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Archives of Endocrinology and Metabolism Nov 2023Calcitonin (CT) is a diagnostic and follow-up marker of medullary thyroid carcinoma. Heterophile antibodies (HAbs) may interfere during immunometric assay measurements...
Calcitonin (CT) is a diagnostic and follow-up marker of medullary thyroid carcinoma. Heterophile antibodies (HAbs) may interfere during immunometric assay measurements and result in falsely high CT levels and different markers. A 50-year-old female patient was referred to our institution for elevated CT levels (3,199 pg/mL [0-11,5]). Physical examination and thyroid ultrasonography show no thyroid nodules. Because of the discrepancy between the clinical picture and the laboratory results, various markers and hormones were examined to determine whether there was any interference in the immunometric assay. Thyroglobulin (Tg) and Adrenocorticotropic hormone (ACTH) levels were also found inaccurately elevated. After precipitation with polyethylene glycol, CT, Tg, and ACTH levels markedly decreased, showing macro-aggregates. Also, serial dilutions showed non-linearity in plasma concentrations. Additionally, CT samples were pretreated with a heterophilic blocking tube before measuring, and the CT level decreased to < 0.1 pg/mL, suggesting a HAb presence. Immunoassay interference should be considered when conflicting laboratory data are observed. This may help reduce the amount of unnecessary laboratory and imaging studies and prevent patients from complex diagnostic procedures.
Topics: Female; Humans; Middle Aged; Calcitonin; Thyroid Neoplasms; Immunoassay; Thyroid Nodule; Adrenocorticotropic Hormone
PubMed: 37988668
DOI: 10.20945/2359-4292-2023-0074 -
Clinical Biochemistry Nov 2023Therapeutic monoclonal antibodies (tmabs) have been hypothesized to interfere with immunoassay measurements, although studies investigating this potential new class of...
BACKGROUND
Therapeutic monoclonal antibodies (tmabs) have been hypothesized to interfere with immunoassay measurements, although studies investigating this potential new class of interference are lacking. This study evaluated the effects of tmabs used in cancers ipilimumab (Bristol Myers Squibb), nivolumab (Bristol Myers Squibb), pembrolizumab (Merck) and autoimmune disorders adalimumab (AbbVie), infliximab (Janssen) and vedolizumab (Takeda) in common immunoassays used in the clinical laboratory.
METHODS
Residual sera from 10 randomly chosen patients were split into two tubes and spiked with same volume (approximately 5 % final volume) of either saline (control) or 6 tmabs (final concentration of 100 μg/mL each). Concentrations from sixteen analytes in 19 different assays were assessed: TSH (Roche and Beckman), free thyroxine (Roche and Siemens), cortisol (Beckman), Cancer Antigens (CA): CA19-9 (Beckman), CA15-3 (Roche), CA125 (Roche), and CA27.29 (Siemens), carcinoembryonic antigen (Beckman), alpha-fetoprotein (Beckman), thyroglobulin (Beckman) and thyroglobulin antibodies (Beckman), thyroid peroxidase antibody (Beckman), beta-human chorionic gonadotropin (Roche and Beckman), total prostate-specific antigen (Roche), parathyroid hormone (Roche) and antinuclear antibodies IgG (Werfen). The tmab spiked residual sera were compared with matched saline spiked sera and percent error was assessed against allowable total error defined from biological variation or CLIA limits.
RESULTS
None of the tested immunoassays were affected by the presence of the tmabs, in samples within or outside assay reference intervals. The median % error among all immunoassays ranged between -2.0% (for TSH) to 2.7% (for TPO Ab assay).
CONCLUSION
These findings demonstrate no detectable tmab interference for the assessed immunoassays using spiked preparations of the tmabs in residual human sera. The findings are limited to the tmabs and immunoassays studied here.
Topics: Male; Humans; Antibodies, Monoclonal; Thyroglobulin; Immunoassay; Autoimmune Diseases; Thyrotropin
PubMed: 37972806
DOI: 10.1016/j.clinbiochem.2023.110685 -
Cancer Reports (Hoboken, N.J.) Aug 2023Hepatocellular carcinoma (HCC) has a high recurrence rate even after radical hepatectomy. More optimal biomarkers may help improve recurrence and prognosis.
BACKGROUND AND OBJECTIVES
Hepatocellular carcinoma (HCC) has a high recurrence rate even after radical hepatectomy. More optimal biomarkers may help improve recurrence and prognosis.
METHODS
We investigated whether the oncological properties of N-glycolylneuraminic acid (NeuGc) can participate in the prognosis of HCC. We evaluated the NeuGc antigen (Ag) expression in the HCC tissues and measured the preoperative anti-NeuGc IgG antibodies (Abs) in the sera of the patients with HCC. We compared the clinical characteristics and survival rate in the hepatectomized patients (initial; n = 66, recurrent; n = 34) with and without the NeuGc Ag or Abs.
