-
Xenotransplantation 2023Pig liver xenotransplantation is limited by a thrombocytopenic coagulopathy that occurs immediately following graft reperfusion. In vitro and ex vivo studies from our...
Pig liver xenotransplantation is limited by a thrombocytopenic coagulopathy that occurs immediately following graft reperfusion. In vitro and ex vivo studies from our lab suggested that the thrombocytopenia may be the result of a species incompatibility in platelet glycosylation. Realization that platelet α-granules contain antibodies caused us to reevaluate whether the thrombocytopenia in liver xenotransplantation could occur because IgM and IgG from inside platelet α-granules bound to pig liver sinusoidal endothelial cells (LSECs). Our in vitro analysis of IgM and IgG from inside α-granules showed that platelets do carry xenoreactive antibodies that can bind to known xenoantigens. This study suggests that thrombocytopenia occurring following liver xenotransplantation could occur because of xenoreactive antibodies tethering human platelets to the pig LSEC enabling the platelet to be phagocytosed. These results suggest genetic engineering strategies aimed at reducing xenoantigens on the surface of pig LSEC will be effective in eliminating the thrombocytopenia that limits survival in liver xenotransplantation.
Topics: Swine; Animals; Humans; Endothelial Cells; Transplantation, Heterologous; Liver; Blood Platelets; Thrombocytopenia; Antigens, Heterophile; Immunoglobulin G; Immunoglobulin M
PubMed: 37971870
DOI: 10.1111/xen.12834 -
Biochemia Medica Feb 2024Accurate measurement of adrenocorticotropic hormone (ACTH) is crucial in the evaluation of pituitary and adrenal disorders. Although great progress has been achieved in...
Accurate measurement of adrenocorticotropic hormone (ACTH) is crucial in the evaluation of pituitary and adrenal disorders. Although great progress has been achieved in ACTH measurement with immunometric assays, interference may occur and adversely affect the clinical management. The report contributes to compiling the evidence on the clinical challenges with the management of the interferences in the ACTH measurement by presenting three cases: two with clinically overt hypercortisolism and discrepant ACTH concentrations within the reference interval; the third case describes the falsely elevated ACTH in a patient with secondary adrenal insufficiency. In all patients, the results obtained with the two immunometric platforms, chemiluminescence (CLIA) immunoassay (Siemens, Immulite) and electrochemiluminescence (ECLIA) immunoassay (Roche, Cobas), were discordant. Serial dilution of plasma samples revealed nonlinearity. After polyethylene glycol (PEG) precipitation recoveries were less than 22%, 26%, and 3%, respectively, supporting interference. Moreover, a decrease in ACTH concentration after incubation in a heterophile antibody-blocking tube was observed in the second case. In the first case, misinterpretation of ACTH led to inferior petrosal sinus sampling (IPSS), whereas timely detection of assay interference prevented further investigations in other cases. Increasing awareness regarding ACTH interference and comprehensive approach in evaluation could allow timely detection, helping to prevent unnecessary testing and perplexing clinical outcomes.
Topics: Humans; Adrenocorticotropic Hormone; Petrosal Sinus Sampling; Immunoassay
PubMed: 38125613
DOI: 10.11613/BM.2024.010802 -
Clinical Laboratory Jun 2024There are many methods for the detection of D-dimer in clinical laboratories. Immunoturbidimetric assays are widely used because of its high sensitivity and specificity...
BACKGROUND
There are many methods for the detection of D-dimer in clinical laboratories. Immunoturbidimetric assays are widely used because of its high sensitivity and specificity [1-3]. However, this method may be affected by the interference of rheumatoid factor (RF), heterophilic antibodies, and other unknown proteins, and its falsity will increase, thus affecting clinical diagnosis.
METHODS
This paper reports the cause analysis of a case of spurious D-dimer increase and four corresponding elimination methods: double dilution of the original specimen, detection of fibrin degradation product (FDP) level, addition of heterophilic blocking reagent, and comparison between different instruments.
RESULTS
It was confirmed that there were special antibodies in the patient's body by four methods, which had non-specific reactions with D-dimer reagents, resulting in false increases of results.
CONCLUSIONS
When the coagulation function results of patients show isolated increases in D-dimer, or the results are inconsistent with clinical symptoms, laboratory personnel should consider the possibility of interference factors, and conduct effective treatment to obtain correct test results, and thus reduce the occurrence of medical adverse events caused by inaccurate test results.
