Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 686
Filtrar
1.
Braz J Med Biol Res ; 52(10): e8926, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31618370

RESUMO

Humoral immunological defects are frequent and important causes of hypogammaglobulinemia, leading to recurrent infections, autoimmunity, allergies, and neoplasias. Usually, its onset occurs in childhood or during the second and third decades of life; however, the diagnosis is made, on average, 6 to 7 years afterwards. As a consequence, antibody defects can lead to sequelae. Here we describe the clinical-laboratory characteristics, treatment, and prognoses of patients with hypogammaglobulinemia. An observational, cross-sectional, and retrospective study of patients attending the recently established outpatient group of Clinical Immunology between 2013 and 2018 was carried out. Patients with IgG levels below 2 standard deviations from the mean values for the age and/or impaired antibody response were included. Eight patients (3 F and 5 M; median age=41 years (16-65), average symptom onset at 25 years (1-59), and time to diagnosis of 10 years were included. The main infections were: sinusitis in 7/8, pneumonia in 6/8, otitis in 2/8, tonsillitis and diarrhea in 2/8, and diarrhea in 2/8 patients. Hypothyroidism was identified in 4/8 (50%) patients. Rhinitis was found in 7/8 (87.5%) and asthma in 3/8 (37.5%) patients. The tomographic findings were consolidations, atelectasis, emphysema, ground glass opacity, budding tree, bronchial thickening, and bronchiectasis. Immunoglobulin reposition was used between 466 and 600 mg/kg monthly (514.3 mg·kg-1·dose-1). Prophylactic antibiotic therapy was included in 7/8 (87.5%) patients. Airway manifestations prevailed in patients with hypogammaglobulinemia. There is a need for educational work to reduce the time of diagnosis and initiation of treatment, avoiding sequelae.


Assuntos
Agamaglobulinemia/diagnóstico , Imunoglobulinas Intravenosas/administração & dosagem , Adolescente , Adulto , Agamaglobulinemia/tratamento farmacológico , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Adulto Jovem
2.
Pan Afr Med J ; 32: 161, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31303930

RESUMO

Serum protein electrophoresis (SPE) is a routine analysis in the daily practice of a medical biology laboratory. This study aimed to analyze the different electrophoretic profiles seen in our current practice. We conducted a cross-sectional study of 410 serum samples collected during the routine analyses in the Laboratory of Biochemistry at the University Hospital Mohammed VI in Oujda. Serum protein electrophoresis was performed using automated instrument CAPILLARYS 2 FLEX-PIERCING, SEBIA. 241 sera from women and 169 sera from men were collected. Patients were aged between 1-91 years, with an average age of 49 years; 19.5% of SPEs were normal, hypoalbuminemia was found in 34% of cases, chronic inflammatory syndrome in 19.5% of cases, nephrotic syndrome in 2% of cases, 5.8% of our patients had betagamma block, hypogammaglobulinemia was found in 8.5% of cases and 29 monoclonal peaks were noted, bisalbuminemia was found in 2 patients. Out of 410 collections: 92 immunofixations were performed, of whom 23 were positive (showing monoclonal gammopathy). This study highlights the variability in prescribing serum protein electrophoresis as well as the importance of clinical data for a better interpretation.


Assuntos
Eletroforese das Proteínas Sanguíneas/métodos , Hipoalbuminemia/diagnóstico , Inflamação/diagnóstico , Paraproteinemias/diagnóstico , Adolescente , Adulto , Agamaglobulinemia/diagnóstico , Agamaglobulinemia/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos Transversais , Feminino , Hospitais Universitários , Humanos , Hipoalbuminemia/epidemiologia , Lactente , Inflamação/epidemiologia , Masculino , Pessoa de Meia-Idade , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/epidemiologia , Paraproteinemias/epidemiologia , Adulto Jovem
3.
Int J Immunopathol Pharmacol ; 33: 2058738419843364, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30968707

