Mikael Åberg

Uppsala University | UU · Department of Medical Sciences

In sub-Saharan Africa, pregnant women are at greater risk of malaria infection than non-pregnant adult women. The infection may lead to pregnancy-associated malaria (PAM) because of the sequestration of Plasmodium falciparum-infected erythrocytes in the placental intervillous space. Although there are several tools for diagnosing malaria infection...

Introduction Several novel vaccine platforms aim at mucosal immunity in the respiratory tract to block SARS-CoV-2 transmission. Standardized methods for mucosal sample collection and quantification of mucosal antibodies are therefore urgently needed for harmonized comparisons and interpretations across mucosal vaccine trials and real-world data. M...

Continued SARS-CoV-2 evolution and immune escape necessitated the development of updated vaccines, and a monovalent vaccine incorporating the XBB.1.5 variant spike protein is currently being rolled out. Amidst the emergence of the highly mutated BA.2.86 lineage and against the backdrop of pronounced immune imprinting, it is important to characteriz...

Background Treatment of cardiovascular diseases (CVD) is a substantial burden to healthcare systems worldwide. New tools are needed to improve precision of treatment by optimizing the balance between efficacy, safety, and cost. We developed a high-throughput multi-marker decision support instrument which simultaneously quantifies proteins associate...

Background: Patients with chronic lymphocytic leukemia (CLL) are vulnerable to coronavirus disease 2019 (COVID-19) and are at risk of inferior response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, especially if treated with the first-generation Bruton's tyrosine kinase inhibitor (BTKi) ibrutinib. We aimed to evaluat...

A comprehensive characterization of blood proteome profiles in cancer patients can contribute to a better understanding of the disease etiology, resulting in earlier diagnosis, risk stratification and better monitoring of the different cancer subtypes. Here, we describe the use of next generation protein profiling to explore the proteome signature...

Background: Immunocompromised patients have varying responses to SARS-CoV-2 mRNA vaccination. However, there is limited information available from prospective clinical trial cohorts with respect to long-term immunogenicity-related responses in these patient groups following three or four vaccine doses, and in applicable cases infection. Methods:...

Background: To inform future preventive measures including repeated vaccinations, we have searched for a clinically useful immune correlate of protection against fatal COVID-19 among nursing homes residents. Methods: We performed repeated capillary blood sampling with analysis of S-binding IgG in an open cohort of nursing home residents in Swede...

Purpose Patients with antibody deficiencies often receive maintenance treatment with donor plasma-derived immunoglobulin (Ig) preparations to decrease the incidence and severity of infections. We have previously shown that IgG antibodies to the original SARS-CoV-2 strain were not consistently present in off-the-shelf Ig batches produced up to appro...

Vaccination offers protection against severe COVID-19 caused by SARS-CoV-2 omicron but is less effective against infection. Characteristics such as serum antibody titer correlation to protection, viral abundance and clearance of omicron infection in vaccinated individuals are scarce. We present a 4-week twice-weekly SARS-CoV-2 qPCR screening in 368...

Background To inform future preventive measures including repeated vaccinations, we have searched for a clinically useful immune correlate of protection against fatal Covid-19 among nursing homes residents. Methods We performed repeated capillary blood sampling with analysis of S-binding IgG in an open cohort study with inclusion of nursing home r...

Patients with chronic lymphocytic leukemia (CLL) were at high risk early in the COVID-19 pandemic. The Omicron SARS-CoV-2 variant is considered less aggressive, but a significant fatality rate was recently reported from CLL register studies. Here we report on Omicron hybrid immunity in CLL after vaccinations against SARS-CoV-2 followed by disease....

A homogeneous PCR-based assay for sensitive and specific detection of antibodies in serum or dried blood spots (DBS) is presented and the method is used to monitor individuals infected with or vaccinated against SARS-CoV-2. Detection probes were prepared by conjugating the recombinant spike protein subunit 1 (S1), containing the receptor binding do...

Cancer is a highly heterogeneous disease in need of accurate and non-invasive diagnostic tools. Here, we describe a novel strategy to explore the proteome signature by comprehensive analysis of protein levels using a pan-cancer approach of patients representing the major cancer types. Plasma profiles of 1,463 proteins from more than 1,400 cancer pa...

Pulmonary hypertension (PH) is defined by increased mean pulmonary artery pressure, and the clinical classification includes five etiologies, of which we investigated subgroup 1, pulmonary arterial hypertension (PAH) and subgroup 4, chronic thrombotic and/or embolic disease (CTEPH). Platelets participate in both innate and adaptive immune responses...