RESULTS
Multivariate analyses showed positive expression of NeuGc Ag in HCC tissues (Odds ratio; initial = 6.3, recurrent = 14.0) and higher titers of preoperative anti-NeuGc Ab (Odds ratio; initial = 4.9; recurrent = 3.8), which could be the predictive factors related to early recurrence. Both the NeuGc Ag-positive and Ab-positive groups in the initial hepatectomized patients exhibited significantly shorter recurrent free survival compared to those in the negative groups.
CONCLUSIONS
Our findings suggested that anti-NeuGc Ab titers and NeuGc Ag expression in the HCC tissues can be used as the predictive factors for the postoperative recurrence and prognosis of HCC.
Topics: Humans; Carcinoma, Hepatocellular; Antigens, Heterophile; Liver Neoplasms; Neuraminic Acids; Biomarkers, Tumor
PubMed: 37265054
DOI: 10.1002/cnr2.1831 -
Clinical Laboratory Aug 2023This study aimed to demonstrate potential measures to discern interference and establish an algorithm for identifying interference in an hs-cTnT assay with a clinical... (Review)
Review
BACKGROUND
This study aimed to demonstrate potential measures to discern interference and establish an algorithm for identifying interference in an hs-cTnT assay with a clinical discrepancy.
METHODS
Laboratory error and disease factors were first excluded. Then, a serial dilution test, polyethylene glycol (PEG) precipitation, and heterophile antibody blocking reagents (HBRs) were performed to confirm the interference substance. In addition, high-speed centrifugation and western blot were tried.
RESULTS
The sample diluted linearly (R2 = 0.9966). However, there was a dramatic reduction in the concentration of hs-cTnT concentration to a normal level after both PEG precipitation and HBR1 treatment. The results were inconclusive in high-speed centrifugation and western blot assay.
CONCLUSIONS
This study elucidated a heterophile antibody interference in measurement of hs-cTnT alone on a Roche analyzer.
Topics: Humans; Troponin T; Antibodies; Indicators and Reagents; Blotting, Western; Biomarkers
PubMed: 37560846
DOI: 10.7754/Clin.Lab.2023.230230 -
Clinica Chimica Acta; International... Aug 2023Vancomycin is associated with potential nephrotoxicity and trough concentrations need to be monitored in certain patients. Falsely decreased vancomycin measurement may...
BACKGROUND
Vancomycin is associated with potential nephrotoxicity and trough concentrations need to be monitored in certain patients. Falsely decreased vancomycin measurement may result in overtreatment and need to be identified promptly by clinicians and pharmacists to avoid toxicities.
METHODS AND RESULTS
We report a case of rheumatoid factor-mediated falsely low vancomycin measurement with Abbott particle-enhanced turbidimetric inhibition immunoassay (PETINIA) method. Reanalyzing the sample using an alternative method, removing the interferences using heterophile blocking reagent as well as rheumatoid factor clean-up solution all helped to solve the false results. Results from alternative method and interference studies showed vancomycin concentrations reached toxic concentrations in the patient and administration of the drug was immediately terminated. The patient experienced a transient increase in serum creatinine.
CONCLUSIONS
Even though most modern immunoassays use blocking agents to neutralize interfering antibodies such as rheumatoid factor, it is important for health care professionals to understand that occasional interference still occurs due to the heterogeneous nature of rheumatoid factor.
Topics: Humans; Vancomycin; Rheumatoid Factor; Immunoassay; Health Personnel; Immunoturbidimetry
PubMed: 37390942
DOI: 10.1016/j.cca.2023.117460 -
Indian Journal of Endocrinology and... 2024Considering the inherent vulnerability of immunoassays for heterophilic interference and the potential of Rheumatoid Factor (RF) to act as a heterophile-like antibody,...
INTRODUCTION
Considering the inherent vulnerability of immunoassays for heterophilic interference and the potential of Rheumatoid Factor (RF) to act as a heterophile-like antibody, we conducted this study to investigate if RF leads to any such heterophilic interference in seropositive rheumatoid arthritis (RA) patients. The study was done on the TSH assay as it is a noncompetitive, double antibody sandwich assay, which is known to be vulnerable to heterophilic interference.
METHODS
In this cross-sectional observational study, eighty-four consecutive newly diagnosed RF-positive RA patients underwent TSH, Free T4, and anti-TPO estimation using the chemiluminescence technique (CLIA) on Siemens Immulite 1000 platform. The samples were screened for TSH interference using four methods: 1) analysis on a different platform, 2) assessment of linearity using doubling dilutions, 3) polyethylene glycol (PEG) precipitation, and 4) addition of a commercial blocker.
RESULTS
Ten samples had a loss of linearity on serial dilution, indicating potential interference. After heterophile blocker treatment, five cases exhibited interference. One patient had diagnostic interpretation discordance on the second platform. No sample on PEG precipitation suggested the influence of antibodies. It is worth noting that even in cases where interference was suspected, the clinical interpretation was largely unaffected by the correction of TSH values based on mean dilution or measurement after heterophile blocker treatment.