RESUMO

Humoral immunodeficiency with accompanying infections is an indication for human immunoglobulin replacement therapy. Whether treatment will be lifelong or necessary only temporarily depends on the nature of deficiency: primary (persistent) or secondary (persistent or transient). It is not always easy to distinguish between primary and secondary immunodeficiency, especially in adults. The article presents a case of a 39-year-old patient with anamnesis and medical tests results that suggested primary humoral immunodeficiency. The deficiency was diagnosed for the first time at the age of 38, when the patient was pregnant. The patient was qualified for immunoglobulin G replacement therapy. Clinical improvement was achieved. After the end of pregnancy, systematic improvement in immunological parameters was observed, suggesting the resolution of immunodeficiency. A decision was made to discontinue immunoglobulin replacement. Due to the ability to respond to vaccine, confirmed during diagnosis, preventive vaccines were recommended. There was no recurrence of serious infections. The clinical course finally enabled a diagnosis of secondary immunodeficiency. The presented case shows the importance of an active approach to the diagnostic and therapeutic process, constant assessment of clinical course, monitoring of IgG concentrations, and the awareness that in the situation when we do not have a genetic confirmation of the disease, the diagnosis may change.


Assuntos
Agamaglobulinemia/tratamento farmacológico , Deficiência de IgG/tratamento farmacológico , Imunoglobulina G/administração & dosagem , Infecção/tratamento farmacológico , Adulto , Agamaglobulinemia/complicações , Agamaglobulinemia/diagnóstico , Esquema de Medicação , Feminino , Humanos , Deficiência de IgG/complicações , Deficiência de IgG/diagnóstico , Infecção/diagnóstico , Infecção/etiologia , Infusões Intravenosas/tendências , Recidiva
4.
Front Immunol ; 9: 2756, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30564228

RESUMO

Background: Primary immunodeficiency disorders (PIDD) comprise a group of life-threatening congenital diseases characterized by absent or impaired immune responses. Despite the fact that effective, curative treatments are available with optimal clinical outcomes when diagnosed early, newborn screening does not exist for the majority of these diseases due to the lack of detectable, specific biomarkers or validated methods for population-based screening. Peptide immunoaffinity enrichment coupled with selected reaction monitoring mass spectrometry (immuno-SRM) is a sensitive proteomic assay, involving antibody-mediated peptide capture, that allows for concurrent quantification of multiple analytes. This assay has promise for use in potential newborn screening of PIDDs that lead to diminished or absent target proteins in the majority of cases. Objective: To determine and evaluate if a multiplex assay based on immuno-SRM is able to reliably and precisely distinguish affected patients with X-linked agammaglobulinemia (XLA), Wiskott-Aldrich Syndrome (WAS), and CD3ϵ-associated severe combined immunodeficiency (SCID) from one another and from unaffected normal control dried blood spot (DBS) samples. Methods: We performed a blinded, multiplexed analysis of proteolytically-generated peptides from WASp, BTK, and CD3ϵ (for WAS, XLA, and SCID, respectively) in DBS samples from 42 PIDD patients, 40 normal adult controls, and 62 normal newborns. The peptide ATPase copper transporting protein (ATP7B) 1056 was simultaneously monitored for quality assurance purposes. Results: The immuno-SRM assays reliably quantified the target peptides in DBS and accurately distinguished affected patients from normal controls. Analysis of signature peptides found statistically significant reduction or absence of peptide levels in affected patients compared to control groups in each case (WASp and BTK: p = 0.0001, SCID: p = 0.05). Intra and inter-assay precision ranged from 11 to 22% and 11 to 43% respectively; linearity (1.39-2000 fmol peptide), and stability (≤ 0.09% difference in 72 h) showed high precision for the multiplexed assay. Inter-laboratory assay comparison showed high concordance for measured peptide concentrations, with R2 linearity ≥ 0.97 for the WASp 274, CD3ϵ 197, BTK 407, and ATP7B 1056 peptides. Conclusion: Immuno-SRM-based quantification of proteotypic peptides from WASp, BTK, and CD3ϵ in DBS distinguishes relevant PIDD cases from one another and from controls, raising the possibility of employing this approach for large-scale multiplexed newborn screening of selective PIDDs.


