A Pseudo Elevation of CEA Caused by Epidemic Hemorrhagic Fever.

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.

False diagnosis of recurrent thyroid carcinoma: the importance of testing for heterophile antibodies.

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.

Endocrine and dog factors associated with semen quality.

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 × 109 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.

Infectious Mononucleosis: An Updated Review.

BACKGROUND: Infectious mononucleosis is common among adolescents and young adults. Although the majority of cases resolve spontaneously, life-threatening manifestations, and complications have been recognised. OBJECTIVE: The purpose of this article is to familiarize clinicians with the clinical manifestations, evaluation, diagnosis, and management of infectious mononucleosis. METHODS: A search was conducted in October 2022 in PubMed Clinical Queries using the key terms "infectious mononucleosis" OR "Epstein-Barr virus" OR "EBV". The search strategy included all clinical trials, observational studies, and reviews published within the past 10 years. Only papers published in the English literature were included in this review. The information retrieved from the aforementioned search was used in the compilation of the present article. RESULTS: Infectious mononucleosis, caused by Epstein-Barr virus, most commonly affects adolescents and adults aged 15 to 24 years. Epstein-Barr virus is transmitted primarily in saliva. Infectious mononucleosis is characterized by a triad of fever, tonsillar pharyngitis, and lymphadenopathy. Fatigue may be profound but tends to resolve within three months. Periorbital and/or palpebral edema, typically bilateral, occurs in one-third of patients. Splenomegaly and hepatomegaly occur in approximately 50% and 10% of cases, respectively. A skin rash, which is usually widely scattered, erythematous, and maculopapular, occurs in approximately 10 to 45% of cases. Peripheral blood leukocytosis is observed in most patients; lymphocytes make up at least 50% of the white blood cell differential count. Atypical lymphocytes constitute more than 10% of the total lymphocyte count. The classic test for infectious mononucleosis is the demonstration of heterophile antibodies. The monospot test is the most widely used method to detect the serum heterophile antibodies of infectious mononucleosis. When confirmation of the diagnosis of infectious mononucleosis is required in patients with mononucleosis-like illness and a negative mono-spot test, serologic testing for antibodies to viral capsid antigens is recommended. Infectious mononucleosis is a risk factor for chronic fatigue syndrome. Spontaneous splenic rupture occurs in 0.1 to 0.5% of patients with infectious mononucleosis and is potentially life-threatening. Treatment is mainly supportive. Reduction of activity and bed rest as tolerated are recommended. Patients should be advised to avoid contact sports or strenuous exercise for 8 weeks or while splenomegaly is still present. Most patients have an uneventful recovery. CONCLUSION: Infectious mononucleosis is generally a benign and self-limited disease. Prompt diagnosis is essential to avoid unnecessary investigations and treatments and to minimize complications. Splenic rupture is the most feared complication. As avoiding exposure to EBV is almost impossible, the most effective way to prevent EBV infection and infectious mononucleosis is the development of an effective, safe, and affordable EBV vaccine that can confer life-long immunity.

Falsely elevated parathyroid hormone in a patient with osteoporosis: a case report and review.

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.

Infectious Mononucleosis: Rapid Evidence Review.

Infectious mononucleosis is a viral syndrome characterized by fever, pharyngitis, and posterior cervical lymphadenopathy. It is usually caused by Epstein-Barr virus and most often affects adolescents and young adults 15 to 24 years of age. Primary transmission is through close personal contact with a person who is infected, particularly their saliva. Cost-effective, efficient initial laboratory testing for acute infectious mononucleosis includes complete blood count with differential (to assess for greater than 40% lymphocytes and greater than 10% atypical lymphocytes) and a rapid heterophile antibody test. The heterophile antibody test has a sensitivity of 87% and specificity of 91% but can have a false-negative result in children younger than five years and in adults during the first week of illness. The presence of elevated liver enzymes increases clinical suspicion for infectious mononucleosis in the setting of a negative heterophile antibody test result. Epstein-Barr viral capsid antigen-antibody testing is more sensitive and specific but more expensive and takes longer to process than the rapid heterophile antibody test. Treatment of infectious mononucleosis is supportive; routine use of antivirals and corticosteroids is not recommended. Current guidelines recommend that patients with infectious mononucleosis not participate in athletic activity for three weeks from onset of symptoms. Shared decision-making should be used to determine the timing of return to activity. Immunosuppressed populations are at higher risk of severe disease and significant morbidity. Epstein-Barr virus infection has been linked to nine types of cancer, including Hodgkin lymphoma, non-Hodgkin lymphoma, and nasopharyngeal carcinoma, and some autoimmune diseases.

