RESUMEN
The recombination-activating genes (RAG) 1 and 2 are indispensable for diversifying the primary B cell receptor repertoire and pruning self-reactive clones via receptor editing in the bone marrow; however, the impact of RAG1/RAG2 on peripheral tolerance is unknown. Partial RAG deficiency (pRD) manifesting with late-onset immune dysregulation represents an 'experiment of nature' to explore this conundrum. By studying B cell development and subset-specific repertoires in pRD, we demonstrate that reduced RAG activity impinges on peripheral tolerance through the generation of a restricted primary B cell repertoire, persistent antigenic stimulation and an inflammatory milieu with elevated B cell-activating factor. This unique environment gradually provokes profound B cell dysregulation with widespread activation, remarkable extrafollicular maturation and persistence, expansion and somatic diversification of self-reactive clones. Through the model of pRD, we reveal a RAG-dependent 'domino effect' that impacts stringency of tolerance and B cell fate in the periphery.
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Linfocitos B , Proteínas de Unión al ADN , Proteínas de Homeodominio , Proteínas Nucleares , Diferenciación Celular , Proteínas de Unión al ADN/deficiencia , Proteínas de Unión al ADN/genética , Proteínas de Homeodominio/genética , Humanos , Tolerancia Inmunológica , Recuento de Linfocitos , Proteínas Nucleares/deficienciaRESUMEN
Leukocyte adhesion deficiency type II (LAD II, also known as SLC35C1-congenital disorder of glycosylation) is an autosomal recessive disorder characterized by growth and cognitive impairment, peripheral neutrophilia, recurrent infections, and the Bombay blood phenotype. A subset of patients with a milder presentation has been described with short stature and developmental delay but minimal immune and hematologic features. Some patients with LAD II benefit from oral fucose therapy, though this has not been previously studied in patients with milder disease. In this study, we describe two new patients from separate families with the milder variant of LAD II and review the published literature on this rare disorder. We demonstrate improvement in speech and cognition, CD15 expression, and core fucosylation of serum glycoproteins after 27 months of oral fucose supplementation in one patient. These patients further support the stratification of this disorder into distinct subtypes, a classical severe and an attenuated variant, and provide preliminary evidence of benefit of fucose therapy in the latter group.
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Fucosa , Síndrome de Deficiencia de Adhesión del Leucocito , Trastornos Congénitos de Glicosilación , Fucosa/metabolismo , Glicosilación , Humanos , Síndrome de Deficiencia de Adhesión del Leucocito/tratamiento farmacológico , Síndrome de Deficiencia de Adhesión del Leucocito/genética , Leucocitos/metabolismo , Proteínas de Transporte de Monosacáridos/genéticaRESUMEN
Genetic testing has become an integral component of the diagnostic evaluation of patients with suspected primary immunodeficiency diseases. Results of genetic testing can have a profound effect on clinical management decisions. Therefore clinical providers must demonstrate proficiency in interpreting genetic data. Because of the need for increased knowledge regarding this practice, the American Academy of Allergy, Asthma & Immunology Primary Immunodeficiency Diseases Committee established a work group that reviewed and summarized information concerning appropriate methods, tools, and resources for evaluating variants identified by genetic testing. Strengths and limitations of tests frequently ordered by clinicians were examined. Summary statements and tables were then developed to guide the interpretation process. Finally, the need for research and collaboration was emphasized. Greater understanding of these important concepts will improve the diagnosis and management of patients with suspected primary immunodeficiency diseases.
