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2.
Front Oncol ; 14: 1380492, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38715775

RESUMO

Background: Elderly patients diagnosed with diffuse large B-cell lymphoma (DLBCL) undergoing reduced intensity R-CHOP therapy are at a heightened risk of acquiring infections, notably coronavirus disease 2019 (COVID-19) infection. This study aimed to evaluate the efficacy of intravenous immunoglobulin (IVIG) as prophylaxis against COVID-19 in this vulnerable population. Methods: A total of 125 elderly patients with DLBCL undergoing reduced intensity R-CHOP therapy were analyzed in this prospective, multicenter study. Patients with hypogammaglobulinemia were categorized into IVIG and non-IVIG groups, while those with normal immunoglobulin levels constituted the observation group. The study evaluated COVID-19 infection rates, therapy response, and safety outcomes. Results: Among the enrolled patients (median age: 77 years), 89 patients (71.2%) presented with hypogammaglobulinemia at diagnosis, and 56 patients enrolled in the IVIG administration group. IVIG administration remarkably reduced COVID-19 infection rates compared to non-IVIG recipients (8.9% vs. 24.6%; p =0.040). Notably, patients over 80 years old were more susceptible to COVID-19. Patients on IVIG exhibited good tolerance with manageable adverse events. Among patients with hypogammaglobulinemia who received IVIG, 40.5% of patients developed additional immunoglobulin deficiencies during chemotherapy. One or more new hypogammaglobulinemia occurred during chemotherapy in 72% of patients with hypogammaglobulinemia who did not receive IVIG, and in 61.3% of patients who did not have hypogammaglobulinemia at diagnosis. Conclusion: IVIG showed promise in reducing COVID-19 infections among elderly patients with DLBCL receiving reduced intensity R-CHOP therapy. This highlights IVIG's potential as a prophylactic measure, necessitating further investigation to optimize dosing, administration schedules, and potential interactions with vaccination strategies.

3.
Front Neurol ; 15: 1380654, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38699050

RESUMO

Background: Recent years have seen the emergence of disease-modifying therapies in multiple sclerosis (MS), such as anti-cluster of differentiation 20 (anti-CD20) monoclonal antibodies, aiming to modulate the immune response and effectively manage MS. However, the relationship between anti-CD20 treatments and immunoglobulin G (IgG) levels, particularly the development of hypogammaglobulinemia and subsequent infection risks, remains a subject of scientific interest and variability. We aimed to investigate the intricate connection between anti-CD20 MS treatments, changes in IgG levels, and the associated risk of hypogammaglobulinemia and subsequent infections. Method: PubMed, Scopus, Embase, Cochrane, and Web of Science databases have been searched for relevant studies. The "R" software utilized to analyze the occurrence of hypogammaglobulinemia, infections and mean differences in IgG levels pre- and post-treatment. The subgrouping analyses were done based on drug type and treatment duration. The assessment of heterogeneity utilized the I2 and chi-squared tests, applying the random effect model. Results: Thirty-nine articles fulfilled our inclusion criteria and were included in our review which included a total of 20,501 MS patients. The overall prevalence rate of hypogammaglobulinemia was found to be 11% (95% CI: 0.08 to 0.15). Subgroup analysis based on drug type revealed varying prevalence rates, with rituximab showing the highest at 18%. Subgroup analysis based on drug usage duration revealed that the highest proportion of hypogammaglobulinemia occurred in individuals taking the drugs for 1 year or less (19%). The prevalence of infections in MS patients with a focus on different infection types stratified by the MS drug used revealed that pulmonary infections were the most prevalent (9%) followed by urinary tract infections (6%), gastrointestinal infections (2%), and skin and mucous membrane infections (2%). Additionally, a significant decrease in mean IgG levels after treatment compared to before treatment, with a mean difference of 0.57 (95% CI: 0.22 to 0.93). Conclusion: This study provides a comprehensive analysis of the impact of anti-CD20 drugs on serum IgG levels in MS patients, exploring the prevalence of hypogammaglobulinemia, based on different drug types, treatment durations, and infection patterns. The identified rates and patterns offer a foundation for clinicians to consider in their risk-benefit. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=518239, CRD42024518239.