Persistent increase of carbohydrate antigen 19-9 with an unknown reason: A seven-year follow-up case.

BACKGROUND: We described a patient who exhibited a gradual increase in carbohydrate antigen 19-9 (CA19-9) concentrations for 4 years at three hospitals, with no associated clinical manifestations; however, we were unable to define the cause of this increase, forcing us to consider whether it was a false-positive result. METHODS: Given the potential for interference, this study used multiple system detection, gradient dilution, Polyethylene glycol (PEG) precipitation and heterophilic antibody blocking assay to evaluate the reliability of CA19-9 concentration increase. RESULTS: Analysis of the patient sample using multiple systems indicated that CA19-9 concentrations showed an obvious increase (154.0, and 889.2 IU/ml, respectively) using the Cobas E602 and Advia Centaur XP systems, and were within the reference ranges (<10 IU/ml) on other modules. PEG precipitation on the Cobas E602 and Advia Centaur XP systems reduced the CA19-9 concentration, as did heterophilic blocking tube (HBT-6, HBT-1) blockade. CONCLUSION: CA19-9 was incorrectly identified to increase due to the presence of heterophilic antibodies. We recommend that heterophilic antibodies should be evaluated in cases with elevated CA19-9 level but no associated clinical manifestations to prevent false positives.

[Clinical implications of falsely elevated prostate-specific antigen].

Heterophile antibodies can cause falsely elevated levels of prostate-specific antigen (PSA), which is illustrated in this case report with two patient cases. In the first case, the falsely elevated PSA resulted in thorough and unnecessary examinations with multiple transrectal biopsies causing psychological distress and a risk of infection. In the second case, a patient was diagnosed with prostate cancer, and falsely rising levels of PSA possibly resulted in prolonged treatment with medical castration. These cases underline the importance of suspecting interference, when clinical findings and PSA levels do not match.

The utility of liver function tests and abdominal ultrasound in infectious mononucleosis-A systematic review.

INTRODUCTION: A large proportion of patients with infectious mononucleosis (IM) have abnormal liver function tests (LFT) at presentation. There is no guideline regarding the management and follow-up of these patients. Some patients also have abdominal ultrasound (US) due to deranged LFT, the need for this practice is unclear. The aim of this systematic review was to evaluate the evidence base on LFT assessment in IM, time to resolution of derangement, and the role of abdominal US. METHODS: A systematic search of PubMed, EMBASE and the Cochrane library was done. Two authors independently screened records for eligibility using pre-defined criteria. We included both adult and paediatric populations. Quality assessment of included studies was done. RESULTS: A total of 3924 patients were included from 32 studies, of which LFT values were reported on 2779 patients. A combination of typical clinical features, heterophile antibodies and Epstein-Barr virus-specific antibodies were used to ascertain diagnosis. The following proportion of patients had abnormal LFT: aspartate transaminase (57%); alanine transaminase (62%); alkaline phosphatase (65%); bilirubin (16%); gamma-glutamyltransferase (41%). Reported median (interquartile range) time to resolution of LFT was 8 (6-12) weeks (n = 438). Maximum time to resolution was >6 months. Clinical hepatomegaly and splenomegaly were found in 35% and 44% of patients, respectively. Enlarged liver and spleen on US were seen in 16 of 29 and 38 of 38 of patients, respectively. There were no reports of decompensated liver disease. CONCLUSION: Current evidence questions the need for routine assessment of LFT in immunocompetent patients presenting with IM; serial LFT assessments following initial abnormalities are not required in immunocompetent patients with subclinical derangement of LFT; routine US abdomen in IM to evaluate for derangement of LFT is not required.