Objective: To determine the long-term impact of prior SARS-CoV-2 infection on immune responses after COVID-19 vaccination. Methods: Using longitudinally collected blood samples from the COMMUNITY study, we determined binding (WHO BAU mL-1) and neutralising antibody titres against ten SARS-CoV-2 variants over 7 months following BNT162b2 in SARS-C...

Background Booster vaccine doses offer protection against severe COVID-19 caused by omicron but are less effective against infection. Characteristics such as serological correlates of protection, viral abundance and clearance of omicron infections in triple vaccinated individuals are scarce. Methods We conducted a 4-week twice-weekly SARS-CoV-2 qP...

Introduction: Ulcerative colitis (UC) associated with primary sclerosing cholangitis (PSC-UC) is considered a unique IBD entity. PSC diagnosis in an IBD individual entails a significantly higher risk of gastrointestinal cancer, however, biomarkers for identifying UC patients at risk for PSC are lacking. We therefore performed a thorough PSC-UC bio...

Background: Ovarian cancer is the eighth most common cancer among women and has a 5-year survival of only 30-50%. The survival is close to 90% for patients in stage I but only 20% for patients in stage IV. The presently available biomarkers have insufficient sensitivity and specificity for early detection and there is an urgent need to identify no...

Objectives: Periodontal disease (PD) and rheumatoid arthritis (RA) are known chronic conditions with sustained inflammation leading to osteolysis. Cardiovascular diseases (CVD) are frequent comorbidities that may arise from sustained inflammation associated with both PD and RA. In order to determine CVD risk, alterations at the molecular level nee...

Heterologous primary immunization against SARS-CoV-2 is part of applied recommendations. However, little is known about duration of immune responses after heterologous vaccine regimens. To evaluate duration of immune responses after primary vaccination with homologous adeno-vectored ChAdOx1 nCoV-19 vaccine (ChAd) or heterologous ChAd/BNT162b2 mRNA...

People with previous SARS-CoV-2 infection mount potent immune responses to COVID-19 vaccination, but long-term effects of prior infection on these immune responses are unknown. We investigated the long-term impact of prior SARS-CoV-2 infection on humoral and cellular immune responses in healthcare workers receiving the mRNA BNT162b2 or the adenovir...

Background : Emerging data supports detectable immune responses for months after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination, but it is not yet established to what degree and for how long protection against reinfection lasts. Methods : We investigated SARS-CoV-2-specific humoral and cellular immune respon...

Background: SARS-CoV-2 variants, such as Alpha, Beta, Gamma and Delta, are raising concern about the efficiency of neutralizing antibodies (NAb) induced by wild-type infection or vaccines based on the wild-type spike. Methods: We determined IgG and NAb against SARS-CoV-2 variants one year following mild wild-type infection (n=104) and two-dose regi...

Background: Recent reports demonstrate robust serological responses to a single dose of messenger RNA (mRNA) vaccines in individuals previously infected with SARS-CoV-2. Data on immune responses following a single-dose adenovirus-vectored vaccine expressing the SARS-CoV-2 spike protein (ChAdOx1 nCoV-19) in individuals with previous SARS-CoV-2 infe...

Background Oral anticoagulants (OAC) in patients with atrial fibrillation (AF) prevent thromboembolic events, but are associated with significant risk of bleeding. Objectives To explore associations between a wide range of biomarkers and bleeding risk in patients with AF on OAC. Method Biomarkers were analyzed in a random sample of 4,200 patients...

Background Recent reports demonstrate robust serological responses to a single dose of messenger RNA (mRNA) vaccines in individuals previously infected with SARS-CoV-2. Data on immune responses following a single-dose adenovirus-vectored vaccine expressing the SARS-CoV-2 spike protein (ChAdOx1 nCoV-19) in individuals with previous SARS-CoV-2 infect...

Background Acute kidney injury is common in COVID-19 patients admitted to the ICU. Urinary biomarkers are a non-invasive way of assaying renal damage, and so far, urinary cytokines are not fully investigated. The current study aimed to assess urinary cytokine levels in COVID-19 patients. Methods Urine was collected from COVID-19 patients (n= 29) i...

Workplace-collected blood spots deposited on filter paper were analysed with multiplexed affinity-based protein assays and found to be suitable for proteomics analysis. The protein extension assay (PEA) was used to characterize 92 proteins using 1.2 mm punches in repeated samples collected from 20 workers. Overall, 97.8% of the samples and 91.3% of...

Background Circulating biomarkers are associated with the development of coronary heart disease (CHD) and its complications by reflecting pathophysiological pathways and/or organ dysfunction. We explored the associations between 157 cardiovascular (CV) and inflammatory biomarkers and CV death using proximity extension assays (PEA) in patients with...

