A5040920731- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Adrenal Hormones and Disorders
- SARS-CoV-2 and COVID-19 Research
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Cytomegalovirus and herpesvirus research
- Monoclonal and Polyclonal Antibodies Research
- Cancer Immunotherapy and Biomarkers
- Dementia and Cognitive Impairment Research
- Diabetes and associated disorders
- Hematopoietic Stem Cell Transplantation
- Peripheral Neuropathies and Disorders
- Intensive Care Unit Cognitive Disorders
- Immunodeficiency and Autoimmune Disorders
- vaccines and immunoinformatics approaches
- Transgenic Plants and Applications
- Platelet Disorders and Treatments
- Exercise and Physiological Responses
- Health disparities and outcomes
- Health Promotion and Cardiovascular Prevention
- Herpesvirus Infections and Treatments
- Blood groups and transfusion
- Bacillus and Francisella bacterial research
- COVID-19 Clinical Research Studies
University of Helsinki
2011-2024
Helsinki University Hospital
2021-2024
University of Geneva
2022-2024
BackgroundInfections have been hypothesised to increase the risk of dementia. Existing studies included a narrow range infectious diseases, relied on short follow-up periods, and provided little evidence for whether increased is limited specific dementia subtypes or attributable microbes rather than infection burden. We aimed compare Alzheimer's disease other dementias across wide hospital-treated bacterial viral infections in two large cohorts with long periods.MethodsIn this large,...
The SARS-CoV-2 variant B.1.1.529 (Omicron) escapes neutralizing antibodies elicited after COVID-19 vaccination, while T-cell responses might be better conserved. It is crucial to assess how a third vaccination modifies these responses, particularly for immunocompromised patients with readily impaired antibody responses.To determine the Omicron spike protein in anti-CD20-treated multiple sclerosis (MS) before and messenger RNA vaccination.In this prospective cohort study conducted from March...
The excess risk of cardiovascular disease associated with a wide array infectious diseases is unknown. We quantified the short- and long-term major events in people severe infection estimated population-attributable fraction. analyzed data from 331 683 UK Biobank participants without at baseline (2006-2010) replicated our main findings an independent population 3 prospective cohort studies comprising 271 329 community-dwelling Finland (baseline 1986-2005). Cardiovascular factors were...
A truncated variant of Helios causes a human immunodeficiency disease with signs immune overactivation.
Prolonged T cell lymphopenia is common in COVID-19, caused by SARS-CoV-2. While the mechanisms of during COVID-19 remain elusive, it especially pronounced a specialized innate-like population called Mucosal Associated Invariant cells (MAITs). MAITs has been suggested to express Angiotensin-Converting Enzyme 2 (ACE2), which well-known cellular receptor for However, still unclear if SARS-CoV-2 can infect or affect MAIT directly. In this study, we performed multicolor flow cytometry on...
Abstract Autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy (APECED) is a monogenic autoimmune disease that caused by mutations in the AIRE gene. Murine studies have linked to thymocyte selection and peripheral deletional tolerance, but pathogenesis of human remains unclear. In this study, we show APECED patients elevated IL-7 levels drastically decreased expression IL-7R on CD8+ T cells. This associated with increased proliferation negative TCR regulator CD5 CD45RO− subset. The...
Abstract Importance The SARS-CoV-2 variant Omicron escapes neutralizing antibody responses elicited after COVID-19 vaccination, while T-cell might be better conserved. It is crucial to assess how a third dose of vaccination modifies these responses, particularly for immunocompromised patients with readily impaired responses. Objective To determine the Spike (S)-protein in anti-CD20 treated before and their mRNA Design Prospective observational monocentric study Setting Conducted since March...
In biomedical infectious disease research new models to bridge preclinical and clinical are needed. Mouse still one of the most-interrogated experimental systems with caveat biological differences in pathogen-host-interaction for some human-relevant pathogens increasing ethical concerns. Arguably most complex cell culture precision cut organ slices, volume defined tissue blocks which can be cultured ex vivo exposed various stimuli including human pathogens. They could applied as 3R model...
Autoimmune polyendocrinopathy - candidiasis ectodermal dystrophy (APECED) is caused by mutations in the regulator (AIRE) gene and associated with neutralizing anti-cytokine autoantibodies. We have used an vivo challenge model to analyze antigen-specific CD4(+) T cell responses. Bacille Calmette-Guérin (BCG)-vaccinated patients controls were injected tuberculin intradermally, skin blisters induced suction on indurations unexposed skin, infiltrating cells harvested. The had a quantitatively...