4.
Cureus ; 16(3): e56940, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38665746

RESUMO

Epiglottitis is an uncommon condition in adults, and recurrent episodes are rare. We report a 58-year-old male who had a second episode of epiglottitis nine years after his first. Our patient's immunologic profile obtained during his hospitalization revealed a significantly low absolute cluster of differentiation 4+ (CD4+) T lymphocyte count of 77 cells/mcL and a low immunoglobulin G (IgG) level of 635 mg/dL. Our patient was successfully managed with broad-spectrum antibiotics and corticosteroids. Given the known ability of short-term corticosteroids and acute inflammation's effect on lymphocyte populations, the significance of these laboratory values remains unclear due to our patient's unwillingness to undergo further diagnostic testing following discharge from our facility. We have considered multiple underlying etiologies for our patient's predisposition to developing this rare, recurrent, infectious manifestation; however, the exact cause is yet to be fully elucidated.

5.
Allergy Asthma Clin Immunol ; 20(1): 30, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38600554

RESUMO

PURPOSE: Immunoglobulin replacement therapy is a standard treatment for patients with antibody production deficiencies, which is of interest in patients with chronic obstructive pulmonary disease (COPD). This systematic review, registered with PROSPERO (CRD42021281118), assessed the current literature regarding immunoglobulin replacement therapy on COPD clinical outcomes in patients with low immunoglobulin G (IgG) serum concentrations. METHODS: Literature searches conducted from inception to August 23, 2021, in databases including MEDLINE, EMBASE, and CINAHL. Population (sex, age, comorbidities), baseline clinical characteristics (pulmonary function testing results, IgG levels), and outcome (hospitalizations, emergency department visits) were extracted after title/abstract and full text screening. The Cochrane risk of bias assessment form was used for risk of bias assessment of randomized controlled trials and the National Heart, Lung, and Blood Institute (NHLBI) assessment was used for pre and post studies. RESULTS: A total of 1381 studies were identified in the preliminary search, and 874 records were screened after duplicates were removed. Screening 77 full texts yielded four studies that were included in the review. CONCLUSION: It is unclear whether immune globulin replacement therapy reduces acute exacerbation frequency and severity in COPD. Current evidence suggests that it is worth considering, but better developed protocols for administration of immune globulin supplementation is required for future randomized controlled trials.

7.
Pediatr Nephrol ; 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38587560

RESUMO

Nuclear factor kappa B (NF-κB) family plays a central role in the human immune system. Heterozygous variants in NFKB2 typically cause immunodeficiency with various degrees of central adrenal insufficiency, autoimmunity, and ectodermal dysplasia. No reported case has presented kidney failure as an initial symptom. Moreover, documentation of kidney involvement of this disease is limited. CASE DIAGNOSIS: A 2-year-old female who presented with dyspnea and hypertensive emergency in the setting of new-onset nephrotic syndrome with acute-on chronic kidney injury with resultant chronic kidney disease (CKD) was found to have a novel heterozygous N-terminal variant in NFKB2 (c.880del: p. Tyr294Ilefs*4) with mild hypogammaglobulinemia, but no adrenal insufficiency or ectodermal dysplasia. She became dialysis-dependent during her initial hospitalization and developed CKD stage 5D, requiring continued peritoneal dialysis. She is currently awaiting kidney transplantation. CONCLUSIONS: Whether nephrotic syndrome or kidney injury or failure is the primary symptom of this variant or secondary to some event remains unknown. Further case accumulation is warranted.

