Publications by authors named "T Petteri Arstila"

68 Publications

Patients with autoimmune polyendocrine syndrome type 1 have an increased susceptibility to severe herpesvirus infections.

Clin Immunol 2021 10 8;231:108851. Epub 2021 Sep 8.

Department of Bacteriology and Immunology, University of Helsinki, Helsinki, Finland; Translational Immunology Research Program, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Almost all patients with autoimmune polyendocrine syndrome type 1 (APS-1) have neutralizing antibodies against type 1 interferons (IFN), important mediators of antiviral defense. Recently, neutralizing anti-IFN antibodies were shown to be a risk factor of severe COVID-19. Here we show in a cohort of 44 patients with APS-1 that higher titers of neutralizing anti-IFNα4 antibodies are associated with a higher and earlier incidence of VZV reactivation (herpes zoster). The patients also present with uncommonly severe clinical sequelae of herpetic infections. APS-1 patients had decreased humoral immune responses to varicella zoster virus, but cellular responses were comparable to healthy controls. These results suggest that blocking the type I interferon pathway in patients with APS-1 patients leads to a clinically significant immune deficiency, and susceptibility to herpesviruses should be taken into account when treating patients with APS-1.
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http://dx.doi.org/10.1016/j.clim.2021.108851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425955PMC
October 2021

Fecal Bacteria Implicated in Biofilm Production Are Enriched and Associate to Gastrointestinal Symptoms in Patients With APECED - A Pilot Study.

Front Immunol 2021 22;12:668219. Epub 2021 Jul 22.

Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.

Backgrounds And Aims: APECED 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.

Methods: DNA 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.

Results: Analysis of gut microbiota indicated that both alpha- and beta-diversity were altered in patients with APECED compared to healthy controls. The fraction of was reduced in patients with APECED while that of spp. and several gram-negative genera previously implicated in biofilm formation, e.g. and , 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- antibodies (ASCA) and severity of gastrointestinal symptoms.

Conclusions: Gut 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.
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http://dx.doi.org/10.3389/fimmu.2021.668219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339580PMC
October 2021

Heterologous boosting of nonrelated toxoid immunity during acute Puumala hantavirus infection.

Vaccine 2021 03 4;39(13):1818-1825. Epub 2021 Mar 4.

Department of Bacteriology and Immunology, University of Helsinki, PO BOX 21 (Haartmaninkatu 3), FI-00014 Helsinki, Finland; Translational Immunology Research Program, University of Helsinki, PO. Box 63 (Haartmaninkatu 8), FI-00014 Helsinki, Finland.

Persistence of immune memory in humans is a crucial yet poorly understood aspect of immunology. Here we have studied the effect of Puumala hantavirus infection on unrelated, pre-existing immune memory by studying T cell- and antibody responses against toxoid vaccine antigens of diphtheria, tetanus and pertussis in a cohort of 45 patients. We found that tetanus- and pertussis -specific IgG concentrations elevate during acute Puumala virus infection. Increase in vaccine IgG was associated with proliferation of heterologous T cells. Interestingly, increases in tetanus-specific IgG persisted a year after the infection while pertussis-specific IgG declined rapidly; a difference in IgG kinetics resembling the difference seen after vaccination against tetanus and pertussis. These results suggest that persistence of immune memory is facilitated by heterologous boosting of old memory during memory formation against newly encountered antigens. They also show that different toxoid antigens may be treated differently. Our study gives new insight into how immune memory formation may alter pre-existing immune memory, and also shows that heterologous immunity may have an impact on vaccination outcomes.
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http://dx.doi.org/10.1016/j.vaccine.2021.02.046DOI Listing
March 2021

Generation of self-reactive, shared T-cell receptor α chains in the human thymus.

J Autoimmun 2021 05 27;119:102616. Epub 2021 Feb 27.

Research Programs Unit, Translational Immunology, and Medicum, University of Helsinki, Haartmaninkatu 3, 00290, Helsinki, Finland.

The T-cell receptor (TCR) repertoire is generated in a semistochastic process of gene recombination and pairing of TCRα to TCRβ chains with the estimated total TCR diversity of >10. Despite this high diversity, similar or identical TCR chains are found to recur in immune responses. Here, we analyzed the thymic generation of TCR sequences previously associated with recognition of self- and nonself-antigens, represented by sequences associated with autoimmune diabetes and HIV, respectively. Unexpectedly, in the CD4 compartment TCRα chains associated with the recognition of self-antigens were generated in significantly higher numbers than TCRα chains associated with the recognition of nonself-antigens. The analysis of the circulating repertoire further showed that these chains are not lost in negative selection nor predominantly converted to the regulatory T-cell lineage. The high abundance of self-reactive TCRα chains in multiple individuals suggests that the human thymus has a predilection to generate self-reactive TCRα chains independently of the HLA-type and that the individual risk of autoimmunity may be modulated by the TCRβ repertoire associated with these chains.
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http://dx.doi.org/10.1016/j.jaut.2021.102616DOI Listing
May 2021
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