Falsely elevated serum estradiol in woman of reproductive age led to unnecessary intervention and delayed fertility opportunity: a case report and literature review.

BACKGROUND: The optimal management of patients in reproductive endocrinology relies on the accuracy and validity of sex hormone assays. Endogenous or exogenous substances can compete with the analyte. This competition can result in interfering errors and falsely indicate elevated serum levels. Obvious interference in estradiol assays appears to occur rarely. Consequently, clinicians who are not familiar with the potential of interference could be misled. In addition to unnecessary investigations and interventions and severe mental stress, falsely elevated estradiol results can result in missed or delayed fertility opportunities. CASE: A 28-year-old female with pregnancy demand was diagnosed with polycystic ovary syndrome, Hashimoto's thyroiditis and subclinical hypothyroidism. She was found to have persistently elevated levels of serum estradiol in the early follicular phase (between 527 and 642 pg/mL). Screening workup was performed for nearly 11 months to find the causes. Serum tumor biomarkers were normal. Abdominal and pelvic computed tomography were negative for adrenal or adnexal masses. A left mesosalpinx cyst and benign pathological results were achieved by laparoscopic surgery. Hormonal substances and dietary supplements were absent, as determined by dietary records. Ultrasound confirmed follicles could grow slowly and eventually ovulate. Falsely elevated estradiol levels were suspected due to the discrepancy among high estradiol levels, follicle growth and normal gonadotropin levels. Immunological interference by heterophile antibody was finally verified by two competitive chemiluminescent immunoassay platforms (estradiol levels in the early follicle phase: 619 pg/mL, Siemens ADVIA CENTAUR and 60 pg/mL, Beckman, DxI 800). Successful clinical pregnancy was eventually achieved by combining induced ovulation, ultrasound monitoring and intercourse guidance. CONCLUSIONS: Analytical interference and laboratory error should be suspicious at first when the clinical characteristics contradict the laboratory results of serum hormones. Measuring serum estradiol with another immunoassay platform is an easy and non-time-consuming method to exclude the heterophile interfering.

A High Prevalence of Anti-EBNA1 Heteroantibodies in Systemic Lupus Erythematosus (SLE) Supports Anti-EBNA1 as an Origin for SLE Autoantibodies.

BACKGROUND: That Epstein-Barr virus (EBV) infection is associated with systemic lupus erythematosus (SLE) is established. The challenge is to explain mechanistic roles EBV has in SLE pathogenesis. Previous studies identify four examples of autoantibody cross-reactions between SLE autoantigens and Epstein-Barr nuclear antigen 1 (EBNA1). For two of these examples, the earliest detected autoantibody specifically cross-reacts with EBNA1; thereby, defined EBNA1 epitopes induce a robust autoantibody response in animals. These results suggest that the autoantibodies initiating the process leading to SLE may emerge from the anti-EBNA1 heteroimmune response. If this hypothesis is true, then anti-EBNA1 responses would be more frequent in EBV-infected SLE patients than in EBV-infected controls. We tested this prediction. METHODS: We evaluated published East Asian data by selecting those with a positive anti-viral capsid antigen (VCA) antibody immunoglobulin G (IgG) test and determining whether anti-EBNA1 was more common among the EBV-infected SLE cases than among matched EBV-infected controls with conditional logistic regression analysis. RESULTS: All the qualifying SLE patients (100%) in this dataset were EBV-infected compared to age- and sex-matched controls (92.2%) [odds ratio (OR) = 28.6, 95% CI 6.4-∞, p = 8.83 × 10-8], confirming the known close association of EBV infection with SLE. Furthermore, virtually all the SLE cases have both anti-VCA IgG and anti-EBNA1 IgG antibodies [124 of 125 (99.2%)], which are more frequently present than in age- and sex-matched EBV-infected controls [232 of 250 (93.2%)] (OR = 9.7, 95% CI 1.5-414, p = 0.0078) for an 89.7% SLE attributable risk from anti-EBNA1, which is in addition to the 100% SLE risk attributable to EBV infection in these data. CONCLUSIONS: The association of EBV infection with SLE is reconfirmed. The prediction that anti-EBNA1 is more frequent in these SLE cases than in EBV-infected controls is true, consistent with the hypothesis that anti-EBNA1 contributes to SLE. This second EBV-dependent risk factor is consistent with a molecular mimicry model for the generation of SLE, starting with EBV infection, progressing to anti-EBNA1 response; then molecular mimicry leads to anti-EBNA1 antibodies cross-reacting with an SLE autoantigen, causing autoantibody epitope spreading, and culminating in clinical SLE. These results support the anti-EBNA1 heteroimmune response being a foundation from which pathogenic SLE autoimmunity emerges.

