulinemia , Atresia Esofágica , Síndromes de Imunodeficiência , Humanos , Atresia Esofágica/imunologia , Atresia Esofágica/cirurgia , Agamaglobulinemia/imunologia , Agamaglobulinemia/diagnóstico , Masculino , Feminino , Lactente , Estudos Prospectivos , Síndromes de Imunodeficiência/imunologia , Imunoglobulina G/sangue , Pré-Escolar , Imunoglobulinas Intravenosas/uso terapêutico , Recém-Nascido
3.
Pediatr Allergy Immunol ; 35(6): e14179, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38923448

RESUMO

LRBA is a cytoplasmic protein that is ubiquitously distributed. Almost all LRBA domains have a scaffolding function. In 2012, it was reported that homozygous variants in LRBA are associated with early-onset hypogammaglobulinemia. Since its discovery, more than 100 pathogenic variants have been reported. This review focuses on the variants reported in LRBA and their possible associations with clinical phenotypes. In this work LRBA deficiency cases reported more than 11 years ago have been revised. A database was constructed to analyze the type of variants, age at onset, clinical diagnosis, infections, autoimmune diseases, and cellular and immunoglobulin levels. The review of cases from 2012 to 2023 showed that LRBA deficiency was commonly diagnosed in patients with a clinical diagnosis of Common Variable Immunodeficiency, followed by enteropathy, neonatal diabetes mellitus, ALPS, and X-linked-like syndrome. Most cases show early onset of presentation at <6 years of age. Most cases lack protein expression, whereas hypogammaglobulinemia is observed in half of the cases, and IgG and IgA levels are isotypes reported at low levels. Patients with elevated IgG levels exhibited more than one autoimmune manifestation. Patients carrying pathogenic variants leading to a premature stop codon show a severe phenotype as they have an earlier onset of disease presentation, severe autoimmune manifestations, premature death, and low B cells and regulatory T cell levels. Missense variants were more common in patients with low IgG levels and cytopenia. This work lead to the conclusion that the type of variant in LRBA has association with disease severity, which leads to a premature stop codon being the ones that correlates with severe disease.


Assuntos
Domínios Proteicos , Humanos , Domínios Proteicos/genética , Fenótipo , Agamaglobulinemia/genética , Agamaglobulinemia/imunologia , Agamaglobulinemia/diagnóstico , Criança , Idade de Início , Mutação , Imunodeficiência de Variável Comum/genética , Imunodeficiência de Variável Comum/diagnóstico , Imunodeficiência de Variável Comum/imunologia , Proteínas Adaptadoras de Transdução de Sinal
4.
J Med Virol ; 96(6): e29738, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38884390

RESUMO

Immunocompromised individuals are at significantly elevated risk for severe courses of coronavirus disease 2019 (COVID-19). In addition to vaccination, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibodies (nAbs) have been applied throughout the pandemic, with time of treatment onset and potency against the currently prevailing virus variant identified as relevant factors for medical benefit. Using data from the European Society for Immunodeficiencies (ESID) registry, the present study evaluated COVID-19 cases in three groups of patients with inborn errors of immunity (IEI; 981 agammaglobulinemia patients on immunoglobulin replacement therapy (IGRT); 8960 non-agammaglobulinemia patients on IGRT; 14 428 patients without IGRT), and the neutralizing capacity of 1100 immunoglobulin lots against SARS-CoV-2 ("Wuhan" and Omicron strains), throughout 3 years. From the first (2020/2021) to the second (2021/2022) cold season, i.e., during the virus drift to the more contagious Omicron variants, an increase in case numbers was recorded that was comparable (~2- to 3-fold) for all three study groups. During the same period, immunoglobulin lots showed a profound nAb increase against the archetypal SARS-CoV-2 strain, yet only low levels of Omicron nAbs. Notably, shortly before the third (2022/2023) cold season, Omicron-neutralizing capacity of released immunoglobulin lots had plateaued at high levels. From the second to the third cold season, COVID-19 cases dropped markedly. While a ~6-fold case reduction was recorded for the groups of non-agammaglobulinemia patients on IGRT and IEI patients not receiving IGRT, the decline was ~30-fold for the group of agammaglobulinemia patients on IGRT. These findings suggest a substantial COVID-19-protective effect of IGRT, at least for distinct groups of antibody-deficient patients.


