False-positive Serologic Test Research Articles

Content and specificity of the Anti-SARS-CoV-2 antibodies in solutions for immunoglobulin replacement therapy

BackgroundSpecific antibodies are important for post-vaccination and post-infection immune responses against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The role of antibodies in preventing and treating Coronavirus disease 2019 (COVID-19) in high-risk populations has been highlighted through the use of virus-specific monoclonal antibodies, which has raised the question of immunoglobulin replacement therapy (IRT) used in immunocompromised patients. MethodsVirus-specific anti-receptor-binding domain (RBD) and anti-nucleocapsid protein (NCAP) antibodies (assessed using a chemiluminescence assay and virus-neutralizing antibodies (virus neutralization test against Delta and Omicron variants)) were analyzed in 20 batches of 10 % (100 mg/mL) immunoglobulin solutions for intravenous IRT from two commercially available producers between January 2022 and March 2023 for clinical use. ResultsAnti-RBD and anti-NCAP antibodies were detected in all 20 batches of assessed IRT solutions (mean concentrations of 2817 IU/mL and 2380 IU/mL, respectively). Notably, the concentration of the virus-specific antibodies increased continuously during the follow-up period (from 822.5 IU/mL to 4066.4 IU/mL and 102 IU/mL to 3455.9 IU/mL). These antibodies demonstrated high virus-neutralizing activity against the Delta variant (mean titers of 436 and 325) but were limited to the Omicron variant (mean titers 78 and 70). The differences observed between the two brands were not statistically significant. ConclusionIRT solutions contain high concentrations of anti-SARS-CoV-2 specific antibodies, which may prevent COVID-19; however, the efficacy can be influenced by variable virus-neutralizing activities against different viral strains. Therefore, appropriate IRT should be combined with other approaches, such as vaccination or pre- and post-exposure prophylaxis. Passively transmitted specific antibodies may also lead to false-positive serological test results.

False-positive typhidot IgM assay in COVID-19 patients: A potential public health problem in tropical countries during COVID-19 endemic phase

BACKGROUND: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, reports of false-positive serological test results were reported in COVID-19 patients. Typhidot IgM test is reported in a few studies to give false-positive results in various viral illnesses in the past. The aim of this study was to estimate the typhidot IgM positivity rate in reverse transcription-polymerase chain reaction (RT-PCR)-confirmed COVID-19 patients. MATERIALS AND METHODS: The present study was a cross-sectional study conducted at a tertiary care hospital. All symptomatic patients having fever that were admitted between April 1, 2021, and July 15, 2021, with a confirmed RT-PCR-positive result for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) were included in the study. Serological testing was done by typhoid IgM/IgG rapid diagnostic test for all SARS-CoV-2 RT-PCR-positive patients. The primary outcome studied was to estimate the typhidot IgM positivity rate among RT-PCR-confirmed COVID-19 patients. The secondary outcome studied was to determine the correlation between SARS-CoV-2 RT PCR cycle threshold (CT) value and typhidot-positive result. RESULTS: Three hundred and five (17.99%) out of 1695 samples of confirmed COVID-19 patients were positive for typhoid serology by typhidot IgM test. However, upon performing Point-Biserial correlation analysis (P = 0.832, r = 0.021), no correlation was seen between RT-PCR CT value and typhidot result. CONCLUSIONS: Typhidot test is a nonspecific diagnostic test for typhoid fever which can be false positive in COVID-19 patients. Hence, physicians should take this into consideration to avoid misdiagnosis and delay in accurate treatment of acute febrile illness cases, especially in the present scenario of COVID-19 endemicity.

Dengue & COVID-19: A Comparison and the Challenges at Hand.

The COVID-19 pandemic caused by SARS-CoV-2spread across many countries between 2020 and 2022. The similarities in clinical presentation with other endemic diseases pose a challenge to physicians in effectively diagnosing and treating the infection. Approximately129 nations have a risk of dengue infection, and more than 100 of those are endemic to dengue. During the COVID-19 pandemic, the number of dengue cases decreased in many countries owing to the isolation measures followed. However, the common clinical presentation between them has led to misdiagnosis. Both COVID-19 and dengue fever cause a surge in pro-inflammatory cytokines and chemokines, thus sharing a common pathophysiology. False positive serological test results also posed difficulty differentiating between COVID-19 and dengue fever. This review aims to compare the clinical features, pathophysiology, and immune response between dengue and COVID-19, to benefit public health management during the pandemic.

Challenge of hepatitis B testing following intravenous immunoglobulin therapy in patients with autoimmune skindiseases.

