Publications by authors named "Melissa Snyder"

Objective: To evaluate whether children with type 1 diabetes mellitus (T1DM) have optimal humoral immune response to pneumococcal polysaccharide vaccination (PPSV23) and to study factors affecting that response.

Methods: In this prospective pilot study, we recruited 29 children with T1DM who were vaccine naïve to PPSV23 and assessed serum-serotype specific IgG at baseline and 4-6 weeks post-immunization. We tested association between independent variables (age, gender, body mass index (BMI), hemoglobin A1c (HbA1c), glucose variability, and time in range assessed by continuous glucose monitors (CGM), insulin dose and outcome (log-2-fold change of immunoassay response between pre- and post-immunization testing) using linear regression.

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Article Synopsis
  • Monitoring anti-drug antibodies (ADAs) to medications like infliximab and adalimumab is essential for managing treatment in autoimmune disorders and requires detecting these antibodies even when drug levels are present.
  • Two new automated ImmunoCAP™ immunoassays were developed to measure serum ADAs without needing a complicated acid-dissociation step and show good precision and the ability to differentiate between antibodies for the two drugs.
  • Although the quantitative results from these new assays are not directly comparable to existing tests, they demonstrate a strong qualitative agreement when identifying positive and negative patient samples and may face interference from factors like biotin and rheumatoid factors.
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Background: Over 30% of patients with COVID-19 have persistent symptoms that last beyond 30 days and referred to as Long COVID. Long COVID has been associated with a persistent elevation in peripheral cytokines including interleukin-6, interleukin-1β, and tumor necrosis factor-α. This study reports cytokine profiles of patients in our clinic across SARS-COV-2 variant epochs.

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Introduction: Therapeutic drug monitoring of infliximab has become the standard of care for inflammatory bowel disease in the setting of loss of response to therapy, and occasionally in proactive therapy personalization. Measurement of infliximab by tryptic peptide HPLC-MS/MS has been available since 2015, mostly in reference laboratories.

Objectives: Here, we present method improvements to our original published method leading to a more efficient, robust, and high throughput tryptic peptide HPLC-MS/MS assay for infliximab quantitation.

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Background: Clot based assays used for lupus anticoagulant (LAC) detection are typically interpreted in a qualitative fashion and may not reflect LAC potency. In this cross-sectional study, we describe a method for quantifying the LAC titer using serial (dependent) two-fold dilutions in normal pooled plasma.

Methods: Serial dilutions of 51 residual plasma samples from 50 patients were tested using the Russell's viper venom screening time (DRVVT) and activated partial thromboplastin screening time (APTT) methodologies.

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  • Fecal calprotectin (FC) is identified as an effective biomarker for evaluating endoscopic activity in ulcerative colitis (UC), with specific cutoff levels enhancing diagnostic accuracy.
  • A study of 177 UC patients found a strong correlation between FC levels and Mayo endoscopic subscores (MES), suggesting that specific FC cutoffs can differentiate between varying levels of endoscopic inflammation.
  • The research concluded that an FC cutoff of 60 mcg/g effectively distinguishes no inflammation (MES 0) from mild to severe inflammation (MES 1-3), supporting the use of FC in clinical settings for monitoring UC.
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The diagnosis of alpha-1-antitrypsin (A1AT) deficiency is established by quantitation of protein concentration in serum (immunoassay) followed by determination of specific allelic variants by phenotyping (isoelectric focusing (IEF) gel electrophoresis) and/or allele-specific genotyping. Various phenotyping and genotyping methodologies are available, and each has their own advantages and disadvantages. As an alternative, mass spectrometry is emerging as a powerful tool in the identification and quantitation of proteins and peptides.

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  • This study investigates whether therapeutic monoclonal antibodies (tmabs) commonly used in cancer and autoimmune treatments interfere with clinical immunoassays, which are tests used to measure various analytes in the lab.
  • Researchers tested samples from 10 patients by adding tmabs and comparing the results to control samples spiked with saline, measuring analyte concentrations across several assays.
  • The results showed no significant interference from tmabs in the immunoassays evaluated, indicating that these treatments do not negatively affect lab test accuracy within the tested concentrations.
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Objectives: There are multiple assays for infliximab (IFX) drug level (IFX-DL) and antibody to infliximab (ATI) measurement. The aims of this study are to examine the correlation and outcomes of IFX-DL and ATI in inflammatory bowel disease (IBD) patients, simultaneously measured with different methods in different institutions.

