Pre-symptomatic autoimmunity in rheumatoid arthritis: when does the disease start?

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Pre-symptomatic autoimmunity in rheumatoid arthritis: when does the disease start? / Raza, Karim; Buckley, Christopher.

In: Seminars in immunopathology, Vol. 39, No. 4, 06.2017, p. 423–435.

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@article{36e65ad38f654aceb138b935c0fa0047,
title = "Pre-symptomatic autoimmunity in rheumatoid arthritis: when does the disease start?",
abstract = "It is well recognised that a state of autoimmunity, in which immunological tolerance is broken, precedes the development of symptoms in the majority of patients with rheumatoid arthritis (RA). For individuals who will later develop seropositive disease, this manifests as autoantibodies directed against proteins that have undergone specific post-translational modifications. There is evidence that the induction of this autoantibody response occurs at peripheral extra-articular mucosal sites, such as the periodontium and lung. In addition to their utility as diagnostic markers, these autoantibodies may have a pathogenic role that helps localise disease to the synovium. Alongside the development of autoantibodies, other factors contributing to pre-symptomatic autoimmunity may include dysbiosis of the gastrointestinal tract, abnormal development of lymphoid tissue, and dysregulated autonomic and lipid-mediated anti-inflammatory signalling. These factors combine to skew the balance between pro-inflammatory and anti-inflammatory signalling in a manner that is permissive for the development of clinical arthritis. We present data to support the concept that the transitions from at-risk states to systemic autoimmunity and then to classifiable RA depend on multiple “switches”. However, further prospective studies are necessary to define the molecular basis of these switches and the specific features of pre-symptomatic autoimmunity, so that preventative treatments can be targeted to individuals at high risk for RA. In this review, we analyse mechanisms that may contribute to the development of autoimmunity in at-risk individuals, and discuss the relationship between this pre-symptomatic state and subsequent development of RA.",
keywords = "Rheumatoid arthritis, Autoimmunity, Inflammation, Autoantibodies ",
author = "Karim Raza and Christopher Buckley",
year = "2017",
month = jun,
doi = "10.1007/s00281-017-0620-6",
language = "English",
volume = "39",
pages = "423–435",
journal = "Seminars in immunopathology",
issn = "1863-2297",
publisher = "Springer",
number = "4",

}

RIS

TY - JOUR

T1 - Pre-symptomatic autoimmunity in rheumatoid arthritis: when does the disease start?

AU - Raza, Karim

AU - Buckley, Christopher

PY - 2017/6

Y1 - 2017/6

N2 - It is well recognised that a state of autoimmunity, in which immunological tolerance is broken, precedes the development of symptoms in the majority of patients with rheumatoid arthritis (RA). For individuals who will later develop seropositive disease, this manifests as autoantibodies directed against proteins that have undergone specific post-translational modifications. There is evidence that the induction of this autoantibody response occurs at peripheral extra-articular mucosal sites, such as the periodontium and lung. In addition to their utility as diagnostic markers, these autoantibodies may have a pathogenic role that helps localise disease to the synovium. Alongside the development of autoantibodies, other factors contributing to pre-symptomatic autoimmunity may include dysbiosis of the gastrointestinal tract, abnormal development of lymphoid tissue, and dysregulated autonomic and lipid-mediated anti-inflammatory signalling. These factors combine to skew the balance between pro-inflammatory and anti-inflammatory signalling in a manner that is permissive for the development of clinical arthritis. We present data to support the concept that the transitions from at-risk states to systemic autoimmunity and then to classifiable RA depend on multiple “switches”. However, further prospective studies are necessary to define the molecular basis of these switches and the specific features of pre-symptomatic autoimmunity, so that preventative treatments can be targeted to individuals at high risk for RA. In this review, we analyse mechanisms that may contribute to the development of autoimmunity in at-risk individuals, and discuss the relationship between this pre-symptomatic state and subsequent development of RA.

AB - It is well recognised that a state of autoimmunity, in which immunological tolerance is broken, precedes the development of symptoms in the majority of patients with rheumatoid arthritis (RA). For individuals who will later develop seropositive disease, this manifests as autoantibodies directed against proteins that have undergone specific post-translational modifications. There is evidence that the induction of this autoantibody response occurs at peripheral extra-articular mucosal sites, such as the periodontium and lung. In addition to their utility as diagnostic markers, these autoantibodies may have a pathogenic role that helps localise disease to the synovium. Alongside the development of autoantibodies, other factors contributing to pre-symptomatic autoimmunity may include dysbiosis of the gastrointestinal tract, abnormal development of lymphoid tissue, and dysregulated autonomic and lipid-mediated anti-inflammatory signalling. These factors combine to skew the balance between pro-inflammatory and anti-inflammatory signalling in a manner that is permissive for the development of clinical arthritis. We present data to support the concept that the transitions from at-risk states to systemic autoimmunity and then to classifiable RA depend on multiple “switches”. However, further prospective studies are necessary to define the molecular basis of these switches and the specific features of pre-symptomatic autoimmunity, so that preventative treatments can be targeted to individuals at high risk for RA. In this review, we analyse mechanisms that may contribute to the development of autoimmunity in at-risk individuals, and discuss the relationship between this pre-symptomatic state and subsequent development of RA.

KW - Rheumatoid arthritis

KW - Autoimmunity

KW - Inflammation

KW - Autoantibodies

U2 - 10.1007/s00281-017-0620-6

DO - 10.1007/s00281-017-0620-6

M3 - Article

C2 - 28337522

VL - 39

SP - 423

EP - 435

JO - Seminars in immunopathology

JF - Seminars in immunopathology

SN - 1863-2297

IS - 4

ER -