Assuntos
Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/metabolismo , Agamaglobulinemia/diagnóstico , Agamaglobulinemia/metabolismo , Anticorpos/metabolismo , Bioensaio/métodos , Biomarcadores/metabolismo , Cromatografia Líquida/métodos , Estudos de Coortes , ATPases Transportadoras de Cobre/metabolismo , Teste em Amostras de Sangue Seco/métodos , Feminino , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico , Doenças Genéticas Ligadas ao Cromossomo X/metabolismo , Humanos , Recém-Nascido , Espectrometria de Massas/métodos , Triagem Neonatal/métodos , Peptídeos/metabolismo , Proteômica/métodos
5.
Artigo em Inglês | MEDLINE | ID: mdl-30559311

RESUMO

X-linked agammaglobulinemia (XLA, OMIM#300300) is a rare monogenic primary immunodeficiency caused by mutations in the Bruton tyrosine kinase (BTK) gene. XLA is characterized by insufficient immunoglobulin levels and susceptibility to life-threatening bacterial infections. We report on a patient that presented with ecthyma gangrenosum and septicemia. Rapid trio whole-genome sequencing (rWGS) revealed an apparently de novo hemizygous pathogenic variant (c.726dupT; p.Ile243TyrfsTer15) in the BTK gene. Metagenomic analysis of rWGS sequences that did not align to the human genome revealed 770 aligned to the Pseudomonas aeruginosa PAO1 genome. The patient was diagnosed with XLA and pseudomonal sepsis.


Assuntos
Tirosina Quinase da Agamaglobulinemia/genética , Agamaglobulinemia/genética , Ectima/genética , Doenças Genéticas Ligadas ao Cromossomo X/genética , Tirosina Quinase da Agamaglobulinemia/metabolismo , Agamaglobulinemia/diagnóstico , Bacteriemia , Ectima/diagnóstico , Gangrena/microbiologia , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico , Humanos , Síndromes de Imunodeficiência , Lactente , Masculino , Infecções por Pseudomonas/genética , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/patogenicidade , Sepse/genética , Sepse/metabolismo , Pele/microbiologia , Sequenciamento Completo do Genoma/métodos
6.
Scand J Immunol ; 88(4): e12709, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30152873

RESUMO

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


Assuntos
Agamaglobulinemia/imunologia , Subpopulações de Linfócitos B/imunologia , Linfócitos B/imunologia , Doenças do Recém-Nascido/imunologia , Infecção/imunologia , Agamaglobulinemia/diagnóstico , Autoimunidade , Separação Celular , Criança , Pré-Escolar , Feminino , Citometria de Fluxo , Seguimentos , Humanos , Imunoglobulina G/sangue , Memória Imunológica , Lactente , Recém-Nascido , Doenças do Recém-Nascido/diagnóstico , Infecção/diagnóstico , Masculino , Avaliação de Resultados da Assistência ao Paciente , Turquia
7.
BMC Neurol ; 18(1): 97, 2018 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-30016937

RESUMO

BACKGROUND: Immunoglobulin associated meningitis is a rare disease that mimics infectious meningitis. This is, to our knowledge, the first case of Immunoglobulin-associated meningitis described in a patient with Systemic Lupus Erythematosus and hypogammaglobulinemia secondary to Rituximab. CASE PRESENTATION: A 46-year-old female with a past medical history of Systemic Lupus Erythematosus, presented with meningismus 36 h after first infusion of intravenous immunoglobulin. The cerebrospinal fluid analysis showed neutrophilic pleocytosis and hyperproteinorrachia. All microbiological tests were negative. The patient recovered remarkably fast without sequela after just five days of antibiotic therapy. CONCLUSION: Systemic Lupus Erythematosus is a well-documented risk factor for aseptic meningitis associated with other drugs. Possibly, it is also a risk factor for Immunoglobulin associated meningitis. This diagnosis, although rare, should be considered in patients receiving Immunoglobulin since it is a self-limited condition and treatment is supportive.