Assuntos
Agamaglobulinemia , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19 , SARS-CoV-2 , Humanos , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Agamaglobulinemia/imunologia , Agamaglobulinemia/terapia , COVID-19/imunologia , COVID-19/terapia , Masculino , SARS-CoV-2/imunologia , Feminino , Adulto , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/uso terapêutico , Pessoa de Meia-Idade , Adolescente , Idoso , Adulto Jovem , Criança , Pré-Escolar , Resultado do Tratamento , Imunoglobulinas/uso terapêutico , Imunoglobulinas/imunologia
5.
Nutrients ; 16(11)2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38892708

RESUMO

Propionate defects (PDs) mainly include methylmalonic (MMA) and propionic acidemia (PA) defects. Lifelong PD patients progress from the compensated to the decompensated stages, the latter of which are characterized by life-threatening acidemia and hyperammonemia crises. PD patients can suffer immunocompromise, especially during the decompensation stage. There is a significant gap in the research regarding the humoral immune response in PD patients. Here, we analyzed serum immunoglobulin concentrations and hemograms across compensated and decompensated stages in PD patients. Nutritional status and crisis triggers of decompensation were also explored. Twenty patients were studied, and 25 decompensation events (DE) and 8 compensation events (CE) were recorded. Compared with those in the CE group, the IgG levels in the DE group (513.4 ± 244.5 mg/dL) were significantly lower than those in the CE group (860.8 ± 456.5 mg/dL) (p < 0.0087). The mean hemoglobin concentration was significantly lower in the DE group (11.8 g/dL) than in the CE group (13.4 g/dL) (p < 0.05). The most frequent (48%) possible decompensation trigger factor was infection. Most of the events were registered in eutrophic patients (87.9%), despite which 65.2% and 50% of patients who experienced decompensated and compensated events, respectively, presented with hypogammaglobulinemia G. These findings provide evidence of the immunodeficiency of PD patients, independent of their nutritional status. We suggest that PD patients be managed as immunocompromised independently of their nutritional status or metabolic state (compensated or decompensated).


Assuntos
Agamaglobulinemia , Estado Nutricional , Humanos , Masculino , Feminino , Agamaglobulinemia/sangue , Agamaglobulinemia/imunologia , Agamaglobulinemia/complicações , Pessoa de Meia-Idade , Idoso , Imunoglobulina G/sangue , Adulto , Propionatos/sangue , Acidemia Propiônica
6.
Zhonghua Jie He He Hu Xi Za Zhi ; 47(5): 430-436, 2024 May 12.
Artigo em Chinês | MEDLINE | ID: mdl-38706064

RESUMO

Objective: To summarize the clinical characteristics of coronavirus disease 2019 (COVID-19) in patients with Good's syndrome. Methods: We included all cases of COVID-19 in patients with Good's syndrome in the Second Xiangya Hospital of Central South University from January 1, 2023 to August 31, 2023. In addition to our cases, we searched the published literature in Wanfang database and PubMed database using the keywords "Good's syndrome" and "COVID-19". The clinical characteristics, treatment and outcome of the patients were summarized and analyzed. Results: A total of four patients with Good's syndrome complicated by COVID-19 were identified in our hospital, all of them were male, and the days of hospitalization were 17, 23, 7, and 13 days, respectively. Databases were searched for a total of six patients with Good's syndrome complicated by COVID-19, including three females and three males, all foreign patients, with hospitalization days of 12, 22, 13, 25, 21, and 34 days respectively. All ten patients met the diagnostic criteria for severe or critical COVID-19, and three(all middle-aged males) of them died, two from sepsis and one from respiratory failure. They were. Conclusion: COVID-19 in patients with Good's syndrome are prone to develop severe or critical disease and are more likely to be infected with multiple pathogens. Timely immunoglobulin supplementation is the key to treatment.