Intravenous immunoglobulin (IVIg) contains pooled immunoglobulins from the plasma of healthy blood donors. All plasma samples are tested for HIV, hepatitis viruses (A, B, and C), and parvovirus B19. As part of this screening step, nucleic acid amplification technology (NAT) is used and allows the presence of specific antibodies targeting viral structures that are commonly used to test for infection status, such as anti-hepatitis B surface antigen (HBs) or anti-hepatitis B virus core (HBc) antibodies. For this reason, manufacturers point to the possibility of false-positive viral serological test results following IVIg treatment due to the passive transfer of antibodies. IVIg therapy is commonly used to manage patients with severe, treatment-refractory autoimmune skin diseases. The aim of this cohort study was to retrospectively quantify newly-discovered positive serological HBV test results after IVIg treatment in patients with autoimmune skin diseases. Between March 2018 and June 2021, 28 patients with autoimmune skin diseases received IVIg therapy, of whom 17 were longitudinally followed-up. None of the patients had evidence of active HBV infection prior to IVIg therapy. All patients (n=17) had detectable anti-HBs antibodies and 12 patients had anti-HBc antibodies 4 weeks after commencing IVIg treatment. Passive antibody transfer seems the most likely interpretation. Nevertheless, complete serological hepatitis assessment should be performed to exclude a new infection. We recommend hepatitis screening before IVIg therapy to prevent diagnostic confusion which may arise due to passive antibody transfer.

False-positive HIV and viral hepatitis serologic test results in a cluster of pork processing plant workers

BackgroundAccuracy of screening tests is vital in the diagnosis of HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV) infection. ObjectiveOur goal is to report false-positive serologic tests secondary to heterophile antibodies in a group of pork processing plant workers. MethodsWe conducted a case series study of seven pork processing plant workers referred to our clinic between 2017 and 2020 for a positive fourth-generation HIV test. ResultsAll patients had undetectable HIV-1 and HIV-2 RNA viral load, ruling out HIV infection. Five patients had initial positive HBV serologies but were negative upon retesting with neutralizing antibodies or heterophile antibody binding reagent. Three patients presented with respiratory symptoms. After extensive workup, they were diagnosed with interstitial lung disease of unknown etiology. For patients who left the plant, their symptoms resolved, and serologic test results reverted to negative. Conclusions: Occupational exposure to pork meat products may elicit heterophile antibody development and yield false-positive serologic results for HIV and viral hepatitis. Clinicians should interpret serologic tests carefully together with other relevant patient history and molecular tests. Further investigation is warranted to determine the etiology, pathophysiology, and occupational link of the pneumonitis syndrome.

Development and research of a model for differential diagnosis of latent late syphilis and false-positive serological reactions on immunochips with a panel of 12 Treponema pallidum antigens

The aim - to find the optimal attributing rules to distinguish groups of latent stages of syphilis and false positive serological tests of using multivariate discriminant analysis
 Material and methods. The objects of the study were serum samples from patients with late latent (N=34) syphilis and false positive serological tests (N=31).
 The samples were studied to determine IgG and IgM levels using indirect immunofluorescent reaction with immunochip containing recombinant antigens T. pallidum
 Results The mathematical model allows to differentiate with a high degree of confidence patients with late latent syphilis and with false-positive serological reactions to syphilis.
 Conclusions. . Multivariate discriminant analysis makes possible to create reliable mathematical models to classify patients with late latent syphilis and with false-positive serological reactions to syphilis.

Documentation of a false positive Lyme disease serologic test in a patient with untreated Babesia microti infection carries implications for accurately determining the frequency of Lyme disease coinfections

Although many infections may potentially cause a false positive Borrelia burgdorferi antibody test, particularly for IgM antibody, babesiosis is not regarded as an infection that does this. A patient with untreated babesiosis is described here who developed transient IgM seropositivity for antibodies to B. burgdorferi. Thus, the diagnosis of Lyme disease coinfection in patients with active babesiosis, as in patients with human granulocytic anaplasmosis, is more convincingly accomplished if an objective clinical manifestation of Lyme disease is present, such as an erythema migrans skin lesion.