8.
Immunogenetics ; 76(3): 189-202, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38683392

RESUMO

Hypogammaglobulinemia without B-cells is a subgroup of inborn errors of immunity (IEI) which is characterized by a significant decline in all serum immunoglobulin isotypes, coupled with a pronounced reduction or absence of B-cells. Approximately 80 to 90% of individuals exhibit genetic variations in Bruton's agammaglobulinemia tyrosine kinase (BTK), whereas a minority of cases, around 5-10%, are autosomal recessive agammaglobulinemia (ARA). Very few cases are grouped into distinct subcategories. We evaluated phenotypically and genetically 27 patients from 13 distinct families with hypogammaglobinemia and no B-cells. Genetic analysis was performed via whole-exome and Sanger sequencing. The most prevalent genetic cause was mutations in BTK. Three novel mutations in the BTK gene include c.115 T > C (p. Tyr39His), c.685-686insTTAC (p.Asn229llefs5), and c.163delT (p.Ser55GlnfsTer2). Our three ARA patients include a novel homozygous stop-gain mutation in the immunoglobulin heavy constant Mu chain (IGHM) gene, a novel frameshift mutation of the B-cell antigen receptor complex-associated protein (CD79A) gene, a novel bi-allelic stop-gain mutation in the transcription factor 3 (TCF3) gene. Three patients with agammaglobulinemia have an autosomal dominant inheritance pattern, which includes a missense variant in PIK3CD, a novel missense variant in PIK3R1 and a homozygous silent mutation in the phosphoinositide-3-kinase regulatory subunit (RASGRP1) gene. This study broadens the genetic spectrum of hypogammaglobulinemia without B-cells and presented a few novel variants within the Iranian community, which may also have implications in other Middle Eastern populations. Notably, disease control was better in the second affected family member in families with multiple cases.


Assuntos
Tirosina Quinase da Agamaglobulinemia , Agamaglobulinemia , Linfócitos B , Mutação , Sistema de Registros , Humanos , Agamaglobulinemia/genética , Agamaglobulinemia/imunologia , Masculino , Linfócitos B/imunologia , Feminino , Tirosina Quinase da Agamaglobulinemia/genética , Criança , Pré-Escolar , Adolescente , Lactente , Linhagem , Classe Ia de Fosfatidilinositol 3-Quinase
10.
Clin Exp Immunol ; 216(2): 120-131, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38306460

RESUMO

Selective IgA deficiency (sIgAD), common variable immunodeficiency (CVID), and transient hypogammaglobulinemia of infancy (THI) are the most frequent forms of primary antibody deficiencies. Difficulties in initial diagnosis, especially in the early childhood, the familiar occurrence of these diseases, as well as the possibility of progression to each other suggest common cellular and molecular patomechanism and a similar genetic background. In this review, we discuss both similarities and differences of these three humoral immunodeficiencies, focusing on current and novel therapeutic approaches. We summarize immunoglobulin substitution, antibiotic prophylaxis, treatment of autoimmune diseases, and other common complications, i.e. cytopenias, gastrointestinal complications, and granulomatous disease. We discuss novel therapeutic approaches such as allogenic stem cell transplantation and therapies targeting-specific proteins, dependent on the patient's genetic defect. The diversity of possible therapeutics models results from a great heterogeneity of the disease variants, implying the need of personalized medicine approach as a future of primary humoral immunodeficiencies treatment.

11.
Cureus ; 16(1): e52705, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38384652

RESUMO

Good Syndrome is a rare disease that comprises the presence of a thymoma, immunodeficiency, and recurrent opportunistic infections. We report the case of a young woman who was diagnosed with Good Syndrome, who had a long-term history of recurrent infections, often due to atypical agents, and who also had a previous history of immunodeficiency and a B1 thymoma invading the large vessels, lung, and pericardium (Masaoka stage IV). She underwent surgical resection of the mediastinal mass, requiring vena cava superior reconstruction due to the extent of invasion, followed by adjuvant radiotherapy and immunoglobulin G supplementation. Despite relative stability in the subsequent years, without serious infections, after three years she had a thymoma recurrence requiring a new therapeutic approach. This case highlights the importance of a thorough investigation of the underlying causes of recurrent infections, which may be the result of an immunodeficiency secondary to malignancy. In young patients, early diagnosis is crucial to avoid disease progression and to reduce mortality rates. To achieve such outcomes, a multidisciplinary team and a comprehensive therapeutic strategy are necessary.

