Serum NfL predicts outcome and secondary autoimmunity in herpes-simplex encephalitis.

Objectives: Herpes simplex virus 1 encephalitis (HSE) is the most common infectious encephalitis in developed countries. We aimed to evaluate the association of serum neurofilament light chain (sNfL) with disease severity, outcome and secondary anti-neuronal autoantibodies in a retrospective cohort study.

Methods: We retrospectively identified 30 patients with HSE and 132 controls (bacterial meningoencephalitis BM n = 27, non-bacterial meningitis NBM n = 33, healthy controls = 72).

Tryptophan degradation as a systems phenomenon in inflammation - an analysis across 13 chronic inflammatory diseases.

Background: Chronic inflammatory diseases (CIDs) are systems disorders that affect diverse organs including the intestine, joints and skin. The essential amino acid tryptophan (Trp) can be broken down to various bioactive derivatives important for immune regulation. Increased Trp catabolism has been observed in some CIDs, so we aimed to characterise the specificity and extent of Trp degradation as a systems phenomenon across CIDs.

Cycle threshold of SARS-CoV-2 RT-PCR as a driver of retesting.

SARS-CoV-2 RT-PCR is a critical and, at times, limited resource. Frequent Retesting of patients may strain testing infrastructure unduly. Recommendations that include cycle threshold (Ct) cutoffs may incentivize early retesting when the Ct value is reported.

Analysis of the Seasonal Fluctuation of γδ T Cells and Its Potential Relation with Vitamin D.

In addition to its role in bone metabolism, vitamin D exerts immunomodulatory effects and has been proposed to contribute to seasonal variation of immune cells. This might be linked to higher vitamin D levels in summer than in winter due to differential sun exposure. γδ T cells comprise a numerically small subset of T cells in the blood, which contribute to anti-infective and antitumor immunity.

B-cell responses to vaccination with BNT162b2 and mRNA-1273 6 months after second dose.

Objectives: To examine the state of B-cell immunity 6 months after the second vaccination against SARS-CoV-2 in comparison to the state observed 2 weeks after vaccination.

Methods: Sera of 439 participants, whose immune responses to two doses of an mRNA-based vaccine (BNT162b2 or mRNA-1273) were previously characterized, was examined for anti-S1 IgG and IgA, anti-NCP IgG and neutralizing antibodies (nAb), and antinuclear antibodies (ANA).

Results: Levels of all examined markers decreased significantly from 2 weeks to 6 months after second vaccination (anti-S1 IgG: 3744 ± 2571.

Kinetics of the Antibody Response to Boostering With Three Different Vaccines Against SARS-CoV-2.

Background: Heterologous vaccinations against SARS-CoV-2 with ChAdOx1 nCoV-19 and a second dose of an mRNA-based vaccine have been shown to be more immunogenic than homologous ChAdOx1 nCoV-19. In the current study, we examined the kinetics of the antibody response to the second dose of three different vaccination regimens (homologous ChAdOx1 nCoV-19 vs. ChAdOx1 nCoV-19 + BNT162b2 or mRNA-1273) against SARS-CoV-2 in a longitudinal manner; whether there are differences in latency or amplitude of the early response and which markers are most suitable to detect these responses.

Validation of a predictive model for identifying an increased risk for recurrence in adolescents and young adults with a first provoked thromboembolism.

Background: To develop and validate a predictive model to determinate patients at increased risk to suffer from recurrence following a first provoked deep vein thrombosis (VTE).

Methods: Predictive variables, i.e.

The temporal course of T- and B-cell responses to vaccination with BNT162b2 and mRNA-1273.

Objectives: To investigate the response of the immune system (and its influencing factors) to vaccination with BNT162b2 or mRNA-1273.

Methods: 531 vaccinees, recruited from healthcare professionals, donated samples before, in between, and after the administration of the two doses of the vaccine. T- and B-cell responses were examined via interferon-γ (IFN-γ) release assay, and antibodies against different epitopes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (S1 and NCP) were detected via ELISA and surrogate neutralization assay.

Analysis of SARS-CoV-2 reverse transcription-quantitative polymerase chain reaction cycle threshold values vis-à-vis anti-SARS-CoV-2 antibodies from a high incidence region.

Objectives: To examine the relationship between antibody status and cycle threshold (Ct) values, the prognostic value of the latter for COVID-19 patients, and the inter-assay comparability of SARS-CoV-2 Ct values.

Methods: In 347 COVID-19 inpatients, SARS-CoV-2 Ct values (via reverse transcription-quantitative polymerase chain reaction) on admission were compared between 2 assays and correlated with the antibody response (in the course of the disease), the clinical course and the time since onset of symptoms.

Results: Ct values for 2 of 3 target genes showed significant differences between the 2 assays used (P=0.

Short-term physical exercise impacts on the human holobiont obtained by a randomised intervention study.

Background: Human well-being has been linked to the composition and functional capacity of the intestinal microbiota. As regular exercise is known to improve human health, it is not surprising that exercise was previously described to positively modulate the gut microbiota, too. However, most previous studies mainly focused on either elite athletes or animal models.

Genome-wide analysis of 944 133 individuals provides insights into the etiology of haemorrhoidal disease.

Objective: Haemorrhoidal disease (HEM) affects a large and silently suffering fraction of the population but its aetiology, including suspected genetic predisposition, is poorly understood. We report the first genome-wide association study (GWAS) meta-analysis to identify genetic risk factors for HEM to date.

Design: We conducted a GWAS meta-analysis of 218 920 patients with HEM and 725 213 controls of European ancestry.

