A5054772275- Chronic Lymphocytic Leukemia Research
- Virus-based gene therapy research
- Viral Infectious Diseases and Gene Expression in Insects
- Monoclonal and Polyclonal Antibodies Research
- CAR-T cell therapy research
- Immunodeficiency and Autoimmune Disorders
- Chronic Myeloid Leukemia Treatments
- T-cell and B-cell Immunology
- Cancer Research and Treatments
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Lymphoma Diagnosis and Treatment
- Acute Myeloid Leukemia Research
- Biomedical and Engineering Education
- Rheumatoid Arthritis Research and Therapies
- Hematopoietic Stem Cell Transplantation
- Mycobacterium research and diagnosis
- Eosinophilic Disorders and Syndromes
- HER2/EGFR in Cancer Research
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Cancer Genomics and Diagnostics
- ECG Monitoring and Analysis
- Cardiac Imaging and Diagnostics
- Erythropoietin and Anemia Treatment
- Bone and Joint Diseases
Helsinki University Hospital
2016-2025
University of Helsinki
2016-2025
Eastern Finland Laboratory Center
1961
Somatic mutations contribute to tumorigenesis. Although these occur in all proliferating cells, their accumulation under non-malignant conditions, such as autoimmune disorders, has not been investigated. Here, we show that patients with newly diagnosed rheumatoid arthritis have expanded CD8+ T-cell clones; 20% (5/25) of T but CD4+ harbour somatic mutations. In healthy controls (n=20), only one mutation is identified the pool. Mutations exist exclusively effector-memory subset, persist during...
Although iron deficiency anemia is common, interpreting laboratory test results can be challenging in patients with comorbidities. We aimed to study the accuracy of common biomarkers compared bone marrow staining a large retrospective dataset hematological patients. collected from 6610 (median age 66 years) staining, their concurrent ferritin, transferrin saturation, soluble receptor, transferrin, hemoglobin, and mean red blood cell volume Helsinki University Hospital electronic health...
Felty syndrome is a rare disease defined by neutropenia, splenomegaly, and rheumatoid arthritis. Sometimes the differential diagnosis between large granular lymphocyte leukemia problematic. Recently, somatic STAT3 STAT5B mutations were discovered in 30–40% of patients with leukemia. Herein, we aimed to study whether these can also be detected syndrome, which would imply existence common pathogenic mechanism two entities. We collected samples clinical information from 14 who monitored at...
Dasatinib, a broad-range tyrosine kinase inhibitor, induces rapid mobilization of lymphocytes and clonal expansion cytotoxic cells in leukemia patients. Here, we investigated whether dasatinib could induce beneficial immunomodulatory effects solid tumor models. The on growth the immune system were studied four different syngeneic mouse models (B16.OVA melanoma, 1956 sarcoma, MC38 colon, 4T1 breast carcinoma). Both peripheral blood (PB) samples immunophenotyped during treatment. Although...
Significance Our analysis shows that sex can be associated with the degree to which HLA molecules propagate selection and expansion of T cells as characterized by their cell receptor variable beta chain (TCRBV). Furthermore, CD8 cells, especially in men autoimmune diseases such multiple sclerosis or rheumatoid arthritis, are capable expanding unison other even without expressing TCRBVs biochemical similarity pivotal HLA-binding regions. findings add understanding bias immune system...
Abstract Monoclonal anti-HER2 antibody trastuzumab has significantly improved the survival of patients with HER2-overexpressing tumors. Nevertheless, systemic therapy is expensive, limited in efficacy due to physical tumor barriers, and carries risk severe side effects such as cardiomyopathy. Oncolytic viruses mediate cancer-selective transgene expression, kill infected cancer cells while mounting antitumor immune responses, have recently demonstrated promising combination treatments. Here,...
Clonal hematopoiesis (CH) becomes more prevalent with aging and may influence inflammatory diseases by altering immune function. While CH of indeterminate potential (CHIP) promotes inflammation in nonmalignant conditions, its relationship rheumatoid arthritis (RA) remains unknown. We analyzed CHIP mutations RA using two population-level cohorts patients newly diagnosed RA. was associated 10,089 FINRISK study participants whole-exome sequencing (OR, 2.06; P = 0.029) the FinnGen cohort (n...
Common variable immunodeficiency and other late-onset immunodeficiencies often co-manifest with autoimmunity lymphoproliferation. The pathogenesis of most cases is elusive, as only a minor subset harbors known monogenic germline causes. involvement both B T cells however implicated. To study whether somatic mutations in CD4+ CD8+ associate immunodeficiency, we recruited 17 patients 21 healthy controls. Eight had common nine and/or severe autoimmunity. In total, occurred 94%...
Somatic mutations in T cells can cause cancer but also have implications for immunological diseases and cell therapies. The mutation spectrum nonmalignant is unclear. Here, we examined somatic CD4 + CD8 from 90 patients with hematological disorders used receptor (TCR) single-cell sequencing to link expansions phenotypes. had a higher burden than cells. Notably, the biggest variant allele frequency (VAF) of non-synonymous variants was synonymous cells, indicating non-random occurrence. VAF...
The role of somatic variants in diseases beyond cancer is increasingly being recognized, with potential roles autoinflammatory and autoimmune diseases. However, as mutation rates allele fractions are lower, studies these substantially less tolerant false positives, bio-informatics algorithms require high replication rates. We developed a pipeline combining two variant callers, MuTect2 VarScan2, technical filtering prioritization. Our detects low 0.5% achieves rate >55%. Validation an...
Rheumatoid arthritis (RA) is a complex autoimmune disease targeting synovial joints. Traditionally, RA divided into seropositive (SP) and seronegative (SN) forms, the latter consisting of an array unrelated diseases with joint involvement. Recently, we described severe form SN-RA that associates characteristic destruction. Here, sought biological characteristics to differentiate this rare but aggressive anti-citrullinated peptide antibody-negative destructive (CND-RA) from early (SP-RA)...
Abstract Clonal hematopoiesis (CH) becomes more prevalent with age and may impact the pathophysiology of inflammatory diseases by altering immune cell function. While clonal indeterminate potential (CHIP) can promote inflammation in non-malignant conditions, relationship rheumatoid arthritis (RA) has not been systematically investigated. We tested whether CHIP mutations are common RA using two population-level cohorts newly diagnosed patients. was associated FINRISK study 10 089 participants...
A Correction to this paper has been published: https://doi.org/10.1038/s41408-021-00427-1