Search results

(1 - 20 of 27)

Pages

Moel, E.C. de; Trouw, L.A.; Terao, C.; Govind, N.; Tikly, M.; El-Gabalawy, H.; ... ; Woude, D. van der 2023

Geo-epidemiology of autoantibodies in rheumatoid arthritis: comparison between four ethnically diverse populations

Article / Letter to editor

open access

Background: Rheumatoid arthritis (RA) occurs across the globe in different ethnic populations. Most RA patients harbor anti-modified protein antibodies (AMPA); however, it is unclear whether... Show moreBackground: Rheumatoid arthritis (RA) occurs across the globe in different ethnic populations. Most RA patients harbor anti-modified protein antibodies (AMPA); however, it is unclear whether differences exist in autoantibody responses at different geographic locations and between different ethnic groups, which could provide new clues regarding factors underlying autoantibody development. We therefore investigated AMPA prevalence and association with HLA DRB1 alleles and smoking in four ethnically diverse populations on four different continents. Methods: Anti-carbamylated (anti-CarP), anti-malondialdehyde acetaldehyde (anti-MAA), and anti-acetylated protein antibodies (anti-AcVim) IgG were determined in anti-citrullinated protein antibody-positive Dutch (NL, n = 103), Japanese (JP, n = 174), First Nations Peoples in Canada (FN, n = 100), and black South African (SA, n = 67) RA patients. Ethnicity-matched local healthy controls were used to calculate cut-offs. Risk factors associated with AMPA seropositivity in each cohort were identified using logistic regression. Results: Median AMPA levels were higher in First Nations Peoples in Canada and especially South African patients, as reflected by percentage seropositivity: NL, JP, FN, and SA: anti-CarP: 47%, 43%, 58%, and 76% (p < 0.001); anti-MAA: 29%, 22%, 29%, and 53% (p < 0.001); and anti-AcVim: 20%, 17%, 38%, and 28% (p < 0.001). Total IgG levels also differed markedly, and when autoantibody levels were normalized to total IgG, differences between cohorts became less pronounced. Although there were some associations with AMPA and HLA risk alleles and smoking, none was consistent across all four cohorts. Conclusions: AMPA against various post-translational modifications could consistently be detected on different continents across ethnically diverse RA populations. Differences in AMPA levels corresponded to differences in total serum IgG levels. This suggests that, despite differences in risk factors, a common pathway may be involved in AMPA development across geographic locations and ethnicities. Show less

Moel, E.C. de; Trouw, L.A.; Terao, C.; Govind, N.; Tikly, M.; El-Gabalawy, H.; ... ; Woude, D. van der 2023

Geo-epidemiology of autoantibodies in rheumatoid arthritis: comparison between four ethnically diverse populations

Article / Letter to editor

open access

BackgroundRheumatoid arthritis (RA) occurs across the globe in different ethnic populations. Most RA patients harbor anti-modified protein antibodies (AMPA); however, it is unclear whether... Show moreBackgroundRheumatoid arthritis (RA) occurs across the globe in different ethnic populations. Most RA patients harbor anti-modified protein antibodies (AMPA); however, it is unclear whether differences exist in autoantibody responses at different geographic locations and between different ethnic groups, which could provide new clues regarding factors underlying autoantibody development. We therefore investigated AMPA prevalence and association with HLA DRB1 alleles and smoking in four ethnically diverse populations on four different continents.MethodsAnti-carbamylated (anti-CarP), anti-malondialdehyde acetaldehyde (anti-MAA), and anti-acetylated protein antibodies (anti-AcVim) IgG were determined in anti-citrullinated protein antibody-positive Dutch (NL, n = 103), Japanese (JP, n = 174), First Nations Peoples in Canada (FN, n = 100), and black South African (SA, n = 67) RA patients. Ethnicity-matched local healthy controls were used to calculate cut-offs. Risk factors associated with AMPA seropositivity in each cohort were identified using logistic regression.ResultsMedian AMPA levels were higher in First Nations Peoples in Canada and especially South African patients, as reflected by percentage seropositivity: NL, JP, FN, and SA: anti-CarP: 47%, 43%, 58%, and 76% (p < 0.001); anti-MAA: 29%, 22%, 29%, and 53% (p < 0.001); and anti-AcVim: 20%, 17%, 38%, and 28% (p < 0.001). Total IgG levels also differed markedly, and when autoantibody levels were normalized to total IgG, differences between cohorts became less pronounced. Although there were some associations with AMPA and HLA risk alleles and smoking, none was consistent across all four cohorts.ConclusionsAMPA against various post-translational modifications could consistently be detected on different continents across ethnically diverse RA populations. Differences in AMPA levels corresponded to differences in total serum IgG levels. This suggests that, despite differences in risk factors, a common pathway may be involved in AMPA development across geographic locations and ethnicities. Show less