Assuntos
Agamaglobulinemia , Fatores Imunológicos/efeitos adversos , Lúpus Eritematoso Sistêmico , Meningite Asséptica , Rituximab/efeitos adversos , Agamaglobulinemia/induzido quimicamente , Agamaglobulinemia/complicações , Agamaglobulinemia/diagnóstico , Feminino , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Meningite Asséptica/diagnóstico , Meningite Asséptica/etiologia , Meningite Asséptica/fisiopatologia , Pessoa de Meia-Idade , Fatores de Risco
9.
Hum Immunol ; 79(7): 571-577, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29709555

RESUMO

The precise diagnosis of an immunodeficiency is sometimes difficult to assess, especially due to the large spectrum of phenotypic variation reported among patients. Common variable immunodeficiency disorders (CVID) do not have, for a large part, an identified genetic cause. The identification of a causal genetic mutation is important to confirm, or in some cases correct, the diagnosis. We screened >150 male patients with hypogammaglobulinemia for mutations in three genes involved in pediatric X-linked primary immunoglobulin deficiency: CD40LG, SH2D1A and BTK. The SH2D1A screening allowed to reclassify two individuals with an initial CVID presentation as XLP after mutations identification. All these mutations were associated with a lack of protein expression. In addition, 4 patients with a primary diagnosis of CVID and one with a primary IgG subclass deficiency were requalified as XLA after identifying BTK mutations. Interestingly, two out of these 5 patients carried a damaging coding BTK mutation associated with a lower, but detectable, BTK expression in monocytes, suggesting that a dysfunctional protein explains the disease phenotype in these patients. In conclusion, our results advocate to include SH2D1A and BTK in newly developed targeted NGS genetic testing, to contribute to providing the most appropriate medical treatment and genetic counselling.


Assuntos
Agamaglobulinemia/diagnóstico , Monócitos/fisiologia , Proteínas Tirosina Quinases/genética , Proteínas Recombinantes de Fusão/genética , Proteína Associada à Molécula de Sinalização da Ativação Linfocitária/genética , Tirosina Quinase da Agamaglobulinemia , Biomarcadores/metabolismo , Pré-Escolar , Análise Mutacional de DNA , Aconselhamento Genético , Testes Genéticos , Humanos , Lactente , Masculino , Mutação/genética , Fenótipo
11.
Scand J Immunol ; 87(3)2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29424453

RESUMO

X-linked agammaglobulinemia is a primary immunodeficiency disorder resulting from BTK gene mutations. There are many studies in the literature suggesting contradictory ideas about phenotype-genotype correlation. The aim of this study was to identify the mutations and clinical findings of patients with XLA in Turkey, to determine long-term complications related to the disease and to analyse the phenotype-genotype correlation. Thirty-two patients with XLA diagnosed between 1985 and 2016 in Pediatric Immunology Department of Hacettepe University Ihsan Dogramaci Children's Hospital were investigated. A clinical survey including clinical features of the patients was completed, and thirty-two patients from 26 different families were included in the study. Getting early diagnosis and regular assessment with imaging techniques seem to be the most important issues for improving the health status of the patients with XLA. Early molecular analysis gives chance for definitive diagnosis and genetic counselling, but not for predicting the clinical severity and prognosis.


Assuntos
Agamaglobulinemia/diagnóstico , Agamaglobulinemia/genética , Anticorpos/sangue , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico , Doenças Genéticas Ligadas ao Cromossomo X/genética , Proteínas Tirosina Quinases/genética , Adolescente , Adulto , Tirosina Quinase da Agamaglobulinemia , Agamaglobulinemia/patologia , Infecções Bacterianas/imunologia , Criança , Pré-Escolar , Doenças Genéticas Ligadas ao Cromossomo X/patologia , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Lactente , Estudos Retrospectivos , Turquia , Adulto Jovem
12.
Ann Saudi Med ; 38(1): 65-68, 2018 Jan-Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29313528

