Umeå universitets logga

umu.sePublikationer
Ändra sökning
Länk till posten
Permanent länk

Direktlänk
Hultdin, Magnus
Publikationer (10 of 40) Visa alla publikationer
Carlund, O., Thörn, E., Osterman, P., Fors, M., Dernstedt, A., Forsell, M. N. E., . . . Hultdin, M. (2024). Semimethylation is a feature of diffuse large B-cell lymphoma, and subgroups with poor prognosis are characterized by global hypomethylation and short telomere length. Clinical Epigenetics, 16(1), Article ID 68.
Öppna denna publikation i ny flik eller fönster >>Semimethylation is a feature of diffuse large B-cell lymphoma, and subgroups with poor prognosis are characterized by global hypomethylation and short telomere length
Visa övriga...
2024 (Engelska)Ingår i: Clinical Epigenetics, E-ISSN 1868-7083, Vol. 16, nr 1, artikel-id 68Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Background: Large B-cell lymphoma (LBCL) is the most common lymphoma and is known to be a biologically heterogeneous disease regarding genetic, phenotypic, and clinical features. Although the prognosis is good, one-third has a primary refractory or relapsing disease which underscores the importance of developing predictive biological markers capable of identifying high- and low-risk patients. DNA methylation (DNAm) and telomere maintenance alterations are hallmarks of cancer and aging. Both these alterations may contribute to the heterogeneity of the disease, and potentially influence the prognosis of LBCL.

Results: We studied the DNAm profiles (Infinium MethylationEPIC BeadChip) and relative telomere lengths (RTL) with qPCR of 93 LBCL cases: Diffuse large B-cell lymphoma not otherwise specified (DLBCL, n = 66), High-grade B-cell lymphoma (n = 7), Primary CNS lymphoma (n = 8), and transformation of indolent B-cell lymphoma (n = 12). There was a substantial methylation heterogeneity in DLBCL and other LBCL entities compared to normal cells and other B-cell neoplasms. LBCL cases had a particularly aberrant semimethylated pattern (0.15 ≤ β ≤ 0.8) with large intertumor variation and overall low hypermethylation (β > 0.8). DNAm patterns could not be used to distinguish between germinal center B-cell-like (GC) and non-GC DLBCL cases. In cases treated with R-CHOP-like regimens, a high percentage of global hypomethylation (β < 0.15) was in multivariable analysis associated with worse disease-specific survival (DSS) (HR 6.920, 95% CI 1.499–31.943) and progression-free survival (PFS) (HR 4.923, 95% CI 1.286–18.849) in DLBCL and with worse DSS (HR 5.147, 95% CI 1.239–21.388) in LBCL. These cases with a high percentage of global hypomethylation also had a higher degree of CpG island methylation, including islands in promoter-associated regions, than the cases with less hypomethylation. Additionally, telomere length was heterogenous in LBCL, with a subset of the DLBCL-GC cases accounting for the longest RTL. Short RTL was independently associated with worse DSS (HR 6.011, 95% CI 1.319–27.397) and PFS (HR 4.689, 95% CI 1.102–19.963) in LBCL treated with R-CHOP-like regimens.

Conclusion: We hypothesize that subclones with high global hypomethylation and hypermethylated CpG islands could have advantages in tumor progression, e.g. by inactivating tumor suppressor genes or promoting treatment resistance. Our findings suggest that cases with high global hypomethylation and thus poor prognosis could be candidates for alternative treatment regimens including hypomethylating drugs.

