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BACKGROUND: Interest in the use of omalizumab to treat bullous pemphigoid (BP) in the event of resistance or contraindication to conventional therapies is currently based on limited evidence. OBJECTIVES: To assess the effectiveness and safety of omalizumab in BP and to identify predictive factors in response to treatment. METHODS: We conducted a French national multicentre retrospective study including patients with a confirmed diagnosis of BP treated with omalizumab after failure of one or several treatment lines. We excluded patients with clinically atypical BP, as per Vaillant's criteria. The criteria for clinical response to omalizumab were defined according to the 2012 international consensus conference. Anti-BP180-NC16A IgE enzyme-linked immunosorbent assay was performed on sera collected before initiating omalizumab, when available. RESULTS: Between 2014 and 2021, 100 patients treated in 18 expert departments were included. Median age at diagnosis was 77â years (range 20-98). Complete remission (CR) was achieved in 77% of patients, and partial remission in an additional 9%. CR was maintained 'off therapy' in 11.7%, 'on minimal therapy' in 57.1%, and 'on non-minimal therapy' in 31.2%. Median time to CR was 3â months (range 2.2-24.5). Relapse rate was 14%, with a median follow-up time of 12â months (range 6-73). Adverse events occurred in four patients. CR was more frequently observed in patients with an increased serum baseline level of anti-BP180-NC16A IgE (75% vs. 41%; P = 0.011). Conversely, urticarial lesions, blood total IgE concentration or eosinophil count were not predictive of CR. Patients with an omalizumab dosage > 300â mg every 4 weeks showed a similar final outcome to those with a dosage ≤ 300â mg every 4 weeks, but control of disease activity [median 10â days (range 5-30) vs. 15â days (range 10-60); P < 0.001] and CR [median 2.4â months (range 2.2-8.2) vs. 3.9â months (range 2.3-24.5); P < 0.001] were achieved significantly faster. CONCLUSIONS: We report the largest series to date of BP treated by omalizumab and confirm its effectiveness and safety in this indication. Serum baseline level of anti-BP180-NC16A IgE may predict response to treatment.
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Penfigoide Bolhoso , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Penfigoide Bolhoso/diagnóstico , Colágeno Tipo XVII , Omalizumab/uso terapêutico , Estudos Retrospectivos , Colágenos não Fibrilares , Autoantígenos , Imunoglobulina E , AutoanticorposRESUMO
Identification of the molecular culprits of allergic reactions leveraged molecular allergology applications in clinical laboratory medicine. Molecular allergology shifted the focus from complex, heterogeneous allergenic extracts, e.g. pollen, food, or insect venom, towards genetically and immunologically defined proteins available for in vitro diagnosis. Molecular allergology is a precision medicine approach for the diagnosis, stratification, therapeutic management, follow-up and prognostic evaluation of patients within a large range of allergic diseases. Exclusively available for in vitro diagnosis, molecular allergology is nonredundant with any of the current clinical tools for allergy investigation. As an example of a major application, discrimination of genuine sensitization from allergen cross-reactivity at the molecular level allows the proper targeting of the culprit allergen and thus dramatically improves patient management. This review aims at introducing clinical laboratory specialists to molecular allergology, from the biochemical and genetic bases, through immunological concepts, to daily use in the diagnosis and management of allergic diseases.
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INTRODUCTION: We described a case of alveolar hemorrhage (AH) after marijuana smoking using a water pipe made with plastic bottle (bong) before making a narrative review of the literature. CASE REPORT: A 19-year-old male was admitted for hemoptysis and dyspnea evolving since the previous day. He smoked marijuana ten times a day using bongs. Computed tomography scan of the chest (chest CT-scan) evidenced ground glass opacities involving upper lobes with crazy-paving pattern. Bronchoalveolar lavage (BAL) yielded fluid becoming progressively bloody suggestive of AH. Screening of drug metabolites ruled out the presence of cocaine degradation products. Treatment with prednisone was prescribed and oxygen requirements decreased rapidly. The patient accepted to stop bongs, but kept on smoking marijuana using joints. He was asymptomatic 2 months later; all ground glass opacities had vanished. REVIEW OF THE LITERATURE: Four cases described exactly the same circumstances as ours. All were young male patients containing ground glass opacities with diffuse or bilateral pattern in their chest CT-scan. The explanation suggested by the authors of these cases was the potential concomitant inhalation of acid anhydrides derived from use of heated plastic bottle. No acid anhydrides were experimentally evidenced after thermodesorption of heated polyethylene terephthalate (PET) (in which a majority of plastic bottles are made) we performed, but other compounds were. E-cigarette, or vaping, product use-associated lung injuries cases share some chest CT-scan patterns with those of AH following bong use and we tried to draw a parallel between these two latter before discussing a physiopathological hypothesis.
