Dyslipidemia as Predictor of Missed Miscarriage

Background: This study aimed at finding the diagnostic and prognostic possibilities of determining apoC-II, as a serological marker for MM in early gestation. Methods and Results: The study included 182 pregnant women aged between 18 and 45 years at gestational age under 11 weeks. All women were divided into 3 groups. Group 1 (Gr1) included 90 women with MM; Group 2 (Gr2) included 52 women with spontaneous miscarriage; Group 3 included 40 women without pathology (control group [CG]). Lipid metabolism disorders were diagnosed according to the Russian national recommendations of the VII revision(the Russian Society of Cardiologists [RSC, 2020]), considering the European recommendations (2019). Proteomic analysis of the blood serum was performed using LC-MS. Abnormalities in the lipid profile were more common in patients with MM and spontaneous abortions: 62.2% and 59.7% of cases, respectively, which correlates with the identified marker apoC-II in Gr1 and Gr2. Conclusion: ApoC-II can be considered as the most promising serologic marker for MM in the early gestation period for women with dyslipidemia.

Immune Correlates Analysis of the mRNA-1273 COVID-19 Vaccine Efficacy Trial

Background: In the Coronavirus Efficacy (COVE) trial, estimated mRNA-1273 vaccine efficacy against coronavirus disease-19 (COVID-19) was 94%. SARS-CoV-2 antibody measurements were assessed as correlates of COVID-19 risk and as correlates of protection. Methods: Through case-cohort sampling, participants were selected for measurement of four serum antibody markers at Day 1 (first dose), Day 29 (second dose), and Day 57: IgG binding antibodies (bAbs) to Spike, bAbs to Spike receptor-binding domain (RBD), and 50% and 80% inhibitory dilution pseudovirus neutralizing antibody titers calibrated to the WHO International Standard (cID50 and cID80). Participants with no evidence of previous SARS-CoV-2 infection were included. Cox regression assessed in vaccine recipients the association of each Day 29 or 57 serologic marker with COVID-19 through 126 or 100 days of follow-up, respectively, adjusting for risk factors. Results: Day 57 Spike IgG, RBD IgG, cID50, and cID80 neutralization levels were each inversely correlated with risk of COVID-19: hazard ratios 0.66 (95% CI 0.50, 0.88; p=0.005); 0.57 (0.40, 0.82; p=0.002); 0.41 (0.26, 0.65; p<0.001); 0.35 (0.20, 0.60; p<0.001) per 10-fold increase in marker level, respectively, multiplicity adjusted P-values 0.003-0.010. Results were similar for Day 29 markers (multiplicity adjusted P-values <0.001-0.003). For vaccine recipients with Day 57 reciprocal cID50 neutralization titers that were undetectable (<2.42), 100, or 1000, respectively, cumulative incidence of COVID-19 through 100 days post Day 57 was 0.030 (0.010, 0.093), 0.0056 (0.0039, 0.0080), and 0.0023 (0.0013, 0.0036). For vaccine recipients at these titer levels, respectively, vaccine efficacy was 50.8% (-51.2, 83.0%), 90.7% (86.7, 93.6%), and 96.1% (94.0, 97.8%). Causal mediation analysis estimated that the proportion of vaccine efficacy mediated through Day 29 cID50 titer was 68.5% (58.5, 78.4%). Conclusions: Binding and neutralizing antibodies correlated with COVID-19 risk and vaccine efficacy and likely have utility in predicting mRNA-1273 vaccine efficacy against COVID-19. Trial registration number: COVE ClinicalTrials.gov number, NCT04470427