Boeters, D.M. 2020

Early identification and resolution of rheumatoid arthritis

Doctoral Thesis

open access

overzicht van verschillende voorspellers voor het ontwikkelen van RA binnen patiënten met artralgie

rol van nieuwe autoantistoffen en MRI in vroege diagnostiek RA

onderzoek naar behalen van DMARD...

overzicht van verschillende voorspellers voor het ontwikkelen van RA binnen patiënten met artralgie

rol van nieuwe autoantistoffen en MRI in vroege diagnostiek RA

onderzoek naar behalen van DMARD-vrije remissie: voorkomen van immunologische remissie en identificatie van subgroep van RA-patiënten met verhoogde kans op remissie

Show less

Hafkenscheid, L. 2020

Anti Citrullinated Protein Antibodies-IgG variable domain glycosylation in rheumatoid arthritis

Doctoral Thesis

open access

Rheumatoid arthritis (RA) is an auto-inflammatory disease, affecting ~1% of the world population. RA is hallmarked by the presence of autoantibodies, one of the well-known autoantibodies in RA are... Show moreRheumatoid arthritis (RA) is an auto-inflammatory disease, affecting ~1% of the world population. RA is hallmarked by the presence of autoantibodies, one of the well-known autoantibodies in RA are the anti-citrullinated protein antibodies (ACPA). ACPA is highly specific for RA and about 70-80% of the RA patients are positive for ACPA. Previously, we discovered that ACPA-IgG are extensively glycosylated in the variable (V) region. In this thesis, we determined that over 90% of the ACPA-IgG carries glycans in the v-domain were as only 17% of the conventional IgG carries additional glycans. Additionally, the glycans were highly sialylated. Intriguingly, we also showed that the glycans are introduced via somatic hyper mutations in the germinal center reaction. Furthermore, we discovered that ACPA-IgG v-domain glycosylation is a predictive marker for the development of ACPA positive RA. Lastly, we found that the binding strength is not influenced by the glycans but it influences the amount of available binding sites. Nevertheless, the ACPA-BCR still overcome negative selection which might suggest that the glycans can trigger an alternative way for positive selection in the germinal center. This will be subject for further studies regarding the role of ACPA-IgG v-domain glycosylation. Show less

Al-Laith, M.; Jasenecova, M.; Abraham, S.; Bosworth, A.; Bruce, I.N.; Buckley, C.D.; ... ; Cope, A.P. 2019

Arthritis prevention in the pre-clinical phase of RA with abatacept (the APIPPRA study): a multi-centre, randomised, double-blind, parallel-group, placebo-controlled clinical trial protocol

Article / Letter to editor

metadata only

Al-Laith, M.; Jasenecova, M.; Abraham, S.; Bosworth, A.; Bruce, I.N.; Buckley, C.D.; ... ; Cope, A.P. 2019

Arthritis prevention in the pre-clinical phase of RA with abatacept (the APIPPRA study): a multi-centre, randomised, double-blind, parallel-group, placebo-controlled clinical trial protocol