RESUMO

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


Assuntos
Agamaglobulinemia , Linfócitos B , Epilepsia/tratamento farmacológico , Linfopenia , Piracetam/análogos & derivados , Agamaglobulinemia/induzido quimicamente , Agamaglobulinemia/diagnóstico , Agamaglobulinemia/imunologia , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/efeitos adversos , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Linfócitos B/patologia , Relação Dose-Resposta a Droga , Epilepsia/etiologia , Feminino , Humanos , Levetiracetam , Linfopenia/induzido quimicamente , Linfopenia/imunologia , Linfopenia/patologia , Pessoa de Meia-Idade , Piracetam/administração & dosagem , Piracetam/efeitos adversos , Resultado do Tratamento , Suspensão de Tratamento
13.
Rheumatol Int ; 38(1): 129-136, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28516235

RESUMO

Deficiency of adenosine deaminase type 2 (DADA2) is a rare form of autoinflammatory disorder with limited reported cases. In this paper, we have presented the clinico-immunological, radiological and genetic characteristics of five surviving and three deceased childhood-onset DADA2 patients. We aimed to compare surviving and deceased patients in terms of clinical features and treatment modalities. Moreover, we have evaluated the causes of death in our DADA2 subjects together with the previously reported cases. Demographic features, clinical characteristics, imaging findings, mutations and pharmacological treatments of DADA2 subjects were noted from patient records of pediatric and adult rheumatology clinics in a retrospective and longitudinal nature. Eight patients from seven families were enrolled. While five of them were surviving, three of them had died due to various reasons. Median age of the patients at disease onset and diagnosis was 7 years (range 0.5-13 years) and 14 years (range 5-27 years), respectively. The main clinical manifestations were cutaneous findings (7/8), recurrent low-grade fever (6/8), neurological involvement (6/8) and gastrointestinal involvement (5/8). All patients had increased acute phase reactants at presentation and also during the disease flares. Until the diagnosis of DADA2 was confirmed, five patients have been followed-up with the diagnosis of PAN: two patients both with PAN and FMF, and one patient with CAPS and vasculitis. Demographic, clinical, neurological features and genetic mutations did not differ in surviving and deceased DADA2 patients. Deceased and surviving subjects differed in terms of treatment modalities after the diagnosis of DADA2. Anti-TNF alpha treatment has been initiated in five surviving patients as soon as the diagnosis of DADA2 was established. However, three patients who have died were not able to use sufficient doses of anti-TNF alpha treatment; in one case due to reluctance of patient and in two cases due to establishment of the definite diagnosis by genetic analysis at the same time with the last fatal DADA2 episode. Despite limited number of patients, this case series for the first time compares the phenotypic, genotypic and medication differences between surviving and deceased DADA2 patients. Anti-TNF alpha treatment seems to be efficient and lifesaving in DADA2 patients.


Assuntos
Adenosina Desaminase/deficiência , Agamaglobulinemia/diagnóstico , Produtos Biológicos/uso terapêutico , Imunodeficiência Combinada Severa/diagnóstico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adenosina Desaminase/genética , Adolescente , Adulto , Agamaglobulinemia/diagnóstico por imagem , Agamaglobulinemia/tratamento farmacológico , Agamaglobulinemia/genética , Idade de Início , Criança , Pré-Escolar , Genótipo , Humanos , Lactente , Angiografia por Ressonância Magnética , Imunodeficiência Combinada Severa/diagnóstico por imagem , Imunodeficiência Combinada Severa/tratamento farmacológico , Imunodeficiência Combinada Severa/genética , Adulto Jovem
15.
Rev Med Interne ; 39(4): 297-306, 2018 Apr.
Artigo em Francês | MEDLINE | ID: mdl-29273180

