Publications by authors named "Karina de Leeuw"

Objectives: To investigate the levels of plasma neutrophil extracellular traps (NETs) and free thiols, the latter reflecting systemic oxidative stress (OS), and to explore the relationship between NETs and OS in quiescent systemic lupus erythematosus (SLE) patients with and without renal involvement.

Methods: Plasma levels of NETs and free thiols were measured cross-sectionally in 100 SLE patients with low disease activity (SLEDAI < 5), of whom 73 patients had no renal involvement (non-LN) and 27 patients had lupus nephritis (LN). Additionally, 22 healthy controls (HCs) were included.

View Article and Find Full Text PDF

Systemic lupus erythematosus (SLE) is a complex autoimmune disease in which kidney involvement, so-called lupus nephritis (LN), is common and one of the most severe manifestations. Oxidative stress (OS) may play a role in the pathogenesis of LN through the exacerbation of inflammation and immune cell dysfunction/dysregulation. Nuclear factor erythroid 2-related factor 2 (Nrf2), also known as nuclear factor erythroid-derived 2-like 2, is a transcription factor that in humans is encoded by the NFE2L2 gene and is regarded as a central regulator of the antioxidative response.

View Article and Find Full Text PDF

Background: The modified Short QUestionnaire to ASsess Health-enhancing physical activity (mSQUASH) was originally developed and validated in Dutch patients with axial spondyloarthritis (axSpA). To support world-wide distribution, applicability and comparability of measuring physical activity, our aim was to perform translation and cross-cultural adaptation of the mSQUASH into English, field testing in other rheumatic diseases and clinical validation in patients with axSpA.

Methods: The Dutch mSQUASH was translated into English according to forward-backward Beaton protocol.

View Article and Find Full Text PDF

Background: To enhance patient-tailored preconception risk assessment for women with systemic lupus erythematosus (SLE), knowledge on risk factors associated with adverse pregnancy outcomes is required. Therefore, we did a systematic review and meta-analysis to identify and provide unambiguous effect sizes of preconception predictors of pregnancy outcomes in women with SLE.

Methods: In this systematic review and meta-analysis, we searched PubMed and Embase for studies reporting preconception predictors of pregnancy outcomes in women with SLE, from database inception to Aug 22, 2023.

View Article and Find Full Text PDF

Objective: To investigate the proportion of low-density granulocytes (LDGs), circulating plasma neutrophil extracellular traps (NETs), and serum-induced NET formation in patients with incomplete systemic lupus erythematosus (iSLE) and systemic lupus erythematosus (SLE).

Methods: LDGs were measured cross-sectionally in 18 iSLE patients, 11 SLE patients and 14 healthy controls (HCs), whereas circulating NETs and serum-induced NET formation were assessed in 35 iSLE patients, 41 SLE patients and 16 HCs. LDGs (CD14lowCD15+) were measured in PBMCs using flow cytometry and circulating plasma NETs were measured using anti-myeloperoxidase-DNA, anti-citrullinated histone H3 and anti-elastase-DNA complex ELISAs.

View Article and Find Full Text PDF

Hydroxychloroquine (HCQ) is obtained by hydroxylation of chloroquine (CQ) and the first indication was malaria. Nowadays, HCQ is commonly used in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) with favorable results. Antiphospholipid syndrome (APS) is an autoimmune disease characterized by thrombosis and/or pregnancy morbidity and persistent positivity of antiphospholipid antibodies.

View Article and Find Full Text PDF

Objective: To identify preconception clinical factors associated with adverse pregnancy outcomes (APO) in patients with systemic lupus erythematosus (SLE) or primary Sjögren's syndrome (pSS).

Methods: A single-centre, retrospective cohort study was conducted, which included pregnant women treated at the University Medical Center Groningen between January 2010 and August 2021 who fulfilled classification criteria for SLE or pSS. Demographic data, relevant comorbidities, disease duration, disease activity before and during pregnancy, APO, laboratory parameters and treatment regimens were recorded.

View Article and Find Full Text PDF

Oxidative stress plays an important role in systemic lupus erythematosus (SLE) and especially in lupus nephritis (LN). The aim of this study was to compare redox-related biomarkers between patients with active LN, quiescent SLE (Q-SLE) and healthy controls (HC) and to explore their association with clinical characteristics such as disease activity in patients. We investigated levels of plasma free thiols (R-SH, sulfhydryl groups), levels of soluble receptor for advanced glycation end products (sRAGE) and levels of malondialdehyde (MDA) in SLE patients with active LN ( = 23), patients with quiescent SLE ( = 47) and HC ( = 23).

