Microstructural Bone Changes Are Associated With Broad‐Spectrum Autoimmunity and Predict the Onset of Rheumatoid Arthritis

Abstract

Objective. To assess if microstructural bone lesions in individuals at risk of developing rheumatoid arthritis (RA) are related to the spectrum of anti-modified protein antibodies (AMPAs) and affect the risk of developing RA.Methods. Cortical microchannels as well as cortical and trabecular bone mineral density (BMD) volumes (expressed as mg hydroxyapatite/cm 3 ) were analyzed by high-resolution peripheral quantitative computed tomography of the hand joints of individuals at risk of RA. AMPA response was profiled, including reactivities against citrullinated proteins (vimentin, enolase, and fibrinogen) as well as carbamylated and acetylated vimentin. All subjects were followed up for the development of RA.Results. Subjects at risk of developing RA (n = 75) who had broad-spectrum AMPAs (6-8 reactivities) had significantly more severe microstructural changes, including a higher mean AE SD number of cortical microchannels per joint (95 AE 3) and lower total volumetric BMD (vBMD; 265 AE 45), trabecular vBMD (176 AE 42), and cortical vBMD (585 AE 138), than those with moderate AMPA reactivity (3-5 reactivities) (number of cortical microchannels, 79 AE 30; total vBMD, 293 AE 33; trabecular vBMD, 195 AE 32; and cortical vBMD, 627 AE 91) and those with narrow AMPA reactivity (1-2 reactivities) (number of cortical microchannels, 47 AE 20; total vBMD, 311 AE 34; trabecular vBMD, 211 AE 30; and cortical vBMD, 674 AE 56). Progressors to RA had significantly higher numbers of cortical microchannels (103 AE 30 versus 71 AE 35) and lower bone volume (258 AE 37 versus 295 AE 34) compared to nonprogressors. Furthermore, rate of progression to RA was high in subjects with broad AMPA reactivity (48%) versus those with medium AMPA reactivity (26%) or narrow AMPA reactivity (0%), as well as in those with a high number of cortical microchannels (44%) versus those with a low number of cortical microchannels (10%).Conclusion. Microstructural changes in individuals at risk of RA are associated with broad-spectrum autoimmunity and predict the onset of RA. These data support the concept of structural priming of joints by autoimmunity before the onset of the inflammatory phase of the disease.

MiRNA-6089 inhibits rheumatoid arthritis fibroblast-like synoviocytes proliferation and induces apoptosis by targeting CCR4

“…Accumulating evidence suggests that miRNAs regulate 1/3rd of the human genome via translational inhibition or degradation of the cognate genes, and form complex regulatory networks that have been implicated in malignant progression [10,11]. Aberrant expression of miRNAs has been detected in RAassociated in ammatory innate immune responses, and they are increasingly being considered as prognostic biomarkers as well as therapeutic targets [12,13]. For example, Yu et al showed that miR-92a could target AKT2 to inhibit broblast-like synoviocyte proliferation and migration in RA [14].…”

MiRNA-6089 inhibits rheumatoid arthritis fibroblast-like synoviocytes proliferation and induces apoptosis by targeting CCR4

“…Accumulating evidence suggests that miRNAs regulate 1/3rd of the human genome via translational inhibition or degradation of the cognate genes, and form complex regulatory networks that have been implicated in malignant progression [10,11]. Aberrant expression of miRNAs has been detected in RAassociated inflammatory innate immune responses, and they are increasingly being considered as prognostic biomarkers as well as therapeutic targets [12,13]. For example, Yu et al showed that miR-92a could target AKT2 to inhibit fibroblast-like synoviocyte proliferation and migration in RA [14].…”

Computertomografie in der Rheumatologie – Update 2020

“…Interessanterweise konnten hochauflösende CT-Studien das Konzept der strukturellen Veränderung der Gelenke durch Autoimmunität vor dem Beginn der entzündlichen Phase der Erkrankung stützen. So konnte kürzlich gezeigt werden, dass mikrostrukturelle Veränderungen (Cortical micro-channels [CoMiCs]) [16] bei RA-at-risk-Personen mit einer Breitspektrum-Autoimmunität verbunden sind und den Ausbruch einer klinisch manifesten RA voraussagen [15]. Auch weitere CT-Arbeiten konnten die Bedeutung der Autoimmunität für den Knochen hervorarbeiten.…”

“…Jedoch können CT-Forschungs ergebnisse einen wertvollen Beitrag zu einem besseren Verständnis der Krankheit sowie des Therapieansprechens leisten. Insbesondere Studien unter Verwendung der hochauflösenden peripheren quantitativen Computertomografie (HR-pQCT) waren hierbei in den letzten Jahren hilfreich [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16].…”