To assess if microstructural bone lesions in RA at-risk individuals are related to the spectrum of anti-modified protein antibodies (AMPA) and affect the risk to develop RA.
Cortical micro-channels (CoMiCs) as well as cortical and trabecular bone volumes were analyzed by high-resolution computed tomography in the hand joints of RA at-risk individuals. Anti-modified protein antibody (AMPA) response was profiled including reactivities against citrullinated proteins (vimentin, enolase, fibrinogen) as well as carbamylated and acetylated vimentin. All subjects were followed for the development of RA.
RA at-risk subjects (all N=74) with broad spectrum AMPA (6-8 reactivties) had significantly more severe microstructural changes (CoMiCs: 95±35/joint; total bone volume: 265±45 HA/cm3; trabecular bone volume: 176±42; cortical bone volume: 585±138) compared to subjects with moderate (3-5 reactivties; 79±30; 293±33; 195±32, 627±91, respectively) or narrow (1-2 reactivties; 47±20, 311±34, 211±30, 674±56, respectively) AMPA reactivity. Progressors to RA had significantly higher numbers of CoMiCs and lower bone volumes (CoMiCs: 103±30 vs. 71±35; total bone volume: 258±37 vs.295±34). Furthermore, progression to RA was high in subjects with broad (48%) vs. those with medium (26%) or narrow (0%) AMPA as well as in those with high (44%) vs. low (10%) CoMiCs.
Microstructural changes in RA at-risk individuals 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.