RESUMO

Deficiency of adenosine deaminase 2 (DADA2) is a recently described auto-inflammatory disorder. It is an autosomal recessive inherited disease, caused by mutations in the ADA2 gene (formerly known as CECR1) encoding ADA2 enzyme. Besides its role in the purine metabolism, it has been postulated that ADA2 may act as a growth factor for endothelial cells and in the differenciation of monocytes. Thus, deficiency of ADA2 would lead to endothelial damage and a skewing of monocytes into M1 pro-inflammatory macrophage, causing DADA2 manifestations. Three core clinical features have been described: inflammatory-vascular signs, hematologic abnormalities and immunodeficiency. Clinically, patients display intermittent fever, cutaneous vascular manifestations, such as livedo, ischemic strokes, arthralgia and abdominal pain crisis. Corticosteroids and immunosuppressive agents (i.e. cyclophosphamide, azathioprine, ciclosporin, methotrexate) appear to be poorly effective. Although the mechanism has not been elucidated, anti-TNF agents have been proven efficient in DADA2 and should therefore be used as first line therapy for vasculitis. Role of anti-platelet and anticoagulant therapies in stroke-prophylaxis remains to be discussed, as those patients display a high risk of intracranial bleeding.


Assuntos
Adenosina Desaminase/deficiência , Agamaglobulinemia/diagnóstico , Peptídeos e Proteínas de Sinalização Intercelular/genética , Imunodeficiência Combinada Severa/diagnóstico , Adenosina Desaminase/genética , Agamaglobulinemia/complicações , Agamaglobulinemia/tratamento farmacológico , Feminino , Humanos , Imunossupressores/uso terapêutico , Masculino , Mutação , Fenótipo , Imunodeficiência Combinada Severa/complicações , Imunodeficiência Combinada Severa/tratamento farmacológico , Vasculite/tratamento farmacológico , Vasculite/etiologia
16.
Expert Rev Clin Immunol ; 14(1): 83-93, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29202590

RESUMO

BACKGROUND: X-linked agammaglobulinemia (XLA) is characterized by the absence of immunoglobulin and B cells. Patients suffer from recurrent bacterial infections from early childhood, and require lifelong immunoglobulin replacement therapy. Mutations in BTK (Bruton's Tyrosine Kinase) are associated with this phenotype. Some patients that present XLA do not show typical clinical symptoms, resulting in delayed diagnosis due to the lack of a severe phenotype. This study presents a report of five XLA patients from four different families and attempts to determine a relationship between delayed diagnosis and the occurrence of BTK mutations. METHODS: Samples from patients with antibody deficiency were analyzed to determine BTK expression, immunophenotyping and mutation analysis. Clinical and laboratory data was analyzed and presented for each patient. RESULTS: Most patients presented here showed atypical clinical and laboratory data for XLA, including normal IgM, IgG, or IgA levels. Most patients expressed detectable BTK protein. Sequencing of BTK showed that these patients harbored missense mutations in the pleckstrin homology and Src-homology-2 domains. When it was compared to public databases, BTK sequencing exhibited a new change, along with three other previously reported changes. CONCLUSIONS: Delayed diagnosis and atypical manifestations in XLA might be related to mutation type and BTK expression.


Assuntos
Agamaglobulinemia/diagnóstico , Linfócitos B/imunologia , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico , Infecção/diagnóstico , Mutação de Sentido Incorreto/genética , Domínios de Homologia à Plecstrina/genética , Proteínas Tirosina Quinases/genética , Domínios de Homologia de src/genética , Adolescente , Adulto , Tirosina Quinase da Agamaglobulinemia , Criança , Pré-Escolar , Análise Mutacional de DNA , Diagnóstico Tardio , Humanos , Imunoglobulinas/sangue , Imunoglobulinas/deficiência , Imunofenotipagem , Fenótipo , Adulto Jovem
17.
JAMA Netw Open ; 1(7): e184169, 2018 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-30646343