Article / Letter to editor

metadata only

Trial designWe present a study protocol for a multi-centre, randomised, double-blind, parallel-group, placebo-controlled trial that seeks to test the feasibility, acceptability and effectiveness of... Show moreTrial designWe present a study protocol for a multi-centre, randomised, double-blind, parallel-group, placebo-controlled trial that seeks to test the feasibility, acceptability and effectiveness of a 52-week period of treatment with the first-in-class co-stimulatory blocker abatacept for preventing or delaying the onset of inflammatory arthritis.MethodsThe study aimed to recruit 206 male or female subjects from the secondary care hospital setting across the UK and the Netherlands. Participants who were at least 18 years old, who reported inflammatory sounding joint pain (clinically suspicious arthralgia) and who were found to be positive for serum autoantibodies associated with rheumatoid arthritis (RA) were eligible for enrolment. All study subjects were randomly assigned to receive weekly injections of investigational medicinal product, either abatacept or placebo treatment over the course of a 52-week period. Participants were followed up for a further 52weeks. The primary endpoint was defined as the time to development of at least three swollen joints or to the fulfilment of the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for RA using swollen but not tender joints, whichever endpoint was met first. In either case, swollen joints were confirmed by ultrasonography. Participants, care givers, and those assessing the outcomes were all blinded to group assignment. Clinical assessors and ultrasonographers were also blinded to each other's assessments for the duration of the study.ConclusionsThere is limited experience of the design and implementation of trials for the prevention of inflammatory joint diseases. We discuss the rationale behind choice and duration of treatment and the challenges associated with defining the at risk state and offer pragmatic solutions in the protocol to enrolling subjects at risk of RA.Trial registrationCurrent Controlled Trials, ID: ISRCTN46017566. Registered on 4 July 2014. Show less

Moel, E.C. de; Derksen, V.F.A.M.; Trouw, L.A.; Bang, H.; Collee, G.; Lard, L.R.; ... ; Woude, D. van der 2019

In rheumatoid arthritis, changes in autoantibody levels reflect intensity of immunosuppression, not subsequent treatment response

Article / Letter to editor

metadata only

Verheul, M.K. 2019

Unravelling the anti-carbamylated protein antibody response in rheumatoid arthritis

Doctoral Thesis

open access

Although quite some data is available on anti-CarP antibodies, several questions remain unanswered, including the reproducibility of the clinical data on anti-CarP antibodies, such as their... Show moreAlthough quite some data is available on anti-CarP antibodies, several questions remain unanswered, including the reproducibility of the clinical data on anti-CarP antibodies, such as their presence before disease onset and association with joint damage. It is also unknown whether these findings can be expanded to non-caucasian populations. Furthermore, it is unclear how anti-CarP antibodies are induced, what proteins they recognize, whether they are able to recognize multiple carbamylated proteins and what the characteristics of these autoantibodies are. Here, some of these questions will be answered. In this thesis, I will first discuss the clinical implications of the presence of anti-CarP antibodies compared to RA-specific autoantibodies in both RA patients other relevant conditions (chapters 2 till 7). This is followed by more detailed investigations into the characteristics of anti-CarP antibodies and their antigens (chapters 8 till 12). Show less

Brinck, R.M. ten; Toes, R.E.M.; Helm-van Mil, A.H.M. van der 2018

Inflammation functions as a key mediator in the link between ACPA and erosion development: an association study in Clinically Suspect Arthralgia

Article / Letter to editor

open access

Woude, D. van der; Helm-van Mil, A.H.M. van der 2018

Update on the epidemiology, risk factors, and disease outcomes of rheumatoid arthritis

Article / Letter to editor

open access

Moel, E.C. de; Derksen, V.F.A.M.; Stoeken, G.; Trouw, L.A.; Bang, H.; Goekoop, R.J.; ... ; Woude, D. van der 2018

Baseline autoantibody profile in rheumatoid arthritis is associated with early treatment response but not long-term outcomes

Article / Letter to editor

open access

Verheul, M.K.; Vierboom, M.P.M.; Hart, B.A. 't; Toes, R.E.M.; Trouw, L.A. 2017

Anti-carbamylated protein antibodies precede disease onset in monkeys with collagen-induced arthritis

Article / Letter to editor

metadata only

Boeters, D.M.; Gaujoux-Viala, C.; Constantin, A.; Helm-van Mil, A.H.M. van der 2017

The 2010 ACR/EULAR criteria are not sufficiently accurate in the early identification of autoantibody-negative rheumatoid arthritis: Results from the Leiden-EAC and ESPOIR cohorts

Article / Letter to editor

metadata only

Delft, M.A.M. van; Verheul, M.K.; Burgers, L.E.; Derksen, V.F.A.M.; Helm-van Mil, A.H.M. van der; Woude, D. van der; ... ; Trouw, L.A. 2017