Ort, förlag, år, upplaga, sidor
BioMed Central (BMC), 2024
Nyckelord
Diffuse large-B cell lymphoma, DNA methylation, High-grade B-cell lymphoma, Predictive markers, Primary CNS lymphomas, Survival, Telomere length
Nationell ämneskategori
Hematologi Cancer och onkologi
Identifikatorer
urn:nbn:se:umu:diva-225340 (URN)10.1186/s13148-024-01680-4 (DOI)001228885200001 ()38773655 (PubMedID)2-s2.0-85193701494 (Scopus ID)
Forskningsfinansiär
KempestiftelsernaCancerforskningsfonden i NorrlandLions Cancerforskningsfond i Norr
Tillgänglig från: 2024-06-03 Skapad: 2024-06-03 Senast uppdaterad: 2024-06-04Bibliografiskt granskad
Carlund, O., Norberg, A., Osterman, P., Landfors, M., Degerman, S. & Hultdin, M. (2023). DNA methylation variations and epigenetic aging in telomere biology disorders. Scientific Reports, 13(1), Article ID 7955.
Öppna denna publikation i ny flik eller fönster >>DNA methylation variations and epigenetic aging in telomere biology disorders
Visa övriga...
2023 (Engelska)Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 13, nr 1, artikel-id 7955Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Telomere Biology Disorders (TBDs) are characterized by mutations in telomere-related genes leading to short telomeres and premature aging but with no strict correlation between telomere length and disease severity. Epigenetic alterations are also markers of aging and we aimed to evaluate whether DNA methylation (DNAm) could be part of the pathogenesis of TBDs. In blood from 35 TBD cases, genome-wide DNAm were analyzed and the cases were grouped based on relative telomere length (RTL): short (S), with RTL close to normal controls, and extremely short (ES). TBD cases had increased epigenetic age and DNAm alterations were most prominent in the ES-RTL group. Thus, the differentially methylated (DM) CpG sites could be markers of short telomeres but could also be one of the mechanisms contributing to disease phenotype since DNAm alterations were observed in symptomatic, but not asymptomatic, cases with S-RTL. Furthermore, two or more DM-CpGs were identified in four genes previously linked to TBD or telomere length (PRDM8, SMC4, VARS, and WNT6) and in three genes that were novel in telomere biology (MAS1L, NAV2, and TM4FS1). The DM-CpGs in these genes could be markers of aging in hematological cells, but they could also be of relevance for the progression of TBD.

Ort, förlag, år, upplaga, sidor
Springer Nature, 2023
Nationell ämneskategori
Mikrobiologi inom det medicinska området
Identifikatorer
urn:nbn:se:umu:diva-209273 (URN)10.1038/s41598-023-34922-1 (DOI)000992335400030 ()37193737 (PubMedID)2-s2.0-85159474361 (Scopus ID)
Forskningsfinansiär
KempestiftelsernaCancerforskningsfonden i NorrlandUmeå universitetRegion Västerbotten
Tillgänglig från: 2023-06-08 Skapad: 2023-06-08 Senast uppdaterad: 2023-09-05Bibliografiskt granskad
Kolijn, P. M., Späth, F., Khouja, M., Hengeveld, P. J., van der Straten, L., Darzentas, N., . . . Langerak, A. W. (2023). Genetic drivers in the natural history of chronic lymphocytic leukemia development as early as 16 years before diagnosis [Letter to the editor]. Blood, 142(16), 1399-1403
Öppna denna publikation i ny flik eller fönster >>Genetic drivers in the natural history of chronic lymphocytic leukemia development as early as 16 years before diagnosis
Visa övriga...
2023 (Engelska)Ingår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 142, nr 16, s. 1399-1403Artikel i tidskrift, Letter (Refereegranskat) Published
Ort, förlag, år, upplaga, sidor
Elsevier, 2023
Nationell ämneskategori
Hematologi
Identifikatorer
urn:nbn:se:umu:diva-213399 (URN)10.1182/blood.2023019609 (DOI)001098039300001 ()37523714 (PubMedID)2-s2.0-85168011461 (Scopus ID)
Forskningsfinansiär
Cancerfonden
Tillgänglig från: 2023-08-31 Skapad: 2023-08-31 Senast uppdaterad: 2023-12-20Bibliografiskt granskad
Schäfer Hackenhaar, F., Josefsson, M., Nordin Adolfsson, A., Landfors, M., Kauppi, K., Porter, T., . . . the Australian Imaging Biomarkers and Lifestyle Study, . (2023). Sixteen-year longitudinal evaluation of blood-based DNA methylation biomarkers for early prediction of Alzheimer’s disease. Journal of Alzheimer's Disease, 94(4), 1443-1464
Öppna denna publikation i ny flik eller fönster >>Sixteen-year longitudinal evaluation of blood-based DNA methylation biomarkers for early prediction of Alzheimer’s disease
Visa övriga...
2023 (Engelska)Ingår i: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 94, nr 4, s. 1443-1464Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Background: DNA methylation (DNAm), an epigenetic mark reflecting both inherited and environmental influences, hasshown promise for Alzheimer’s disease (AD) prediction.Objective: Testing long-term predictive ability (>15 years) of existing DNAm-based epigenetic age acceleration (EAA)measures and identifying novel early blood-based DNAm AD-prediction biomarkers.

