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Background: Lymphopenia is common in COVID-19. This has raised concerns that COVID-19 could affect the immune system akin to measles infection, which causes immune amnesia and a reduction in protective antibodies. Methods: We recruited COVID-19 patients (n = 59) in Helsinki, Finland, and collected plasma samples on 2 to 3 occasions during and after infection. We measured IgG antibodies to diphtheria toxin, tetanus toxoid, and pertussis toxin, along with total IgG, SARS-CoV-2 spike protein IgG, and neutralizing antibodies. We also surveyed the participants for up to 17 months for long-term impaired olfaction as a proxy for prolonged post-acute COVID-19 symptoms. Results: No significant differences were found in the unrelated vaccine responses while the serological response against COVID-19 was appropriate. During the acute phase of the disease, the SARS-CoV-2 IgG levels were lower in outpatients when compared to inpatients. SARS-CoV-2 serology kinetics matched expectations. In the acute phase, anti-tetanus and anti-diphtheria IgG levels were lower in patients with prolonged impaired olfaction during follow up than in those without. Conclusions: We could not detect significant decline in overall humoral immunity during or after COVID-19 infection. In severe COVID-19, there appears to be a temporary decline in total IgG levels.

Abstract Background The number of mutations in cancer cells is an important predictor of a positive response to cancer immunotherapy. It has been suggested that the neoantigens produced by these mutations are more immunogenic than nonmutated tumor antigens, which are likely to be protected by immunological tolerance. However, the mechanisms of tolerance as regards tumor antigens are incompletely understood. Methods Here, we have analyzed the impact of thymic negative selection on shared T‐cell receptor (TCR) repertoire associated with the recognition of either mutated or nonmutated tumor antigens by comparing previously known TCR—antigen—pairs to TCR repertoires of 21 immunologically healthy individuals. Results Our results show that TCRα chains associated with either type of tumor antigens are readily generated in the thymus, at a frequency similar to TCRα chains associated with nonself. In the peripheral repertoire, the relative clone size of nonself‐associated chains is higher than that of the tumor antigens, but importantly, there is no difference between TCRα chains associated with mutated or nonmutated tumor antigens. Conclusion This suggests that the tolerance mechanisms protecting nonmutated tumor antigens are non‐deletional and therefore potentially reversible. As unmutated antigens are, unlike mutations, shared by a large number of patients, they may offer advantages in designing immunological approaches to cancer treatment.

Backgrounds and AimsAPECED is a rare autoimmune disease caused by mutations in the Autoimmune Regulator gene. A significant proportion of patients also have gastrointestinal symptoms, including malabsorption, chronic diarrhea, and obstipation. The pathological background of the gastrointestinal symptoms remains incompletely understood and involves multiple factors, with autoimmunity being the most common underlying cause. Patients with APECED have increased immune responses against gut commensals. Our objective was to evaluate whether the intestinal microbiota composition, predicted functions or fungal abundance differ between Finnish patients with APECED and healthy controls, and whether these associate to the patients’ clinical phenotype and gastrointestinal symptoms.MethodsDNA was isolated from fecal samples from 15 patients with APECED (median age 46.4 years) together with 15 samples from body mass index matched healthy controls. DNA samples were subjected to analysis of the gut microbiota using 16S rRNA gene amplicon sequencing, imputed metagenomics using the PICRUSt2 algorithm, and quantitative PCR for fungi. Extensive correlations of the microbiota with patient characteristics were determined.ResultsAnalysis of gut microbiota indicated that both alpha- and beta-diversity were altered in patients with APECED compared to healthy controls. The fraction of Faecalibacterium was reduced in patients with APECED while that of Atopobium spp. and several gram-negative genera previously implicated in biofilm formation, e.g. Veillonella, Prevotella, Megasphaera and Heamophilus, were increased in parallel to lipopolysaccharide (LPS) synthesis in imputed metagenomics. The differences in gut microbiota were linked to patient characteristics, especially the presence of anti-Saccharomyces cerevisiae antibodies (ASCA) and severity of gastrointestinal symptoms.ConclusionsGut microbiota of patients with APECED is altered and enriched with predominantly gram-negative bacterial taxa that may promote biofilm formation and lead to increased exposure to LPS in the patients. The most pronounced alterations in the microbiota were associated with more severe gastrointestinal symptoms.

Autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy (APECED, also called APS-1) is an inborn error of immunity with clear signs of B-cell autoimmunity such as neutralizing anti-IFN antibodies. In APECED, mutations in the AIRE gene impair thymic negative selection of T cells. The resulting T-cell alterations may then cause dysregulation of B-cell responses. However, no analysis of interactions of T and B cells in the germinal centers (GCs) in patients' secondary lymphatic tissues has been reported. This study examined the relationship between B cells and follicular T helper cells (TfH) in peripheral blood and lymph node (LN) GCs in patients with APECED. Immunophenotyping of peripheral blood B cells and TfH was performed for 24 patients with APECED. Highly multiplexed fluorescent immunohistochemical staining was performed on 7 LN biopsy samples from the patients to study spatial interactions of lymphocytes in the GCs at the single-cell level. The patients' peripheral B-cell phenotype revealed skewing toward a mature B-cell phenotype with marked loss of transitional and naive B cells. The frequency of circulating TfH cells was diminished in the patients, while in the LNs the TfH population was expanded. In LNs the overall frequency of Treg cells and interactions of Treg cells with nonfollicular T cells were reduced, suggesting that aberrant Treg cell function might fail to restrain TfH differentiation. GC reactions are disrupted in APECED as a result of defective T-cell control. [ABSTRACT FROM AUTHOR]

T cell receptor (TCR) is a heterodimer consisting of TCRα and TCRβ chains that are generated by somatic recombination of multiple gene segments. Nascent TCR repertoire undergoes thymic selections where non-functional and potentially autoreactive receptors are removed. During the last years, the development of high-throughput sequencing technology has allowed a large scale assessment of TCR repertoire and multiple analysis tools are now also available.In our recent manuscript, Human thymic T cell repertoire is imprinted with strong convergence to shared sequences [1], we show highly overlapping thymic TCR repertoires in unrelated individuals. In the current Data in Brief article, we provide a more detailed characterization of the basic features of these thymic and related peripheral blood TCR repertoires. The thymus samples were collected from eight infants undergoing corrective cardiac surgery, two of whom were monozygous twins [2]. In parallel with the surgery, a small aliquot of peripheral blood was drawn from four of the donors. Genomic DNA was extracted from mechanically released thymocytes and circulating leukocytes. The sequencing of TCRα and TCRβ repertoires was performed at ImmunoSEQ platform (Adaptive Biotechnologies). The obtained repertoire data were analysed applying relevant features from immunoSEQ® 3.0 Analyzer (Adaptive Biotechnologies) and a freely available VDJTools software package for programming language R [3].The current data analysis displays the basic features of the sequenced repertoires including observed TCR diversity, various descriptive TCR diversity measures, and V and J gene usage. In addition, multiple methods to calculate repertoire overlap between two individuals are applied. The raw sequence data provide a large database of reference TCRs in healthy individuals at an early developmental stage. The data can be exploited to improve existing computational models on TCR repertoire behaviour as well as in the generation of new models.

Essential for successful interaction with the environment is the human capacity to resolve events in time. Typical event timing paradigms are judgements of simultaneity (SJ) and of temporal order (TOJ). It remains unclear whether SJ and TOJ are based on the same underlying mechanism and whether there are fixed thresholds for resolution. The current study employed four visual event timing task versions: horizontal and vertical SJ and TOJ. Binary responses were analysed using multilevel binary regression modelling. Modulatory effects of potential explanatory variables on event timing perception were investigated: (1) Individual factors (sex and age), (2) temporal factors (SOA, trial number, order of experiment, order of stimuli orientation, time of day) and (3) spatial factors (left or right stimulus first, top or bottom stimulus first, horizontal vs. vertical orientation). The current study directly compares for the first time, performance on SJ and TOJ tasks using the same paradigm and presents evidence that a variety of factors and their interactions selectively modulate event timing functions in humans, explaining the variance found in previous studies. We conclude that SJ and TOJ are partially independent functions, because they are modulated differently by individual and contextual variables.

The philosophical debate over the nature of color has been governed by what we have learnt from color vision science and what color phenomenology suggests to us. It is usually thought that color eliminativism, which maintains that physical objects do not have any properties that can be identified with colors, can account for the former but not the latter. After all, what could be more obvious than the external world to be colored? Here I outline one color eliminativistic response to the objections based on phenomenology.

Before the era of tyrosine kinase inhibitors (TKIs), interferon-alpha (IFN-α) was the treatment of choice in chronic myeloid leukemia (CML). Curiously, some IFN-α treated patients were able to discontinue therapy without disease progression. The aim of this project was to study the immunomodulatory effects of IFN-α in CML patients in prolonged remission and isolate biological markers predicting response. Due to rarity of patients on IFN-α monotherapy, a relatively small cohort of patients still on treatment (IFN-ON, n = 10, median therapy duration 11.8 years) or had discontinued IFN-α therapy but remained in remission for >2 years (IFN-OFF, n = 9) were studied. The lymphocyte immunophenotype was analyzed with a comprehensive flow cytometry panel and plasma cytokine levels were measured with multiplex bead-based assay. In addition, the clonality status of different lymphocyte subpopulations was analyzed by TCR γ/δ rearrangement assay. Median NK-cell absolute number and proportion from lymphocytes in blood was higher in IFN-OFF patients as compared to IFN-ON patients or controls (0.42, 0.19, 0.21×10(9)/L; 26%, 12%, 11%, respectively, p