Assuntos
COVID-19 , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Agamaglobulinemia/complicações , COVID-19/complicações , Hospitalização , SARS-CoV-2
7.
Curr Opin Infect Dis ; 37(4): 227-231, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38747352

RESUMO

PURPOSE OF REVIEW: The purpose of this focused review is to discuss unusual presentations of viral infections in the context of specific inborn errors of immunity. We will discuss hyper immunoglobulin E (IgE) syndromes, epidermodysplasia verruciformis, and X-linked agammaglobulinemia as examples of inborn errors of immunity associated with specific presentations of viral infection and disease. RECENT FINDINGS: Advances in both genetic and viral diagnostics have broadened our understanding of viral pathogenesis in the setting of immune dysfunction and the variable phenotype of inborn errors of immunity. Dedicator of cytokinesis 8 (DOCK8) deficiency is now recognized as an inborn error of immunity within the hyper IgE syndrome phenotype and is associated with unusually aggressive cutaneous disease caused by herpes simplex and other viruses. Studies of patients with epidermodysplasia verruciformis have proven that rarely detected human papillomavirus subtypes may cause malignancy in the absence of adequate host defenses. Finally, patients with X-linked agammaglobulinemia may remain at risk for severe and chronic viral infections, even as immune globulin supplementation reduces the risk of bacterial infection. SUMMARY: Susceptibility to viral infections in patients with inborn errors of immunity is conferred by specific, molecular defects. Recurrent, severe, or otherwise unusual presentations of viral disease should prompt investigation for an underlying genetic defect.


Assuntos
Agamaglobulinemia , Doenças Genéticas Ligadas ao Cromossomo X , Viroses , Humanos , Agamaglobulinemia/imunologia , Viroses/imunologia , Viroses/complicações , Doenças Genéticas Ligadas ao Cromossomo X/imunologia , Doenças Genéticas Ligadas ao Cromossomo X/genética , Epidermodisplasia Verruciforme/imunologia , Epidermodisplasia Verruciforme/genética , Síndrome de Job/imunologia , Síndrome de Job/genética , Fatores de Troca do Nucleotídeo Guanina
9.
Int J Technol Assess Health Care ; 40(1): e32, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38751245

RESUMO

OBJECTIVES: Patients with hematological malignancies are likely to develop hypogammaglobulinemia. Immunoglobulin (Ig) is commonly given to prevent infections, but its overall costs and cost-effectiveness are unknown. METHODS: A systematic review was conducted following the PRISMA guidelines to assess the evidence on the costs and cost-effectiveness of Ig, administered intravenously (IVIg) or subcutaneously (SCIg), in adults with hematological malignancies. RESULTS: Six studies met the inclusion criteria, and only two economic evaluations were identified; one cost-utility analysis (CUA) of IVIg versus no Ig, and another comparing IVIg with SCIg. The quality of the evidence was low. Compared to no treatment, Ig reduced hospitalization rates. One study reported no significant change in hospitalizations following a program to reduce IVIg use, and an observational study comparing IVIg with SCIg suggested that there were more hospitalizations with SCIg but lower overall costs per patient. The CUA comparing IVIg versus no Ig suggested that IVIg treatment was not cost-effective, and the other CUA comparing IVIg to SCIg found that home-based SCIg was more cost-effective than IVIg, but both studies had serious limitations. CONCLUSIONS: Our review highlighted key gaps in the literature: the cost-effectiveness of Ig in patients with hematological malignancies is very uncertain. Despite increasing Ig use worldwide, there are limited data regarding the total direct and indirect costs of treatment, and the optimal use of Ig and downstream implications for healthcare resource use and costs remain unclear. Given the paucity of evidence on the costs and cost-effectiveness of Ig treatment in this population, further health economic research is warranted.


Assuntos
Análise Custo-Benefício , Neoplasias Hematológicas , Imunoglobulinas Intravenosas , Humanos , Neoplasias Hematológicas/terapia , Neoplasias Hematológicas/tratamento farmacológico , Imunoglobulinas Intravenosas/economia , Imunoglobulinas Intravenosas/uso terapêutico , Imunoglobulinas Intravenosas/administração & dosagem , Agamaglobulinemia/tratamento farmacológico , Agamaglobulinemia/economia , Hospitalização/economia , Imunoglobulinas/uso terapêutico , Imunoglobulinas/administração & dosagem , Imunoglobulinas/economia
10.
Eur J Neurol ; 31(8): e16331, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38794973