Clinical correlates of anti-SARS-CoV-2 antibody profiles in Spanish COVID-19 patients from a high incidence region.

Laboratory testing for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) consists of two pillars: the detection of viral RNA via rt-PCR as the diagnostic gold standard in acute cases, and the detection of antibodies against SARS-CoV-2. However, concerning the latter, questions remain about their diagnostic and prognostic value and it is not clear whether all patients develop detectable antibodies. We examined sera from 347 Spanish COVID-19 patients, collected during the peak of the epidemic outbreak in Spain, for the presence of IgA and IgG antibodies against SARS-CoV-2 and evaluated possible associations with age, sex and disease severity (as measured by duration of hospitalization, kind of respiratory support, treatment in ICU and death).

Single- and Multimarker Genome-Wide Scans Evidence Novel Genetic Risk Modifiers for Venous Thromboembolism.

Previous genome-wide association studies (GWASs) have established several susceptibility genes for venous thromboembolism (VTE) and suggested many others. However, a large proportion of the genetic variance in VTE remains unexplained. Here, we report genome-wide single- and multimarker as well as gene-level associations with VTE in 964 cases and 899 healthy controls of European ancestry.

Acquired von Willebrand syndrome in ECMO patients: A 3-year cohort study.

Background: Bleeding is a common but possibly underreported side effect of Extracorporeal Membrane Oxygenation (ECMO). Impairment of primary hemostasis by acquired von Willebrand syndrome (aVWS) and platelet dysfunction as well as activation and consumption of plasmatic coagulation factors contribute to hemorrhage. The aim of the present cohort study of consecutively enrolled patients admitted to our ECMO center was to collect demographic, medical and laboratory data possibly associated with i) development of clinically relevant bleeding and/or ii) death during a 12-months follow-up.

Antibody-related movement disorders - a comprehensive review of phenotype-autoantibody correlations and a guide to testing.

Background: Over the past decade increasing scientific progress in the field of autoantibody-mediated neurological diseases was achieved. Movement disorders are a frequent and often prominent feature in such diseases which are potentially treatable.

Main Body: Antibody-mediated movement disorders encompass a large clinical spectrum of diverse neurologic disorders occurring either in isolation or accompanying more complex autoimmune encephalopathic diseases.

Longitudinal Multi-omics Analyses Identify Responses of Megakaryocytes, Erythroid Cells, and Plasmablasts as Hallmarks of Severe COVID-19.

Temporal resolution of cellular features associated with a severe COVID-19 disease trajectory is needed for understanding skewed immune responses and defining predictors of outcome. Here, we performed a longitudinal multi-omics study using a two-center cohort of 14 patients. We analyzed the bulk transcriptome, bulk DNA methylome, and single-cell transcriptome (>358,000 cells, including BCR profiles) of peripheral blood samples harvested from up to 5 time points.

Circulating levels of soluble Dipeptidylpeptidase-4 are reduced in human subjects hospitalized for severe COVID-19 infections.

Dipeptidylpeptidase (DPP)-4 is a key regulator of the incretin system. For several years DPP-4 inhibitors in addition to GLP-1 analogues are of major importance in the clinical management of obesity and type 2 diabetes. DPP-4 is also known as CD26 and represents a membrane bound protease on the surface of several eukaryotic cell types.

Gender issues of antibody-mediated diseases in neurology: (NMOSD/autoimmune encephalitis/MG).

Neuromyelitis optica spectrum disorder (NMOSD), autoimmune encephalitis (AE), myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS) are antibody-mediated neurological diseases. They have mostly female predominance, affecting many women during childbearing age. Interactions between the underlying disease (or necessary treatment) and pregnancy can occur in every of these illnesses.

ADAMTS12, a new candidate gene for pediatric stroke.

We recently reported a family-based genome wide association study (GWAS) for pediatric stroke pointing our attention to two significantly associated genes of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) gene family ADAMTS2 (rs469568, p = 8x10-6) and ADAMTS12 (rs1364044, p = 2.9x10-6). To further investigate these candidate genes, we applied a targeted resequencing approach on 48 discordant sib-pairs for pediatric stroke followed by genotyping of the detected non-synonymous variants in the full cohort of 270 offspring trios and subsequent fine mapping analysis.

Antiparanodal antibodies and IgG subclasses in acute autoimmune neuropathy.

Objective: To determine whether IgG subclasses of antiparanodal autoantibodies are related to disease course and treatment response in acute- to subacute-onset neuropathies, we retrospectively screened 161 baseline serum/CSF samples and 66 follow-up serum/CSF samples.

Methods: We used ELISA and immunofluorescence assays to detect antiparanodal IgG and their subclasses and titers in serum/CSF of patients with Guillain-Barré syndrome (GBS), recurrent GBS (R-GBS), Miller-Fisher syndrome, and acute- to subacute-onset chronic inflammatory demyelinating polyradiculoneuropathy (A-CIDP). We evaluated clinical data retrospectively.

Role of prothrombin 19911 A>G polymorphism, blood group and male gender in patients with venous thromboembolism: Results of a German cohort study.

The role of the A>G polymorphism at position 19911 in the prothrombin gene (factor [F] 2 at rs3136516) as a risk factor for venous thromboembolism [VTE] is still unclear. To evaluate the presence of the F2 polymorphism in VTE patients compared to healthy blood donors and to adjust the results for common inherited thrombophilias [IT], age at onset and blood group [BG], and to calculate the risk of VTE recurrence. We investigated 1012 Caucasian patients with a diagnosis of VTE for the presence of the F2 rs3136516 polymorphism and compared these with 902 healthy blood donors.