12.
Clin Immunol ; 261: 110165, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38423196

RESUMO

Mutations in NFkB pathway genes can cause inborn errors of immunity (IEI), with NFKB1 haploinsufficiency being a significant etiology for common variable immunodeficiency (CVID). Indeed, mutations in NFKB1 are found in 4 to 5% of in European and United States CVID cohorts, respectively; CVID representing almost » of IEI patients in European countries registries. This case study presents a 49-year-old patient with respiratory infections, chronic diarrhea, immune thrombocytopenia, hypogammaglobulinemia, and secondary lymphoma. Comprehensive genetic analysis, including high-throughput sequencing of 300 IEI-related genes and copy number variation analysis, identified a critical 2.6-kb deletion spanning the first untranslated exon and its upstream region. The region's importance was confirmed through genetic markers indicative of enhancers and promoters. The deletion was also found in the patient's brother, who displayed similar but milder symptoms. Functional analysis supported haploinsufficiency with reduced mRNA and protein expression in both patients. This case underscores the significance of copy number variation (CNV) analysis and targeting noncoding exons within custom gene panels, emphasizing the broader genomic approaches needed in medical genetics.


Assuntos
Imunodeficiência de Variável Comum , Irmãos , Masculino , Adulto , Humanos , Pessoa de Meia-Idade , Haploinsuficiência/genética , Variações do Número de Cópias de DNA , NF-kappa B/genética , Imunodeficiência de Variável Comum/genética , Sequências Reguladoras de Ácido Nucleico , Subunidade p50 de NF-kappa B/genética
13.
Med. clín (Ed. impr.) ; 162(4): 170-178, Feb. 2024. ilus, graf, tab
Artigo em Inglês | IBECS | ID: ibc-230573

RESUMO

Background and objective: IgG replacement therapy (IgG-RT) has radically changed the clinical evolution of primary immunodeficiencies, yet the information regarding secondary hypogammaglobulinemia (SHG) is insufficient or conflicting. We aim to describe clinical features, evolution and treatment of SHG patients in our center. Methods: Dynamic retrospective cohort between January 2001 and July 2021 of adults with gamma globulin fraction <0.6g/dL in a serum protein electrophoresis and a coincident decrease of IgG levels – with a disease-related SHG or treatment that reduces serum immunoglobulins. Results: We included 1012 patients with SHG with a median follow-up of 5 years (IQR 2–8). Hematological diseases were identified in 95% of the patients and 61% received drugs related to SHG. Sixty five percent had more than one etiological factor associated with SHG. Infectious diseases were present in 69% of the patients, 48% had respiratory infections and 17% had severe infections. There was statistical association between respiratory and severe infections with multiple myeloma (MM), lymphoma and rituximab. MGUS had less infections and death compared with other etiologies. IgG-RT was indicated in 18.7% of the patients and 4.6% received it for more than 6 months with variable intervals. Among the latter group, there was a significant reduction of all-type infections and respiratory infections with IgG-RT (p<0.001), and it was consistent with similar findings in lymphoma, MM and all IgG levels subgroups. Conclusion: SHG was associated with more than one etiological factor and a high frequency of infections. IgG-RT indication was irregular yet still effective. It is relevant to consider IgG levels screening, monitoring and accurate indication of IgG-RT.(AU)


Antecedentes y objetivos: La IgG sustitutiva ha cambiado radicalmente la evolución de las inmunodeficiencias primarias, mientras que la información sobre hipogammaglobulinemia secundaria (HGS) es insuficiente y discordante. El objetivo del estudio es describir las características clínicas, evolución y tratamiento de pacientes con HGS. Métodos: Cohorte retrospectiva dinámica entre enero de 2001 y julio de 2021 de adultos con proteinograma y fracción de gammaglobulina <0,6g/dL y dosaje disminuido de IgG, con enfermedad o tratamiento que produzcan HGS. Resultados: Se incluyó a 1.012 pacientes con HGS con una mediana de seguimiento de 5 años (IIC 2-8). El 95% tenía enfermedad hematológica y el 61% recibió fármacos asociados a HGS. El 65% tenía más de un factor etiológico asociado con HGS. El 69% presentó infecciones de cualquier tipo, el 48% infecciones respiratorias y el 17%, infecciones graves. Hubo asociación significativa entre infecciones respiratorias y graves entre los subgrupos de mieloma múltiple, linfoma y rituximab. Los pacientes con MGUS tuvieron menor frecuencia de infecciones y muerte comparados con otros factores etiológicos. El 18,7% de los pacientes recibió IgG sustitutiva y el 4,6% de forma crónica, con intervalos variables. Los últimos tuvieron disminución significativa de infecciones de cualquier tipo e infecciones respiratorias con IgG sustitutiva (p<0,001), que se mantuvo en los subgrupos con mieloma múltiple, linfoma y todos los niveles de IgG. Conclusión: La HGS asoció más de un factor etiológico y alta frecuencia de infecciones. La indicación de IgG sustitutiva fue irregular, pero, aún así, efectiva. Se plantea considerar el dosaje de inmunoglobulinas, monitoreo y la adecuada indicación de IgG sustitutiva.(AU)