View Article and Find Full Text PDF

Puffy fingers and Raynaud's phenomenon (RP) are important clinical predictors of the development of systemic sclerosis (SSc). We aim to assess the prevalence of SSc-related symptoms, explore pulmonary symptoms, and test the usefulness of skin autofluorescence (SAF) as a non-invasive marker for Advanced Glycation Endproducts (AGEs). Subjects from the Lifelines Cohort Study with known connective tissue disease (CTD) were excluded.

View Article and Find Full Text PDF

Background: Patients with immune-mediated inflammatory diseases (IMIDs) on immunosuppressants (ISPs) may have impaired long-term humoral immune responses and increased disease activity after SARS-CoV-2 infection. We aimed to investigate long-term humoral immune responses against SARS-CoV-2 and increased disease activity after a primary SARS-CoV-2 infection in unvaccinated IMID patients on ISPs.

Methods: IMID patients on active treatment with ISPs and controls (i.

View Article and Find Full Text PDF

Phage-displayed immunoprecipitation sequencing (PhIP-seq) has enabled high-throughput profiling of human antibody repertoires. However, a comprehensive overview of environmental and genetic determinants shaping human adaptive immunity is lacking. In this study, we investigated the effects of genetic, environmental, and intrinsic factors on the variation in human antibody repertoires.

View Article and Find Full Text PDF

Background: Increased prevalence of autoantibody Fab glycosylation has been demonstrated for several autoimmune diseases.

Objectives: To study whether elevated Fab glycosylation is a common feature of autoimmunity, this study investigated Fab glycosylation levels on serum IgG and its subclasses for autoantibodies associated with a range of different B cell-mediated autoimmune diseases, including rheumatoid arthritis, myasthenia gravis subtypes, pemphigus vulgaris, antineutrophil cytoplasmic antibody-associated vasculitis, systemic lupus erythematosus, anti-glomerular basement membrane glomerulonephritis, thrombotic thrombocytopenic purpura, and Guillain-Barré syndrome.

Methods: The level of Fab glycosylated IgG antibodies was assessed by lectin affinity chromatography and autoantigen-specific immunoassays.

View Article and Find Full Text PDF

For patients with immune-mediated inflammatory diseases (IMIDs), concerns exist about increased disease activity after vaccination. We aimed to assess changes in disease activity after SARS-CoV-2 vaccination in patients with IMIDs, and determine risk factors for increased disease activity. In this substudy of a prospective observational cohort study (Target-to-B!), we included patients with IMIDs who received a SARS-CoV-2 vaccine.

View Article and Find Full Text PDF

Background: Recurrence risk of systemic lupus erythematosus (SLE)-associated venous thromboembolism (VTE) is unclear.

Aim: To determine the recurrence risk of SLE-associated VTE overall and by presence of provoking factors and SLE flares.

Methods: A multicenter, retrospective cohort study was conducted among patients with first SLE-associated VTE who discontinued anticoagulation.

View Article and Find Full Text PDF

Background: Belimumab, an anti-B-cell activating factor antibody, is approved for the treatment of auto-antibody positive systemic lupus erythematosus with a high degree of disease activity. Anti-CD20 B cell depletion with rituximab is used in refractory SLE as well, although with variable responses. We hypothesized that incomplete B cell depletion, related to a surge in BAFF levels following rituximab treatment, can cause ongoing disease activity and flares.

View Article and Find Full Text PDF

Objectives: To compare the cumulative incidence and disease severity of reported SARS-CoV-2 omicron breakthrough infections between patients with immune-mediated inflammatory diseases (IMID) on immunosuppressants and controls, and to investigate determinants for breakthrough infections.

Methods: Data were used from an ongoing national prospective multicentre cohort study on SARS-CoV-2 vaccination responses in patients with IMID in the Netherlands (Target-to-B! (T2B!) study). Patients wih IMID on immunosuppressants and controls (patients with IMID not on immunosuppressants and healthy controls) who completed primary immunisation were included.

View Article and Find Full Text PDF

Background: Patients with inborn errors of immunity (IEI) are at increased risk of severe coronavirus disease-2019 (COVID-19). Effective vaccination against COVID-19 is therefore of great importance in this group, but little is known about the immunogenicity of COVID-19 vaccines in these patients.

Objectives: We sought to study humoral and cellular immune responses after mRNA-1273 COVID-19 vaccination in adult patients with IEI.

View Article and Find Full Text PDF

Background: Disease-specific studies have reported impaired humoral responses after SARS-CoV-2 vaccination in patients with immune-mediated inflammatory disorders treated with specific immunosuppressants. Disease-overarching studies, and data on recall responses and third vaccinations are scarce. Our primary objective was to investigate the effects of immunosuppressive monotherapies on the humoral immune response after SARS-CoV-2 vaccination in patients with prevalent immune-mediated inflammatory disorders.

View Article and Find Full Text PDF