Falsely elevated serum estradiol due to heterophile antibody interference: a case report

SUMMARY Falsely elevated estradiol is rare, may result from heterophile antibody interference, and can result in unnecessary investigation and intervention. We present the case of a 56-year-old female with falsely elevated estradiol levels inconsistent with her overall clinical picture, which ultimately led to an unnecessary surgical procedure. With the use of alternative analytical platforms and a heterophile antibody blocking agent, we determined the false elevation was due to heterophile antibody interference. Clinicians must suspect and investigate for laboratory error when the clinical picture contradicts laboratory results.

Knockdown of AKT3 Activates HER2 and DDR Kinases in Bone-Seeking Breast Cancer Cells, Promotes Metastasis In Vivo and Attenuates the TGFß/CTGF Axis.

Bone metastases frequently occur in breast cancer patients and lack appropriate treatment options. Hence, understanding the molecular mechanisms involved in the multistep process of breast cancer bone metastasis and tumor-induced osteolysis is of paramount interest. The serine/threonine kinase AKT plays a crucial role in breast cancer bone metastasis but the effect of individual AKT isoforms remains unclear. Therefore, AKT isoform-specific knockdowns were generated on the bone-seeking MDA-MB-231 BO subline and the effect on proliferation, migration, invasion, and chemotaxis was analyzed by live-cell imaging. Kinome profiling and Western blot analysis of the TGFß/CTGF axis were conducted and metastasis was evaluated by intracardiac inoculation of tumor cells into NOD scid gamma (NSG) mice. MDA-MB-231 BO cells exhibited an elevated AKT3 kinase activity in vitro and responded to combined treatment with AKT- and mTOR-inhibitors. Knockdown of AKT3 significantly increased migration, invasion, and chemotaxis in vitro and metastasis to bone but did not significantly enhance osteolysis. Furthermore, knockdown of AKT3 increased the activity and phosphorylation of pro-metastatic HER2 and DDR1/2 but lowered protein levels of CTGF after TGFß-stimulation, an axis involved in tumor-induced osteolysis. We demonstrated that AKT3 plays a crucial role in bone-seeking breast cancer cells by promoting metastatic potential without facilitating tumor-induced osteolysis.

What Therapeutic Regimen Will Be Optimal for Initial Clinical Trials of Pig Organ Transplantation?

We discuss what therapeutic regimen might be acceptable/successful in the first clinical trial of genetically engineered pig kidney or heart transplantation. As regimens based on a calcineurin inhibitor or CTLA4-Ig have proved unsuccessful, the regimen we administer to baboons is based on induction therapy with antithymocyte globulin, an anti-CD20 mAb (Rituximab), and cobra venom factor, with maintenance therapy based on blockade of the CD40/CD154 costimulation pathway (with an anti-CD40 mAb), with rapamycin, and a corticosteroid. An anti-inflammatory agent (etanercept) is administered for the first 2 wk, and adjuvant therapy includes prophylaxis against thrombotic complications, anemia, cytomegalovirus, and pneumocystis. Using this regimen, although antibody-mediated rejection certainly can occur, we have documented no definite evidence of an adaptive immune response to the pig xenograft. This regimen could also form the basis for the first clinical trial, except that cobra venom factor will be replaced by a clinically approved agent, for example, a C1-esterase inhibitor. However, none of the agents that block the CD40/CD154 pathway are yet approved for clinical use, and so this hurdle remains to be overcome. The role of anti-inflammatory agents remains unproven. The major difference between this suggested regimen and those used in allotransplantation is the replacement of a calcineurin inhibitor with a costimulation blockade agent, but this does not appear to increase the complications of the regimen.