RESUMO

BACKGROUND AND PURPOSE: Mechanisms behind hypogammaglobulinaemia during rituximab treatment are poorly understood. METHODS: In this register-based multi-centre retrospective cohort study of multiple sclerosis (MS) patients in Sweden, 2745 patients from six participating Swedish MS centres were identified via the Swedish MS registry and included between 14 March 2008 and 25 January 2021. The exposure was treatment with at least one dose of rituximab for MS or clinically isolated syndrome, including data on treatment duration and doses. The degree of yearly decrease in immunoglobulin G (IgG) and immunoglobulin M (IgM) levels was evaluated. RESULTS: The mean decrease in IgG was 0.27 (95% confidence interval 0.17-0.36) g/L per year on rituximab treatment, slightly less in older patients, and without significant difference between sexes. IgG or IgM below the lower limit of normal (<6.7 or <0.27 g/L) was observed in 8.8% and 8.3% of patients, respectively, as nadir measurements. Six out of 2745 patients (0.2%) developed severe hypogammaglobulinaemia (IgG below 4.0 g/L) during the study period. Time on rituximab and accumulated dose were the main predictors for IgG decrease. Previous treatment with fingolimod and natalizumab, but not teriflunomide, dimethyl fumarate, interferons or glatiramer acetate, were significantly associated with lower baseline IgG levels by 0.80-1.03 g/L, compared with treatment-naïve patients. Switching from dimethyl fumarate or interferons was associated with an additional IgG decline of 0.14-0.19 g/L per year, compared to untreated. CONCLUSIONS: Accumulated dose and time on rituximab treatment are associated with a modest but significant decline in immunoglobulin levels. Previous MS therapies may influence additional IgG decline.


Assuntos
Agamaglobulinemia , Fatores Imunológicos , Esclerose Múltipla , Rituximab , Humanos , Suécia , Feminino , Masculino , Agamaglobulinemia/induzido quimicamente , Agamaglobulinemia/sangue , Rituximab/efeitos adversos , Rituximab/uso terapêutico , Adulto , Pessoa de Meia-Idade , Fatores Imunológicos/efeitos adversos , Fatores Imunológicos/administração & dosagem , Esclerose Múltipla/tratamento farmacológico , Estudos Retrospectivos , Sistema de Registros , Estudos de Coortes , Imunoglobulina G/sangue
11.
J Clin Immunol ; 44(6): 137, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38805163

RESUMO

The pre BCR complex plays a crucial role in B cell production, and its successful expression marks the B cell differentiation from the pro-B to pre-B. The CD79a and CD79b mutations, encoding Igα and Igß respectively, have been identified as the cause of autosomal recessive agammaglobulinemia (ARA). Here, we present a case of a patient with a homozygous CD79a mutation, exhibiting recurrent respiratory infections, diarrhea, growth and development delay, unique facial abnormalities and microcephaly, as well as neurological symptoms including tethered spinal cord, sacral canal cyst, and chronic enteroviral E18 meningitis. Complete blockade of the early B cell development in the bone marrow of the patient results in the absence of peripheral circulating mature B cells. Whole exome sequencing revealed a Loss of Heterozygosity (LOH) of approximately 19.20Mb containing CD79a on chromosome 19 in the patient. This is the first case of a homozygous CD79a mutation caused by segmental uniparental diploid (UPD). Another key outcome of this study is the effective management of long-term chronic enteroviral meningitis using a combination of intravenous immunoglobulin (IVIG) and fluoxetine. This approach offers compelling evidence of fluoxetine's utility in treating enteroviral meningitis, particularly in immunocompromised patients.


Assuntos
Agamaglobulinemia , Cromossomos Humanos Par 19 , Fluoxetina , Dissomia Uniparental , Humanos , Fluoxetina/uso terapêutico , Cromossomos Humanos Par 19/genética , Agamaglobulinemia/genética , Agamaglobulinemia/tratamento farmacológico , Antígenos CD79/genética , Masculino , Infecções por Enterovirus/tratamento farmacológico , Infecções por Enterovirus/genética , Mutação/genética , Imunoglobulinas Intravenosas/uso terapêutico , Feminino
12.
Int J Mol Sci ; 25(10)2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38791420