Assuntos
Humanos , Masculino , Feminino , Adulto , Agamaglobulinemia/diagnóstico , gama-Globulinas , Pneumonia , Neoplasias Hematológicas/cirurgia , Medicina Clínica , Estudos Retrospectivos , Estudos de Coortes
14.
Surv Ophthalmol ; 69(3): 418-426, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38176471

RESUMO

Good syndrome (GS) is a rare primary immunodeficiency in adults consisting of hypogammaglobulinemia and thymoma that affects both cellular and humoral immunity. It usually appears in patients between the 4th and 6th decade of life and affects both genders equally. Ophthalmological clinical presentation is highly variable; associations with herpetic keratitis, toxoplasmosis, and cytomegalovirus retinitis (CMVR) have been described. GS associated with CMVR is uncommon. Ophthalmologists may be the first to diagnose systemic disease and change the outcome. Only18 cases of CMVR have been described, most of them unilateral with poor visual outcomes. We discuss the clinical features of CMVR in patients with reported GS, pathogenesis, and outline a work-up for diagnosis. CMVR in an apparently healthy patient should encourage the clinician to search for human immunodeficiency virus (HIV) and non-HIV-associated immunosuppression.


Assuntos
Agamaglobulinemia , Retinite por Citomegalovirus , Timoma , Humanos , Retinite por Citomegalovirus/diagnóstico , Retinite por Citomegalovirus/tratamento farmacológico , Timoma/complicações , Timoma/diagnóstico , Agamaglobulinemia/diagnóstico , Agamaglobulinemia/complicações , Neoplasias do Timo/complicações , Neoplasias do Timo/diagnóstico
15.
Int Arch Allergy Immunol ; 185(4): 370-381, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38194943

RESUMO

INTRODUCTION: X-linked lymphoproliferative syndrome (XLP) is a rare primary immune deficiency. Two types of XLP have been described: XLP-1 and XLP-2. METHODS: We found 7 patients with XLP (3 had XLP-1 and 4 had XLP-2) after reviewing the data from Pediatric Immunodeficiency Clinic from 1997 to 2021. RESULTS: Mean age at diagnosis was 3.8 years, and mean delay in diagnosis was 2.6 years. Five patients had recurrent episodes of infections. Four patients developed at least one episode of hemophagocytic lymphohistiocytosis (HLH) (2 with XLP-1 and 2 with XLP-2). Of these, 2 had recurrent HLH (both with XLP-2). Epstein-Barr virus (EBV) infection was detected in 2 (1 with XLP-1 and 1 with XLP-2). Both these patients had HLH. One child with XLP-2 had inflammatory bowel disease. Hypogammaglobulinemia was seen in 3 (2 with XLP-1 and 1 with XLP-2). Genetic analysis showed previously reported variants in 5, while 2 had novel variants (one in exon 7 of XIAP gene [c.1370dup p.Asn457Lysfs Ter16] and other had splice site variant in intron 1 of SH2D1A gene [c.138-2_138-1insG]). Episodes of HLH were managed with intravenous immunoglobulin (IVIg), methylprednisolone, oral prednisolone, cyclosporine, and rituximab. Inflammatory bowel disease was managed using oral prednisolone and azathioprine. One patient underwent haploidentical hematopoietic stem cell transplantation. One child with XLP-2 and WAS died because of fulminant pneumonia. DISCUSSION/CONCLUSIONS: XLP should be considered as a strong possibility in any patient with features of HLH, repeated infections with hypogammaglobulinemia, persistent EBV infection, and early-onset IBD.