Falsely elevated serum estradiol due to heterophile antibody interference: a case report.

Falsely elevated estradiol is rare, may result from heterophile antibody interference, and can result in unnecessary investigation and intervention. We present the case of a 56-year-old female with falsely elevated estradiol levels inconsistent with her overall clinical picture, which ultimately led to an unnecessary surgical procedure. With the use of alternative analytical platforms and a heterophile antibody blocking agent, we determined the false elevation was due to heterophile antibody interference. Clinicians must suspect and investigate for laboratory error when the clinical picture contradicts laboratory results.

False Positives in Thyroglobulin Determinations Due to the Presence of Heterophile Antibodies: An Underrecognized and Consequential Clinical Problem.

OBJECTIVE: To report a case series of thyroid cancer patients in whom false positive results in immunometric assays for thyroglobulin (TgIMA) were caused by heterophilic antibody interference, describe the clinical scenario in which this interference should be suspected, and recommend methods to demonstrate the interference. METHODS: Three patients with unexpectedly elevated thyroglobulin results (range, 1.6-75 ng/mL) were studied. In the first patient, thyroglobulin was elevated despite the presence of Tg antibody. In the second patient, suppressed thyroglobulin was higher than a recent stimulated thyroglobulin. In the third patient, thyroglobulin became detectable years after treatment and did not change after thyroid-stimulating hormone stimulation. TgIMA concentration determination was compared to determination by a mass spectrometry method (TgMS). Thyroglobulin was also remeasured after preabsorption with heterophile antibody blocking reagents and after serial dilutions. RESULTS: In all cases, thyroglobulin was undetectable by TgMS. In 2 of 3 patients, dilutions provided nonlinear thyroglobulin results. After blocking agent preabsorption, thyroglobulin dropped by 35%, 45%, and 91% in the 3 samples. CONCLUSION: False positive thyroglobulin concentrations from heterophilic antibody interference have significant impact on the management of thyroid cancer. Here we show that TgMS assays can be used to rule out heterophilic antibody interference. This interference should be suspected when a detectable thyroglobulin by TgIMA does not respond to thyroid-stimulating hormone or is discordant from the clinical assessment.

Heterophilic antibody interference with TSH measurement on different immunoassay platforms.

INTRODUCTION: Interference due to the presence of heterophilic antibodies may lead to falsely low or high analyte concentrations, but falsely elevated values are more common in most immunoassay platforms. We report a case of a 53-y old female patient underwent radical thyroidectomy for thyroid papillary carcinoma and the results of TSH in the Siemens Advia Centaur XP after surgery were not suppressed, ranging from 5.73 and 6.61 µIU/ml. METHODS: The status of the thyroid was then assessed using 4 assay platforms from Siemens, Abbott, Roche and Beckman. RESULTS: The results of TSH were 5.52, 0.54, 0.12, and <0.015 µIU/ml, respectively. After the samples were pretreated with the heterophilic antibody blocker, results given by Siemens, Abbott, and Roche showed significant decreases of 0.003, 0.001, and 0.005 µIU/ml, respectively. Therefore, it was confirmed that the presence of heterophilic antibodies in the patient samples interfered with the TSH measurements in multiple assay systems. CONCLUSIONS: Clinicians must be aware of the possible assay interference, including the measurements of FT4, FT3 and TSH, results may be misleading in the presence of heterophilic antibodies, in particular when the results of thyroid function tests do not fit the patient clinical presentation.

m6A RNA methylation-mediated HNF3γ reduction renders hepatocellular carcinoma dedifferentiation and sorafenib resistance.