Methods: EAA measures calculated from Illumina EPIC data from blood were tested with linear mixed-effects models(LMMs) in a longitudinal case-control sample (50 late-onset AD cases; 51 matched controls) with prospective data up to 16years before clinical onset, and post-onset follow-up. NovelDNAmbiomarkers were generated with epigenome-wide LMMs,and Sparse Partial Least Squares Discriminant Analysis applied at pre- (10–16 years), and post-AD-onset time-points.

Results: EAA did not differentiate cases from controls during the follow-up time (p > 0.05). Three new DNA biomarkersshowed in-sample predictive ability on average 8 years pre-onset, after adjustment for age, sex, and white blood cell proportions(p-values: 0.022-<0.00001). Our longitudinally-derived panel replicated nominally (p = 0.012) in an external cohort (n = 146cases, 324 controls). However, its effect size and discriminatory accuracy were limited compared to APOE 4-carriership(OR = 1.38 per 1 SD DNAmscore increase versus OR= 13.58 for 4-allele carriage; AUCs = 77.2% versus 87.0%). Literaturereview showed low overlap (n = 4) across 3275 AD-associated CpGs from 8 published studies, and no overlap with ouridentified CpGs.

Conclusion: The limited predictive value of EAA for AD extends prior findings by considering a longer follow-up time, andwith appropriate control for age, sex, APOE, and blood-cell proportions. Results also highlight challenges with replicatingdiscriminatory or predictive CpGs across studies.

Ort, förlag, år, upplaga, sidor
IOS Press, 2023
Nyckelord
Alzheimer’s disease, biomarkers, DNA methylation, epigenomics, longitudinal studies
Nationell ämneskategori
Annan medicinsk grundvetenskap
Identifikatorer
urn:nbn:se:umu:diva-214007 (URN)10.3233/jad-230039 (DOI)37393498 (PubMedID)2-s2.0-85168428453 (Scopus ID)
Forskningsfinansiär
Vetenskapsrådet, 2018-01729Kempestiftelserna, JCK-1922.1
Tillgänglig från: 2023-09-02 Skapad: 2023-09-02 Senast uppdaterad: 2024-04-08Bibliografiskt granskad
Kolijn, P. M., Hosnijeh, F. S., Späth, F., Hengeveld, P. J., Agathangelidis, A., Saleh, M., . . . Langerak, A. W. (2022). High-risk subtypes of chronic lymphocytic leukemia are detectable as early as 16 years prior to diagnosis. Blood, 139(10), 1557-1563
Öppna denna publikation i ny flik eller fönster >>High-risk subtypes of chronic lymphocytic leukemia are detectable as early as 16 years prior to diagnosis
Visa övriga...
2022 (Engelska)Ingår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 139, nr 10, s. 1557-1563Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Chronic lymphocytic leukemia (CLL) is preceded by monoclonal B-cell lymphocytosis (MBL), a CLL precursor state with a prevalence of up to 12% in aged individuals; however, the duration of MBL and the mechanisms of its evolution to CLL remain largely unknown. In this study, we sequenced the B-cell receptor (BcR) immunoglobulin heavy chain (IGH) gene repertoire of 124 patients with CLL and 118 matched controls in blood samples taken up to 22 years prior to diagnosis. Significant skewing in the BcR IGH gene repertoire was detected in the majority of patients, even before the occurrence of lymphocytosis and irrespective of the clonotypic IGH variable gene somatic hypermutation status. Furthermore, we identified dominant clonotypes belonging to major stereotyped subsets associated with poor prognosis up to 16 years before diagnosis in 14 patients with CLL. In 22 patients with longitudinal samples, the skewing of the BcR IGH gene repertoire increased significantly over time to diagnosis or remained stable at high levels. For 14 of 16 patients with available samples at diagnosis, the CLL clonotype was already present in the prediagnostic samples. Overall, our data indicate that the preclinical phase of CLL could be longer than previously thought, even in adverse-prognostic cases.