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Hemorragia/induzido quimicamente , Lesão Pulmonar/etiologia , Fumar Maconha/efeitos adversos , Plásticos/toxicidade , Cachimbos de Água , Humanos , Lesão Pulmonar/patologia , Masculino , Adulto JovemRESUMO
Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disease of the skin. Investigation of the BP-associated pathophysiological processes during the last decades showed that the generation of autoantibodies directed against the hemidesmosome proteins BP180 and BP230, a hallmark of the BP-associated autoimmune response, leads to the recruitment of inflammatory immune cells at the dermal-epidermal junction, and subsequently to the release of a large amount of inflammatory molecules involved in blister formation. Analysis in transversal and longitudinal studies of autoantibodies and inflammatory molecules production both at the time of diagnosis and under treatment was mainly performed within the serum but also in the blister fluid. Some autoimmune or inflammatory molecules expression was related to the presence of clinical signs, while others were mere bystanders. In this review, we focused on the autoimmune and inflammatory molecules that have been identified as potential biomarkers of BP development and outcome.
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Autoanticorpos/metabolismo , Biomarcadores/metabolismo , Penfigoide Bolhoso/imunologia , Animais , Humanos , Inflamação/metabolismo , Penfigoide Bolhoso/metabolismoRESUMO
PURPOSE OF REVIEW: The purpose of this narrative review was to summarize data and official recommendations purporting to paired tryptase determination in patients experiencing drug-induced anaphylaxis, published between January 1, 2023 and June 1, 2024. RECENT FINDINGS: Three main lines of evidence obtained through paired acute and baseline tryptase determination were identified: diagnostic criterion for hypersensitivity reactions involving systemic mast cell activation; differential diagnostic criterion for hypersensitivity reactions involving other mechanisms of immediate reactions; and added value of acute and baseline tryptase levels for personalized management following drug-induced anaphylaxis: cause, risk of recurrence, underlying mast cell conditions including hereditary α-tryptasemia, familial clusters. SUMMARY: The implementation of existing guidelines which consensually recommend paired tryptase measurement is a persistent unmet need hampering optimal diagnosis of drug-induced anaphylaxis and patient management. Another major unmet need is the lack of standardized recommendations for hereditary α-tryptasemia testing and counselling. Progress in this field is seen at a rapid pace, requiring significant efforts of continued medical education for practicing clinicians and laboratory specialists worldwide.
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HLA-B*15:648 differs from HLA-B*15:02:01:01 by one nucleotide substitution in codon 77 in exon 2.
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Genes MHC Classe I , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Alelos , Éxons/genética , Antígenos HLA-B/genéticaRESUMO
HLA-DQA1*04:14N differs from HLA-DQA1*04:01:01:03 by a single nucleotide deletion in codon 113 in exon 3.
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Alelos , Éxons , Cadeias alfa de HLA-DQ , Sequenciamento de Nucleotídeos em Larga Escala , Teste de Histocompatibilidade , Humanos , Cadeias alfa de HLA-DQ/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Teste de Histocompatibilidade/métodos , Códon , Sequência de Bases , Análise de Sequência de DNA/métodos , Deleção de SequênciaRESUMO
Viral detection in heart tissues has become a central issue for the diagnosis and exploration of the pathogenesis of idiopathic dilated cardiomyopathy (IDCM). In the present study, common cardiotropic viruses in 67 explanted heart samples of 31 IDCM adult patients were detected and semiquantified by using for the first time a new technology based on PCR assay coupled to electrospray ionization-time of flight mass spectrometry analysis (PCR-MS), with comparison to reference quantitative real-time PCR (RT-qPCR) assay. PCR-MS identified single or mixed enterovirus (EV) and parvovirus B19 (PVB19) infections in 27 (40.2%) of 67 samples, corresponding to 15 (48.3%) of the 31 patients, whereas RT-qPCR identified viral infections in 26 (38.8%) samples, corresponding to 16 (51.6%) of the patients. The PCR-MS results correlated well with EV and PVB19 detection by RT-qPCR (kappa = 0.85 [95% confidence interval {CI}, 0.72 to 1.00] and kappa = 0.82 [95% CI, 0.66 to 0.99], respectively). The levels of EV RNA (median, 550 [range, 178 to 3,200] copies/µg of total extracted nucleic acids) and of PVB19 DNA (median, 486 [range, 80 to 1,157] copies/µg of total extracted nucleic acids) were measured using PCR-MS and correlated with those obtained by RT-qPCR (r(2) = 0.57, P = 0.002 and r(2) = 0.64, P < 0.001 for EV and PVB19, respectively). No viruses other than EV and PVB19 strains were detected using the new PCR-MS technology, which is capable of simultaneously identifying 84 known human viruses in one assay. In conclusion, we identified single or mixed EV and PVB19 cardiac infections as potential causes of IDCM. The PCR-MS analysis appeared to be a valuable tool to rapidly detect and semiquantify common viruses in cardiac tissues and may be of major interest to better understand the role of viruses in unexplained cardiomyopathies.
