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OBJECTIVES: Individuals carrying antibodies against citrullinated proteins (ACPA) are at high risk of developing RA. EULAR provided a clinical definition of individuals with arthralgia suspicious for progression to RA (clinically suspect arthralgia, CSA). The alteration of monocyte subpopulations in patients with established RA has been previously described. We analysed peripheral blood monocyte subpopulations in individuals with arthralgia at risk of RA. METHODS: We included 70 at-risk individuals, defined as having arthralgia without arthritis and being either ACPA+ or meeting the clinical CSA definition, 23 patients with early RA (ERA) and 19 healthy controls (HCs). Monocytes classified as classical (CD14++CD16-), intermediate (CD14++CD16+/++) and nonclassical (CD14-/+CD16++) were analysed by flow cytometry. RESULTS: Of the 70 at-risk individuals, 46 were ACPA+ and 45 met the CSA definition. The at-risk individuals and, especially, ERA patients had a lower percentage of classical monocytes and a higher percentage of nonclassical monocytes than the HCs. ACPA positivity had no effect on the difference in the distribution of the monocyte subsets between at-risk individuals and ERA patients, but a difference was determined in those reaching the ERA phase. However, when compared with HCs, the shift of monocyte subsets was more significant in ACPA+ than in ACPA- individuals with arthralgia. This trend was observed in individuals who did not meet the CSA definition. This finding was, however, determined by a selection bias, as these individuals were solely ACPA+. CONCLUSION: The shift from classical to nonclassical monocyte subpopulations was observed already in individuals at risk of developing RA.

MeSH
artralgie etiologie MeSH
C-reaktivní protein analýza MeSH
dospělí MeSH
lidé středního věku MeSH
lidé MeSH
monocyty metabolismus MeSH
následné studie MeSH
progrese nemoci MeSH
protilátky proti citrulinovaným peptidům krev MeSH
revmatoidní artritida krev diagnóza MeSH
studie případů a kontrol MeSH
Check Tag
dospělí MeSH
lidé středního věku MeSH
lidé MeSH
mužské pohlaví MeSH
ženské pohlaví MeSH
Publikační typ
časopisecké články MeSH
práce podpořená grantem MeSH

Článek

The pre-clinical phase of rheumatoid arthritis: From risk factors to prevention of arthritis

Autoimmunity reviews. 2021 ; 20 (5) : 102797. [pub] 20210318

Autoimmun Rev
ISSN 1873-0183
Medvik
Zdroj

Rheumatoid arthritis (RA) is a chronic autoimmune disease considered as a multistep process spanning from the interaction of genetic (e.g., shared epitope or non-HLA loci), environmental and behavioral risk factors (e.g., smoking) leading to breaking immune tolerance and autoimmune processes such as the production of autoantibodies (e.g., antibodies against citrullinated proteins ACPA or rheumatoid factors, RF), development of the first symptoms without clinical arthritis, and, finally, the manifestation of arthritis. Despite the typical joint involvement in established RA, the pathogenesis of the disease likely begins far from joint structures: in the lungs or periodontium in association with citrullination, intestinal microbiome, or adipose tissue, which supports normal findings in synovial tissue in ACPA+ patients with arthralgia. The presence of ACPA is detectable even years before the first manifestation of RA. The pre-clinical phase of RA is the period preceding clinically apparent RA with ACPA contributing to the symptoms without subclinical inflammation. While the combination of ACPA and RF increases the risk of progression to RA by up to 10 times, increasing numbers of novel autoantibodies are to be investigated to contribute to the increased risk and pathogenesis of RA. With growing knowledge about the course of RA, new aspiration emerges to cure and even prevent RA, shifting the "window of opportunity" to the pre-clinical phases of RA. The clinical definition of individuals at risk of developing RA (clinically suspect arthralgia, CSA) makes it possible to unify these at-risk individuals' clinical characteristics for "preventive" treatment in ongoing clinical trials using mostly biological or conventional synthetic disease-modifying drugs. However, the combination of symptoms, laboratory, and imaging biomarkers may be the best approach to select the correct target at-risk population. The current review aims to explore different phases of RA and discuss the potential of (non)pharmacological intervention aiming to prevent RA.