Ort, förlag, år, upplaga, sidor
American Society of Hematology, 2022
Nationell ämneskategori
Hematologi Cancer och onkologi
Identifikatorer
urn:nbn:se:umu:diva-203104 (URN)10.1182/blood.2021012890 (DOI)000769559500017 ()34662377 (PubMedID)2-s2.0-85122045401 (Scopus ID)
Forskningsfinansiär
Region VästerbottenRegion SkåneCancerfondenEuropeiska kommissionenNordForskVetenskapsrådetEuropeiska regionala utvecklingsfonden (ERUF), PI13/00061Europeiska regionala utvecklingsfonden (ERUF), PI13/01162Europeiska regionala utvecklingsfonden (ERUF), PI14/01219Europeiska regionala utvecklingsfonden (ERUF), PI17/01280
Tillgänglig från: 2023-01-16 Skapad: 2023-01-16 Senast uppdaterad: 2023-01-16Bibliografiskt granskad
Framme, J. L., Lundqvist, C., Lundell, A.-C., van Schouwenburg, P. A., Lemarquis, A. L., Thörn, K., . . . Ekwall, O. (2022). Long-Term Follow-Up of Newborns with 22q11 Deletion Syndrome and Low TRECs. Journal of Clinical Immunology, 42, 618-633
Öppna denna publikation i ny flik eller fönster >>Long-Term Follow-Up of Newborns with 22q11 Deletion Syndrome and Low TRECs
Visa övriga...
2022 (Engelska)Ingår i: Journal of Clinical Immunology, ISSN 0271-9142, E-ISSN 1573-2592, Vol. 42, s. 618-633Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Background: Population-based neonatal screening using T-cell receptor excision circles (TRECs) identifies infants with profound T lymphopenia, as seen in cases of severe combined immunodeficiency, and in a subgroup of infants with 22q11 deletion syndrome (22q11DS).

Purpose: To investigate the long-term prognostic value of low levels of TRECs in newborns with 22q11DS.

Methods: Subjects with 22q11DS and low TRECs at birth (22q11Low, N=10), matched subjects with 22q11DS and normal TRECs (22q11Normal, N=10), and matched healthy controls (HC, N=10) were identified. At follow-up (median age 16 years), clinical and immunological characterizations, covering lymphocyte subsets, immunoglobulins, TRECs, T-cell receptor repertoires, and relative telomere length (RTL) measurements were performed.

Results: At follow-up, the 22q11Low group had lower numbers of naïve T-helper cells, naïve T-regulatory cells, naïve cytotoxic T cells, and persistently lower TRECs compared to healthy controls. Receptor repertoires showed skewed V-gene usage for naïve T-helper cells, whereas for naïve cytotoxic T cells, shorter RTL and a trend towards higher clonality were found. Multivariate discriminant analysis revealed a clear distinction between the three groups and a skewing towards Th17 differentiation of T-helper cells, particularly in the 22q11Low individuals. Perturbations of B-cell subsets were found in both the 22q11Low and 22q11Normal group compared to the HC group, with larger proportions of naïve B cells and lower levels of memory B cells, including switched memory B cells.

Conclusions: This long-term follow-up study shows that 22q11Low individuals have persistent immunologic aberrations and increased risk for immune dysregulation, indicating the necessity of lifelong monitoring.

Clinical Implications: This study elucidates the natural history of childhood immune function in newborns with 22q11DS and low TRECs, which may facilitate the development of programs for long-term monitoring and therapeutic choices.