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Pruebas Genéticas , Enfermedades de Inmunodeficiencia Primaria , Asma , Humanos , Enfermedades de Inmunodeficiencia Primaria/diagnóstico , Enfermedades de Inmunodeficiencia Primaria/genética , Enfermedades de Inmunodeficiencia Primaria/terapia , Estados UnidosAsunto(s)
Proteínas de Unión al ADN/genética , Enfermedades de Inmunodeficiencia Primaria/genética , Factores de Transcripción/genética , Adulto , Animales , Linfocitos B/inmunología , Recuento de Células Sanguíneas , Células HEK293 , Humanos , Masculino , Ratones Endogámicos C57BL , Enfermedades de Inmunodeficiencia Primaria/sangre , Secuenciación del ExomaRESUMEN
Common variable immunodeficiency (CVID) is a heterogeneous disorder characterized by antibody deficiency, poor humoral response to antigens, and recurrent infections. To investigate the molecular cause of CVID, we carried out exome sequence analysis of a family diagnosed with CVID and identified a heterozygous frameshift mutation, c.2564delA (p.Lys855Serfs(∗)7), in NFKB2 affecting the C terminus of NF-κB2 (also known as p100/p52 or p100/p49). Subsequent screening of NFKB2 in 33 unrelated CVID-affected individuals uncovered a second heterozygous nonsense mutation, c.2557C>T (p.Arg853(∗)), in one simplex case. Affected individuals in both families presented with an unusual combination of childhood-onset hypogammaglobulinemia with recurrent infections, autoimmune features, and adrenal insufficiency. NF-κB2 is the principal protein involved in the noncanonical NF-κB pathway, is evolutionarily conserved, and functions in peripheral lymphoid organ development, B cell development, and antibody production. In addition, Nfkb2 mouse models demonstrate a CVID-like phenotype with hypogammaglobulinemia and poor humoral response to antigens. Immunoblot analysis and immunofluorescence microscopy of transformed B cells from affected individuals show that the NFKB2 mutations affect phosphorylation and proteasomal processing of p100 and, ultimately, p52 nuclear translocation. These findings describe germline mutations in NFKB2 and establish the noncanonical NF-κB signaling pathway as a genetic etiology for this primary immunodeficiency syndrome.
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Inmunodeficiencia Variable Común/genética , Mutación de Línea Germinal , Subunidad p52 de NF-kappa B/genética , Transducción de Señal , Adolescente , Adulto , Secuencia de Aminoácidos , Animales , Linfocitos B/citología , Linfocitos B/metabolismo , Línea Celular , Niño , Inmunodeficiencia Variable Común/patología , Modelos Animales de Enfermedad , Femenino , Pruebas Genéticas , Heterocigoto , Humanos , Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Masculino , Microscopía Confocal , Datos de Secuencia Molecular , Subunidad p52 de NF-kappa B/metabolismo , Linaje , Fenotipo , Adulto JovenRESUMEN
The mouse MHC class Ib gene H2-T11 is 95% identical at the DNA level to H2-T23, which encodes Qa-1, one of the most studied MHC class Ib molecules. H2-T11 mRNA was observed to be expressed widely in tissues of C57BL/6 mice, with the highest levels in thymus. To circumvent the availability of a specific mAb, cells were transduced with cDNA encoding T11 with a substituted α3 domain. Hybrid T11D3 protein was expressed at high levels similar to control T23D3 molecules on the surface of both TAP(+) and TAP(-) cells. Soluble T11D3 was generated by folding in vitro with Qa-1 determinant modifier, the dominant peptide presented by Qa-1. The circular dichroism spectrum of this protein was similar to that of other MHC class I molecules, and it was observed to bind labeled Qa-1 determinant modifier peptide with rapid kinetics. By contrast to the Qa-1 control, T11 tetramers did not react with cells expressing CD94/NKG2A, supporting the conclusion that T11 cannot replace Qa-1 as a ligand for NK cell inhibitory receptors. T11 also failed to substitute for Qa-1 in the presentation of insulin to a Qa-1-restricted T cell hybridoma. Despite divergent function, T11 was observed to share peptide-loading specificity with Qa-1. Direct analysis by tandem mass spectrometry of peptides eluted from T11D3 and T23D3 isolated from Hela cells demonstrated a diversity of peptides with a clear motif that was shared between the two molecules. Thus, T11 is a paralog of T23 encoding an MHC class Ib molecule that shares peptide-binding specificity with Qa-1 but differs in function.