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Cardiomiopatia Dilatada/complicações , Coinfecção/diagnóstico , Infecções por Enterovirus/diagnóstico , Infecções por Parvoviridae/diagnóstico , Reação em Cadeia da Polimerase/métodos , Espectrometria de Massas por Ionização por Electrospray/métodos , Carga Viral/métodos , Adulto , Idoso , Cardiomiopatia Dilatada/virologia , Coinfecção/virologia , Enterovirus/isolamento & purificação , Infecções por Enterovirus/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Parvoviridae/virologia , Parvovirus B19 Humano/isolamento & purificação , Fatores de Tempo , Adulto JovemRESUMO
Measles is a highly contagious viral infection causing congenital infections with a risk of neurological complications in the newborn. Two cases of measles, which occurred in pregnant women within 14 days before the delivery, are described. Mother-to-child transmission of the virus was documented in the newborns either by RT-PCR in saliva or by IgM detection in blood. The measles strains evidenced in saliva samples were genotyped and belonged to the D4 Genotype. An early viral RT-PCR detection allowed successful immunoglobulin prophylaxis in one newborn taking into account that the duration between the onset of the skin rash in the mother and the delivery was less than 6 days. Twenty-four months later, none of the newborns developed classical or neurological clinical signs of measles infection. Measles RT-PCR assay in salivary samples can be used before symptoms develop in the infant to confirm early mother-to-child transmission, therefore permitting the use of an immunoglobulin prophylaxis in the newborn.
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Transmissão Vertical de Doenças Infecciosas , Vírus do Sarampo/genética , Vírus do Sarampo/imunologia , Sarampo/diagnóstico , Sarampo/transmissão , Adulto , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Feminino , Genótipo , Humanos , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Recém-Nascido , Gravidez , Sorotipagem , Adulto JovemRESUMO
HLA-A*01:383 differs from HLA-A*01:01:01:01 by two nucleotide substitutions at positions 28 and 48 in exon 1.
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Sequenciamento de Nucleotídeos em Larga Escala , Nucleotídeos , Humanos , Alelos , Éxons/genética , Antígenos HLA-A/genéticaRESUMO
HLA-A*33:220 differs from HLA-A*33:03:01:01 by one nucleotide substitution in codon 245 in exon 4.
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HLA-C*16:184 differs from HLA-C*16:02:01:01 by one nucleotide substitution at position 737 in exon 3.
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Genes MHC Classe I , Antígenos HLA-C , Alelos , Éxons/genética , Antígenos HLA-C/genética , Sequenciamento de Nucleotídeos em Larga Escala , HumanosRESUMO
HLA-B*53:64 differs from HLA-B*53:01:01:01 by one nucleotide substitution at position 1617 in exon 4.
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Antígenos HLA-B , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Alelos , Antígenos HLA-B/genética , Éxons/genética , Genes MHC Classe IRESUMO
HLA-C*03:04:94 differs from HLA-C*03:04:01:01 by one nucleotide substitution at position 737 in exon 4.
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Antígenos HLA-C , Sequenciamento de Nucleotídeos em Larga Escala , Alelos , Éxons/genética , Genes MHC Classe I , Antígenos HLA-C/genética , HumanosRESUMO
HLA-C*07:1001N differs from HLA-C*07:01:01:01 by a deletion of 17 nucleotides in exon 1.