RESUMO

Patients with predominantly antibody deficiencies (PADs) display hypogammaglobulinemia with a high prevalence of infections, along with autoimmune manifestations, benign and malignant lymphoproliferation and granulomatous disease. It is noteworthy that PAD patients, even those with defects in the same causative genes, display a variable clinical phenotype, suggesting that additional genetic polymorphisms, located in either immune-related or non-immune-related genes, may affect their clinical and laboratory phenotype. In this context, we analyzed 80 PAD patients, including 70 with common variable immunodeficiency (CVID) for SERPINA1 defects, in order to investigate the possible contribution to PAD clinical phenotype. Ten CVID patients carried heterozygous pathogenic SERPINA1 defects with normal alpha-1 antitrypsin levels. Interestingly, the presence of the Z allele (rs28929474), which was found in three patients, was significantly associated with liver disease; hepatic complications were also observed in patients carrying the p.Leu23Gln (rs1379209512) and the p.Phe76del (rs775982338) alleles. Conversely, no correlation of SERPINA1 defective variants with respiratory complications was observed, although patients with pathogenic variants exhibit a reduced probability of developing autoimmune diseases. Therefore, we recommend SERPINA1 genetic analysis in PAD in order to identify patients with a higher risk for liver disease.


Assuntos
Imunodeficiência de Variável Comum , Heterozigoto , alfa 1-Antitripsina , Humanos , alfa 1-Antitripsina/genética , Masculino , Feminino , Imunodeficiência de Variável Comum/genética , Imunodeficiência de Variável Comum/imunologia , Adulto , Pessoa de Meia-Idade , Fenótipo , Alelos , Adolescente , Criança , Adulto Jovem , Idoso , Agamaglobulinemia/genética , Agamaglobulinemia/imunologia , Predisposição Genética para Doença
13.
Front Immunol ; 15: 1374535, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38707898

RESUMO

Introduction: Kidney transplant recipients often experience significant alterations in their immune system, which can lead to increased susceptibility to infections. This study aimed to analyze time-dependent changes in serum immunoglobulin and complement levels and determine the risk factors associated with infection. Methods: A retrospective analysis of serum samples from 192 kidney transplant recipients who received transplantations between August 2016 and December 2019 was conducted. The serum samples were obtained at preoperative baseline (T0), postoperative 2 weeks (T1), 3 months (T2), and 1 year (T3). The levels of serum C3, C4, IgG, IgA, and IgM were measured to evaluate immune status over time. Results: The analysis revealed significant decreases in IgG and IgA levels at T1. This period was associated with the highest occurrence of hypogammaglobulinemia (HGG) and hypocomplementemia (HCC), as well as an increased incidence of severe infection requiring hospitalization and graft-related viral infections. Using a time-dependent Cox proportional hazards model adjusted for time-varying confounders, HGG was significantly associated with an increased risk of infection requiring hospitalization (HR, 1.895; 95% CI: 1.871-1.920, P-value<0.001) and graft-related viral infection (HR, 1.152; 95% CI: 1.144-1.160, P-value<0.001). Discussion: The findings suggest that monitoring serum immunoglobulin levels post-transplant provides valuable insights into the degree of immunosuppression. Hypogammaglobulinemia during the early post-transplant period emerges as a critical risk factor for infection, indicating that serum immunoglobulins could serve as feasible biomarkers for assessing infection risk in kidney transplant recipients.


Assuntos
Transplante de Rim , Humanos , Transplante de Rim/efeitos adversos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto , Fatores de Tempo , Imunoglobulinas/sangue , Fatores de Risco , Agamaglobulinemia/sangue , Agamaglobulinemia/imunologia , Agamaglobulinemia/etiologia , Biomarcadores/sangue , Infecções/etiologia , Infecções/imunologia , Infecções/sangue , Infecções/epidemiologia
14.
Medicina (Kaunas) ; 60(5)2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38792965

