Quantitative assessment of multiple pathogen exposure and immune dynamics at scale.

IMPORTANCE: Serology reveals exposure to pathogens, as well as the state of autoimmune and other clinical conditions. It is used to evaluate individuals and their histories and as a public health tool to track epidemics. Employing a variety of formats, studies nearly always perform serology by testing response to only one or a few antigens. However, clinical outcomes of new infections also depend on which previous infections may have occurred. We developed a high-throughput serology method that evaluates responses to hundreds of antigens simultaneously. It can be used to evaluate thousands of samples at a time and provide a quantitative readout. This tool will enable doctors to monitor which pathogens an individual has been exposed to and how that changes in the future. Moreover, public health officials could track populations and look for infectious trends among large populations. Testing many potential antigens at a time may also aid in vaccine development.

A systematic review of maternal TORCH serology as a screen for suspected fetal infection.

BACKGROUND: The acronym 'TORCH' refers to well-recognised causes of perinatal infections: toxoplasmosis, rubella, cytomegalovirus (CMV) and herpes simplex virus (HSV). A TORCH serology panel is often used to test for maternal primary infection following detection of ultrasound abnormalities in pregnancy. AIM: This review aims to estimate the diagnostic yield of maternal TORCH serology in pregnancy following fetal ultrasound abnormalities. MATERIALS AND METHODS: Primary studies published since 2000 that assessed maternal TORCH serology for suspected fetal infection and included information on indications for testing, definition of positive TORCH serology results, and perinatal outcomes were included. RESULTS: Eight studies with a total of 2538 pregnancies were included. The main indications for testing were polyhydramnios, fetal growth restriction and hyperechogenic bowel. There were 26 confirmed cases of congenital CMV, of which 15 had multiple ultrasound abnormalities. There were no cases of congenital toxoplasmosis, rubella or HSV confirmed in any of the eight studies. CONCLUSIONS: The clinical utility of TORCH serology for non-specific ultrasound abnormalities such as isolated fetal growth restriction or isolated polyhydramnios is low. It is time to retire the TORCH acronym and the reflex ordering of 'TORCH' panels, as their continued use obscures, rather than illuminates, appropriate investigation for fetal ultrasound abnormalities.

Why current quantitative serology is not quantitative and how systems immunology could provide solutions.

Determination of the presence of antibodies against infectious agents, self-antigens, allogeneic antigens and environmental antigens is the goal of medical serology. Along with the standardization of these tests the community also started to use the expression "quantitative serology," referring to the fact that arbitrary units are used for the expression of results. In this review I will argue against the use of the term quantitative serology for current tests. Because each test and each antibody isotype determination uses its own references, the term semiquantitative better describes these methods. The introduction of really quantitative serology could both benefit from and drive forward systems immunological approach to immunity.

Serological investigation and genotyping of Mycobacterium avium subsp. paratuberculosis in sheep and goats in Inner Mongolia, China.

Paratuberculosis a contagious and chronic disease in domestic and wild ruminants, is caused by Mycobacterium avium subspecies paratuberculosis (MAP). Typical clinical signs include intractable diarrhea, progressive emaciation, proliferative enteropathy, and mesenteric lymphadenitis. Paratuberculosis is endemic to many parts of the world and responsible for considerable economic losses. In this study, different types of paratuberculosis and MAP in sheep and goats were investigated in Inner Mongolia, a northern province in China contiguous with two countries and eight other provinces. A total of 4434 serum samples were collected from six cities in the western, central, and eastern regions of Inner Mongolia and analyzed using the ELISA test. In addition, tissue samples were collected from seven animals that were suspected to be infected with MAP. Finally, these tissues samples were analyzed by histopathological examination followed by polymerase chain reaction (PCR), IS1311 PCR-restriction enzyme analysis (PCR-REA), and a sequence analysis of five genes. Among all 4434 ruminant serum samples collected from the six cities in the western, central, and eastern regions of Inner Mongolia, 7.60% (337/4434) measured positive for the MAP antibody. The proportions of positive MAP antibody results for serum samples collected in the western, central, and eastern regions were 5.10% (105/2058), 6.63% (85/1282), and 13.44% (147/1094), respectively. For the seven suspected infected animals selected from the herd with the highest rate of positivity, the gross pathology and histopathology of the necropsied animals were found to be consistent with the pathological features of paratuberculosis. The PCR analysis further confirmed the diagnosis of paratuberculosis. The rest of the results demonstrated that herds of sheep and goats in Inner Mongolia were infected with both MAP type II and type III. To the best of our knowledge, this is the first study of the two subtypes of MAP strains in sheep and goats in Inner Mongolia.

Positive Rate of Serology and RT-PCR for COVID-19 among Community Residents and Healthcare Workers in Wuhan, China.