Assuntos
Agamaglobulinemia , Infecções por Vírus Epstein-Barr , Doenças Inflamatórias Intestinais , Linfo-Histiocitose Hemofagocítica , Transtornos Linfoproliferativos , Criança , Humanos , Agamaglobulinemia/diagnóstico , Agamaglobulinemia/genética , Agamaglobulinemia/terapia , Infecções por Vírus Epstein-Barr/diagnóstico , Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4/genética , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/genética , Transtornos Linfoproliferativos/terapia , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/genética , Linfo-Histiocitose Hemofagocítica/terapia , Prednisolona
16.
Ann Hematol ; 103(5): 1655-1664, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38236391

RESUMO

Chronic Lymphocytic Leukemia (CLL) is well-known for increasing susceptibility to infections. Factors such as immune dysregulation, IGHV status, hypogammaglobulinemia, and patient comorbidity and treatment, contribute to higher infection rates and mortality. However, the impact of hypogammaglobulinemia on infection rates is controversial. We aimed to identify clinical and biological parameters linked to the risk of severe infectious events. Additionally, we set up a straightforward risk infection score to stratify CLL patients at diagnosis, thereby enabling the development of suitable infection prevention strategies. We retrospectively evaluated 210 unselected CLL patients diagnosed between 1988 and 2018. This evaluation encompassed demographics, Binet stage, immunoglobulin (Ig) levels, treatment history, comorbidities, and IGHV mutational status at diagnosis. The frequency and severity of infectious events were recorded. Analysis revealed that age, IGHV mutational status, Binet stage, and hypogammaglobulinemia were statistically associated with the Time to First Infection (TTFI) in univariate and multivariate analyses. Using hazard ratios from the multivariate analysis, we finally devised a risk scoring system that integrated age, IGHV mutational status, immunoglobulin levels, and Binet stage to stratify patients at diagnosis based on their specific infection risk. In our cohort, disease progression and infections were the leading cause of death. These findings pointed out the clinical need for a screening process strategic for defining infectious risk at the time of CLL diagnosis, with a significant enhancement in the clinical management of these patients.


Assuntos
Agamaglobulinemia , Leucemia Linfocítica Crônica de Células B , Humanos , Leucemia Linfocítica Crônica de Células B/complicações , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/epidemiologia , Prognóstico , Estudos Retrospectivos , Agamaglobulinemia/diagnóstico , Agamaglobulinemia/epidemiologia , Mutação , Fatores de Risco , Imunoglobulinas
18.
Immunol Med ; : 1-4, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38270551

RESUMO

Congenital Myotonic Dystrophy (CMD) is an autosomal dominant hereditary disease caused by mutations in the dystrophia myotonica protein kinase gene. Patients with CMD often exhibit low immunoglobulin (Ig) G levels. While Ig replacement therapy for low IgG levels has been reported in several adult cases, there have been no reports on pediatric patients. This study presents a first pediatric case where Ig replacement therapy effectively eliminated susceptibility to infections. The CMD patient, a 1-year-old Japanese female with a history of premature birth and necrotizing enterocolitis, developed recurrent severe bacterial infections due to hypogammaglobulinemia. Intravenous immunoglobulin (IVIG) (600 mg/kg/month) was administered but failed to maintain sufficient serum trough IgG levels. The dosage was increased to 2 g/kg/month, and later, the treatment shifted to subcutaneous immunoglobulin (SCIG), resulting in a stable serum trough IgG level above 700 mg/dL for one year. The cause of hypogammaglobulinemia in CMD patients remains unclear, but potential mechanisms, including IgG-mediated hypercatabolism by alterations in the neonatal Fc receptor, have been considered. Genetic testing ruled out common variable immunodeficiency, and other potential causes were excluded. The study suggests that higher doses of IVIG or SCIG can effectively prevent severe infections associated with CMD-induced hypogammaglobulinemia in children.