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Regulación de la Expresión Génica/inmunología , Antígenos H-2/genética , Antígenos de Histocompatibilidad Clase I/genética , Péptidos/metabolismo , Animales , Línea Celular , Epítopos/inmunología , Antígenos H-2/metabolismo , Células HeLa , Antígenos de Histocompatibilidad Clase I/metabolismo , Humanos , Ratones , Ratones de la Cepa 129 , Ratones Endogámicos A , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Noqueados , Péptidos/genética , Unión Proteica/genética , Unión Proteica/inmunologíaRESUMEN
PURPOSE: Combined immunodeficiency (CID) presents a unique challenge to clinicians. Two patients presented with the prior clinical diagnosis of common variable immunodeficiency (CVID) disorder marked by an early age of presentation, opportunistic infections, and persistent lymphopenia. Due to the presence of atypical clinical features, next generation sequencing was applied documenting RAG deficiency in both patients. METHODS: Two different genetic analysis techniques were applied in these patients including whole exome sequencing in one patient and the use of a gene panel designed to target genes known to cause primary immunodeficiency disorders (PIDD) in a second patient. Sanger dideoxy sequencing was used to confirm RAG1 mutations in both patients. RESULTS: Two young adults with a history of recurrent bacterial sinopulmonary infections, viral infections, and autoimmune disease as well as progressive hypogammaglobulinemia, abnormal antibody responses, lymphopenia and a prior diagnosis of CVID disorder were evaluated. Compound heterozygous mutations in RAG1 (1) c256_257delAA, p86VfsX32 and (2) c1835A>G, pH612R were documented in one patient. Compound heterozygous mutations in RAG1 (1) c.1566G>T, p.W522C and (2) c.2689C>T, p. R897X) were documented in a second patient post-mortem following a fatal opportunistic infection. CONCLUSION: Astute clinical judgment in the evaluation of patients with PIDD is necessary. Atypical clinical findings such as early onset, granulomatous disease, or opportunistic infections should support the consideration of atypical forms of late onset CID secondary to RAG deficiency. Next generation sequencing approaches provide powerful tools in the investigation of these patients and may expedite definitive treatments.
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Inmunodeficiencia Variable Común/genética , Proteínas de Homeodominio/genética , Mutación , Agammaglobulinemia/diagnóstico , Agammaglobulinemia/etiología , Biopsia , Preescolar , Inmunodeficiencia Variable Común/complicaciones , Inmunodeficiencia Variable Común/diagnóstico , Análisis Mutacional de ADN , Resultado Fatal , Femenino , Humanos , Inmunohistoquímica , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/etiología , Linfopenia/diagnóstico , Linfopenia/etiología , Tomografía Computarizada por Rayos X , Adulto JovenRESUMEN
Three related males presented with a newly recognized x-linked syndrome associated with neurodegeneration, cutaneous abnormalities, and systemic iron overload. Linkage studies demonstrated that they shared a haplotype on Xp21.3-Xp22.2 and exome sequencing was used to identify candidate variants. Of the segregating variants, only a PIGA mutation segregated with disease in the family. The c.328_330delCCT PIGA variant predicts, p.Leu110del (or c.1030_1032delCTT, p.Leu344del depending on the reference sequence). The unaffected great-grandfather shared his X allele with the proband but he did not have the PIGA mutation, indicating that the mutation arose de novo in his daughter. A single family with a germline PIGA mutation has been reported; affected males had a phenotype characterized by multiple congenital anomalies and severe neurologic impairment resulting in infantile lethality. In contrast, affected boys in the family described here were born without anomalies and were neurologically normal prior to onset of seizures after 6 months of age, with two surviving to the second decade. PIGA encodes an enzyme in the GPI anchor biosynthesis pathway. An affected individual in the family studied here was deficient in GPI anchor proteins on granulocytes but not erythrocytes. In conclusion, the PIGA mutation in this family likely causes a reduction in GPI anchor protein cell surface expression in various cell types, resulting in the observed pleiotropic phenotype involving central nervous system, skin, and iron metabolism.
