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Article ; Online: Pathophysiology and immunolgical basis of axial spondyloarthritis.

van de Sande, Marleen G H / Elewaut, Dirk

Best practice & research. Clinical rheumatology

2023 Volume 37, Issue 3, Page(s) 101897

Abstract: Over the recent years the wider availability and application of state-of-the-art immunological technologies greatly advanced the insight into the mechanisms that play an important role in axial spondyloarthritis (axSpA) pathophysiology. This increased ... ...

Abstract	Over the recent years the wider availability and application of state-of-the-art immunological technologies greatly advanced the insight into the mechanisms that play an important role in axial spondyloarthritis (axSpA) pathophysiology. This increased understanding has facilitated the development of novel treatments that target disease relevant pathways, hereby improving outcome for axSpA patients. In axSpA pathophysiology genetic and environmental factors as well as immune activation by mechanical or bacterial stress resulting in a chronic inflammatory response have a central role. The TNF and IL-23/IL-17 immune pathways play a pivotal role in these disease mechanisms. This review provides an outline of the immunological basis of axSpA with a focus on key genetic risk factors and their link to activation of the pathological immune response, as well as on the role of the gut and entheses in the initiation of inflammation with subsequent new bone formation in axSpA.
MeSH term(s)	Humans ; Spondylarthritis ; HLA-B27 Antigen/genetics ; Spondylitis, Ankylosing ; Axial Spondyloarthritis ; Inflammation
Chemical Substances	HLA-B27 Antigen
Language	English
Publishing date	2023-11-28
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2052323-3
ISSN	1532-1770 ; 1521-6942
ISSN (online)	1532-1770
ISSN	1521-6942
DOI	10.1016/j.berh.2023.101897
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Article ; Online: The Role of the IL-23/IL-17 Axis in Disease Initiation in Spondyloarthritis: Lessons Learned From Animal Models.

Mandour, Mohamed / Chen, Sijia / van de Sande, Marleen G H

Frontiers in immunology

2021 Volume 12, Page(s) 618581

Abstract: Spondyloarthritis (SpA) is a spectrum of chronic inflammatory joint diseases that frequently presents with inflammation of the axial skeleton, peripheral joints, entheses, skin, and gut. Understanding SpA pathogenesis has been proven challenging due to ... ...

Abstract	Spondyloarthritis (SpA) is a spectrum of chronic inflammatory joint diseases that frequently presents with inflammation of the axial skeleton, peripheral joints, entheses, skin, and gut. Understanding SpA pathogenesis has been proven challenging due to the limited availability of human target tissues. In recent years, the interleukin (IL)-23/IL-17 pathway has been implicated in the pathogenesis of SpA, in addition to the Tumor Necrosis Factor Alpha (TNF-α) cytokine. The underlying molecular mechanisms by which the IL-23/IL-17 pathway triggers disease initiation, both in the joints as well as at extra-musculoskeletal sites, are not precisely known. Animal models that resemble pathological features of human SpA have provided possibilities for in-depth molecular analyses of target tissues during various phases of the disease, including the pre-clinical initiation phase of the disease before arthritis and spondylitis are clinically present. Herein, we summarize recent insights gained in SpA animal models on the role of the IL-23/IL-17 pathway in immune activation across affected sites in SpA, which include the joint, entheses, gut and skin. We discuss how local activation of the IL-23/IL-17 axis may contribute to the development of tissue inflammation and the onset of clinically manifest SpA. The overall aim is to provide the reader with an overview of how the IL-23/IL-17 axis could contribute to the onset of SpA pathogenesis. We discuss how insights from animal studies into the initiation phase of disease could instruct validation studies in at-risk individuals and thereby provide a perspective for potential future preventive treatment.
MeSH term(s)	Animals ; Disease Models, Animal ; Humans ; Inflammation ; Interleukin-17/genetics ; Interleukin-17/immunology ; Interleukin-23/genetics ; Interleukin-23/immunology ; Mice ; Rats ; Spondylarthritis/etiology ; Spondylarthritis/immunology
Chemical Substances	IL17A protein, human ; Interleukin-17 ; Interleukin-23
Language	English
Publishing date	2021-06-29
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.618581
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Article ; Online: The Role of the Lymphatic System in the Pathogenesis and Treatment of Inflammatory Bowel Disease.