Ort, förlag, år, upplaga, sidor
Springer, 2022
Nyckelord
22q11.2 deletion syndrome, DiGeorge syndrome, long-term outcome, newborn screening, severe combined immunodeficiency, T lymphopenia, TREC
Nationell ämneskategori
Immunologi inom det medicinska området
Identifikatorer
urn:nbn:se:umu:diva-192261 (URN)10.1007/s10875-021-01201-5 (DOI)000749126700001 ()35080750 (PubMedID)2-s2.0-85123620385 (Scopus ID)
Forskningsfinansiär
Vetenskapsrådet, 2018-02752Cancerforskningsfonden i Norrland, AMP 20-1000
Tillgänglig från: 2022-03-11 Skapad: 2022-03-11 Senast uppdaterad: 2022-07-12Bibliografiskt granskad
Bovinder Ylitalo, E., Thysell, E., Landfors, M., Brattsand, M., Jernberg, E., Crnalic, S., . . . Wikström, P. (2021). A novel DNA methylation signature is associated with androgen receptor activity and patient prognosis in bone metastatic prostate cancer. Clinical Epigenetics, 13(1), Article ID 133.
Öppna denna publikation i ny flik eller fönster >>A novel DNA methylation signature is associated with androgen receptor activity and patient prognosis in bone metastatic prostate cancer
Visa övriga...
2021 (Engelska)Ingår i: Clinical Epigenetics, E-ISSN 1868-7083, Vol. 13, nr 1, artikel-id 133Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Background: Patients with metastatic prostate cancer (PC) are treated with androgen deprivation therapy (ADT) that initially reduces metastasis growth, but after some time lethal castration-resistant PC (CRPC) develops. A better understanding of the tumor biology in bone metastases is needed to guide further treatment developments. Subgroups of PC bone metastases based on transcriptome profiling have been previously identified by our research team, and specifically, heterogeneities related to androgen receptor (AR) activity have been described. Epigenetic alterations during PC progression remain elusive and this study aims to explore promoter gene methylation signatures in relation to gene expression and tumor AR activity.

Materials and methods: Genome-wide promoter-associated CpG methylation signatures of a total of 94 tumor samples, including paired non-malignant and malignant primary tumor areas originating from radical prostatectomy samples (n = 12), and bone metastasis samples of separate patients with hormone-naive (n = 14), short-term castrated (n = 4) or CRPC (n = 52) disease were analyzed using the Infinium Methylation EPIC arrays, along with gene expression analysis by Illumina Bead Chip arrays (n = 90). AR activity was defined from expression levels of genes associated with canonical AR activity.

Results: Integrated epigenome and transcriptome analysis identified pronounced hypermethylation in malignant compared to non-malignant areas of localized prostate tumors. Metastases showed an overall hypomethylation in relation to primary PC, including CpGs in the AR promoter accompanied with induction of AR mRNA levels. We identified a Methylation Classifier for Androgen receptor activity (MCA) signature, which separated metastases into two clusters (MCA positive/negative) related to tumor characteristics and patient prognosis. The MCA positive metastases showed low methylation levels of genes associated with canonical AR signaling and patients had a more favorable prognosis after ADT. In contrast, MCA negative patients had low AR activity associated with hypermethylation of AR-associated genes, and a worse prognosis after ADT.

Conclusions: A promoter methylation signature classifies PC bone metastases into two groups and predicts tumor AR activity and patient prognosis after ADT. The explanation for the methylation diversities observed during PC progression and their biological and clinical relevance need further exploration.

