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INTRODUCTION: The time-dependent nature of factor VIII (FVIII) inhibitors is well described, and the standard FVIII Bethesda assay used to measure inhibitors incorporates a 2-hour incubation. Despite case reports and reviews describing the immediate-acting nature of factor IX (FIX) inhibitors, many coagulation laboratories continue to use a traditional prolonged incubation for FIX Bethesda assays. To our knowledge, a comprehensive evaluation of the FIX Bethesda assay without incubation has not been reported. AIM: The goal of this study was to evaluate the performance of a rapid FIX Bethesda (ie no incubation) compared with the standard Bethesda assay (2-hour incubation). METHODS: The analysis used a Bethesda assay configured for either immediate testing or a 2-hour incubation. Samples from 14 haemophilia B patients with inhibitors and 9 non-human controls were tested. RESULTS: The two assays yielded similar performance overall. The average per cent difference in inhibitor titre between the rapid and standard FIX Bethesda assay was -3% (range -15% to +13%; P = .175) for patient samples and -2% (range -17% to +14%; P = .376) for controls. CONCLUSION: The rapid Bethesda assay showed good agreement with the standard Bethesda assay for determination of inhibitor levels in patients with severe haemophilia B. The rapid assay allows for faster assessment of inhibitors in patients with severe haemophilia B and has the potential to improve the ability of the coagulation laboratory to perform testing from a logistical viewpoint. Further studies involving larger numbers of patients would be important to confirm our findings.
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Inhibidores de Factor de Coagulación Sanguínea/análisis , Pruebas de Coagulación Sanguínea/normas , Factor IX/antagonistas & inhibidores , Hemofilia B/sangre , Animales , Coagulación Sanguínea/fisiología , Pruebas de Coagulación Sanguínea/estadística & datos numéricos , Pruebas de Coagulación Sanguínea/tendencias , Factor IX/inmunología , Factor IX/metabolismo , Cabras/sangre , Hemofilia B/diagnóstico , Humanos , Indicadores y Reactivos/química , Masculino , Ratones/sangre , Modelos Animales , Estándares de Referencia , Índice de Severidad de la Enfermedad , Ovinos/sangreRESUMEN
BACKGROUND: In 6.5 years of newborn screening for severe combined immunodeficiency in California, 3,252,156 infants had DNA from dried blood spots (DBSs) assayed for T-cell receptor excision circles. Infants with T-cell receptor excision circle values of less than a designated cutoff on a single DBS, 2 DBS samples with insufficient PCR amplification, or known genetic risk of immunodeficiency had peripheral blood complete blood counts and lymphocyte subsets assayed in a single flow cytometry laboratory. Cases in which immune defects were ruled out were available for analysis. OBJECTIVE: We sought to determine reference intervals for lymphocyte subsets in racially/ethnically diverse preterm and term newborns who proved to be unaffected by any T-lymphopenic immune disorder. METHODS: Effective gestational age (GA) was defined as GA at birth plus postnatal age at the time of sample collection. After determining exclusion criteria, we analyzed demographic and clinical information, complete and differential white blood cell counts, and lymphocyte subsets for 301 infants, with serial measurements for 33 infants. Lymphocyte subset measurements included total T cells, helper and cytotoxic T-cell subsets, naive and memory phenotype of each T-cell subset, B cells, and natural killer cells. RESULTS: Reference intervals were generated for absolute numbers and lymphocyte subsets from infants with effective GAs of 22 to 52 weeks. Sex and ethnicity were not significant determinants of lymphocyte subset counts in this population. Lymphocyte counts increased postnatally. CONCLUSION: This study provides a baseline for interpreting comprehensive lymphocyte data in preterm and term infants, aiding clinicians to determine which newborns require further evaluations for immunodeficiency.