RESUMO

Importance: Rituximab is an anti-CD20 chimeric antibody used in a wide variety of clinical indications. There has not been widespread adoption of consistent immune monitoring before and after rituximab therapy. However, there is a subset of patients who develop prolonged, symptomatic hypogammaglobulinemia following rituximab, and monitoring before and after rituximab therapy could help to identify these patients and initiate measures to prevent excess morbidity and mortality. Objective: To determine the current levels of screening for hypogammaglobulinemia (specifically, low immunoglobulin G), infectious risks associated with hypogammaglobulinemia, and variables associated with an increased risk of mortality. Design, Setting, and Participants: A cohort study was conducted of 8633 patients receiving rituximab from January 1, 1997, to December 31, 2017, at a large, tertiary referral center (Partners HealthCare System). Exposures: Rituximab administration. Main Outcomes and Measures: The primary outcome measures were immunoglobulin measurements, infectious complications, and mortality. Cox regression analysis was used to examine the results of infectious complications on survival, adjusted for age, sex, and indication for rituximab use. Results: Of the 8633 patients who received rituximab in the large, academic, health care system, 4479 satisfied inclusion criteria, with a mean (SD) age of 59.8 (16.2) years; 2280 patients (50.9%) were women. Most patients (3824 [85.4%]) did not have immunoglobulin levels checked before rituximab therapy. Of those who had levels determined, hypogammaglobulinemia was noted in 313 (47.8%) patients before initiation of rituximab. Following rituximab administration, worsening hypogammaglobulinemia was noted. There was an increase in severe infections after rituximab use in the study cohort (from 17.2% to 21.7%; P < .001). In the survival analysis, increased mortality was associated with increasing age (hazard ratio [HR], 1.02; 95% CI, 1.01-1.02; P < .001), male sex (HR, 1.14; 95% CI, 1.02-1.28; P = .02), and severe infectious complications in the 6 months before (HR, 3.14; 95% CI, 2.77-3.55; P < .001) and after (HR, 4.97; 95% CI, 4.41-5.60; P < .001) the first rituximab infusion. A total of 201 patients (4.5%) received immunoglobulin replacement following rituximab, and among these patients, higher cumulative immunoglobulin replacement dose was associated with a reduced risk of serious infectious complications (HR, 0.98; 95% CI, 0.96-0.99; P = .002). Conclusions and Relevance: Many patients are not being screened or properly identified as having hypogammaglobulinemia both before and after rituximab administration. Monitoring of immunoglobulin levels both before and after rituximab therapy may allow for earlier identification of risk for developing significant infection and identify patients who may benefit from immunoglobulin replacement, which may in turn help to avoid excess morbidity and mortality.


Assuntos
Agamaglobulinemia/complicações , Causas de Morte , Imunoglobulina G/sangue , Infecção/etiologia , Programas de Rastreamento , Rituximab/efeitos adversos , Adulto , Agamaglobulinemia/diagnóstico , Agamaglobulinemia/mortalidade , Idoso , Animais , Estudos de Coortes , Monitoramento de Medicamentos , Feminino , Humanos , Infecção/sangue , Masculino , Camundongos , Pessoa de Meia-Idade , Prevalência , Modelos de Riscos Proporcionais , Fatores de Risco , Índice de Gravidade de Doença
18.
Immunotherapy ; 9(13): 1061-1066, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-29032736

RESUMO

Treatment of patients with relapsed or refractory lymphoma may require allogenic hematopoietic stem cell transplant (HSCT), but treatment of post-transplant relapse disease remains very challenging. Donor lymphocyte infusion and blinatumomab have been used with limited success for the treatment of relapse. Initial data on donor-derived CAR T cells has shown this modality to be safe and highly effective in various hematological malignancies. We present a case of a patient with highly refractory, transformed follicular lymphoma who failed both autologous and allogenic HSCT. Patient achieved long-lasting complete remission with the use of donor origin CD19 CAR T-cell therapy, without any evidence of graft-versus-host disease flare. Our patient later developed disseminated coccidioidomycosis and persistent hypogammaglobulinemia. Immunotherapy using CD19 CAR T cells can be a highly effective salvage modality, especially in cases of focal lymphoma relapse. Long-term immunosuppression secondary to B cell lymphopenia, hypogammaglobulinemia, immunoglobulin subclass deficiency, fungal infections and other infectious complications need to be monitored and promptly treated as indicated.