RESUMO

Background and Objectives: Predominantly antibody deficiencies (PAD) represent the most common type of primary immunodeficiencies in humans, characterized by a wide variation in disease onset, clinical manifestations, and outcome. Considering that the prevalence of PAD in Greece is unknown, and there is limited knowledge on the clinical and laboratory characteristics of affected patients, we conducted a nationwide study. Materials and Methods: 153 patients (male/female: 66/87; median age: 43.0 years; range: 7.0-77.0) diagnosed, and followed-up between August 1979 to September 2023. Furthermore, we classified our cohort into five groups according to their medical history, immunoglobulin levels, and CTLA4-mutational status: 123 had common variable immunodeficiency (CVID), 12 patients with "secondary" hypogammaglobulinemia due to a previous B-cell depletion immunotherapy for autoimmune or malignant disease several years ago (median: 9 years, range 6-14) displaying a typical CVID phenotype, 7 with combined IgA and IgG subclass deficiencies, 5 patients with CVID-like disease due to CTLA4-mediated immune dysregulation syndrome, and 6 patients with unclassified hypogammaglobulinemia. Results: We demonstrated a remarkable delay in PAD diagnosis, several years after the onset of related symptoms (median: 9.0 years, range: 0-43.0). A family history of PAD was only present in 11.8%, with the majority of patients considered sporadic cases. Most patients were diagnosed in the context of a diagnostic work-up for recurrent infections, or recurrent/resistant autoimmune cytopenias. Interestingly, 10 patients (5.6%) had no history of infection, diagnosed due to either recurrent/resistant autoimmunity, or during a work-up of their medical/family history. Remarkable findings included an increased prevalence of lymphoproliferation (60.1%), while 39 patients (25.5%) developed bronchiectasis, and 16 (10.5%) granulomatous disease. Cancer was a common complication in our cohort (25 patients, 16.3%), with B-cell malignancies representing the most common neoplasms (56.7%). Conclusion: Our findings indicate the necessity of awareness about PAD and their complications, aiming for early diagnosis and the appropriate management of affected patients.


Assuntos
Antígeno CTLA-4 , Diagnóstico Tardio , Humanos , Grécia/epidemiologia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Criança , Idoso , Diagnóstico Tardio/estatística & dados numéricos , Adolescente , Imunodeficiência de Variável Comum/diagnóstico , Imunodeficiência de Variável Comum/complicações , Imunodeficiência de Variável Comum/epidemiologia , Adulto Jovem , Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/epidemiologia , Síndromes de Imunodeficiência/complicações , Síndromes de Imunodeficiência/imunologia , Agamaglobulinemia/diagnóstico , Agamaglobulinemia/epidemiologia , Agamaglobulinemia/imunologia , Agamaglobulinemia/complicações
15.
Front Immunol ; 15: 1334899, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38745669

RESUMO

Introduction: Non-Hodgkin's lymphoma (NHL) encompasses a diverse group of lymphoma subtypes with a wide range in disease course. Previous studies show that hypogammaglobulinemia in treatment-naïve patients is associated with poorer survival in high grade B-cell non-Hodgkin's lymphomas, though it is not known how this applies across all B-cell lymphoid malignancies. Methods: We conducted a retrospective study of immunoglobulin levels and clinical outcomes including survival, hospitalization, and infection rates in patients diagnosed with B-cell non-Hodgkin lymphomas of all grades at our institution. Results: Two-hundred twenty-three adults (aged = 18 years) with available pre-treatment IgG levels were selected, with hypogammaglobulinemia defined as IgG< 500 mg/mL. For this analysis, we grouped DLBCL (n=90), Primary CNS (n=5), and Burkitt lymphoma (n=1) together as high-grade, while CLL (n=52), mantle cell (n=20), marginal zone (n=25), follicular (n=21), and Waldenstrom macroglobulinemia (n=5) were low-grade. The incidence of hypogammaglobulinemia in our cohort of both high and low-grade lymphoma patients was 13.5% (n=30). Across all NHL subtypes, individuals with baseline IgG< 500 mg/dL showed an increased rate of hospitalization (4.453, CI: 1.955-10.54, p= 0.0005) and higher mortality (3.325, CI: 1.258, 8.491, p= 0.013), yet no association in number of infections when compared with those with IgG=500 mg/dL. There was a higher hospitalization rate (3.237, CI: 1.77-6.051, p=0.0017) in those with high-grade lymphoma with hypogammaglobulinemia when compared with low-grade. There was no statistically significant difference in individuals who were alive after three years in those with baseline IgG<500 mg/dL. Discussion: Our study is the first to analyze incidence of hypogammaglobulinemia at the time of diagnosis of NHL as a potential biomarker of interest for future outcomes including hospitalization and infection.