In addition to its effector functions, complement is an important regulator of adaptive immune responses. Murine studies suggest that modulates helper T‐cell differentiation, and Th1 responses in particular are impaired the absence functional complement. Here, we have studied humoral toxoid vaccines eight patients with C3 deficiency, representing more than 25% all known worldwide. Serum cytokine levels were also studied. The developed normal Ig tetanus diphtheria toxoids, but IgE low....
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED, also called APS-1) is an inborn error of immunity with clear signs B-cell autoimmunity such as neutralizing anti-IFN antibodies. In APECED, mutations in the AIRE gene impair thymic negative selection T cells. The resulting T-cell alterations may then cause dysregulation responses. However, no analysis interactions and B cells germinal centers (GCs) patients' secondary lymphatic tissues has been reported.
Abstract We studied the associations between inflammation‐related proteins in circulation and complications after pediatric allogenic hematopoietic stem cell transplantation (HSCT), to reveal proteomic signatures or individual soluble associated with specific HSCT. used a proteomics method called Proximity Extension Assay repeatedly measure 180 different together clinical variables, cellular immune reconstitution blood viral copy numbers 27 children (1–18 years of age) during 2‐year...
Next-generation COVID-19 vaccines are being developed to expand the breadth of coverage against existing and future variants extend duration protection. Prime-2-CoV_Beta is an orf virus (ORFV) based multi-antigen vaccine that co-expresses Spike (S) Nucleocapsid (N) antigens. The safety immunogenicity investigated in a phase 1 first-in-human (FIH) dose-finding trial (ORFEUS study, ClinicalTrials.gov: NCT05367843). Participants two age groups (18–55 65–85 years) who previously completed at...
The T-cell receptor (TCR) repertoire is generated in a semistochastic process of gene recombination and pairing TCRα to TCRβ chains with the estimated total TCR diversity >108. Despite this high diversity, similar or identical are found recur immune responses. Here, we analyzed thymic generation sequences previously associated recognition self- nonself-antigens, represented by autoimmune diabetes HIV, respectively. Unexpectedly, CD4+ compartment self-antigens were significantly higher...
T cell receptor (TCR) is a heterodimer consisting of TCRα and TCRβ chains that are generated by somatic recombination multiple gene segments. Nascent TCR repertoire undergoes thymic selections where non-functional potentially autoreactive receptors removed. During the last years, development high-throughput sequencing technology has allowed large scale assessment analysis tools now also available. In our recent manuscript, Human imprinted with strong convergence to shared sequences [1], we...
Abstract Background The number of mutations in cancer cells is an important predictor a positive response to immunotherapy. It has been suggested that the neoantigens produced by these are more immunogenic than nonmutated tumor antigens, which likely be protected immunological tolerance. However, mechanisms tolerance as regards antigens incompletely understood. Methods Here, we have analyzed impact thymic negative selection on shared T‐cell receptor (TCR) repertoire associated with...
Abstract Objective To study kinetics and associations between inflammation related proteins in circulation after pediatric allogenic hematopoietic stem cell transplantation (HSCT) to reveal proteomic signatures or individual soluble associated with specific complications post HSCT. Methods We used a proteomics method called Proximity Extension Assay repeatedly measure 180 different together clinical variables, cellular immune reconstitution, blood viral copy numbers 27 children aged 1-18...
Long-term T-cell memory is dependent on the maintenance of T cells in lymphoid tissues, and at surface interfaces that provide entry routes for pathogens. However, much current information human based analyzing circulating cells. Here, we have studied distribution age-related changes subsets samples from blood, mesenteric LNs, spleen, ileum, obtained donors ranging age 5 days to 67 years age. Our data show main reservoir polyclonal naive found resting capable self-renewal are also prominent...
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is an inborn error of immunity affecting both multiple endocrine organs and susceptibility to candidiasis, each with autoimmune basis. Recently, high titer neutralizing anti-type I interferon (IFN) autoantibodies have been linked increased severity SARS-CoV-2 varicella zoster virus infections in APECED patients. Examining against cytomegalovirus (CMV), we found a higher prevalence anti-CMV IgG antibodies patients (N =...
Mucosal-associated invariant T cells (MAIT) are innate-like lymphocytes enriched in mucosal organs where they contribute to antimicrobial defense. APECED is an inborn error of immunity characterized by immune dysregulation and chronic mucocutaneous candidiasis. Reduction the frequency circulating MAITs has been reported many errors immunity, but only a few them, functional competence assessed. Here, we show cohort 24 patients with APECED, that proportion was reduced compared healthy age...