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Linfocitos B/metabolismo , Linfocitos T CD8-positivos/metabolismo , Recien Nacido Prematuro/sangre , Linfocitos T Colaboradores-Inductores/metabolismo , Linfocitos B/inmunología , Linfocitos B/patología , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/patología , Pruebas con Sangre Seca , Femenino , Edad Gestacional , Humanos , Recién Nacido , Recien Nacido Prematuro/inmunología , Recuento de Linfocitos , Masculino , Reacción en Cadena de la Polimerasa , Receptores de Antígenos de Linfocitos T/sangre , Receptores de Antígenos de Linfocitos T/inmunología , Linfocitos T Colaboradores-Inductores/inmunología , Linfocitos T Colaboradores-Inductores/patologíaRESUMEN
BACKGROUND: Viral infection is implicated in development of autoimmunity. Parvovirus B19 (B19V) nonstructural protein, NS1, a helicase, covalently modifies self double-stranded deoxyribonucleic acid (dsDNA) and induces apoptosis. This study tested whether resulting apoptotic bodies (ApoBods) containing virally modified dsDNA could induce autoimmunity in an animal model. METHODS: BALB/c mice were inoculated with (1) pristane-induced, (2) B19V NS1-induced, or (3) staurosporine-induced ApoBods. Serum was tested for dsDNA autoantibodies by Crithidia luciliae staining and enzyme-linked immunosorbent assay. Brain, heart, liver, and kidney pathology was examined. Deposition of self-antigens in glomeruli was examined by staining with antibodies to dsDNA, histones H1 and H4, and TATA-binding protein. RESULTS: The B19V NS1-induced ApoBod inoculation induced dsDNA autoantibodies in a dose-dependent fashion. Histopathological features of immune-mediated organ damage were evident in pristane-induced and NS1-induced ApoBod groups; severity scores were higher in these groups than in staurosporine-treated groups. Tissue damage was dependent on NS1-induced ApoBod dose. Nucleosomal antigens were deposited in target tissue from pristane-induced and NS1-induced ApoBod inoculated groups, but not in the staurosporine-induced ApoBod inoculated group. CONCLUSIONS: This study demonstrated proof of principle in an animal model that virally modified dsDNA in apoptotic bodies could break tolerance to self dsDNA and induce dsDNA autoantibodies and end-organ damage.
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Anticuerpos Antinucleares/sangre , ADN/inmunología , Vesículas Extracelulares/inmunología , Proteínas no Estructurales Virales/metabolismo , Animales , Anticuerpos Antinucleares/metabolismo , Apoptosis/efectos de los fármacos , Autoinmunidad , Encéfalo/patología , Inhibidores Enzimáticos/farmacología , Femenino , Glomerulonefritis/inmunología , Glomerulonefritis/patología , Inmunosupresores/farmacología , Glomérulos Renales/metabolismo , Glomérulos Renales/patología , Hígado/patología , Ratones , Miocardio/patología , Parvovirus B19 Humano , Estaurosporina/farmacología , Terpenos/farmacologíaRESUMEN
IMPORTANCE: Newborn screening for severe combined immunodeficiency (SCID) using assays to detect T-cell receptor excision circles (TRECs) began in Wisconsin in 2008, and SCID was added to the national recommended uniform panel for newborn screened disorders in 2010. Currently 23 states, the District of Columbia, and the Navajo Nation conduct population-wide newborn screening for SCID. The incidence of SCID is estimated at 1 in 100,000 births. OBJECTIVES: To present data from a spectrum of SCID newborn screening programs, establish population-based incidence for SCID and other conditions with T-cell lymphopenia, and document early institution of effective treatments. DESIGN: Epidemiological and retrospective observational study. SETTING: Representatives in states conducting SCID newborn screening were invited to submit their SCID screening algorithms, test performance data, and deidentified clinical and laboratory information regarding infants screened and cases with nonnormal results. Infants born from the start of each participating program from January 2008 through the most recent evaluable date prior to July 2013 were included. Representatives from 10 states plus the Navajo Area Indian Health Service contributed data from 3,030,083 newborns screened with a TREC test. MAIN OUTCOMES AND MEASURES: Infants with SCID and other diagnoses of T-cell lymphopenia were classified. Incidence and, where possible, etiologies were determined. Interventions and survival were tracked. RESULTS: Screening detected 52 cases of typical SCID, leaky SCID, and Omenn syndrome, affecting 1 in 58,000 infants (95% CI, 1/46,000-1/80,000). Survival of SCID-affected infants through their diagnosis and immune reconstitution was 87% (45/52), 92% (45/49) for infants who received transplantation, enzyme replacement, and/or gene therapy. Additional interventions for SCID and non-SCID T-cell lymphopenia included immunoglobulin infusions, preventive antibiotics, and avoidance of live vaccines. Variations in definitions and follow-up practices influenced the rates of detection of non-SCID T-cell lymphopenia. CONCLUSIONS AND RELEVANCE: Newborn screening in 11 programs in the United States identified SCID in 1 in 58,000 infants, with high survival. The usefulness of detection of non-SCID T-cell lymphopenias by the same screening remains to be determined.