Study of prevalence of biological false positive serological tests for syphilis in pregnancy

Study of prevalence of biological false positive serological tests for syphilis in pregnancy

DIAGNOSIS AND TREATMENT OF SYPHILIS IN PATIENTS COINFECTED WITH HUMAN IMMUNODEFICIENCY

A review article is addressed the issue of the diagnosis and treatment of syphilis that is developing against the background of HIV infection. A small number of HIV-infected patients may have false-negative or false-positive serological tests for syphilis. Patients with co-infection are at higher risk of the nervous system involvement as well as ocular and otological syphilis. The cases of treatment failure and neurorelapses are also more frequent in HIV-positive patients with syphilis. The effectiveness of neurosyphilis treatment in co-infected patients is difficult to assess, as the normalization of the CSF in HIV-positives is going slower comparing to HIV-negatives. The inevitable increase in incidence of syphilis and HIV co-infection is anticipated in the coming years. In this regard, a comprehensive study of the co-infection problem and improvement of approaches to managing patients based on the principles of evidence-based medicine is required.

Evaluation of three competitive ELISAs and a fluorescence polarisation assay for the diagnosis of bovine brucellosis

Bovine brucellosis is an infectious disease of worldwide public health and economic importance. The usual tests for the diagnosis of this disease include the Rose-Bengal test (RBT), complement fixation test (CFT), serum agglutination test (SAT) and indirect ELISA. New tests such as competitive ELISAs (C-ELISA) and fluorescence polarisation assay (FPA) have been developed. However, C-ELISA may correspond to different protocols and a wide variation may exist in their diagnostic performance. The aim of this study was to evaluate three commercially available C-ELISA kits (C-ELISA1–3) and FPA for the diagnosis of bovine brucellosis and compare test performance with RBT, CFT, indirect ELISA and FPA. Sera submitted to EU laboratories in 2011 from 5111 adult cattle were tested. Individual test sensitivities (Se) and specificities (Sp) were estimated. Threshold assessment using the receiver operating characteristic method was also performed.The most sensitive tests were FPA (99.0%; 95% confidence interval [CI], 97.9-100%), C-ELISA1 (98.4%; 95% CI, 97.0-99.8%) and RBT (97.7%; 95% CI, 95.9-99.3%). The most specific tests were CFT (99.98%; 95% CI, 99.93-100%), SAT (99.98%; 95% CI, 99.93-100%) and RBT (99.89%; 95% CI, 99.79-99.99%). Among the new tests, none of the three C-ELISA kits studied could be recommended as a single screening test because of their low specificity, especially when used in a herd. C-ELISA3 could not be recommended as confirmatory test on individual animals to determine whether false positive serological test results had occurred.

Biologically false positive serologic reactions for syphilis in patients with benign uterus tumors

The mechanism of formation of active and chronic false positive reactions serologic syphilis tests is described. Spontaneous negativation of acute false positive serologic reactions develops in 6 months. Chronic false positive serologic reactions persist for a long time, sometimes during the whole life time. Chronic false positive serologic reactions for syphilis are the diagnostic criteria for systemic lupus. Chronic false positive serologic reactions before and during the evaluation of clinical symptoms in other connective tissue diseases, endocrinologic, oncologic pathology are described. The Hughes ’syndrome is the most often cause of false positive serologic syphilis tests. 3 cases of false positive serologic syphilis tests in patients with benign uterus tumors are presented.

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Relationship between M-Protein of Multiple Myeloma and False Positive Syphilis Serological Results

The false positive in conventional syphilis serological test was found in patients with multiple myeloma (MM). To investigate the relationship between the M-protein of patients with MM and the false positive in conventional syphilis serologic test. The M-protein of 68 MM cases was typed with immunofixation electrophoresis and 68 cases of MM were screened with non-specific and specific syphilis serologic tests, then the samples with syphilic serological positive were chosen and confirmed with immonobloting test, finally the relationship between M protein of MM and the false positive of syphilis serological test were analysed. Four out of 68 cases showed the positive in syphilis serological test and further were confimed to be false positive by immunoblotting test, the false positive rate was nearly 6%. The M-protein of MM patients in our hospital mostly possessed IgG, κ type, followed by IgA, κ type, light chain κ type. In general, κ : λ = 2.4 : 1. Among samples of 4 cases with syphilis serological positive 2 cases were of IgG and κ type, 1 case was of IgG, λ type, another 1 case was IgA, κ type. The M-protein of IgG and IgA types in MM patients results in syphilis serological false positive reaction. The clinicians and laboratorial technicians should pay a great attention to screen the MM patients for the false positive syphilis serological test so as to avoid the misdiagnosis and subsequent embarassment.

Frequency of false positive rapid HIV serologic tests in African men and women receiving PrEP for HIV prevention: implications for programmatic roll-out of biomedical interventions.