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Enfermedades Genéticas Ligadas al Cromosoma X/genética , Mutación de Línea Germinal , Trastornos Heredodegenerativos del Sistema Nervioso/genética , Sobrecarga de Hierro/genética , Proteínas de la Membrana/genética , Espasmos Infantiles/genética , Secuencia de Aminoácidos , Sustitución de Aminoácidos , Autopsia , Secuencia de Bases , Biopsia , Encéfalo/patología , Encéfalo/ultraestructura , Análisis Mutacional de ADN , Facies , Resultado Fatal , Genes Ligados a X , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Trastornos Heredodegenerativos del Sistema Nervioso/diagnóstico , Humanos , Lactante , Sobrecarga de Hierro/diagnóstico , Riñón/patología , Hígado/patología , Linfocitos/ultraestructura , Imagen por Resonancia Magnética , Masculino , Proteínas de la Membrana/química , Datos de Secuencia Molecular , Linaje , Alineación de Secuencia , Piel/patología , Espasmos Infantiles/diagnóstico , Bazo/patología , SíndromeRESUMEN
BACKGROUND: The role of T-helper 17 cells (Th17) in neonatal host defense remains to be fully elucidated. Interleukin (IL)-17 plays an important role in the immune response to bacterial and fungal pathogens by promoting inflammation. METHODS: We examined neonatal production of IL-17 in mixed mononuclear cells (MMCs) isolated from umbilical cord blood for comparison with adult peripheral blood mononuclear cell controls. RESULTS: IL-17 production was profoundly diminished in MMCs isolated from cord blood when compared with MMCs from adult blood. This was associated with a marked reduction in the population of CCR6+ IL-17(+) T-cells in the neonatal cord blood. We also found diminished intracellular formation of IL-17, and diminished IL-17 responses to both group B streptococci (GBS) and Escherichia coli. Neonatal mononuclear cells were found to adequately phosphorylate signal transducer and activator of transcription 3, pY705, and pS727. We and others have reported markedly reduced interferon-γ production by neonate mononuclear cells exposed to GBS. Here, we correct that profound abnormality with added IL-17. CONCLUSION: Our results suggest that profound deficiency of IL-17 production associated with a marked decrease in Th17 cells likely contributes significantly to the increased susceptibility of human neonates to invasive bacterial and fungal infections.
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Sangre Fetal/metabolismo , Interleucina-17/metabolismo , Células Th17/metabolismo , Adulto , Recuento de Linfocito CD4 , Células Cultivadas , Regulación hacia Abajo , Escherichia coli/inmunología , Escherichia coli/patogenicidad , Sangre Fetal/citología , Sangre Fetal/inmunología , Interacciones Huésped-Patógeno , Humanos , Recién Nacido , Interferón gamma/metabolismo , Fosforilación , Receptores CCR6/metabolismo , Factor de Transcripción STAT3/metabolismo , Streptococcus/inmunología , Streptococcus/patogenicidad , Células Th17/inmunología , Células Th17/microbiologíaRESUMEN
This study aimed to evaluate and compare the performance of three anti-S and one anti-N assays that were available to the project in detecting antibody levels after three commonly used SARS-CoV-2 vaccines (Pfizer, Moderna, and Johnson & Johnson). It also aimed to assess the association of age, sex, race, ethnicity, vaccine timing, and vaccine side effects on antibody levels in a cohort of 827 individuals. In September 2021, 698 vaccinated individuals donated blood samples as part of the Association for Diagnostics & Laboratory Medicine (ADLM) COVID-19 Immunity Study. These individuals also participated in a comprehensive survey covering demographic information, vaccination status, and associated side effects. Additionally, 305 age- and gender-matched samples were obtained from the ADLM 2015 sample bank as pre-COVID-19-negative samples. All these samples underwent antibody level analysis using three anti-S assays, namely Beckman Access SARS-CoV-2 IgG (Beckman assay), Ortho Clinical Diagnostics VITROS Anti-SARS-CoV-2 IgG (Ortho assay), Siemens ADVIA Centaur SARS-CoV-2 IgG (Siemens assay), and one anti-N antibody assay: Bio-Rad Platelia