Objective: Extracellular vesicles (EVs) have the potential to act as intercellular communicators. The aims were to characterize circulating EVs in patients with pulmonary arterial hypertension (PAH) and to explore whether these EVs contribute to endothelial activation and angiogenesis. Approach and Results: Patients with PAH (n=70) and healthy con...

The tissue factor/coagulation factor VIIa (TF/FVIIa) complex induces transactivation of the IGF-1 receptor (IGF-1R) in a number of different cell types. The mechanism is largely unknown. The transactivation leads to protection from apoptosis and nuclear translocation of the IGF-1R. The aim of this study was to clarify the signaling pathway between...

Background: Ulcerative colitis (UC) in patients with the severe disease primary sclerosing cholangitis (PSC) constitutes a distinct clinical phenotype (PSC-UC) with a high incidence of colorectal cancer. Today, PSC-UC diagnosis is built on clinical observations only. Tissue factor (TF) has a potential use in UC diagnostics, and also in colorectal c...

Background Pulmonary Arterial Hypertension (PAH) is a progressive condition with remodeling of precapillary arteries. Cytokines involved in angiogenesis have been found elevated in PAH but the role of proangiogenic factors and their regulation is far from fully understood. Microvesicles (MVs) can act as intercellular messengers and modify cell prod...

Background: Tissue factor (TF) combined with its ligand FVII initiates blood coagulation and intracellular signaling. Obese and type 2 diabetic subjects have increased TF expression in their adipose tissue and an increased risk for thrombotic complications. Here we address the role of TF/FVII on adipocyte functions. Materials and methods: Subcutane...

Extracellular vesicles (EVs) derived from blood cells are promising biomarkers for various diseases. However, they are difficult to measure accurately in plasma due to their small size. Here, we demonstrate that platelet-derived EVs in plasma can be measured using solid-phase proximity ligation assay with high sensitivity and specificity using very...

Monocytes and monocyte-derived microvesicles (MVs) are the main source of circulating tissue factor (TF). Increased monocyte TF expression and increased circulating levels of procoagulant MVs contribute to the formation of a prothrombotic state in patients with cardiovascular disease. Interleukin (IL)-33 is a pro-inflammatory cytokine involved in a...

Tissue factor (TF) is a 47-kDa transmembrane glycoprotein and the main initiator of the blood coagulation cascade. Binding to its ligand factor VIIa (FVIIa) also initiates noncoagulant signaling with broad biological implications. In this review, we discuss how TF interacts with other cell-surface proteins, which affect biological functions such as...

The insulin-like growth factor 1 receptor (IGF-1R) is known to promote survival and has also been implicated in the pathogenesis of several disease states, including cardiovascular disorders and cancer. Recently, we showed that binding of coagulation factor VIIa (FVIIa) to its receptor tissue factor (TF) protects cancer cells from TNF-related apopt...

Tissue factor (TF), a transmembrane glycoprotein, is the main initiator of the blood coagulation cascade. TF is also recognized as a true signalling receptor. There is accumulating evidence that the downstream signalling events by the TF-complexes are transduced by several mechanisms including; activation of the protease activated receptors (PAR)-1...

This study determines the impact of tissue factor (TF)-signaling on the extrinsic pathway of apoptosis in cancer cells and propose death associated protein kinase-1 (DAPK1) as a novel key regulator. In MDA-MB-231 breast and PC3 prostate cancer cells, mRNA levels were analyzed by real-time PCR and protein expressions were assessed by flow cytometry...

Cancer confers a prothrombotic state and statins are associated with a lowered risk for prostate cancer in vivo by unknown mechanisms. Prostate cancer cells release tissue factor (TF)-bearing, cholesterol-rich prostasomes which are pro-coagulant in vitro and a possible source for the blood-borne TF found in prostate cancer patients. We investigated...

Statins have benefits independent of the plasma cholesterol properties among cancer patients and tissue factor (TF)/FVIIa induce PI3-kinase/AKT dependent anti-apoptosis during serum starvation. We analyzed how simvastatin induces apoptosis in human breast cancer cells and the influence of FVIIa and/or FXa on the proposed apoptosis. MDA-MB-231 cells...

We have previously reported the potentiation of PDGF-BB-induced chemotaxis of fibroblasts, vascular smooth muscle cells, and endothelial cells by FVIIa. Here we studied the role of TF/FVIIa and the induced signaling pathways in regulation of chemotaxis of human monocytes, fibroblasts, and porcine aorta endothelial cells. Human monocytes were obtain...

Tissue factor (TF) is primarily known for its function to initiate blood coagulation. The range of in vivo expression of TF is wide and requires a dynamic assay for monitoring. A general method for TF mRNA quantitation that is dynamic, sensitive and applicable to a variety of experimental systems or clinical situations is therefore desirable. To de...