BackgroundRapid HIV assays are the mainstay of HIV testing globally. Delivery of effective biomedical HIV prevention strategies such as antiretroviral pre-exposure prophylaxis (PrEP) requires periodic HIV testing. Because rapid tests have high (>95%) but imperfect specificity, they are expected to generate some false positive results.MethodsWe assessed the frequency of true and false positive rapid results in the Partners PrEP Study, a randomized, placebo-controlled trial of PrEP. HIV testing was performed monthly using 2 rapid tests done in parallel with HIV enzyme immunoassay (EIA) confirmation following all positive rapid tests.ResultsA total of 99,009 monthly HIV tests were performed; 98,743 (99.7%) were dual-rapid HIV negative. Of the 266 visits with ≥1 positive rapid result, 99 (37.2%) had confirmatory positive EIA results (true positives), 155 (58.3%) had negative EIA results (false positives), and 12 (4.5%) had discordant EIA results. In the active PrEP arms, over two-thirds of visits with positive rapid test results were false positive results (69.2%, 110 of 159), although false positive results occurred at <1% (110/65,945) of total visits.ConclusionsWhen HIV prevalence or incidence is low due to effective HIV prevention interventions, rapid HIV tests result in a high number of false relative to true positive results, although the absolute number of false results will be low. Program roll-out for effective interventions should plan for quality assurance of HIV testing, mechanisms for confirmatory HIV testing, and counseling strategies for persons with positive rapid test results.

Burden of hepatitis C virus infection and its genotypes among the blood donors at Tirupati, Andhra Pradesh

Background: Safe blood donation remains a challenge in resource limited countries. False positive serological tests lead to wastage of large number of blood units. Nucleic acid amplification test (NAAT) technology has greatly enhanced the accuracy in identification of transfusions transmitted infections. Methods: The present study was undertaken to study the seroprevalence of hepatitis C virus (HCV) and asses the concordance between seropositivity with the presence of HCV ribonucleic acid (RNA) and to know the distribution pattern of HCV genotypes in healthy blood donors. Results: Among the 9287 donors screened (88.3% males), 7153 (77%) were voluntary donors while 2134 (23%) were replacement donors. Among blood donors, 27 (0.3%) samples tested HCV seropositive. Among 27 anti-HCV positive samples only 11 (41%) were found positive for HCV RNA. Among the 5 samples subjected to sequencing, three were found to be genotype 1a while two were genotype 3a. Conclusions: Our observations suggest that implementing NAAT test for HCV screening will be helpful in minimizingfalse-positive test results in the Indian setting.

Antiphospholipid syndrome: 30 years and our contribution.

In 1983, Graham Hughes first described the concept of antiphospholipid syndrome (APS). In 1984, we described the enzyme-linked immunosorbent assay (ELISA) system which directly detected circulating aCL in patients with systemic lupus erythematosus (SLE) who revealed biological false positive serological test for syphilis. In 1990, three groups, including our group, independently reported the necessity of a cofactor for the binding of autoimmune anticardiolipin antibodies (aCL) to the solid phase phospholipids. β2-glycoprotein I (β2GPI) was identified as this cofactor. In 1994,the epitope for aCL was shown to develop when β2GPI is adsorbed on polyoxygenated polystyrene plates. In 2000, we described antiprothrombin antibodies bind to prothrombin exposed to immobilized phosphatidylserine and established a phosphatidylserine dependent monoclonal antiprothrombin antibody. In 2004, a novel role of nicked β2GPI was identified in the negative feedback pathway of extrinsic fibrinolysis. Nicked β2GPI was found to bind angiostatin 4.5 and to attenuate its antiangiogenic property. In 2004, we demonstrated that the p38 MAPK pathway mediates induction of the TF gene in stimulated with human monoclonal anti- β2GPI antibodies. Very recently, β2GPI was identified as a complement regulator. The cross-link between complement activation and prothrombotic status in patients with APS has been drawn much attention. Genetic factors are hypothesized to play a role in the susceptibility to APS based on several family studies in patients with antiphospholipid antibodies (aPL) and/or clinical manifestations of APS. The genetics of β2GPI has been extensively studied. 247 Val/Leu polymorphism can affect the conformational change of β2-GPI and the exposure of the epitopes for aCL. We found that 247 Val was correlated with anti-β2-GPI production in patients with primary APS, and 247 Val may be important for β2-GPI antigenicity. STAT4 SNP in Japanese patients with SLE and/or APS. T allele frequencies in SLE and APS were significantly elevated compared with that in healthy controls. When analyzed only in primary APS patients, T allele frequency was further higher. BANK1, BLK and SNP in 1q25.1 region were associated with not only SLE but also APS in Japanese population. These results suggest that APS and SLE, in part, share a common genetic background.