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Linfopenia/diagnóstico , Tamizaje Neonatal/métodos , Inmunodeficiencia Combinada Grave/diagnóstico , Inmunodeficiencia Combinada Grave/epidemiología , Femenino , Humanos , Incidencia , Recién Nacido , Masculino , Pronóstico , Receptores de Antígenos de Linfocitos T/genética , Estudios Retrospectivos , Inmunodeficiencia Combinada Grave/terapia , Análisis de Supervivencia , Linfocitos T/inmunología , Estados UnidosRESUMEN
Availability of relevant biological samples supports both basic science research and patient-centered clinical studies. Establishing a biorepository faces challenges at multiple levels. These tasks include defining mission definition and scope; selection of subjects and sample types; recruitment strategies; timing of collection in the patient's journey; sample logistics and processing; determining what clinical data to collect; ensuring sample integrity on transport, processing, and storage; defining governance structures and oversight responsibilities; clarifying sample provenance and ownership; establishing procedures for sample and data access; selecting testing to be performed routinely versus upon request, and management of results; data security; funding sources; and regulatory compliance. Establishing and maintaining a biorepository therefore requires careful planning, diligent and sustained execution, technical and financial resources, stakeholder support, and flexible and resilient management to respond to changing environments and needs.
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Bancos de Muestras Biológicas , Manejo de Especímenes , Embarazo , Femenino , Humanos , Manejo de Especímenes/métodosRESUMEN
Lyme disease in pregnancy is understudied. The few available reports of Borrelia infection during pregnancy collecting clinical outcomes, with or without confirmed fetal infection both in utero and neonatal, are limited to case reports and small series. Population-based studies are not available. We propose a prospective study of Borrelia infection during pregnancy based in obstetrical practices in both endemic and nonendemic areas, with long term follow-up of pregnancy outcomes and development assessment of offspring infected or exposed to Borrelia in utero using current serological, microscopic, culture, and molecular techniques. In addition to detection of Borrelia burgdorferi sensu stricto, additional Borrelia species and other pathogens known to be transmitted by ticks will be tested. Serial biospecimens including maternal and cord blood, maternal peripheral blood mononuclear cells and urine, and, when clinically indicated, amniotic fluid, chorionic villi, intrauterine cord blood, will be collected with clinical data, imaging, and for infections treatment medications. Offspring will be followed until age 5 years with annual developmental assessments to assess pregnancy outcomes. The study will require parallel development of a biorepository with strategies for management, data security and data sharing. A public-private partnership will be required to support the study.
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Grupo Borrelia Burgdorferi , Borrelia burgdorferi , Enfermedad de Lyme , Garrapatas , Animales , Estudios Prospectivos , Leucocitos Mononucleares , Enfermedad de Lyme/diagnóstico , Enfermedad de Lyme/epidemiologíaRESUMEN
BACKGROUND: Neopterin, a pyrazino-[2,3-d]-pyrimidine compound, is a metabolite of cyclic guanosine monophosphate that is released by activated T lymphocytes and macrophages after induction by γ interferon. We sought to determine whether neopterin concentration in stool, serum, or urine is a useful marker of disease activity in patients with Crohn's disease or ulcerative colitis. METHODS: We prospectively studied 70 outpatients (33 M, 37 F, aged 39.2 ± 14.0 y) with Crohn's disease (33 clinically in remission, 37 active), 52 outpatients (29 M, 23 F, aged 39.8 ± 12.2 y) with ulcerative colitis (29 clinically in remission, 23 active), and 141 healthy control subjects. Fecal, serum, and urine samples were analyzed for neopterin concentration and other analytes of interest. The following clinical indices were calculated at enrollment: for Crohn's disease, the Capetown Index and Harvey Bradshaw Index; for ulcerative colitis, Simple Clinical Colitis Activity Index, Disease Activity Index, and endoscopic disease severity (rated on a scale of 0 to 3). Crohn's disease was considered active if the Harvey Bradshaw Index was ≥ 5, and ulcerative colitis was considered active if the Simple Clinical Colitis Activity Index was >3. RESULTS: Among Crohn's disease patients, fecal neopterin was higher in those with either clinically active (96.0 ng/g) or inactive (87.2 ng/g) disease than in control subjects (12.0 ng/g; P<0.05; inactive or active disease vs. controls). For ulcerative colitis patients, fecal neopterin concentration was higher in those with active (135.2 ng/g) disease than in those with inactive disease (62.7 ng/g; P<0.05) or healthy controls (12.0 ng/g; P<0.05). Neither serum nor urine neopterin concentrations were increased in patients with active inflammatory bowel disease. Nonsignificant trends toward greater fecal neopterin concentration were observed with increased colonic disease involvement, although not with endoscopic severity or clinical disease activity indices. CONCLUSIONS: Fecal neopterin concentration is increased in patients with clinically active or inactive Crohn's disease and in patients with clinically active ulcerative colitis when compared with controls, and therefore represents a new biomarker for disease activity.