SARS-CoV-2 Total Ab assay (BioRad assay). A total of 827 samples (580 COVID-19 samples and 247 pre-COVID-19 samples) received results for all four assays and underwent further analysis. Beckman, Ortho, and Siemens anti-S assays showed an overall sensitivity of 99.5%, 97.6%, and 96.9%, and specificity of 90%, 100%, and 99.6%, respectively. All three assays indicated 100% sensitivity for individuals who received the Moderna vaccine and boosters, and over 99% sensitivity for the Pfizer vaccine. Sensitivities varied from 70.4% (Siemens), 81.5% (Ortho), and 96.3% (Beckman) for individuals who received the Johnson & Johnson vaccine. BioRad anti-N assays demonstrated 46.2% sensitivity and 99.25% specificity based on results from individuals with self-reported infection. The highest median anti-S antibody levels were measured in individuals who received the Moderna vaccine, followed by Pfizer and then Johnson & Johnson vaccines. Higher anti-S antibody levels were significantly associated with younger age and closer proximity to the last vaccine dose but were not associated with gender, race, or ethnicity. Participants with higher anti-S levels experienced significantly more side effects as well as more severe side effects (e.g., muscle pain, chills, fever, and moderate limitations) (p < 0.05). Anti-N antibody levels only indicated a significant correlation with headache. This study indicated performance variations among different anti-S assays, both among themselves and when analyzing individuals with different SARS-CoV-2 vaccines. Caution should be exercised when conducting large-scale studies to ensure that the same platform and/or assays are used for the most effective interpretation of the data.
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COVID-19 , Vacunas , Humanos , SARS-CoV-2 , Vacunas contra la COVID-19 , COVID-19/diagnóstico , COVID-19/prevención & control , Anticuerpos Antivirales , Inmunoglobulina G , InmunoensayoRESUMEN
In 2021, the Association for Diagnostics & Laboratory Medicine (ADLM) (formerly the American Association for Clinical Chemistry [AACC]) developed a scientific study that aimed to contribute to the understanding of SARS-CoV-2 immunity during the evolving course of the pandemic. This study was led by a group of expert member volunteers and resulted in survey data from 975 individuals and blood collection from 698 of those participants. This paper describes the formulation and execution of this large-scale scientific study, encompassing best practices and insights gained throughout the endeavor.
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COVID-19 , Humanos , Pandemias , SARS-CoV-2 , Química Clínica , SociedadesAsunto(s)
Inmunodeficiencia Variable Común/genética , Hemoglobina Fetal/genética , Heterocigoto , Factor de Transcripción Ikaros/genética , Mutación Missense , Adulto , Niño , Preescolar , Inmunodeficiencia Variable Común/sangre , Familia , Femenino , Silenciador del Gen/fisiología , Humanos , Masculino , LinajeAsunto(s)
Proteínas de Unión al ADN/genética , Bases de Datos de Ácidos Nucleicos , Exoma , Proteínas de Homeodominio/genética , Mutación , Proteínas Nucleares/genética , Inmunodeficiencia Combinada Grave/genética , Proteínas de Unión al ADN/inmunología , Femenino , Proteínas de Homeodominio/inmunología , Humanos , Incidencia , Lactante , Proteínas Nucleares/inmunología , Inmunodeficiencia Combinada Grave/epidemiología , Inmunodeficiencia Combinada Grave/inmunologíaRESUMEN
Primary immunodeficiencies were initially identified on the basis of recurrent, severe or unusual infections. Subsequently, it was noted that these diseases can also manifest with autoimmunity, autoinflammation, allergy, lymphoproliferation and malignancy, hence a conceptual change and their renaming as inborn errors of immunity. Ongoing advances in flow cytometry provide the opportunity to expand or modify the utility and scope of existing laboratory tests in this field to mirror this conceptual change. Here we have used the B cell subset, variably known as CD21low B cells, age-associated B cells and T-bet+ B cells, as an example to demonstrate this possibility.
