Background/Purpose: Rheumatoid arthritis (RA) is characterized by autoantibodies such as rheumatoid factor (RF) and anti-modified protein autoantibodies (AMPAs) like anti-citrullinated protein antibodies (ACPA) and anti-carbamylated protein antibodies (anti-CarP). Recently, another AMPA: anti-acetylated protein antibodies (AAPA) have been found in RA patients [1]. The prevalence of AAPA antibodies and their isotypes have yet to be determined. Since isotype profiles reflect the breadth of an immune response, the prevalence of AAPA isotypes in arthritis patients with and without RA can help to understand the relevance of this autoantibody response in RA. 

Objective: To describe the prevalence of AAPA isotypes in arthritis patients with and without RA. 

Methods: In 650 RA patients fulfilling the 1987 RA criteria and 555 non-RA arthritis patients from the Leiden Early Arthritis Cohort, baseline serum samples were screened by ELISA for IgG, IgM and IgA to an acetylated- and control peptide that was based upon the CCP-2 backbone  . The cutoff for positivity was based on 80 controls (mean + 2SD). A sample was considered positive if it was above the cutoff and was 0.1 optical density higher on the acetylated peptide than on the control peptide.

Results: AAPA IgG was found in 36% of RA patients versus 6.7% of non-RA arthritis patients (figure 1a). Within RA patients, AAPA IgG antibodies were mostly present in the ACPA-(CCP-2) positive group (64% in ACPA-positive, compared to 5% in ACPA-negative). Levels of AAPA IgG and IgA were higher in RA patients than in healthy controls and non-RA arthritis patients (figure 1b), however, surprisingly, no difference in levels was found for IgM.

If isotypes profiles in AAPA- positive arthritis patients were compared, patients with RA were more often positive for two or more isotypes then patients without RA, and thus displayed considerably more overlap in AAPA isotypes compared to non-RA patients (figure 2). Intriguingly, IgM AAPA was the most prevalent isotype in non-RA patients, versus IgG in RA patients.

Conclusion: AAPA are detected in a minority of RA patients, and mainly in the ACPA-positive subgroup. The predominance of IgM AAPA in non-RA arthritis patients and healthy controls suggests that healthy persons can develop AAPA IgM without the development of RA. These results also suggest that in healthy individuals, AAPA responses can occur, but do not mature past the IgM-stage, while in RA patients, the AAPA-response does mature and might form  a “starting point”  for development of other AMPA leading to the concurrent present of several AMPA in disease.

Figure 1. Prevalence and levels of anti-acetylated protein antibodies (AAPA) in rheumatoid arthritis (RA)- and non-RA arthritis patients. 1a. Prevalence of AAPA IgG in RA- and non-RA arthritis patients, 1b. Levels of AAPA IgG, IgA and IgM in healthy controls, RA and non-RA arthritis patients

Figure 2. Anti-acetylated protein antibody (AAPA) isotype overlap in AAPA positive patients. 2a. in rheumatoid arthritis (RA) patients (n=310), b. in non-RA arthritis patients (n=106)

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/anti-acetylated-protein-antibodies-in-rheumatoid-arthritis-ra-clues-for-the-starting-point-of-autoantibody-responses-in-ra/