Hepatocyte nuclear factor 3γ (HNF3γ) is a hepatocyte nuclear factor, but its role and clinical significance in hepatocellular carcinoma (HCC) remain unclear. Herein, we report that HNF3γ expression is downregulated in patient HCC and inversely correlated with HCC malignancy and patient survival. Moreover, our data suggested that the HNF3γ reduction in HCC could be mediated by METTL14-dependent m6A methylation of HNF3γ mRNA. HNF3γ expression was increased during hepatic differentiation and decreased in dedifferentiated HCC cells. Interestingly, HNF3γ delivery promoted differentiation of not only HCC cells but also liver CSCs, which led to suppression of HCC growth. Mechanistic analysis suggested an HNF3γ-centered regulatory network that includes essential liver differentiation-associated transcription factors and functional molecules, which could synergistically facilitate HCC cell differentiation. More importantly, enforced HNF3γ expression sensitized HCC cells to sorafenib-induced growth inhibition and cell apoptosis through transactivation of OATP1B1 and OATP1B3 expression, which are major membrane transporters for sorafenib uptake. Clinical investigation showed that patient-derived HCC xenografts with high HNF3γ expression exhibited a sorafenib response and patients with high HCC HNF3γ levels benefited from sorafenib therapy. Together, these results suggest that HNF3γ plays an essential role in HCC differentiation and may serve as a therapeutic target and predictor of sorafenib benefit in patients.

Anti-goat antibodies as a rare cause of high gonadotropin levels during menopausal transition.

Objective: To understand the origin of extremely high gonadotropin levels in a perimenopausal woman.Methods: A 52-year-old woman with a 2 months of amenorrhea followed spontaneous menstrual cycles recovery was referred to our outpatient clinic with elevated follicle-stimulating hormone (FSH, 483 mUI/ml), luteinizing hormone (LH, 475 mUI/ml) and prolactin (PRL, 173 ng/ml). She was known to take levosulpiride. The gonadotropin levels did not fit with the clinical features.Results: A gonadotroph tumor was ruled out. Further analysis confirmed constantly high FSH, LH and PRL levels. The measurements were repeated using different analytical platforms with different results. After serial dilutions, nonlinearity was present suggesting an immunoassay interference. After post-polyethylene glycol recovery, hormone levels appeared in the normal range. Anti-goat antibodies were recognized in the serum of the patient.Conclusions: This case report shows a case of falsely abnormal high gonadotropin and PRL levels in a woman during menopause transition. In the clinical practice the evaluation of gonadotropin profile is not recommended at this age, but the abnormal levels stimulated further evaluation. An interference in the assay due to anti-goat antibodies resulted in abnormally high level of FSH and LH. A strict collaboration between clinicians and the laboratory is needed, when laboratory findings do not correspond to clinical findings.

Heterophile antibody interference associated with natural killer cell therapy.

The adoptive transfer of ex vivo-expanded natural killer (NK) cells has recently been employed as an alternative cancer treatment in certain institutions. However, the safety profiles of this strategy remain uncharacterized. We evaluated three patients who exhibited elevated serum parathyroid hormone (PTH) levels without the relevant clinical manifestations and had a history of autologous NK cell therapy. The serum PTH concentration was measured using a second-generation PTH assay, and the serum thyroglobulin concentration was measured using a second-generation thyroglobulin assay. Subsequently, the PTH or thyroglobulin concentration obtained using heterophile-blocking tube (HBT) for a secondary confirmation assay was measured and compared with the result of the initial assay. The three patients had falsely elevated serum PTH and thyroglobulin levels owing to heterophile antibody interference associated with NK cell therapy that persisted for at least up to 12 months after the treatment and was confirmed by normalization of hormone levels after HBT treatment. We propose that certain types of mouse monoclonal antibodies used to stimulate NK cells can induce heterophile antibodies. Abnormal laboratory test results in individuals administered NK cell therapy without the relevant clinical manifestations must be examined in the context of heterophile antibody interference to avoid misdiagnosis and unnecessary testing.