Nikolakis, Dimitrios / de Voogd, Floris A E / Pruijt, Maarten J / Grootjans, Joep / van de Sande, Marleen G / D'Haens, Geert R

International journal of molecular sciences

2022 Volume 23, Issue 3

Abstract: Although the number of therapeutic options for the treatment of inflammatory bowel disease (IBD) has increased in recent years, patients suffer from decreased quality of life due to non-response or loss of response to the currently available treatments. ... ...

Abstract	Although the number of therapeutic options for the treatment of inflammatory bowel disease (IBD) has increased in recent years, patients suffer from decreased quality of life due to non-response or loss of response to the currently available treatments. An increased understanding of the disease's etiology could provide novel insights for treatment strategies in IBD. Lymphatic system components are generally linked to immune responses and presumably related to inflammatory diseases pathophysiology. This review aims to summarize findings on immune-mediated mechanisms in lymphoid tissues linked with IBD pathogenesis and (potential) novel treatments. Enhanced innate and adaptive immune responses were observed in mesenteric lymph nodes (MLNs) and other lymphoid structures, such as Peyer's patches, in patients with IBD and in animal models. Furthermore, the phenomenon of lymphatic obstruction in the form of granulomas in MLNs and lymphatic vessels correlates with disease activity. There is also evidence that abnormalities in the lymphatic stromal components and lymph node microbiome are common in IBD and could be exploited therapeutically. Finally, novel agents targeting lymphocyte trafficking have been added to the treatment armamentarium in the field of IBD. Overall, gut-associated lymphoid tissue plays a key role in IBD immunopathogenesis, which could offer novel therapeutic targets.
MeSH term(s)	Adaptive Immunity ; Animals ; Humans ; Immunity, Innate ; Inflammatory Bowel Diseases/immunology ; Inflammatory Bowel Diseases/pathology ; Lymph Nodes/immunology ; Lymphatic System/immunology ; Quality of Life
Language	English
Publishing date	2022-02-06
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23031854
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Article ; Online: Can rheumatologists unequivocally diagnose axial spondyloarthritis in patients with chronic back pain of less than 2 years duration? Primary outcome of the 2-year SPondyloArthritis Caught Early (SPACE) cohort.

Marques, Mary Lucy / Ramiro, Sofia / van Lunteren, Miranda / Stal, Rosalinde Anne / Landewé, Robert Bm / van de Sande, Marleen / Fagerli, Karen Minde / Berg, Inger Jorid / van Oosterhout, Maikel / Exarchou, Sofia / Ramonda, Roberta / van der Heijde, Désirée / van Gaalen, Floris A

Annals of the rheumatic diseases

2024 Volume 83, Issue 5, Page(s) 589–598

Abstract: Objectives: To investigate the prevalence of axial spondyloarthritis (axSpA) in patients with chronic back pain (CBP) of less than 2 years (2y) duration referred to the rheumatologist, the development of diagnosis over time, and patient characteristics ... ...

Abstract	Objectives: To investigate the prevalence of axial spondyloarthritis (axSpA) in patients with chronic back pain (CBP) of less than 2 years (2y) duration referred to the rheumatologist, the development of diagnosis over time, and patient characteristics of those developing Methods: We analysed the 2y data from SPondyloArthritis Caught Early, a European cohort of patients (<45 years) with CBP (≥3 months, ≤2y) of unknown origin. The diagnostic workup comprised evaluation of clinical SpA features, acute phase reactants, HLA-B27, radiographs and MRI (sacroiliac joints and spine), with repeated assessments. At each visit (baseline, 3 months, 1y and 2y), rheumatologists reported a diagnosis of Main outcome: axSpA diagnosis with LoC≥7 ( Results: In 552 patients with CBP, Conclusion: A diagnosis of
MeSH term(s)	Humans ; Male ; Rheumatologists ; Sacroiliitis/diagnostic imaging ; HLA-B27 Antigen ; Spondylarthritis/diagnosis ; Spondylarthritis/diagnostic imaging ; Back Pain/diagnosis ; Magnetic Resonance Imaging/methods ; Axial Spondyloarthritis ; Spondylitis, Ankylosing/diagnosis
Chemical Substances	HLA-B27 Antigen
Language	English
Publishing date	2024-04-11
Publishing country	England
Document type	Journal Article
ZDB-ID	7090-7
ISSN	1468-2060 ; 0003-4967
ISSN (online)	1468-2060
ISSN	0003-4967
DOI	10.1136/ard-2023-224959
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Article ; Online: Hyaluronic Acid in Synovial Fluid Prevents Neutrophil Activation in Spondyloarthritis.

Mol, Sanne / Taanman-Kueter, Esther W M / van der Steen, Baltus A / Groot Kormelink, Tom / van de Sande, Marleen G H / Tas, Sander W / Wauben, Marca H M / de Jong, Esther C

International journal of molecular sciences

2023 Volume 24, Issue 4

Abstract: Spondyloarthritis (SpA) patients suffer from joint inflammation resulting in tissue damage, characterized by the presence of numerous neutrophils in the synovium and synovial fluid (SF). As it is yet unclear to what extent neutrophils contribute to the ... ...

Abstract	Spondyloarthritis (SpA) patients suffer from joint inflammation resulting in tissue damage, characterized by the presence of numerous neutrophils in the synovium and synovial fluid (SF). As it is yet unclear to what extent neutrophils contribute to the pathogenesis of SpA, we set out to study SF neutrophils in more detail. We analyzed the functionality of SF neutrophils of 20 SpA patients and 7 disease controls, determining ROS production and degranulation in response to various stimuli. In addition, the effect of SF on neutrophil function was determined. Surprisingly, our data show that SF neutrophils in SpA patients have an inactive phenotype, despite the presence of many neutrophil-activating stimuli such as GM-CSF and TNF in SF. This was not due to exhaustion as SF neutrophils readily responded to stimulation. Therefore, this finding suggests that one or more inhibitors of neutrophil activation may be present in SF. Indeed, when blood neutrophils from healthy donors were activated in the presence of increasing concentrations of SF from SpA patients, degranulation and ROS production were dose-dependently inhibited. This effect was independent of diagnosis, gender, age, and medication in the patients from which the SF was isolated. Treatment of SF with the enzyme hyaluronidase strongly reduced the inhibitory effect of SF on neutrophil activation, indicating that hyaluronic acid that is present in SF may be an important factor in preventing SF neutrophil activation. This finding provides novel insights into the role of soluble factors in SF regulating neutrophil function and may lead to the development of novel therapeutics targeting neutrophil activation via hyaluronic acid or associated pathways.
MeSH term(s)	Humans ; Synovial Fluid/metabolism ; Hyaluronic Acid/pharmacology ; Neutrophil Activation ; Reactive Oxygen Species/metabolism ; Spondylarthritis/metabolism ; Neutrophils/metabolism
Chemical Substances	Hyaluronic Acid (9004-61-9) ; Reactive Oxygen Species
Language	English
Publishing date	2023-02-04
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24043066
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Article ; Online: Treatment decisions in axial spondyloarthritis daily clinical practice are more than treat-to-target.

Bolt, Janne W / Aalbers, Caroline J / Walet, Laura / van Mens, Leonieke J J / van Denderen, Christiaan / van der Horst-Bruinsma, Irene / van Baarsen, Lisa G M / Landewé, Robert / van de Sande, Marleen G H

Rheumatology (Oxford, England)

2023 Volume 63, Issue 1, Page(s) 34–40

Abstract: Objective: 'Treat-to-target principles' are advised for axial spondyloarthritis (axSpA), although a clear target is not yet defined and targets do not always reflect inflammation. Treat-to-target use and motives for treatment choices in clinics are ... ...

Abstract	Objective: 'Treat-to-target principles' are advised for axial spondyloarthritis (axSpA), although a clear target is not yet defined and targets do not always reflect inflammation. Treat-to-target use and motives for treatment choices in clinics are unknown. Therefore, we studied the presence of residual disease activity according physician's opinion, patient's opinion and composite indices and compared them to the subsequent treatment decisions. Methods: This cross-sectional multicentre study included 249 patients with a clinical diagnosis of axSpA ≥6 months. Remission and low disease activity according to the BASDAI (<1.9 and <3.5, respectively) and physician's and patient's opinion were assessed. Questionnaires included patient-reported outcomes and patients and physicians completed questions regarding treatment decisions. Results: A total of 115/249 (46%) patients were in remission according to the physician and 37% (n = 43) of these patients reached remission according to the BASDAI. In 51/83 (60%) of the patients with residual disease activity according to the physician and a BASDAI >3.5 the treatment was left unchanged, either because of low disease activity as rated by the physician [n = 15 (29%)] or because of a combination of low disease activity with non-inflammatory complaints or comorbidities [n = 11 (25%)]. Retrospective treat-to-target evaluations showed that treatments were most frequently intensified in patients with arthritis or inflammatory back pain and less often in patients with other (non-inflammatory) musculoskeletal comorbidities. Conclusion: This study shows that physicians do not always strictly apply treat-to-target in case of residual disease activity in axSpA. Usually, they accept low disease activity as satisfactory.
MeSH term(s)	Humans ; Spondylitis, Ankylosing/drug therapy ; Retrospective Studies ; Cross-Sectional Studies ; Inflammation ; Axial Spondyloarthritis ; Pain ; Spondylarthritis/diagnosis ; Spondylarthritis/drug therapy
Language	English
Publishing date	2023-04-04
Publishing country	England
Document type	Multicenter Study ; Journal Article
ZDB-ID	1464822-2
ISSN	1462-0332 ; 1462-0324
ISSN (online)	1462-0332
ISSN	1462-0324
DOI	10.1093/rheumatology/kead155
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Article ; Online: Evolution of clinical trials for rheumatoid arthritis and spondyloarthritis.

van de Sande, Marleen G H / van Vollenhoven, Ronald F

Current opinion in rheumatology

2018 Volume 30, Issue 4, Page(s) 340–346

Abstract: Purpose of review: The present review presents an overview of the evolution in trial design from mainly randomized placebo-controlled efficacy trials to more strategic clinical trials in rheumatoid arthritis and spondyloarthritis. Additionally, it ... ...

Abstract	Purpose of review: The present review presents an overview of the evolution in trial design from mainly randomized placebo-controlled efficacy trials to more strategic clinical trials in rheumatoid arthritis and spondyloarthritis. Additionally, it relates to how these differently designed trials have affected clinical practice. Recent findings: Placebo-controlled clinical trials, comparing a new agent to placebo on a stable background, have resulted in the development of a wide array of therapeutic agents in rheumatoid arthritis and spondyloarthritis. However, these kind of trials do have some down sides as they do not provide evidence on the optimal strategy to use this multitude of treatments in daily clinical practice and the ethics concerning a placebo phase are often discussed. These and other concerns resulted in the emergence of various different types of trials in rheumatoid arthritis. A similar change of focus is now observed in spondyloarthritis clinical trials. We address literature on direct comparison ('head-to-head'), noninferiority trials, induction-maintenance, discontinuation, and treat-to-target/tight control clinical trials. Summary: In recent years various clinical trials have been published with a design different from placebo-controlled clinical trials. These novel trial designs aimed to provide guidance on the optimal way to use the full range of targeted treatments available and to make it possible, in some design, to leave out the placebo. In rheumatoid arthritis, some of these more strategic type of trials have had a large impact on common practice. In spondyloarthritis, the first steps toward trials with a more strategic design have been taken, and it stands to reason that more will follow.
MeSH term(s)	Arthritis, Rheumatoid/drug therapy ; Clinical Trials as Topic ; Humans
Language	English
Publishing date	2018-04-26
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1045317-9
ISSN	1531-6963 ; 1040-8711
ISSN (online)	1531-6963
ISSN	1040-8711
DOI	10.1097/BOR.0000000000000516
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Article: Translational Research Studies Unraveling the Origins of Psoriatic Arthritis: Moving Beyond Skin and Joints.

Bolt, Janne W / van Ansenwoude, Chaja M J / Hammoura, Ihsan / van de Sande, Marleen G / van Baarsen, Lisa G M

Frontiers in medicine

2021 Volume 8, Page(s) 711823

Abstract: Patients with psoriatic arthritis (PsA) are suffering from a decreased quality of life despite currently available treatments. In the latest years, novel therapies targeting the IL-17/IL-23 and TNF pathways improved clinical outcome. Despite this, ... ...

Abstract	Patients with psoriatic arthritis (PsA) are suffering from a decreased quality of life despite currently available treatments. In the latest years, novel therapies targeting the IL-17/IL-23 and TNF pathways improved clinical outcome. Despite this, remission of disease is not achieved in a considerable group of patients, continuous treatment is very often required to reach clinical remission, and prevention of PsA in patients with psoriasis (PsO) is currently impossible. A better understanding of PsA pathogenesis is required to develop novel treatment strategies that target inflammation and destruction more effectively and at an early stage of the disease, or even before clinically manifest disease. The skin is considered as one of the sites of onset of immune activation, triggering the inflammatory cascade in PsA. PsO develops into PsA in 30% of the PsO patients. Influenced by environmental and genetic factors, the inflammatory process in the skin, entheses, and/or gut may evolve into synovial tissue inflammation, characterized by influx of immune cells. The exact role of the innate and adaptive immune cells in disease pathogenesis is not completely known. The involvement of activated IL-17A+ T cells could implicate early immunomodulatory events generated in lymphoid organs thereby shaping the pathogenic inflammatory response leading to disease. In this perspective article, we provide the reader with an overview of the current literature regarding the immunological changes observed during the earliest stages of PsA. Moreover, we will postulate future areas of translational research aimed at increasing our knowledge on the molecular mechanisms driving disease development, which will aid the identification of novel potential therapeutic targets to limit the progression of PsA.
Language	English
Publishing date	2021-08-17
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2775999-4
ISSN	2296-858X
ISSN	2296-858X
DOI	10.3389/fmed.2021.711823
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Article: Corrigendum: Translational Research Studies Unraveling the Origins of Psoriatic Arthritis: Moving Beyond Skin and Joints.

Bolt, Janne W / van Ansenwoude, Chaja M J / Hammoura, Ihsan / van de Sande, Marleen G / van Baarsen, Lisa G M

Frontiers in medicine

2021 Volume 8, Page(s) 761410

Abstract: This corrects the article DOI: 10.3389/fmed.2021.711823.]. ...

Abstract	[This corrects the article DOI: 10.3389/fmed.2021.711823.].
Language	English
Publishing date	2021-09-08
Publishing country	Switzerland
Document type	Published Erratum
ZDB-ID	2775999-4
ISSN	2296-858X
ISSN	2296-858X
DOI	10.3389/fmed.2021.761410
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Article ; Online: Immunopathology of synovitis: from histology to molecular pathways.

van de Sande, Marleen G / Baeten, Dominique L

Rheumatology (Oxford, England)

2016 Volume 55, Issue 4, Page(s) 599–606

Abstract: Increased knowledge about pathological processes active in inflammatory joint diseases is needed to initiate personalized medicine based on targeted treatments in the future. The molecular and cellular pathways that are active during joint inflammation ... ...

Abstract	Increased knowledge about pathological processes active in inflammatory joint diseases is needed to initiate personalized medicine based on targeted treatments in the future. The molecular and cellular pathways that are active during joint inflammation may differ between the various inflammatory joint diseases, between different patient subgroups within one disease, or even between different stages of the disease in a single patient. In this review, we evaluate synovial inflammation in terms of descriptive histopathology through to more functional studies on human synovial tissue inflammation in RA and SpA, in phenotypic subgroups of RA and SpA patients, and during the disease course of both diseases.
MeSH term(s)	Arthritis, Rheumatoid/genetics ; Arthritis, Rheumatoid/immunology ; Arthritis, Rheumatoid/pathology ; Gene Expression Profiling ; Humans ; Spondylarthropathies/genetics ; Spondylarthropathies/immunology ; Spondylarthropathies/pathology ; Synovial Membrane/immunology ; Synovial Membrane/pathology ; Synovitis/genetics ; Synovitis/immunology ; Synovitis/pathology
Language	English
Publishing date	2016-04
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1464822-2
ISSN	1462-0332 ; 1462-0324
ISSN (online)	1462-0332
ISSN	1462-0324
DOI	10.1093/rheumatology/kev330
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