Ort, förlag, år, upplaga, sidor
BioMed Central, 2021
Nyckelord
Androgen receptor, DNA methylation, Gene expression, MetA, Metastasis, MetB, MetC, Prognosis, Prostate cancer, Subtypes
Nationell ämneskategori
Cancer och onkologi
Identifikatorer
urn:nbn:se:umu:diva-185893 (URN)10.1186/s13148-021-01119-0 (DOI)000670704300001 ()34193246 (PubMedID)2-s2.0-85109041809 (Scopus ID)
Tillgänglig från: 2021-07-12 Skapad: 2021-07-12 Senast uppdaterad: 2023-09-05Bibliografiskt granskad
Patthey, A., Boman, K., Tavelin, B., Lindquist, D., Lundin, E. & Hultdin, M. (2021). Combination of aneuploidy and high S-phase fraction indicates increased risk of relapse in stage I endometrioid endometrial carcinoma. Acta Oncologica, 60(9), 1218-1224
Öppna denna publikation i ny flik eller fönster >>Combination of aneuploidy and high S-phase fraction indicates increased risk of relapse in stage I endometrioid endometrial carcinoma
Visa övriga...
2021 (Engelska)Ingår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 60, nr 9, s. 1218-1224Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

INTRODUCTION: Endometrioid endometrial carcinoma is a cancer type with generally excellent prognosis when diagnosed at an early stage, but there is a subset of patients with relapsing disease in spite of early diagnosis and surgical treatment. There is a need to find prognostic markers to identify these patients with increased risk of relapse. Depth of myometrial invasion, histological grade, and presence of lymphovascular invasion are known risk factors. DNA content (ploidy) and proliferation measured as S-phase fraction (SPF) have been discussed as prognostic markers but need additional evaluation.

MATERIAL AND METHODS: We evaluated relapse-free survival (RFS) with respect to ploidy and SPF, which was analyzed by flow cytometry on fresh tumor tissue, in a cohort of 1001 women treated for stage I endometrioid endometrial carcinoma in northern Sweden during the period of 1993-2010, with a median follow up time of 12.0 years. Data were obtained from historical records.

RESULTS: In simple analysis, both aneuploidy and high SPF were associated to increased risk of relapse with hazard ratios (HR) 2.37 (95% CI 1.52-3.70) and 1.94 (95% CI 1.24-3.02), respectively. Our data also confirmed stage, tumor grade, and ploidy as independent prognostic markers in an age adjusted cox regression multivariable analysis but we did not find SPF to contribute to prognosis. However, the combination of aneuploidy and high SPF identified a group of patients with increased risk of relapse, HR 2.02 (95% CI 1.19-3.44).

CONCLUSION: In this study, which is the largest study of ploidy and SPF in stage I endometrioid endometrial carcinoma using fresh frozen tissue, aneuploidy was shown to be an independent prognostic marker. Furthermore, the combination of aneuploidy and high SPF could be used to identify patients with increased risk of relapse.

Ort, förlag, år, upplaga, sidor
Taylor & Francis Group, 2021
Nyckelord
Endometrioid Endometrial Carcinoma, Ploidy, Prognosis, S-phase fraction
Nationell ämneskategori
Cancer och onkologi
Identifikatorer
urn:nbn:se:umu:diva-185073 (URN)10.1080/0284186X.2021.1939146 (DOI)000665673800001 ()34156893 (PubMedID)2-s2.0-85108629114 (Scopus ID)
Forskningsfinansiär
Region Västerbotten
Tillgänglig från: 2021-06-23 Skapad: 2021-06-23 Senast uppdaterad: 2023-03-24Bibliografiskt granskad
Dernstedt, A., Leidig, J., Holm, A., Kerkman, P., Mjösberg, J., Ahlm, C., . . . Forsell, M. N. E. (2021). Regulation of Decay Accelerating Factor Primes Human Germinal Center B Cells for Phagocytosis. Frontiers in Immunology, 11, Article ID 599647.
Öppna denna publikation i ny flik eller fönster >>Regulation of Decay Accelerating Factor Primes Human Germinal Center B Cells for Phagocytosis
Visa övriga...
2021 (Engelska)Ingår i: Frontiers in Immunology, E-ISSN 1664-3224, Vol. 11, artikel-id 599647Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Germinal centers (GC) are sites for extensive B cell proliferation and homeostasis is maintained by programmed cell death. The complement regulatory protein Decay Accelerating Factor (DAF) blocks complement deposition on host cells and therefore also phagocytosis of cells. Here, we show that B cells downregulate DAF upon BCR engagement and that T cell-dependent stimuli preferentially led to activation of DAF(lo) B cells. Consistent with this, a majority of light and dark zone GC B cells were DAF(lo) and susceptible to complement-dependent phagocytosis, as compared with DAF(hi) GC B cells. We could also show that the DAF(hi) GC B cell subset had increased expression of the plasma cell marker Blimp-1. DAF expression was also modulated during B cell hematopoiesis in the human bone marrow. Collectively, our results reveal a novel role of DAF to pre-prime activated human B cells for phagocytosis prior to apoptosis.