Peripheral neuropathy caused by cryoglobulinaemia with false-positive serological tests of syphilis

Peripheral neuropathy caused by cryoglobulinaemia with false-positive serological tests of syphilis

False-Positive Results for Immunoglobulin M Serologic Results: Explanations and Examples.

Scenario* A measles outbreak occurred last month among a cluster of unvaccinated children in a suburban area in your referral region. Two weeks ago, an adolescent who received two doses of measles-containing vaccine in childhood developed a febrile illness with rash. This patient tested positive for measles IgM in a commercial assay. Subsequent testing by the Centers for Disease Control and Prevention demonstrated seronegativity for measles IgM. (A low positive concentration of measles IgG was detected.) The initial IgM test result has been labeled as false positive. The family of the patient is upset about the disruption of life experienced due the false positive IgM result. The pediatrician who ordered the test has called to ask you how this result could have happened. What are potential explanations for this? The false-positive rate of any diagnostic test is a function of the specificity of the test and prevalence of the disease in the population represented by the patient. For serologic assays, the presence of antibodies that cross-react with microbial antigens used in the assay or interfering substances that interact with assay components can also lead to false-positive results. Technical performance issues such as over-reading of weakly reactive bands on immunoblots can also lead to false-positive serologic tests results for microbes for which these assays are used (eg, Borrelia burgdorferi )[ 1]. Thus, positive IgM assay results can require cautious interpretation—consideration of clinical course compatibility and epidemiological factors—and/or confirmation by other serological or molecular testing methods. The issue of reactivation of IgM production against herpes viruses is beyond the scope of this review.

Pediatric Systemic Lupus Erythematosus: More Than a Positive Antinuclear Antibody

Based on strong research evidence and consensus, the most common disease manifestations at diagnosis of pSLE are constitutional symptoms, arthritis, and malar rash. Based on some research evidence and consensus, patients with pSLE tend to have major organ system involvement (renal/central nervous system) and a greater disease burden compared with adults. Despite these findings, mortality is low. Based on some research evidence and consensus, the diagnosis of pSLE is unlikely if the ANA is negative, and most patients with SLE have a positive ANA at a titer ≥1:160. Based on strong research evidence, both MMF and cyclophosphamide can be used for induction therapy in class III and IV lupus nephritis. Based on strong research evidence, patients with SLE and anticardiolipin antibodies or LA have a two and six times greater risk of venous thrombosis, respectively, compared with patients with SLE without antiphospholipid antibodies. Based on strong research evidence, patients with pSLE have a higher risk for subclinical atherosclerosis when there is weight-adjusted prednisone use, azathioprine use, increasing age, male gender, high BMI, abnormal creatinine clearance, and elevated lipoprotein(a) levels.

Interpretation of HIV Serologic Testing Results

A 33-year-old male patient visited the outpatient clinic at Brigham and Women's Hospital for a routine follow-up for obesity, obstructive sleep apnea, allergic rhinitis, and depression. He was maintained on a nocturnal continuous positive airway pressure device, loratadine, duloxetine, and fluticasone nasal spray. He was a resident of Boston and had not traveled outside the country. He denied intravenous drug use or high-risk sexual behavior, and he had not received any blood products. He had received his most recent influenza vaccine about 6 months earlier. He was screened for type 2 diabetes and hyperlipidemia. As a part of routine clinical care, he was also offered HIV screening in accordance with the current CDC recommendations (1). The HIV assay [HIV 1/O/2 Enhanced (EHIV)], which was performed on the ADVIA Centaur analyzer (Siemens Healthcare Diagnostics), yielded a reactive result. As per the assay protocol developed by the manufacturer, the initially reactive sample was retested in duplicate after centrifugation; both results were reactive. The positive screen was followed up with a confirmatory western blot (WB)3 analysis, which yielded an indeterminate result. The presence of an isolated p24 band in the WB (GS Western HIV-1; Bio-Rad Laboratories) was of concern regarding possible early HIV seroconversion. ### QUESTIONS TO CONSIDER 1. What factors are known to cause false-positive HIV serologic test results? 2. What factors are known to cause an indeterminate WB result? 3. What further testing or clinical history would be of help in evaluating a patient with an indeterminate WB result? The Siemens EHIV screen performed in this case is a double antigen-bridging microparticle chemiluminometric immunoassay that detects antibodies against p24, gp41, gp120 (from HIV-1), gp36 (from HIV-2), and a synthetic peptide from group O HIV-1 (Fig. 1). A positive result indicates the presence of antibodies that recognize any of these antigens, regardless of their isotype or subclass. Although …