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Subgrupos de Linfocitos B , Enfermedades del Sistema Inmune , Síndromes de Inmunodeficiencia , Humanos , Enfermedades del Sistema Inmune/diagnóstico , Síndromes de Inmunodeficiencia/diagnóstico , Linfocitos B , Citometría de FlujoRESUMEN
OBJECTIVES: The objective of this prospective study was to investigate the role of adaptive immunity in response to SARS-CoV-2 vaccines. DESIGN AND METHODS: A cohort of 677 vaccinated individuals participated in a comprehensive survey of their vaccination status and associated side effects, and donated blood to evaluate their adaptive immune responses by neutralizing antibody (NAb) and T cell responses. The cohort then completed a follow-up survey to investigate the occurrence of breakthrough infections. RESULTS: NAb levels were the highest in participants vaccinated with Moderna, followed by Pfizer and Johnson & Johnson. NAb levels decreased with time after vaccination with Pfizer and Johnson & Johnson. T cell responses showed no significant difference among the different vaccines and remained stable up to 10 months after the study period for all vaccine types. In multivariate analyses, NAb responses (<95 U/mL) predicted breakthrough infection, whereas previous infection, the type of vaccine, and T cell responses did not. T cell responses to viral epitopes (<0.120 IU/mL) showed a significant association with the self-reported severity of COVID-19 disease. CONCLUSION: This study provides evidence that NAb responses to SARS-CoV-2 vaccination correlate with protection against infection, whereas the T cell memory responses may contribute to protection against severe disease but not against infection.
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Vacunas contra la COVID-19 , COVID-19 , Humanos , COVID-19/prevención & control , SARS-CoV-2 , Autoinforme , Infección Irruptiva , Estudios Prospectivos , Gravedad del Paciente , Anticuerpos Neutralizantes , Vacunación , Anticuerpos AntiviralesRESUMEN
B cells are one of the fundamental components of the adaptive immune system and are best known for their ability to produce antibodies. Among the various types of inborn errors of immunity, antibody deficiencies represent the largest group in terms of the number of affected individuals. Not all antibody deficiencies are due to B cell intrinsic defects but investigating B cell number and function are a critical part of the diagnostic process. B cells studies in clinical practice almost always rely on flow cytometry as the main tool of investigation. The advantage of flow cytometry is that it allows absolute and relative counting of B cells, and their phenotypic and functional evaluation at a single-cell level, while allowing the analysis of a large number of cells. Although versatile and broad in its utility, clinical flow cytometry has both theoretical and practical limitations. These include lack of consensus about definitions and classifications, and the use of non-standardized methods. Patients in all age groups, from newborns to the elderly, may require testing, yet B cells show significant changes in both numbers and subset distribution over the lifespan, requiring distinct reference ranges for narrowly defined age brackets for accurate interpretation. Sampling for testing is usually restricted to peripheral blood samples, and the number of markers routinely used are limited. This paper will provide a brief overview of flow cytometry and B cell biology, describe the human peripheral B cell subsets most commonly identified in clinical flow cytometry and discuss their clinical relevance in different settings.