Topics: Humans; Fibrin Fibrinogen Degradation Products; False Positive Reactions; Immunoturbidimetry; Female; Male; Antibodies, Heterophile; Rheumatoid Factor
PubMed: 38868870
DOI: 10.7754/Clin.Lab.2023.231229 -
Clinical Laboratory Jun 2024TSH and ACTH are crucial hormones for diagnosing thyroid and adrenal diseases, and incorrect test reports can cause significant harm to patients. (Review)
Review
BACKGROUND
TSH and ACTH are crucial hormones for diagnosing thyroid and adrenal diseases, and incorrect test reports can cause significant harm to patients.
METHODS
The TSH and ACTH levels on the testing system of our laboratory were measured using "sandwich" assays. The patient had heterophilic antibodies in their body, causing a false increase in TSH and ACTH levels.
RESULTS
TSH on the Abbott platform was 59.7 μIU/mL and on the Roche platform it was 4.33 μIU/mL. After pretreatment with HBR it was 3.95 μIU/mL; ACTH on the SIEMENS platform was 263.5 pg/mL, on the Abbott platform it was 47.6 pg/mL. After pretreatment with HBR it was 36.5 pg/mL.
CONCLUSIONS
The patient's serum contains heterophilic antibodies, which interfere with the TSH and ACTH tested by this method.
Topics: Humans; Male; Middle Aged; Adrenocorticotropic Hormone; Antibodies, Heterophile; Thyrotropin
PubMed: 38868895
DOI: 10.7754/Clin.Lab.2024.240122 -
Xenotransplantation 2024Attack of donor tissues by pre-formed anti-pig antibodies is well known to cause graft failure in xenotransplantation. Genetic engineering of porcine donors to eliminate...
Attack of donor tissues by pre-formed anti-pig antibodies is well known to cause graft failure in xenotransplantation. Genetic engineering of porcine donors to eliminate targets of these pre-formed antibodies coupled with advances in immunosuppressive medicines have now made it possible to achieve extended survival in the pre-clinical pig-to-non-human primate model. Despite these improvements, antibodies remain a risk over the lifetime of the transplant, and many patients continue to have pre-formed donor-specific antibodies even to highly engineered pigs. While therapeutics exist that can help mitigate the detrimental effects of antibodies, they act broadly potentially dampening beneficial immunity. Identifying additional xenoantigens may enable more targeted approaches, such as gene editing, to overcome these challenges by further eliminating antibody targets on donor tissue. Because we have found that classical class I swine leukocyte antigens are targets of human antibodies, we now examine whether related pig proteins may also be targeted by human antibodies. We show here that non-classical class I swine leukocyte proteins (SLA-6, -7, -8) can be expressed at the surface of mammalian cells and act as antibody targets.
Topics: Animals; Swine; Transplantation, Heterologous; Antigens, Heterophile; Humans; Histocompatibility Antigens Class I; Histocompatibility Antigens Class II; Graft Rejection; Animals, Genetically Modified
PubMed: 38924560
DOI: 10.1111/xen.12872 -
Clinical Laboratory Jun 2024Heterophilic antibodies (HA) are one of the main substances that interfere with immunology, especially chemiluminescence immunoassay. Non-specific binding, labeling...
BACKGROUND
Heterophilic antibodies (HA) are one of the main substances that interfere with immunology, especially chemiluminescence immunoassay. Non-specific binding, labeling antibodies, bridging to capture antibodies, or labeling antigens can interfere with the detection process, leading to serious discrepancies between the measured results and clinical manifestations, and even delaying clinical diagnosis and treatment.
METHODS
This paper is a case of epidemic hemorrhagic fever causing pseudo CEA elevation caused by heterophagy induced antibodies in the body.
RESULTS
The patient's CEA detected on the ABBOTT detection platform was 51.1 ng/mL, and on the ROCHE detection platforms it was 4.66 ng/mL, and treated by PEG precipitation it was 45.2 ng/mL, after diluting the sample the CEA was 50.2 ng/mL, meanwhile the patient's platelets were 96 x 109/L and serum creatinine was 188.4 μmol/L, epidemic hemorrhagic fever IgM antibody was positive.
CONCLUSIONS
When the test results do not match clinical symptoms, further confirmation is required through additional testing. Patients who use mouse monoclonal antibody preparations for diagnosis or treatment may have human anti-mouse antibodies in their serum, and the test results may falsely increase or decrease.
Topics: Humans; Antibodies, Heterophile; Carcinoembryonic Antigen; Immunoglobulin M; Female; Aged
PubMed: 38868871
DOI: 10.7754/Clin.Lab.2024.231230 -
The New Zealand Medical Journal Feb 2024In patients with suspected venous thromboembolism, an elevated D-dimer level provides an important branch-point in the management pathway. This study compared two...
Discrepancies between two D-dimer assays and impact on clinical decisions; a retrospective analysis of samples tested in community and hospital-based laboratories in Auckland.