Assuntos
Imunoglobulina G , Linfoma não Hodgkin , Humanos , Estudos Retrospectivos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Linfoma não Hodgkin/imunologia , Linfoma não Hodgkin/mortalidade , Adulto , Idoso de 80 Anos ou mais , Agamaglobulinemia/imunologia , Agamaglobulinemia/mortalidade
16.
RMD Open ; 10(2)2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38772678

RESUMO

OBJECTIVE: Patients with X linked agammaglobulinemia are susceptible to enterovirus (EV) infections. Similarly, severe EV infections have been described in patients with impaired B-cell response following treatment with anti-CD20 monoclonal antibodies (mAbs), mostly in those treated for haematological malignancies. We aimed to describe severe EV infections in patients receiving anti-CD20 mAbs for immune-mediated inflammatory diseases (IMIDs). METHODS: Patients were included following a screening of data collected through the routine surveillance of EV infections coordinated by the National Reference Center and a review of the literature. Additionally, neutralising antibodies were assessed in a patient with chronic EV-A71 meningoencephalitis. RESULTS: Nine original and 17 previously published cases were retrieved. Meningoencephalitis (n=21/26, 81%) associated with EV-positive cerebrospinal fluid (n=20/22, 91%) was the most common manifestation. The mortality rate was high (27%). EV was the only causal agents in all reported cases. Patients received multiple anti-CD20 mAbs infusions (median 8 (5-10)), resulting in complete B-cell depletion and moderate hypogammaglobulinemia (median 4.9 g/L (4.3-6.7)), and had limited concomitant immunosuppressive treatments. Finally, in a patient with EV-A71 meningoencephalitis, a lack of B-cell response to EV was shown. CONCLUSION: EV infection should be evoked in patients with IMIDs presenting with atypical organ involvement, especially meningoencephalitis. Anti-CD20 mAbs may lead to impaired B-cell response against EV, although an underlying primary immunodeficiency should systematically be discussed.


Assuntos
Anticorpos Monoclonais , Antígenos CD20 , Infecções por Enterovirus , Humanos , Infecções por Enterovirus/imunologia , Infecções por Enterovirus/diagnóstico , Masculino , Feminino , Anticorpos Monoclonais/uso terapêutico , Antígenos CD20/imunologia , Pessoa de Meia-Idade , Adulto , Meningoencefalite/imunologia , Meningoencefalite/virologia , Meningoencefalite/etiologia , Meningoencefalite/diagnóstico , Meningoencefalite/tratamento farmacológico , Idoso , Rituximab/uso terapêutico , Linfócitos B/imunologia , Agamaglobulinemia/imunologia , Agamaglobulinemia/complicações , Inflamação/imunologia
20.
J Clin Immunol ; 44(5): 107, 2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38676811

RESUMO

PURPOSE: Patients with adenosine deaminase 1 deficient severe combined immunodeficiency (ADA-SCID) are initially treated with enzyme replacement therapy (ERT) with polyethylene glycol-modified (PEGylated) ADA while awaiting definitive treatment with hematopoietic stem cell transplant (HSCT) or gene therapy. Beginning in 1990, ERT was performed with PEGylated bovine intestinal ADA (ADAGEN®). In 2019, a PEGylated recombinant bovine ADA (Revcovi®) replaced ADAGEN following studies in older patients previously treated with ADAGEN for many years. There are limited longitudinal data on ERT-naïve newborns treated with Revcovi. METHODS: We report our clinical experience with Revcovi as initial bridge therapy in three newly diagnosed infants with ADA-SCID, along with comprehensive biochemical and immunologic data. RESULTS: Revcovi was initiated at twice weekly dosing (0.2 mg/kg intramuscularly), and monitored by following plasma ADA activity and the concentration of total deoxyadenosine nucleotides (dAXP) in erythrocytes. All patients rapidly achieved a biochemically effective level of plasma ADA activity, and red cell dAXP were eliminated within 2-3 months. Two patients reconstituted B-cells and NK-cells within the first month of ERT, followed by naive T-cells one month later. The third patient reconstituted all lymphocyte subsets within the first month of ERT. One patient experienced declining lymphocyte counts with improvement following Revcovi dose escalation. Two patients developed early, self-resolving thrombocytosis, but no thromboembolic events occurred. CONCLUSION: Revcovi was safe and effective as initial therapy to restore immune function in these newly diagnosed infants with ADA-SCID, however, time course and degree of reconstitution varied. Revcovi dose may need to be optimized based on immune reconstitution, clinical status, and biochemical data.


Assuntos
Adenosina Desaminase , Agamaglobulinemia , Terapia de Reposição de Enzimas , Imunodeficiência Combinada Severa , Animais , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Adenosina Desaminase/deficiência , Adenosina Desaminase/genética , Agamaglobulinemia/terapia , Reconstituição Imune , Proteínas Recombinantes/uso terapêutico , Imunodeficiência Combinada Severa/terapia , Resultado do Tratamento
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