Ort, förlag, år, upplaga, sidor
Frontiers Media S.A., 2021
Nyckelord
human B cell development, germinal center (GC), decay accelerating factor (DAF), complement-mediated phagocytosis, complement regulating proteins
Nationell ämneskategori
Immunologi inom det medicinska området
Identifikatorer
urn:nbn:se:umu:diva-179577 (URN)10.3389/fimmu.2020.599647 (DOI)000608470700001 ()33469456 (PubMedID)2-s2.0-85099651060 (Scopus ID)
Forskningsfinansiär
NIH (National Institute of Health), U19AI142777-01Vetenskapsrådet, 2016-06598
Tillgänglig från: 2021-02-04 Skapad: 2021-02-04 Senast uppdaterad: 2024-01-17Bibliografiskt granskad
Pudas, S., Josefsson, M., Nordin Adolfsson, A., Landfors, M., Kauppi, K., Veng-Taasti, L. M., . . . Degerman, S. (2021). Short leukocyte telomeres, but not telomere attrition rates, predict memory decline in the 20-year longitudinal Betula study. The journals of gerontology. Series A, Biological sciences and medical sciences, 76(6), 955-963
Öppna denna publikation i ny flik eller fönster >>Short leukocyte telomeres, but not telomere attrition rates, predict memory decline in the 20-year longitudinal Betula study
Visa övriga...
2021 (Engelska)Ingår i: The journals of gerontology. Series A, Biological sciences and medical sciences, ISSN 1079-5006, E-ISSN 1758-535X, Vol. 76, nr 6, s. 955-963Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Leukocyte telomere length (LTL) is a proposed biomarker for aging-related disorders, including cognitive decline and dementia. Long-term longitudinal studies measuring intra-individual changes in both LTL and cognitive outcomes are scarce, precluding strong conclusions about a potential aging-related relationship between LTL shortening and cognitive decline. This study investigated associations between baseline levels and longitudinal changes in LTL and memory performance across an up to 20-year follow-up in 880 dementia-free participants from a population-based study (mean baseline age: 56.8 years, range: 40–80; 52% female). Shorter baseline LTL significantly predicted subsequent memory decline (r = .34, 95% confidence interval: 0.06, 0.82), controlling for age, sex, and other relevant covariates. No significant associations were however observed between intra-individual changes in LTL and memory, neither concurrently nor with a 5-year time-lag between LTL shortening and memory decline. These results support the notion of short LTL as a predictive factor for aging-related memory decline, but suggest that LTL dynamics in adulthood and older age may be less informative of cognitive outcomes in aging. Furthermore, the results highlight the importance of long-term longitudinal evaluation of outcomes in biomarker research.

Ort, förlag, år, upplaga, sidor
Oxford University Press, 2021
Nyckelord
Cognitive aging, Leukocyte telomere length, Longitudinal, Memory, Population-based
Nationell ämneskategori
Gerontologi, medicinsk/hälsovetenskaplig inriktning Geriatrik Neurovetenskaper
Forskningsämne
medicinsk beteendevetenskap; geriatrik; psykologi
Identifikatorer
urn:nbn:se:umu:diva-181484 (URN)10.1093/gerona/glaa322 (DOI)000659456700002 ()33367599 (PubMedID)2-s2.0-85107088699 (Scopus ID)
Forskningsfinansiär
Vetenskapsrådet, 2018-01729Region Västerbotten, RV-735451, RV-453141, RV-225461
Tillgänglig från: 2021-03-13 Skapad: 2021-03-13 Senast uppdaterad: 2024-04-08Bibliografiskt granskad
Organisationer

Sök vidare i DiVA

Visa alla publikationer