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Colitis Ulcerosa/fisiopatología , Enfermedad de Crohn/fisiopatología , Neopterin/metabolismo , Adulto , Biomarcadores/metabolismo , Endoscopía , Heces/química , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Índice de Severidad de la EnfermedadRESUMEN
Parvovirus B19 is a widespread virus with diverse clinical presentations. The viral nonstructural protein, NS1, binds to and cleaves the viral genome, and induces apoptosis when transfected into nonpermissive cells, such as hepatocytes. We hypothesized that the cytotoxicity of NS1 in such cells results from chromosomal DNA damage caused by the DNA-nicking and DNA-attaching activities of NS1. Upon testing this hypothesis, we found that NS1 covalently binds to cellular DNA and is modified by PARP, an enzyme involved in repairing single-stranded DNA nicks. We furthermore discovered that the DNA nick repair pathway initiated by poly(ADPribose)polymerase and the DNA repair pathways initiated by ATM/ATR are necessary for efficient apoptosis resulting from NS1 expression.
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Apoptosis/fisiología , Daño del ADN , Parvovirus B19 Humano/fisiología , Proteínas no Estructurales Virales/fisiología , Western Blotting , Línea Celular , Reparación del ADN , Humanos , Inmunoprecipitación , Proteínas no Estructurales Virales/genéticaRESUMEN
BACKGROUND: Prompt diagnosis of juvenile idiopathic arthritis (JIA) is important to avoid long term complications. Elevated serum 14-3-3η levels improve the diagnostic sensitivity of rheumatoid factor (RF) and cyclic citrullinated peptide (CCP) antibody in adult rheumatoid arthritis (RA), and have been associated with more severe phenotype. We investigated the prevalence and clinical significance of serum 14-3-3η in different types of JIA. METHODS: JIA patients (n = 151) followed by the Pediatric Rheumatology Core at Children's Hospital of Los Angeles were categorized into 5 groups: polyarticular JIA RF+ (PJIA RF+; n = 39), PJIA RF- (n = 39), psoriatic arthritis (PsA; n = 19), enthesitis-related arthritis (ERA; n = 18), and oligoarticular JIA (OJIA [control group]; n = 36). RF, CCP antibody, and 14-3-3η were measured for all patients. 14-3-3η serum levels > 0.2 ng/mL were considered positive. Disease activity was assessed by the Juvenile Arthritis Disease Activity Score-71 (JADAS-71). RESULTS: Elevated 14-3-3η levels were detected in 34/151 (23%) patients, and across all groups tested. Most patients with 14-3-3η had titers ≥4 times above the cutoff value. The majority (22, 65%) of 14-3-3η-positive patients were also positive for RF or CCP antibodies, 16 (47%) were positive for all 3, and 12 (35%) were single-positive for 14-3-3η. The highest prevalence of 14-3-3η was in PJIA RF+ patients (49%), followed by OJIA (22%). Positivity for 14-3-3η was not significantly associated with disease activity or age at diagnosis. CONCLUSION: Serum 14-3-3η can be detected in all forms of JIA tested but appears to be most common in PJIA RF+. 14-3-3η does not appear to correlate with disease activity in JIA.