Case Report: Acute presentation of autoimmune hepatitis in a male patient

Introduction: Autoimmune hepatitis (AIH) is one of the major immune mediated chronic liver diseases. It typically affects young and middle-aged females. Acute liver failure (ALF) is an unusual initial form of presentation of AIH and is particularly rare in male patients. Consequently, the clinical characteristics and optimal management of this entity remain poorly defined. Patients with AIH sometimes present features of the spectrum of primary biliary cholangitis (PBC), simultaneously or consecutively, suggesting the diagnosis of overlap syndrome (OS) PBC- AIH. Data concerning PBC-AIH has been scarcely published and mainly comprises small retrospective studies. Case presentation: Herein, we report the case of a 40-year-old man with no history of any chronic liver disease, who presented with ALF. After carrying out extensive etiological screening, we suspected him of having ALF due to auto-immune liver disease namely AIH. The positivity of anti-mitochondrial antibody (AMA) which is a significant serologic marker of PBC, suggested a diagnosis of OS PBC- AIH. Since urgent liver transplantation could not be performed in our country (Tunisia), the only available therapeutic option was the administration of corticosteroids. During the two years of follow up and treatment with ursodeoxycholic acid, azathioprine and a low dose of prednisolone, our patient is still asymptomatic with normal hepatic function tests. Conclusion: ALF due to AIH in a male patient is a very rare condition. The diagnosis should be considered in all patients with acute hepatitis of undetermined etiology. Corticosteroids were an effective and lifesaving therapeutic option. The association of AIH and PBC features could suggest an OS.

Predictive Markers of Missed Miscarriage

The aim of this study was to find useful the serological markers for missed miscarriage (MM) in order to predict the outcome of pregnancy. The study included 141 pregnant women aged between 18 and 45 years at gestational age under 11 weeks. All women were divided into 3 groups. Group 1 included 68 women with MM; Group 2 included 43 women with spontaneous miscarriage; Group 3 included 30 pregnant women without pathology. Proteomic analysis of the blood serum was performed using liquid chromatography-mass spectrometry. The results of our study show that immunoglobulin kappa variable 3-15 (KV315) can be considered as the most promising serologic marker for MM in early gestation. The potential role of KV315 as the serological marker is very important for predicting the course of pregnancy.

Anca negative pauci-immune crescentic glomerulonephritis and mixed connective tissue disease: a case study

One of the most common causes of rapidly progressive glomerulonephritis (RPGN) is pauci-immune crescentic glomerulonephritis (CrGN). In the majority of cases, this condition has a positive serologic marker, the anti-neutrophil cytoplasmic antibodies (ANCAs), but in approximately 10% there are no circulating ANCAs, and this subgroup has been known as the ANCA-negative pauci-immune CrGN. RPGN can be associated with systemic diseases, but there are only few case reports describing the association with mixed connective tissue disease (MCTD). The authors report a case of ANCA-negative CrGN associated with a MCTD.

Early Detection of Severe Acute Respiratory Syndrome Coronavirus 2 Antibodies as a Serologic Marker of Infection in Patients With Coronavirus Disease 2019

Background Thousands of medical staff have been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with hundreds of deaths reported. Such loss could be prevented if there were a serologic assay for SARS-CoV-2–specific antibodies for serological surveillance of its infection at the early stage of disease. Methods Using Chinese hamster ovarian (CHO) cell–expressed full-length SARS-CoV-2 S1 protein as capturing antigen, a coronavirus disease 2019 (COVID-19)/SARS-CoV-2 S1 serology enzyme-linked immunosorbent assay (ELISA) kit was developed and validated with negative samples collected prior to the outbreak or during the outbreak and positive samples from patients confirmed with COVID-19. Results The specificity of the ELISA kit was 97.5%, as examined against total 412 normal human samples. The sensitivity was 97.1% by testing against 69 samples from hospitalized and/or recovered COVID-19 patients. The overall accuracy rate reached 97.3%. The assay was able to detect SARS-CoV-2 antibody on day 1 after the onset of COVID-19 disease. The average antibody levels increased during hospitalization and 14 days after discharge. SARS-CoV-2 antibodies were detected in 28 of 276 asymptomatic medical staff and 1 of 5 nucleic acid test–negative “close contacts” of COVID-19 patients. Conclusions With the assays developed here, we can screen medical staff, incoming patients, passengers, and people who are in close contact with the confirmed patients to identify the “innocent viral spreaders,” protect the medical staff, and stop further spread of the virus.