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Subgrupos de Linfocitos B , Síndromes de Inmunodeficiencia , Anciano , Linfocitos B , Citometría de Flujo/métodos , Humanos , Síndromes de Inmunodeficiencia/diagnóstico , Recién Nacido , Recuento de LinfocitosRESUMEN
The past quarter of a century has witnessed an inordinate increase in our understanding of primary immunodeficiencies / inborn errors of immunity. These include a significant increase in the number of identified conditions, broadening the phenotypes of existing entities, delineation of classical inborn errors of immunity from those with a narrow phenotype, and a gradual shift from supportive to definitive care in patients afflicted with these diseases. It has also seen the discovery of conditions broadly defined as phenocopies of primary immunodeficiencies, where somatic mutations or autoantibodies mimic a recognised primary immunodeficiency's presentation in the absence of the underlying genetic basis for that disease. This article will provide a review of the anti-cytokine autoantibody-mediated phenocopies of inborn errors of immunity and discuss the therapeutic and laboratory aspects of this group of diseases.
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Autoanticuerpos , Citocinas , FenotipoRESUMEN
Importance: Most healthcare institutions require employees to be vaccinated against SARS-CoV-2 and many also require at least one booster. Objective: We determine the impact of vaccine type, demographics, and health conditions on COVID-19 vaccine side effects in healthcare professionals. Design: A COVID-19 immunity study was performed at the 2021 American Association for Clinical Chemistry Annual Scientific meeting. As part of this study, a REDCap survey with cascading questions was administered from September 9, 2021 to October 20, 2021. General questions included participant demographics, past and present health conditions, smoking, exercise, and medications. COVID-19 specific questions asked about SARS-CoV-2 vaccine status and type, vaccine-associated side effects after each dose including any boosters, previous infection with COVID-19, diagnostic testing performed, and type and severity symptoms of COVID-19. Results: There were 975 participants (47.1% male, median age of 50 years) who completed the survey. Pfizer was the most commonly administered vaccine (56.4%) followed by Moderna (32.0%) and Johnson & Johnson (7.1%). There were no significant differences in vaccine type received by age, health conditions, smoking, exercise, or type or number of prescription medications. Side effects were reported more frequently after second dose (e.g., Moderna or Pfizer) (54.1%) or single/only dose of Johnson & Johnson (47.8%). Males were significantly more likely to report no side effects (p < 0.001), while females were significantly more likely to report injection site reactions (p < 0.001), fatigue (p < 0.001), headache (p < 0.001), muscle pain (p < 0.001), chills (p = 0.001), fever (p = 0.007), and nausea (p < 0.001). There was a significant upward trend in participants reporting no side effects with increasing age (p < 0.001). There were no significant trends in side effects among different races, ethnicities, health conditions, medications, smoking status or exercise. In multivariate logistic regressions analyses, the second dose of Moderna was associated with a significantly higher risk of side effects than both the second dose of Pfizer and the single dose of Johnson & Johnson. Conclusions and relevance: Younger people, females, and those receiving the second dose of Moderna had more COVID-19 vaccine side effects that per self-report led to moderate to severe limitations. As reported in other studies, the increase in side effects from Moderna may be explained by higher viral mRNA concentrations but be associated with additional protective immunity.
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Vacunas contra la COVID-19 , COVID-19 , Femenino , Humanos , Masculino , Persona de Mediana Edad , COVID-19/epidemiología , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Atención a la Salud , SARS-CoV-2 , VacunasRESUMEN
Knowledge related to the biology of inborn errors of immunity and associated laboratory testing methods continues to expand at a tremendous rate. Despite this, many patients with inborn errors of immunity suffer for prolonged periods of time before identification of their underlying condition, thereby delaying appropriate care. Understanding that test selection and optimal evaluation for patients with recurrent infections or unusual patterns of inflammation can be unclear, we present a document that distills relevant clinical features of immunologic disease due to inborn errors of immunity and related appropriate and available test options. This document is intended to serve the practicing clinical immunologist and, in turn, patients by describing best available test options for initial and expanded immunologic evaluations across the disease spectrum. Our goal is to demystify the process of evaluating patients with suspected immune dysfunction and to enable more rapid and accurate diagnosis of such individuals.