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Proteínas 14-3-3/sangre , Artritis Juvenil , Péptidos Cíclicos/inmunología , Factor Reumatoide/sangre , Artritis Juvenil/sangre , Artritis Juvenil/diagnóstico , Autoanticuerpos/sangre , Biomarcadores/sangre , Niño , Femenino , Humanos , Masculino , Gravedad del Paciente , Prevalencia , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad , Estados Unidos/epidemiologíaRESUMEN
The 14-3-3η (eta) protein was evaluated as a biomarker in a cohort of patients with juvenile idiopathic arthritis (JIA), as well as disease- and healthy-controls, to determine its potential clinical utility. In this case-control study, levels of 14-3-3η protein were evaluated in archival specimens from patients with JIA, systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA), as well as healthy pediatric controls. Just over 200 patients were evaluated, using specimens banked between 1990 and 2011. Comparisons were made to complete blood cell count (CBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) antibodies, and anti-nuclear antibody (ANA) positivity. 14-3-3η at levels 0.2 ng/mL or higher was considered positive. Fisher's exact tests, odds ratios, 95% confidence intervals, and p-values were reported. 14-3-3η positivity was seen in all included JIA subtypes. The rate of positivity was the highest in RF-positive (pos) polyarticular JIA. In the disease and healthy controls, lower rates of positivity were observed. The frequency of 14-3-3η positivity among RF-positive and RF-negative (neg) polyarticular JIA patients, especially at values ≥0.5 ng/mL (associated with poor outcomes in adults), was also highest. Several JIA patients with 14-3-3η positivity developed RF and anti-CCP positivity later in their disease. Significant levels of 14-3-3η can be found in approximately 30% of RF-pos and RF-neg patients with polyarticular JIA. This protein may represent a new biomarker for polyarticular JIA, particularly RF-neg polyarticular JIA.
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The annual meeting of the Association of Medical Laboratory Immunologists (AMLI) was convened virtually over the month of August. Prior to the emergence of the COVID-19 pandemic, AMLI's scientific committee had chosen the following topics as the focus of its 2020 meeting: Histocompatibility Testing and Transplant Immunology; Secondary Immunodeficiency and Immunotherapy Monitoring; ANA Update; and Emerging Infectious Diseases and New Algorithms for Testing. Given the central role of the discipline in the evaluation of the host response to infection, it was apt to add a separate session on antibody testing for SARS-CoV-2 infections to the original program. The current report provides an overview of the subjects discussed in the course of this meeting.
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Alergia e Inmunología , COVID-19/inmunología , Inmunoterapia/métodos , SARS-CoV-2/fisiología , Sociedades Médicas , Algoritmos , Animales , Procesos de Grupo , Prueba de Histocompatibilidad , Interacciones Huésped-Patógeno , Humanos , Laboratorios , Pandemias , SARS-CoV-2/química , Inmunología del Trasplante , Realidad VirtualRESUMEN
A clinical association between idiopathic liver disease and parvovirus B19 infection has been observed. Fulminant liver failure, not associated with other liver-tropic viruses, has been attributed to B19 in numerous reports, suggesting a possible role for B19 components in the extensive hepatocyte cytotoxicity observed in this condition. A recent report by Abe and colleagues (Int J Med Sci. 2007;4:105-9) demonstrated a link between persistent parvovirus B19 genotype I and III infection and fulminant liver failure. The genetic analysis of isolates obtained from these patients demonstrated a conservation of key amino acids in the nonstructural protein 1 (NS1) of the disease-associated genotypes. In this report we examine a conserved residue identified by Abe and colleagues and show that substitution of isoleucine 181 for methionine, as occurs in B19 genotype II, results in the reduction of B19 NS1-induced cytotoxicity of liver cells. Our results support the hypothesis that in the setting of persistent B19 infection, direct B19 NS1-induced cytotoxicity may play a role in idiopathic fulminant liver failure.
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Apoptosis/efectos de los fármacos , Parvovirus B19 Humano/genética , Parvovirus B19 Humano/metabolismo , Proteínas no Estructurales Virales/genética , Proteínas no Estructurales Virales/toxicidad , Sustitución de Aminoácidos , Citometría de Flujo , Genotipo , Células Hep G2 , Humanos , Relación Estructura-Actividad , Proteínas no Estructurales Virales/químicaRESUMEN
Human parvovirus B19 (B19) infection is often suspected as an etiologic agent in a variety of rheumatologic diseases. It has been hypothesized that this virus potentially induces immune dysregulation by abnormal cytokine expression in susceptible hosts. The objective of this study is to examine the relationship between anti-parvovirus B19 IgG antibody (B19 IgG) and two common markers of immune dysregulation-antinuclear antibody (ANA) and C-reactive protein (CRP) in clinical sera. Qualitative B19 IgG antibody and levels of high-sensitivity CRP were determined in adult serum samples submitted to a university hospital clinical laboratory for ANA testing. Prevalence of B19 IgG was compared among groups by ANA status and CRP tertile. B19 IgG was detected in 72.3% of 318 samples. Among women above the first quartile of age (>38 years), presence of B19 IgG was associated with CRP tertile rank (P = 0.008) and CRP levels > or =1 mg/L (P = 0.001) independent of age and ANA status. B19 IgG was less frequent in ANA-positive than ANA-negative women < or =38 years of age (P = 0.009). Viral antibody was not associated with either biomarker in men. These data suggest parvovirus B19 infection may be associated with chronic inflammation in some women after the third decade of life.