The isotype and IgG subclass distribution of anti-carbamylated protein antibodies in rheumatoid arthritis patients

Article / Letter to editor

metadata only

Verheul, M.K.; Yee, A.; Seaman, A.; Janssen, G.M.; Veelen, P.A. van; Drijfhout, J.W.; ... ; Trouw, L.A. 2017

Identification of carbamylated alpha 1 anti-trypsin (A1AT) as an antigenic target of anti-CarP antibodies in patients with rheumatoid arthritis

Article / Letter to editor

metadata only

Derksen, V.F.A.M.; Huizinga, T.W.J.; Woude, D. van der 2017

The role of autoantibodies in the pathophysiology of rheumatoid arthritis

Article / Letter to editor

open access

Boeters, D.M.; Mangnus, L.; Ajeganova, S.; Lindqvist, E.; Svensson, B.; Toes, R.E.M.; ... ; Helm-van Mil, A.H.M. van der 2017

The prevalence of ACPA is lower in rheumatoid arthritis patients with an older age of onset but the composition of the ACPA response appears identical

Article / Letter to editor

metadata only

Kerkman, P.F. 2017

Identification and characterisation of anti-citrullinated protein antibody (acpa)-producing b cells in patients with rheumatoid arthritis (ra)

Doctoral Thesis

open access

This thesis describes the characterisation of citrullinated antigen-specific B cells in patients with rheumatoid arthritis (RA). These cells express and secrete anti-citrullinated protein... Show moreThis thesis describes the characterisation of citrullinated antigen-specific B cells in patients with rheumatoid arthritis (RA). These cells express and secrete anti-citrullinated protein antibodies (ACPA), which represent the most specific autoantibody system in RA. We started out by identifying ACPA-producing B cells in peripheral blood. FACS sort followed by culture showed that these cells are not confined to the memory B cell subpopulation, as circulating plasmablasts/cells were found that spontaneously produced ACPA in culture (chapter 2). Further characterisation showed an increased frequency of ACPA-secreting plasma cells in synovial fluid (SF), i.e. at the site of inflammation, which harbours the capacity to form a survival niche in culture that promotes sustained (auto-)antibody production (chapter 3). Next, ACPA-expressing B cells were identified directly after isolation using a streptavidin tetramer-based flow cytometry staining technique developed in chapter 4. Furthermore, we provided evidence for altered development of ACPA-producing B cells, as these cells were found to express lambda light chains (LC) more frequently than non-autoreactive B cells (chapter 5). Finally, we investigated CD28 expression on ACPA-expressing B cells and total B cells in RA patients as relevant molecule for an enhanced live span of long-lived plasma cells (chapter 6). Show less

Jansen, D.T.S.L. 2017

Functional aspects of the adaptive immune system in arthritis

Doctoral Thesis

open access

The adaptive immune system is the part of the immune system that is highly specific and generates memory resulting in a fast and specific immune response upon a second infection with the same... Show moreThe adaptive immune system is the part of the immune system that is highly specific and generates memory resulting in a fast and specific immune response upon a second infection with the same pathogen. However, when this response is specific for a part of the body itself instead of a pathogen, inflammation and autoimmune disease can develop. Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation of the joints leading to cartilage and bone destruction. This thesis focused on the role of the adaptive immune system in the development, treatment and diagnosis of rheumatic disorders. The cells of the adaptive immune system play a pivotal role in the development of RA as cross-reactive CD4+ T cells can provide help to B cells which subsequently produce autoantibodies leading to autoantibody-positive RA. They can be a target in therapy as the biological Abatacept inhibits activation of T-cells, however, it potentially targets several players of the adaptive immune system making it an effective treatment strategy. Cells of the adaptive immune system can also be very useful as biomarker or to monitor response to therapy, which makes them very interesting players in the development of new treatment strategies for arthritis. Show less

Suurmond, J.; Velden, D. van der; Kuiper, J.; Bot, I.; Toes, R.E.M. 2016

Mast cells in rheumatic disease

Article / Letter to editor

metadata only

Leiden University Scholarly Publications

Your Search

Enabled Filters

Sort Options

Refine Results

Resource Type

Availability

Creation Date

Faculty

Collection

Topic

Author

Language

Search results

Pages

Pages