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Clinical Chemistry and Laboratory... Jul 2023The International Federation of Clinical Chemistry Committee on Clinical Applications of Cardiac Biomarkers (IFCC C-CB) provides educational documents to facilitate the...
The International Federation of Clinical Chemistry Committee on Clinical Applications of Cardiac Biomarkers (IFCC C-CB) provides educational documents to facilitate the interpretation and use of cardiac biomarkers in clinical laboratories and practice. Our aim is to improve the understanding of certain key analytical and clinical aspects of cardiac biomarkers and how these may interplay. Measurements of cardiac troponin (cTn) have a prominent place in the clinical work-up of patients with suspected acute coronary syndrome. It is therefore important that clinical laboratories know how to recognize and assess analytical issues. Two emerging analytical issues resulting in falsely high cTn concentrations, often several fold higher than the upper reference limit (URL), are antibody-mediated assay interference due to long-lived cTn-antibody complexes, called macrotroponin, and crosslinking antibodies that are frequently referred to as heterophilic antibodies. We provide an overview of antibody-mediated cTn assay interference and provide recommendations on how to confirm the interference and interpret the results.
Topics: Humans; Myocardial Infarction; Biomarkers; Chemistry, Clinical; Antibodies; Troponin
PubMed: 36952681
DOI: 10.1515/cclm-2023-0028 -
The Journal of Clinical Endocrinology... Mar 2024Measurement of free thyroid hormones (THs) and thyrotropin (TSH) using automated immunoassays is central to the diagnosis of thyroid dysfunction. Using illustrative...
Measurement of free thyroid hormones (THs) and thyrotropin (TSH) using automated immunoassays is central to the diagnosis of thyroid dysfunction. Using illustrative cases, we describe a diagnostic approach to discordant thyroid function tests, focusing on entities causing elevated free thyroxine and/or free triiodothyronine measurements with nonsuppressed TSH levels. Different types of analytical interference (eg, abnormal thyroid hormone binding proteins, antibodies to iodothyronines or TSH, heterophile antibodies, biotin) or disorders (eg, resistance to thyroid hormone β or α, monocarboxylate transporter 8 or selenoprotein deficiency, TSH-secreting pituitary tumor) that can cause this biochemical pattern will be considered. We show that a structured approach, combining clinical assessment with additional laboratory investigations to exclude assay artifact, followed by genetic testing or specialized imaging, can establish a correct diagnosis, potentially preventing unnecessary investigation or inappropriate therapy.
Topics: Humans; Thyroxine; Triiodothyronine; Thyroid Hormones; Thyrotropin; Thyroid Function Tests
PubMed: 37988295
DOI: 10.1210/clinem/dgad681 -
Frontiers in Immunology 2023Microbial infections are associated with the occurrence of autoimmune diseases, but the mechanisms of microbial infection inducing autoimmune diseases are not fully...
INTRODUCTION
Microbial infections are associated with the occurrence of autoimmune diseases, but the mechanisms of microbial infection inducing autoimmune diseases are not fully understood. The existence of heterophilic antigens between microorganisms and human tissues may explain part of the pathogenesis of autoimmune diseases. Here, we investigate the distribution of heterophilic antigens and its relationship with autoimmune diseases.
METHODS
Monoclonal antibodies against a variety of microorganisms were prepared. The titer, subclass and reactivity of antibodies with microorganisms were identified, and heterophilic antibodies that cross-reacted with human tissues were screened by human tissue microarray. The reactivity of these heterophilic antibodies with different individuals and different species was further examined by immunohistochemistry.
RESULTS
In this study, 21 strains of heterophilic antibodies were screened. The results showed that these heterophilic antibodies were produced due to the existence of heterophilic antigens between microorganism and human body and the distribution of heterophilic antigens had individual, tissue and species differences.
CONCLUSION
Our study showed that heterophilic antigens exist widely between microorganisms and human body, and the heterophilic antigens carried by microorganisms may break the immune tolerance of the body through carrier effect and initiate immune response, which may be one of the important mechanisms of infection inducing autoimmune diseases.
Topics: Humans; Antigens, Heterophile; Autoimmune Diseases; Antibodies, Monoclonal; Antibodies, Heterophile; Immunohistochemistry
PubMed: 38022676
DOI: 10.3389/fimmu.2023.1275658 -
Scientific Reports Jan 2024Knowledge of factors associated with semen quality may help in investigations of the aetiology and pathophysiology. We investigated the correlation between biomarkers...
Knowledge of factors associated with semen quality may help in investigations of the aetiology and pathophysiology. We investigated the correlation between biomarkers for testicular cell function (anti-müllerian hormone, AMH, Inhibin B, testosterone, free androgen-index (testosterone/sex-hormone binding globulin), insulin like peptide 3, INSL-3), alkaline phosphate (ALP), canine prostate-specific esterase (CPSE), and heterophilic antibodies with dog variables, semen quality, and fertility. Blood and semen were collected from 65 Bernese Mountain Dogs. We evaluated total sperm count, motility and morphological parameters. The semen quality ranged from poor to excellent, with an average total sperm count of 1.1 × 10 and 50% morphologically normal spermatozoa (MNS). Age and abnormal testicular consistency correlated with decreased motility and MNS. Higher ALP correlated with higher total sperm count. AMH could not be detected in seminal plasma. AMH in blood correlated with head defects and high AMH concentration correlated with a severe decline in several semen parameters. Testosterone was negatively and CPSE positively correlated with age. No correlations were found for INSL-3, inhibin B, or heterophilic antibodies. Our findings contribute to the understanding of factors associated with semen quality in dogs, particularly related to Sertoli cell function.
Topics: Male; Dogs; Animals; Semen Analysis; Semen; Anti-Mullerian Hormone; Body Fluids; Peptide Hormones; Testosterone; Antibodies, Heterophile; Esterases
PubMed: 38184699
DOI: 10.1038/s41598-024-51242-0 -
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 -
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 -
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