This case report sheds light on the efficacy of immunoglobulin therapy in pediatric congenital myotonic dystrophy (CMD). We anticipate that our findings will have a positive impact on clinical practice by providing insights into the prevention of severe infections associated with CMD-induced hypogammaglobulinemia. This research is of great interest to the readers of the journal as it addresses an unmet need in pediatric CMD management by providing a strategy for successful immunoglobulin therapy for the treatment of pediatric CMD.

19.
J Autoimmun ; 142: 103130, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37956529

RESUMO

OBJECTIVES: B-cell depletion induced by rituximab (RTX) in ANCA-associated vasculitis (AAV) is a risk factor for hypogammaglobulinemia. Aggregating data on gammaglobulin levels kinetics during RTX and its association with the risk of relapse and severe infection is of interest. METHODS: Gammaglobulin levels were collected before induction therapy and during RTX maintenance therapy. We used different definitions of gammaglobulin decline: 1/gammaglobulin levels <6 g/L after induction; 2/>25 % decline in gammaglobulin levels between induction and maintenance, and 3/both. Our primary objective was the impact of gammaglobulin decline on the risk of relapse and severe infections. RESULTS: We included 98 patients. Patients with gammaglobulin level <6 g/L after induction and gammaglobulin decline >25 % were older (OR 3.9; 95%CI 1.1-16.1), had more frequently baseline gammaglobulin levels <10 g/L (OR 6.0; 95%CI 1.7-25.8) and received more frequent pulses of methylprednisolone at induction (OR 4.6; 95%CI 1.3-18.5). Severe infection-free survival was significantly poorer in patients with both gammaglobulin <6 g/L and gammaglobulin decline >25 % (adjusted HR 2.3; 95%CI 1.0-5.1) and in those who received pulses of methylprednisolone (HR 5.6; 95%CI 2.3-13.4). Gammaglobulin decline was in contrast not associated with the risk of relapse. CONCLUSION: Older age, low gammaglobulin levels and pulses of methylprednisolone at induction increase the likelihood of gammaglobulin decline after induction therapy. Such decline was associated with an increased risk of severe infections but not lower risk of vasculitis relapse. Pulses of methylprednisolone at induction had an independent negative impact on gammaglobulin levels and the risk of severe infections.


Assuntos
Agamaglobulinemia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Humanos , Estudos de Coortes , Agamaglobulinemia/tratamento farmacológico , Agamaglobulinemia/epidemiologia , Rituximab/uso terapêutico , Fatores de Risco , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/epidemiologia , Metilprednisolona/uso terapêutico , Indução de Remissão , Recidiva , Estudos Retrospectivos , Resultado do Tratamento
20.
Br J Haematol ; 204(1): 260-267, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37963427

RESUMO

Immunoglobulin replacement therapy (IgRT) reduces the risk of infection in hypogammaglobulinaemia secondary to chronic lymphocytic leukaemia and multiple myeloma. However, the benefit of IgRT, especially subcutaneous IgRT (ScIgRT), has not been assessed in hypogammaglobulinaemia after allogeneic haematopoietic cell transplantation (allo-HCT). We performed a pre-post comparison of the clinical impact of ScIgRT after allo-HCT in a retrospective analysis of 209 patients who underwent allogeneic HCT at our institution from 2011 to 2019. Since ScIgRT became available at our institution in April 2017, we categorized patients treated from January 2011 to March 2017 as the Pre-ScIgRT group (n = 118) and those treated from April 2017 to December 2019 as the Post-ScIgRT group (n = 91). The 2-year overall survival rate was 65% in the Pre-ScIgRT group and 81% in the Post-ScIgRT group (p = 0.02). The cumulative incidence (CI) of non-relapse mortality at 2 years was 18% and 7% (p = 0.02). There were 78 infectious events in 44 patients in the Pre-ScIgRT group and 28 such events in 19 patients in the Post-ScIgRT group. The CI of the documented infection during the observation period was between 38% and 21% (p = 0.01). Our study suggests that ScIgRT may reduce infection rates and improve prognosis after allo-HCT.


Assuntos
Agamaglobulinemia , Transplante de Células-Tronco Hematopoéticas , Humanos , Transplante Homólogo/efeitos adversos , Estudos Retrospectivos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Imunoglobulinas
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