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Anticuerpos Antinucleares/sangre , Anticuerpos Antivirales/sangre , Proteína C-Reactiva/análisis , Infecciones por Parvoviridae/inmunología , Parvovirus B19 Humano/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Femenino , Humanos , Inmunoglobulina G/sangre , Masculino , Persona de Mediana Edad , Parvovirus B19 Humano/aislamiento & purificación , Factores Sexuales , Adulto JovenRESUMEN
Development of new diagnostic tests in a commercial laboratory for neurologic disorders is challenging. Development occurs in a highly regulated environment. Relevant research infrastructure may not be readily available in-house and may require outsourcing with additional management and costs. Clinically characterized specimens for validation of biomarkers for esoteric diseases may be difficult to acquire, and market size may be difficult to predict. More common diseases with heterogeneous subsets may require better clinical definition. Absence of guidelines may delay health provider acceptance of novel testing. Regulatory agency approval and categorization of tests affects validation requirements and impacts market acceptance and reimbursement.
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Técnicas de Laboratorio Clínico , Laboratorios , Enfermedades del Sistema Nervioso/diagnóstico , Biomarcadores/análisis , Técnicas de Laboratorio Clínico/métodos , Técnicas de Laboratorio Clínico/normas , Humanos , Laboratorios/economía , Laboratorios/organización & administración , Laboratorios/normas , Servicios Externos/economía , Servicios Externos/organización & administración , Servicios Externos/normas , Reproducibilidad de los ResultadosRESUMEN
OBJECTIVE: This study was conducted to determine the spectrum of laboratory practices in antinuclear antibody (ANA) test target, performance, and result reporting. METHODS: A questionnaire on ANA testing was distributed by the Diagnostic Immunology and Flow Cytometry Committee of the College of American Pathologists (CAP) to laboratories participating in the 2016 CAP ANA proficiency survey. RESULTS: Of 5847 survey kits distributed, 1206 (21%) responded. ANA screening method varied: 55% indirect immunofluorescence assay, 21% ELISA, 12% multibead immunoassay, and 18% other methods. The name of the test indicated the method used in only 32% of laboratories; only 39% stated the method used on the report. Of 644 laboratories, 80% used HEp-2 cell substrate, 18% HEp-2000 (HEp-2 cell line engineered to overexpress SSA antigen, Ro60), and 2% other. Slides were prepared manually (67%) or on an automated platform (33%) and examined by direct microscopy (84%) or images captured by an automated platform (16%). Only 50% reported a positive result at the customary 1:40 dilution. Titer was reported to endpoint routinely by 43%, only upon request by 23%, or never by 35%. Of the laboratories, 8% did not report dual patterns. Of those reporting multiple patterns, 23% did not report a titer with each pattern. CONCLUSION: ANA methodology and practice, and test naming and reporting varies significantly between laboratories. Lack of uniformity in testing and reporting practice and lack of transparency in communicating the testing method may misdirect clinicians in their management of patients.