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Antígenos HLA-C , Sequenciamento de Nucleotídeos em Larga Escala , Alelos , Sequência de Bases , Antígenos HLA-C/genética , Teste de Histocompatibilidade , HumanosRESUMO
HLA-C*05:255 differs from HLA-C*05:01:01:02 by one nucleotide substitution at position 2013 in exon 5.
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Genes MHC Classe I , Antígenos HLA-C , Alelos , Éxons/genética , Antígenos HLA-C/genética , Sequenciamento de Nucleotídeos em Larga Escala , HumanosRESUMO
HLA-C*06:317 differs from HLA-C*06:02:01:01 by one nucleotide substitution at position 921 in exon 3.
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Genes MHC Classe I , Antígenos HLA-C , Alelos , Éxons/genética , Antígenos HLA-C/genética , Sequenciamento de Nucleotídeos em Larga Escala , HumanosRESUMO
Background: Patients with primary humoral immunodeficiency are more prone to invasive as well as recurrent pneumococcal infections. Therefore, anti-pneumococcal vaccination including the 13-valent conjugate vaccine is recommended. Nevertheless, to date, no data is available on immunogenicity of this vaccine in this population. Objective: To assess the immunogenicity and the persistence of protection up to one year after a 13-valent pneumococcal conjugate vaccine in patients with primary humoral immunodeficiency. Methods: Twenty-nine patients with common variable immunodeficiency or IgG subclass deficiency were vaccinated. Immune response and immune protection at baseline as well as at one, six and twelve months after vaccination were evaluated by measuring specific IgG serum concentrations (ELISA), and opsonophagocytic activities directed against selected pneumococcal (MOPA). Results: By ELISA, half of the patients had protective IgG concentrations before vaccination, 35.7% showed an immune response one month after vaccination, 71.4%, 66.7% and 56.0% of the patients were protected at one, six and twelve months respectively. Conversely, by MOPA, 3.4% of the patients were protected at baseline, 10.7% showed an immune response and 28.6%, 48.2% and 33.3% were protected at one, six and twelve months respectively. IgG subclass deficiency, Ig replacement therapy and higher IgG2 concentrations at diagnosis were associated with long-term protection. Conclusion: Pneumococcal conjugate vaccine improves immune protection and antibodies' functionality in a subset of patients with primary immunodeficiency. Prime-boost vaccine strategy needs to be better and individually adapted.
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Imunodeficiência de Variável Comum/imunologia , Imunodeficiência de Variável Comum/terapia , Deficiência de IgG/imunologia , Deficiência de IgG/terapia , Vacinas Pneumocócicas/uso terapêutico , Adulto , Idoso , Anticorpos Antibacterianos/sangue , Especificidade de Anticorpos , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/classificação , Masculino , Pessoa de Meia-Idade , Fagocitose/imunologia , Infecções Pneumocócicas/imunologia , Infecções Pneumocócicas/prevenção & controle , Sorogrupo , Streptococcus pneumoniae/classificação , Streptococcus pneumoniae/imunologia , Fatores de Tempo , Vacinas Conjugadas/uso terapêutico , Adulto JovemRESUMO
Despite the well-demonstrated efficacy of infliximab in inflammatory diseases, treatment failure remains frequent. Dose adjustment using Bayesian methods has shown in silico its interest in achieving target plasma concentrations. However, most of the published models have not been fully validated in accordance with the recommendations. This study aimed to submit these models to an external evaluation and verify their predictive capabilities. Eight models were selected for external evaluation, carried out on an independent database (409 concentrations from 157 patients). Each model was evaluated based on the following parameters: goodness-of-fit (comparison of predictions to observations), residual error model (population weighted residuals (PWRES), individual weighted residuals (IWRES), and normalized prediction distribution errors (NPDE)), and predictive performances (prediction-corrected visual predictive checks (pcVPC) and Bayesian simulations). The performances observed during this external evaluation varied greatly from one model to another. The eight evaluated models showed a significant bias in population predictions (from -7.19 to 7.38 mg/L). Individual predictions showed acceptable bias and precision for six of the eight models (mean error of -0.74 to -0.29 mg/L and mean percent error of -16.6 to -0.4%). Analysis of NPDE and pcVPC confirmed these results and revealed a problem with the inclusion of several covariates (weight, concomitant immunomodulatory treatment, presence of anti-drug antibodies). This external evaluation showed satisfactory results for some models, notably models A and B, and highlighted several prospects for improving the pharmacokinetic models of infliximab for clinical-biological application.