AIM
In patients with suspected venous thromboembolism, an elevated D-dimer level provides an important branch-point in the management pathway. This study compared two D-dimer assays, INNOVANCE® DDimer (Innovance) and STA®-Liatest® D-Di Plus (Liatest), to assess potential impact on clinical management.
METHOD
Reflecting current practice in Waitematā, Auckland, we compared paired samples from 805 patients referred to hospital following a community D-dimer test. Samples were determined to be positive or negative using a 500μg/L fibrinogen equivalent units (FEU), and age-adjusted cut-offs.
RESULTS
In the Innovance assay, 2% of samples had a result <500μg/L FEU. In contrast, by Liatest, 18% were below 500μg/L. This positive bias of Innovance was amplified with use of age-adjusted cut-offs; 23% of samples with an elevated Innovance result showed a normal result by Liatest. On average, the Innovance values were 22% higher than Liatest. Results suggestive of interference from heterophile antibodies were seen in 6% of sample-pairs.
CONCLUSION
Innovance D-dimer test yielded higher values than Liatest and experienced interference from suspected heterophile antibodies. Discrepancies in nearly a quarter of patients may be leading to substantial under or over investigation, inefficient use of resources and clinical confusion.
Topics: Humans; Retrospective Studies; Antibodies, Heterophile; Laboratories; New Zealand; Fibrin Fibrinogen Degradation Products; Hospitals
PubMed: 38301197
DOI: 10.26635/6965.6302 -
Archives of Endocrinology and Metabolism Mar 2024Thyroglobulin (Tg) levels are important to predict recurrence in differentiated thyroid cancer patients.However, false-positive results can hence the request of...
Thyroglobulin (Tg) levels are important to predict recurrence in differentiated thyroid cancer patients.However, false-positive results can hence the request of unnecessary tests and treatments. We reported two cases of interference in thyroglobulin measurement and the workup to investigate them. Both patients achieved an excellent response to therapy after total thyroidectomy and one patient had also received radioiodine treatment. During the follow-up, Tg levels increased and there was no evidence of recurrent disease in the imaging studies. The Tg levels by the Access platform were positive but the results by Elecsys platform and LC-MS/MS were undetectable, leading to the hypothesis of heterophile antibodies (HAbs) interference. The possibility of HAbs interference must be considered when the Tg levels do not fit in the clinical picture. The measurement of Tg by another immunoassay or by LC-MS/MS may be useful in these situations.
Topics: Humans; Thyroglobulin; Antibodies, Heterophile; Iodine Radioisotopes; Chromatography, Liquid; Tandem Mass Spectrometry; Thyroid Neoplasms; Thyroidectomy
PubMed: 38456952
DOI: 10.20945/2359-4292-2023-0115 -
Osteoporosis International : a Journal... Apr 2024Parathyroid hormone (PTH) measurements can be falsely elevated due to the hormone binding to other molecules (macro-PTH) or immunoassay interference with heterophile,...
BACKGROUND
Parathyroid hormone (PTH) measurements can be falsely elevated due to the hormone binding to other molecules (macro-PTH) or immunoassay interference with heterophile, human anti-animal or other antibodies. This is rare but could lead to incorrect diagnosis, unnecessary investigations or avoidance of teriparatide treatment. We report a case of falsely high PTH levels due to assay interference and review the literature on cases of spuriously elevated PTH.
CASE REPORT
An 87-year-old woman attending our bone health clinic with osteoporosis had persistently elevated PTH (383-784 pg/ml) using the Roche Cobas e801 immunoassay despite having normal serum calcium, phosphate, 25 hydroxyvitamin D (> 50 nmol/l) and eGFR (> 60 ml/min). To rule out falsely elevated PTH, a polyethylene glycol precipitation (PEG) test was performed which recovered less than 10% of the hormone resulting in a normal level. PTH was also tested on a different assay (Atellica Siemens) that identified a result of 27 pg/ml. The findings were consistent with immunoassay interference likely due to heterophile antibodies giving rise to a spuriously high PTH.
DISCUSSION
The presence of unexpectedly high PTH levels should alert physicians to the possibility of false results due to assay interference or macro-PTH. This highlights the importance of clinically correlating results and of good communication with the testing laboratory. Here, we present the case of an 87-year-old woman with spuriously elevated PTH levels due to immunoassay interference likely mediated by heterophile antibodies. The presence of unexpectedly high PTH levels should prompt consideration of the possibility of false results due to assay interference or macro-PTH.
Topics: Female; Humans; Aged, 80 and over; Antibodies, Heterophile; Parathyroid Hormone; Teriparatide; Immunoassay; Osteoporosis
PubMed: 38151628
DOI: 10.1007/s00198-023-07006-z