CONCLUSION
RF can cause heterophilic interference in TSH immunoassays used commercially. However, in most cases, this interference does not affect clinical decision-making.
PubMed: 38533277
DOI: 10.4103/ijem.ijem_99_23 -
Xenotransplantation 2024Recent clinical xenotransplantation and human decedent studies demonstrate that clinical hyperacute rejection of genetically engineered porcine organs can be reliably...
Recent clinical xenotransplantation and human decedent studies demonstrate that clinical hyperacute rejection of genetically engineered porcine organs can be reliably avoided but that antibody mediated rejection (AMR) continues to limit graft survival. We previously identified porcine glycans and proteins which are immunogenic after cardiac xenotransplantation in non-human primates, but the clinical immune response to antigens present in glycan depleted triple knockout (TKO) donor pigs is poorly understood. In this study we use fluorescence barcoded human embryonic kidney cells (HEK) and HEK cell lines expressing porcine glycans (Gal and SDa) or proteins (tetraspanin-29 [CD9], membrane cofactor protein [CD46], protectin, membrane attack complex inhibition factor [CD59], endothelial cell protein C receptor, and Annexin A2) to screen antibody reactivity in human serum from 160 swine veterinarians, a serum source with potential occupational immune challenge from porcine tissues and pathogens. High levels of anti-Gal IgM were present in all samples and lower levels of anti-SDa IgM were present in 41% of samples. IgM binding to porcine proteins, primarily CD9 and CD46, previously identified as immunogenic in pig to non-human primate cardiac xenograft recipients, was detected in 28 of the 160 swine veterinarian samples. These results suggest that barcoded HEK cell lines expressing porcine protein antigens can be useful for screening human patient serum. A comprehensive analysis of sera from clinical xenotransplant recipients to define a panel of commonly immunogenic porcine antigens will likely be necessary to establish an array of porcine non-Gal antigens for effective monitoring of patient immune responses and allow earlier therapies to reverse AMR.
Topics: Animals; Transplantation, Heterologous; Humans; Swine; Graft Rejection; HEK293 Cells; Veterinarians; Polysaccharides; Animals, Genetically Modified; Antibodies, Heterophile; Heterografts; Immunoglobulin M
PubMed: 38853364
DOI: 10.1111/xen.12865 -
Laboratory Medicine Jul 2023Falsely increased estradiol levels can lead to unnecessary tests and therapeutic interventions. Here, we present a case of a 62-year-old man with falsely elevated...
Falsely increased estradiol levels can lead to unnecessary tests and therapeutic interventions. Here, we present a case of a 62-year-old man with falsely elevated estradiol, which led to subsequent follow-up testing and prescriptions. Alternative immunoassay testing, in conjunction with Scantibodies' blocking reagents, polyethylene glycol precipitation, and liquid chromatography-tandem mass spectrometry confirmation demonstrated that the falsely elevated estradiol was due to the presence of macro-estradiol. This report emphasizes the importance of recognizing analytical interferences in immunoassays to appropriately manage subsequent testing and patient care.
Topics: Male; Humans; Middle Aged; Estradiol; Immunoassay; Chromatography, Liquid; Mass Spectrometry
PubMed: 36221780
DOI: 10.1093/labmed/lmac136 -
Clinical Chemistry and Laboratory... Apr 2024
Topics: Humans; C-Reactive Protein; False Positive Reactions; Antibodies, Heterophile; Immunoassay
PubMed: 38019952
DOI: 10.1515/cclm-2023-1196 -
Cureus Apr 2024Infectious mononucleosis (IM) is a clinical disease caused by the Epstein-Barr virus (EBV). Common presenting symptoms include sore throat, lymph node enlargement,...
Infectious mononucleosis (IM) is a clinical disease caused by the Epstein-Barr virus (EBV). Common presenting symptoms include sore throat, lymph node enlargement, fever, and malaise. Although severe upper airway obstruction is uncommon, it is a potentially fatal complication that requires immediate intervention. We describe the case of an 18-year-old Hispanic man who presented with a progressive sore throat and difficulty speaking, requiring endotracheal intubation for airway protection. CT images showed diffuse swelling of Waldeyer's tonsillar ring, multiple enlarged lymphadenopathies, and splenomegaly. Acute EBV infection was confirmed considering clinical presentation and using the heterophile antibody, anti-nuclear and anti-viral capsid antigens, and quantitative PCR. The patient was managed with ventilatory support, empirical antibiotic therapy, and systemic corticosteroids, achieving a positive outcome. Our case illustrates the use of corticosteroids in managing severe upper airway obstruction complicating IM.
PubMed: 38779228
DOI: 10.7759/cureus.58735