Distribution of Toxoplasma gondii IgM and IgG antibody seropositivity among age groups and gestational periods in pregnant women

Background: Toxoplasmosis is a globally distributed parasitic disease. The present study aimed to estimate the prevalence and geographic distribution of toxoplasmosis as well as determine the percentage of toxoplasmosis-associated IgM and IgG seropositivity among different age groups. In addition, it aimed to estimate the proportion of toxoplasma IgM seropositivity among pregnancy trimesters. Methods: A total of 500 pregnant women were included in this study. From each participant, a 5-ml venous blood sample was collected and centrifuged to obtain serum that was tested for Toxoplasma gondii IgM and IgG antibodies using immunochromatographic testing and ELISA. Results: The overall seroprevalence of toxoplasmosis was 24.8%. Out of the total of 500 participants, only 8% had a serological marker of acute toxoplasmosis). There is a statistically significant difference in the seroprevalence of disease among the study areas. Amongst positive cases of every trimester, 54.34% of first trimester positive cases had a serologic marker for acute toxoplasmosis. Conclusions: In this study, there is a high prevalence of toxoplasmosis. Therefore, it is necessary to test every pregnant woman for toxoplasmosis and distinguish the type of infection, as well as the conduction of public health education programs to generate the awareness.

Primary membranous nephropathy: comprehensive review and historical perspective

Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in non-diabetic Caucasian adults over 40 years of age. It has an estimated incidence of 8–10 cases per 1 million. Fifty per cent of patients diagnosed with primary MN continue to have nephrotic syndrome and 30% of patients may progress to end-stage renal disease over 10 years. Although it was recognised as a distinct clinic-pathological entity in 1940s by immunofluorescence and electron microscopy, the pathogenesis and treatment have become more apparent only in the last decade. Discovery of M-type phospholipase A2 receptor (PLA2R) antibodies and thrombospondin type 1 domain-containing 7A antibodies has given new perspectives in understanding the pathogenesis of the disease process. Anti-PLA2R antibody is the first serologic marker that has promising evidence to be used as a tool to prognosticate the course of the disease. More importantly, therapeutic agents such as rituximab and adrenocorticotropic hormone analogues are the newer therapeutic options that should be considered in the therapy of primary MN.

Chronic Toxoplasma gondii Infection Induces Anti-N-Methyl-D-Aspartate Receptor Autoantibodies and Associated Behavioral Changes and Neuropathology

ABSTRACT Anti-NMDA receptor (NMDAR) autoantibodies have been postulated to play a role in the pathogenesis of NMDAR hypofunction, which contributes to the etiology of psychotic symptoms. Toxoplasma gondii is a pathogen implicated in psychiatric disorders and associated with elevation of NMDAR autoantibodies. However, it remains unclear whether parasite infection is the cause of NMDAR autoantibodies. By using mouse models, we found that NMDAR autoantibody generation had a strong temporal association with tissue cyst formation, as determined by MAG1 antibody seroreactivity (r = 0.96; P < 0.0001), which is a serologic marker for the cyst burden. The presence of MAG1 antibody response, but not T. gondii IgG response, was required for NMDAR autoantibody production. The pathogenic relevance of NMDAR autoantibodies to behavioral abnormalities (blunted response to amphetamine-triggered activity and decreased locomotor activity and exploration) and reduced expression of synaptic proteins (the GLUN2B subtype of NMDAR and PSD-95) has been demonstrated in infected mice. Our study suggests that NMDAR autoantibodies are specifically induced by persistent T. gondii infection and are most likely triggered by tissue cysts. NMDAR autoantibody seroreactivity may be a novel pathological hallmark of chronic toxoplasmosis, which raises questions about NMDAR hypofunction and neurodegeneration in the infected brain.