Design And Methods: Residual samples of IFX-treated IBD patients undergoing drug monitoring for IFX-DL and ATI, both measured by ECLIA (Esoterix Laboratories) were used to simultaneously quantify IFX-DL via LC-MS/MS and ATI via an in-house ECLIA (ih-ECLIA) (Mayo Clinic Laboratories).

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Background: Multiple laboratory tests are employed for detection of monoclonal proteins in patients and include serum protein electrophoresis (SPEP), immunofixation electrophoresis, free light chain (FLC) immunoassay, and mass spectrometry (Mass-Fix). Recently, reports on a drift in FLC quantitation results have been brought to light.

Methods: We studied a cohort of 16 887 patients whose sera were tested for a monoclonal protein by a FLC assay, serum protein electrophoresis, and Mass-Fix.

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Context.—: Antibodies to U1 ribonucleoprotein (U1RNP) were first described more than 50 years ago, and although clinically relevant for antinuclear antibody-associated connective tissue disease (ANA-CTD), test results are challenging to interpret.

Objective.

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Background: Anti-phosphatidylserine prothrombin antibodies (aPSPT) are reported to be highly associated with the lupus anticoagulant (LAC) in established antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE) cohorts. Further, aPSPT has been suggested to be a useful surrogate LAC marker. However, validation studies replicating this relationship in an all-comer study population in the diagnostic clinical setting are lacking.

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Background: Antineutrophil cytoplasmic antibody (ANCA) testing by the indirect immunofluorescence assay (IFA) is important for the diagnosis of autoimmune vasculitis. A common analytical interference for ANCA-IFA is the presence of an antinuclear antibody (ANA), which can cause an apparent perinuclear ANCA (pANCA) result on ethanol-fixed neutrophils. Here, the association of ANA patterns, titers, and concentrations with pANCA interference is investigated.

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Background: The history of how our knowledge of celiac disease (CD) evolved points to its importance in children. Although it is now appreciated that CD can present at any age, it was originally thought to occur only in children and, if untreated, led to serious consequences.

Content: This review includes a brief discussion of small bowel physiology and the pathogenesis of CD.

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Objectives: To verify the analytical performance of a new mass spectrometry-based method, termed MASS-FIX, when screening for plasma cell disorders in a routine clinical laboratory.

Patients And Methods: Results from 19,523 unique patients tested for an M-protein between July 24, 2018, and March 6, 2020, by a combination serum protein electrophoresis (SPEP) and MASS-FIX were examined for consistency with pretest implementation performance. MASS-FIX's ability to verify abnormal results from SPEP and free light chain measurements was then compared with that of immunofixation electrophoresis (IFE) using a separate cohort of 52,586 patients tested by SPEP/IFE during the same period.

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Background: Plasma cell disorders (PCDs) are typically characterized by excessive production of a single immunoglobulin, defined as a monoclonal protein (M-protein). Some patients have more than one identifiable M-protein, termed biclonal. Traditional immunofixation electrophoresis (IFE) cannot distinguish if two bands of the same isotype represent biclonal proteins or M-proteins with some other feature.

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Aims: The aim of this study was to determine the diagnostic accuracy of α defensin (AD) lateral flow assay (LFA) and enzyme-linked immunosorbent assay (ELISA) tests for periprosthetic joint infection (PJI) in comparison to conventional synovial white blood cell (WBC) count and polymorphonuclear neutrophil percentage (PMN%) analysis.

Methods: Patients undergoing joint aspiration for evaluation of pain after total knee arthroplasty (TKA) or total hip arthroplasty (THA) were considered for inclusion. Synovial fluids from 99 patients (25 THA and 74 TKA) were analyzed by WBC count and PMN% analysis, AD LFA, and AD ELISA.

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Antibody responses to pneumococcal polysaccharide vaccination are frequently used as a diagnostic tool for humoral immunodeficiencies, part of the larger collection of inborn errors of immunity. Currently, arbitrary criteria, such as a serotype specific titer of >/= 1.3 µg/mL is most often used as a cut-off for interpretation of pneumococcal antibody responses.

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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.

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Objectives: Failure to produce sufficient quantities of functional α1-antitrypsin (AAT) can result in AAT deficiency (AATD) and significant comorbidities. Laboratory testing plays a vital role in AATD, with diagnosis requiring documentation of both a low AAT level and a mutated allele. This retrospective evaluation examines the efficacy of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) (proteotyping)-based algorithm for AATD detection.

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