Assuntos
Agamaglobulinemia/diagnóstico , Coccidioides/imunologia , Coccidioidomicose/diagnóstico , Transplante de Células-Tronco Hematopoéticas , Imunoterapia Adotiva/métodos , Linfoma Difuso de Grandes Células B/diagnóstico , Linfócitos T/imunologia , Agamaglobulinemia/terapia , Idoso , Antígenos CD19/genética , Coccidioidomicose/terapia , Engenharia Genética , Humanos , Linfoma Difuso de Grandes Células B/terapia , Masculino , Receptores de Antígenos de Linfócitos T/genética , Recidiva , Indução de Remissão , Linfócitos T/transplante
19.
Blood ; 130(23): 2491-2498, 2017 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-29066537

RESUMO

Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome is a genetic disease characterized by neutropenia, lymphopenia, susceptibility to infections, and myelokathexis, which describes degenerative changes of mature neutrophils and hyperplasia of bone marrow myeloid cells. Some patients present with hypogammaglobulinemia and/or refractory warts of skin and genitalia. Congenital cardiac defects constitute uncommon manifestations of the disease. The disorder, which is inherited as an autosomal dominant trait, is caused by heterozygous mutations of the chemokine receptor CXCR4. These mutations lead to an increased sensitivity of neutrophils and lymphocytes to the unique ligand CXCL12 and to an increased accumulation of mature neutrophils in the bone marrow. Despite greatly improved knowledge of the disease, therapeutic choices are insufficient to prevent some of the disease outcomes, such as development of bronchiectasis, anogenital dysplasia, or invasive cancer. The available therapeutic measures aimed at preventing the risk for infection in WHIM patients are discussed. We critically evaluate the diagnostic criteria of WHIM syndrome, particularly when WHIM syndrome should be suspected in patients with congenital neutropenia and lymphopenia despite the absence of hypogammaglobulinemia and/or warts. Finally, we discuss recent results of trials evaluating plerixafor, a selective antagonist of CXCR4, as a mechanism-oriented strategy for treatment of WHIM patients.


Assuntos
Síndromes de Imunodeficiência/terapia , Verrugas/terapia , Agamaglobulinemia/diagnóstico , Agamaglobulinemia/etiologia , Agamaglobulinemia/terapia , Biomarcadores , Criança , Pré-Escolar , Progressão da Doença , Feminino , Humanos , Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/etiologia , Infecção/diagnóstico , Infecção/etiologia , Infecção/terapia , Neutropenia/diagnóstico , Neutropenia/etiologia , Neutropenia/terapia , Fenótipo , Resultado do Tratamento , Verrugas/diagnóstico , Verrugas/etiologia
20.
BMJ Case Rep ; 20172017 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-29030367

RESUMO

Common variable immunodeficiency (CVID), characterised by disordered B cell function, is one of the most common primary immunodeficiency disorders. Patients with CVID are at lifelong risk of recurrent infections, particularly of the respiratory and gastrointestinal tracts. Paradoxically, given their immunocompromised state, patients with CVID are also at significantly increased risk of autoimmune disorders, which are seen in almost 25% of cases. The authors report a 24-year-old female patient with CVID, manifested as severe hypogammaglobulinaemia with recurrent sinopulmonary infections and enterocolitis, who presented with transaminitis, chronic diarrhoea and haematemesis. No infectious aetiologies were identified. She was diagnosed with coeliac disease after a small bowel biopsy and positive response to gluten-free diet. Haematemesis was attributed to portal hypertension due to liver cirrhosis, which was confirmed via liver biopsy. Coeliac disease can be a cause of diarrhoea in patients with immunodeficiency disorders and is often underdiagnosed. It can also be the underlying source of liver disease and is an often under-recognised cause of cirrhosis. The case presented emphasises the paradoxical and challenging relationship that patients with CVID face between immunodeficiency and autoimmune disorders, and also highlights that coeliac disease is an under-recognised cause of liver disease.


Assuntos
Agamaglobulinemia/diagnóstico , Doenças Autoimunes/diagnóstico , Doença Celíaca/diagnóstico , Imunodeficiência de Variável Comum/diagnóstico , Agamaglobulinemia/complicações , Doenças Autoimunes/complicações , Doença Celíaca/complicações , Doença Celíaca/dietoterapia , Imunodeficiência de Variável Comum/complicações , Diagnóstico Diferencial , Feminino , Humanos , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA