Regulatory CD4+ T-Cell Subsets and Anti-Citrullinated Protein Antibody Repertoire: Potential Biomarkers for Arthritis Development in Seropositive Arthralgia Patients?

Janssen, Koen M. J.; Westra, Johanna; Chalan, Paulina; Boots, Annemieke M. H.; Smit, Menke J. de; Winkelhoff, A.J. van; Vissink, Arjan; Brouwer, Elisabeth

doi:10.1371/journal.pone.0162101

Cited by 18 publications

(16 citation statements)

References 36 publications

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“…CD4 + CD25 + FoxP3 + T cells (Treg) can suppress other immune cells by regulating their proliferation and cytokine production. No differences were detected in the number of total Treg and bona fide Treg subsets (CD45RA + FoxP3 low naïve Treg, CD45RA − FoxP3 high activated Treg, and CD45RA − FoxP3 low non-Treg) from seropositive arthralgia patients compared to healthy donors [ 27 ]. Whether Tregs are functionally different is still unknown [ 14 ].…”

Section: An Introduction To the Physiopathology Of Rheumatoid Arthmentioning

confidence: 99%

The Anti-Inflammatory Mediator, Vasoactive Intestinal Peptide, Modulates the Differentiation and Function of Th Subsets in Rheumatoid Arthritis

Villanueva‐Romero

Gutiérrez‐Cañas

Carrión

et al. 2018

Journal of Immunology Research

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Genetic background, epigenetic modifications, and environmental factors trigger autoimmune response in rheumatoid arthritis (RA). Several pathogenic infections have been related to the onset of RA and may cause an inadequate immunological tolerance towards critical self-antigens leading to chronic joint inflammation and an imbalance between different T helper (Th) subsets. Vasoactive intestinal peptide (VIP) is a mediator that modulates all the stages comprised between the arrival of pathogens and Th cell differentiation in RA through its known anti-inflammatory and immunomodulatory actions. This “neuroimmunopeptide” modulates the pathogenic activity of diverse cell subpopulations involved in RA as lymphocytes, fibroblast-like synoviocytes (FLS), or macrophages. In addition, VIP decreases the expression of pattern recognition receptor (PRR) such as toll-like receptors (TLRs) in FLS from RA patients. These receptors act as sensors of pathogen-associated molecular pattern (PAMP) and damage-associated molecular pattern (DAMP) connecting the innate and adaptive immune system. Moreover, VIP modulates the imbalance between Th subsets in RA, decreasing pathogenic Th1 and Th17 subsets and favoring Th2 or Treg profile during the differentiation/polarization of naïve or memory Th cells. Finally, VIP regulates the plasticity between theses subsets. In this review, we provide an overview of VIP effects on the aforementioned features of RA pathology.

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Section: An Introduction To the Physiopathology Of Rheumatoid Arthmentioning

confidence: 99%

The Anti-Inflammatory Mediator, Vasoactive Intestinal Peptide, Modulates the Differentiation and Function of Th Subsets in Rheumatoid Arthritis

Villanueva‐Romero

Gutiérrez‐Cañas

Carrión

et al. 2018

Journal of Immunology Research

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“…The number of regulatory T cells (Tregs) in the peripheral blood appeared not to be indicative of RA development in patients with seropositive arthralgia. 30 In contrast, others showed that reduced naïve T cells and Tregs and increased inflammation-related cells were predictive of progression to arthritis in ACPA-positive persons with non-specific MSK symptoms. 49 Seropositive patients who developed arthritis had a significantly decreased number of peripheral CD8+ T cells and memory B cells compared with non-converters.…”

Section: Markers Characterising Immune Cell Dysfunctionmentioning

confidence: 98%

“… Patients in refs 22 31 36 37 52 54 55 , in refs 30 34 , in refs 27 49 and in refs 38 50 51 56 are derived from the same cohort. Studies depicted in grey have provided absolute risks.…”

Section: The Predictive Accuracy Of Non-antibody Serological Markers mentioning

confidence: 99%

Which patients presenting with arthralgia eventually develop rheumatoid arthritis? The current state of the art

2017

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Early initiation of treatment in patients with inflammatory arthritis at risk of persistence and/or erosive progression is important because it is associated with a reduced rate of progression of joint damage and functional disability. It has been proposed that a window of opportunity exists, during which disease processes are less matured and disease modification can be more effective. The phase of arthralgia preceding clinical arthritis is likely to be an important part of this window of opportunity, during which treatment might prevent progression to clinical arthritis. Several proof-of-concept trials in individuals with arthralgia are now evaluating this hypothesis. Central to such trials is the ability to identify groups at high risk of rheumatoid arthritis (RA) in whom preventive treatment can be tested. This review describes the relevance of adequate prediction making, as well as the accuracy of different types of predictors (including imaging and serological markers) with their value in predicting the progression of arthralgia to arthritis. Despite promising results, studies have been performed in heterogeneous patient populations and most findings have not been validated in independent studies. Future observational or preventive studies should be conducted with homogeneous patient groups (eg, patients fulfilling the European League Against Rheumatism criteria for arthralgia at risk of RA) in order to increase interstudy comparability and to allow result validation.

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“…In a study on patients with seropositive arthralgia, no differences were detected in the percentage and number of naïve CD4 + CD25 + FoxP3 + T cells compared with healthy controls. 10 The same was found for activated CD4 + CD25 + FoxP3 + T cells. Comparing the CD4 + CD25 + FoxP3 + T cells from patients with seropositive arthralgia who converted to patients with RA with those who did not resulted again in no detectable differences.…”

Section: Introductionmentioning

confidence: 52%

From patients with arthralgia, pre-RA and recently diagnosed RA: what is the current status of understanding RA pathogenesis?

2018

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It is believed that therapy for rheumatoid arthritis (RA) is the most effective and beneficial within a short time frame around RA diagnosis. This insight has caused a shift from research in patients with established RA to patients at risk of developing RA and recently diagnosed patients. It is important for improvement of RA therapy to understand when and what changes occur in patients developing RA. This is true for both seropositive and seronegative patients. Activation of the immune system as presented by autoantibodies, increased cytokine and chemokine production, and alterations within several immune cells occur during RA development. In this review we describe RA pathogenesis with a focus on knowledge obtained from patients with arthralgia, pre-RA and recently diagnosed RA. Connections are proposed between altered immune cells, cytokines and chemokines, and events like synovial hyperplasia, pain and bone damage.

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Regulatory CD4+ T-Cell Subsets and Anti-Citrullinated Protein Antibody Repertoire: Potential Biomarkers for Arthritis Development in Seropositive Arthralgia Patients?

Cited by 18 publications

References 36 publications

The Anti-Inflammatory Mediator, Vasoactive Intestinal Peptide, Modulates the Differentiation and Function of Th Subsets in Rheumatoid Arthritis

The Anti-Inflammatory Mediator, Vasoactive Intestinal Peptide, Modulates the Differentiation and Function of Th Subsets in Rheumatoid Arthritis

Which patients presenting with arthralgia eventually develop rheumatoid arthritis? The current state of the art

From patients with arthralgia, pre-RA and recently diagnosed RA: what is the current status of understanding RA pathogenesis?

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