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Anticuerpos Antinucleares , Patólogos , Ensayo de Inmunoadsorción Enzimática , Técnica del Anticuerpo Fluorescente Indirecta , Humanos , Encuestas y Cuestionarios , Estados UnidosRESUMEN
OBJECTIVES: Newborn screening for severe combined immunodeficiency (SCID) was instituted in California in 2010. In the ensuing 6.5 years, 3 252 156 infants in the state had DNA from dried blood spots assayed for T-cell receptor excision circles (TRECs). Abnormal TREC results were followed-up with liquid blood testing for T-cell abnormalities. We report the performance of the SCID screening program and the outcomes of infants who were identified. METHODS: Data that were reviewed and analyzed included demographics, nursery summaries, TREC and lymphocyte flow-cytometry values, and available follow-up, including clinical and genetic diagnoses, treatments, and outcomes. RESULTS: Infants with clinically significant T-cell lymphopenia (TCL) were successfully identified at a rate of 1 in 15 300 births. Of these, 50 cases of SCID, or 1 in 65 000 births (95% confidence interval 1 in 51 000-1 in 90 000) were found. Prompt treatment led to 94% survival. Infants with non-SCID TCL were also identified, diagnosed and managed, including 4 with complete DiGeorge syndrome who received thymus transplants. Although no cases of typical SCID are known to have been missed, 2 infants with delayed-onset leaky SCID had normal neonatal TREC screens but came to clinical attention at 7 and 23 months of age. CONCLUSIONS: Population-based TREC testing, although unable to detect immune defects in which T cells are present at birth, is effective for identifying SCID and clinically important TCL with high sensitivity and specificity. The experience in California supports the rapid, widespread adoption of SCID newborn screening.
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Pruebas con Sangre Seca/métodos , Linfopenia/sangre , Linfopenia/diagnóstico , Tamizaje Neonatal/métodos , Inmunodeficiencia Combinada Grave/sangre , Inmunodeficiencia Combinada Grave/diagnóstico , Linfocitos T/metabolismo , California/epidemiología , Femenino , Humanos , Recién Nacido , Linfopenia/epidemiología , Masculino , Inmunodeficiencia Combinada Grave/epidemiologíaRESUMEN
Accelerated identification of autoantibodies associated with previously idiopathic neurological disease has provided insights into disease mechanisms, enhanced understanding of neurological function, and opportunities for improved therapeutic interventions. The role of the laboratory in the expanding field of neuroimmunology is critical as specific autoantibody identification provides guidance to clinicians in diagnosis, prognosis, tumor search strategies, and therapeutic interventions. The number of specific autoantibodies identified continues to increase and newer testing strategies increase efficiencies in the laboratory and availability to clinicians. The need for broadly targeted efficient testing is underscored by the variability in clinical presentation and tumor associations attributable to a specific autoantibody, and conversely the various autoantibody specificities that can be the cause of a given clinical presentation. While many of the antineural antibodies were first recognized in the setting of neoplastic disease, idiopathic autoimmune neurological disease in the absence of underlying tumor is increasingly recognized. Appropriation of therapeutic modalities used to treat autoimmune disease to treat these autoantibody mediated neurological diseases has improved patient outcomes. Interaction between clinicians and laboratorians is critical to our understanding of these diseases and optimization of the clinical benefits of our increasing knowledge in neuroimmunology.
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Anticuerpos Antineoplásicos/inmunología , Autoanticuerpos/inmunología , Enfermedades Autoinmunes del Sistema Nervioso/diagnóstico , Enfermedades Autoinmunes del Sistema Nervioso/inmunología , Técnicas de Laboratorio Clínico/métodos , Neoplasias/diagnóstico , Neoplasias/inmunología , Enfermedades Autoinmunes del Sistema Nervioso/terapia , Técnicas de Laboratorio Clínico/tendencias , Humanos , Neoplasias/terapiaRESUMEN
CONTEXT: -Variability in testing for antineutrophil cytoplasmic antibodies (ANCAs) contributes to confusion and controversy related to testing for vasculitis and other ANCA-associated diseases. OBJECTIVES: -To survey laboratory testing practices regarding ANCA testing and to investigate differences in testing algorithms. DESIGN: -Supplemental questions were sent to the 333 laboratories participating in the College of American Pathologists proficiency testing program for ANCA as part of the Special Immunology S2 Survey. RESULTS: -A total of 315 laboratories submitted responses to the supplemental questions. Only 88 of 315 participants (28%) reported using a combination of indirect immunofluorescence (IFA) and enzyme immunoassay (EIA) techniques as recommended by current guidelines, with a few additional labs using IFA and multiplex bead assay as an acceptable alternative to EIA. Other labs reported using only IFA, EIA, or multiplex bead assays. CONCLUSIONS: -A wide variety of testing algorithms are in use for ANCA testing despite evidence to suggest that a combination of IFA and EIA testing provides the most comprehensive information. Laboratories should inform clinicians clearly about testing practices and utility of testing in specific disease states.