This study aimed to evaluate the infection rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among different populations in Wuhan, China. This cross-sectional survey-based study examined the results of SARS-CoV-2-specific serological tests and RT-PCR tests for 4,454 community residents and 4,614 healthcare workers performed from May 15 to May 29, 2020. The healthcare workers were classified as administrative and logistical staff (n = 1,378), non-first-line healthcare workers (n = 2,630), or first-line healthcare workers (n = 606) according to their frequency of contact with coronavirus disease (COVID-19) patients. The positive rates of SARS-CoV-2-specific IgG, IgM, and RNA were 2.9%, 0.4%, and 0.1% for the community residents and 3.3%, 0.6%, and 0.2% for the healthcare workers, respectively. There were no statistically significant differences between the rates of the two groups. Spearman's correlation analysis showed that the frequency of contact with COVID-19 patients negatively correlated with the positive rates of RT-PCR (rs = -0.036, P = 0.016), but did not significantly correlate with the positive rates of IgM (rs = -0.006, P = 0.698) or IgG (rs = 0.017, P = 0.239). There was no statistically significant difference between the SARS-CoV-2-specific IgG, IgM, or RNA positive rates of the community residents and those of the healthcare workers. The positive rate of SARS-CoV-2 RNA was lower for the first-line healthcare workers than for the non-first-line healthcare workers and the administrative and logistical staff.

Diagnostic role of CXCL13 and CSF serology in patients with neurosyphilis.

BACKGROUND: Considering the unknown prevalence of neurosyphilis in West China, and the confusing diagnosis of neurosyphilis, the role of CSF_CXCL13 and syphilis serology was studied to provide a more accurate reference for the clinical detection and diagnosis of neurosyphilis. METHODS: A retrospective data set I was used to investigate the prevalence of neurosyphilis, as well as the laboratory characteristics of 244 patients. Besides, to explore the diagnostic value of CSF_CXCL13 and syphilis serology for neurosyphilis, another 116 CSF_serum paired samples (data set II) were collected from 44 neurosyphilis and 72 non-neurosyphilis/syphilis patients. RESULTS: About 6.25% (156 out of 2494) syphilis was neurosyphilis. When Treponema pallidum infection occurs, syphilis serology (sero_TRUST ≥1:16 and sero_TPPA titre ≥1:10240) can be good predictors of neurosyphilis, as well as syphilis CSF serology (CSF_TPPA ≥1:320, CSF_TRUST and venereal disease research laboratory). The sensitivity of serology in neurosyphilis can be complemented by CSF_CXCL13, which could be the therapy monitor of neurosyphilis. CONCLUSION: Due to the lack of ideal biomarkers for neurosyphilis, the importance of syphilis serology cannot be ignored, and their combination with CSF_CXCL13 or other biomarkers should be further investigated.

Luminex screening first vs. direct single antigen bead assays: Different strategies for HLA antibody monitoring after kidney transplantation.

MAIN PROBLEM: Luminex panel and single antigen beads (SAB) are used for screening and DSA specificity determination respectively. The cost of SAB may limit its general use, so some labs perform SAB tests only after positive screening. METHODS: We compared both strategies: 1) SAB only if positive screening with kits from manufacturer A, and 2) direct SAB from manufacturer B, and correlate their sensitivity with histological findings. RESULTS: We selected 118 kidney transplant recipients with a normal biopsy (n = 19), histological antibody-mediated damage (ABMR, n = 52) or interstitial fibrosis/tubular atrophy (IFTA, n = 47) following Banff 2015 and 2017 classification. Direct SAB detected DSA in 13 patients missed by screening. Strategy 1 detected DSA in 0% normal, 61.5% ABMR and 8.5% IFTA patients; percentages with strategy 2 were 5.2%, 78.8% and 14.8% (p=0.004). Strategy 2 identified DSA allowing full ABMR diagnosis in 17% cases missed by strategy 1. Thereafter, direct SAB from manufacturer A confirmed DSA in 46% DSA-positive cases with strategy 2 (55.5% ABMR cases). CONCLUSIONS: Luminex screening failed to identify clinically relevant HLA antibodies, hampering DSA detection in patients with possible ABMR. Direct SAB testing should be the chosen strategy for post-transplantation monitoring, albeit direct SAB from the two existing manufacturers may diverge in as much as 50% of cases.

Utility of HSV Serology for Chronic Corneal Pathology.

OBJECTIVES: The purpose of this study is to determine the utility of obtaining herpes simplex virus (HSV) serology for patients presenting with chronic corneal pathology of unknown etiology for which HSV is a diagnostic consideration. METHODS: A retrospective analysis was performed of all patients presenting to one cornea specialist (J.M.G.) between August 2011 and April 2018 with a chronic (>6 weeks) corneal condition for which HSV was suspected and serology was performed. Patient demographics, clinical presentation, treatment, final diagnosis, and follow-up duration were recorded. RESULTS: Fifty-four patients with a median age of 52 (range: 5-85) years were included in the study. Patients were classified by presenting clinical features as corneal ulcer (46.2%), stromal keratitis (24.1%), superficial keratitis (18.5%), or keratouveitis (11.1%). The seroprevalence of HSV-1 and HSV-2 antibodies were 42.6% and 18.5%, including 5 patients (9.3%) positive for both HSV-1 and HSV-2. Serology impacted management for all patients with negative titers (48.1%), defined as discontinuing antiviral medication, electing not to start antiviral medication, or continuing antiviral medication for a non-HSV etiology (e.g., varicella zoster keratitis). No patients with HSV serology were ultimately diagnosed with HSV keratitis. Median follow-up duration was 1.5 years (range 0.8-6.6 years). CONCLUSION: Although only useful when negative, our study confirms that serology may be useful for excluding HSV as a diagnostic consideration for patients presenting with chronic corneal pathology. The seroprevalence of HSV antibodies for our patient cohort was comparable with previous population-based studies.