Session Type: Abstract Submissions (ACR)
Antibodies against citrullinated proteins (especially anti citrullinated-vimentin antibodies) and high levels of RANKL have been linked to altered bone metabolism in early RA. We aimed to investigate ACPA fine specificities in relation to serum RANKL and disease activity in early-untreated RA.
186 patients with newly diagnosed RA (patient reported symptom duration less than 1 year), naïve to disease anti modifying drug (DMARD) were started on methotrexate (MTX) monotherapy. Treatment response at 3 months was defined by EULAR response criteria. Disease activity using DAS28-ESR score, anti CCP2 antibodies (anti-CCP2 kit, Euro-Diagnostica, Malmö, Sweden), specific antibodies (Abs) against citrullinated (cit) alpha-enolase (CEP-1) aa5-21, cit vimentin aa60-75 and cit fibrinogen aa563-583 peptides (ELISA) were measured in serum samples at baseline and after 3 months. To avoid RF interference with RANKL ELISA (Biovendor Human sRANKL, Brno, Czech Republic) results, only RF negative samples (baseline and 3 month samples) were analyzed. Mann-Whitney and Wilcoxon sign tests were used to analyze differences between independent and paired variables respectively with a p< 0.05 being considered statistical significant.
Anti-CCP2 Abs were detected in 68% (126 out of 186) of the patient sera. 54% (101 of 186) of the patients tested positive for any ACPA specificities at baseline and 46% (85 of 186) tested negative. Positive anti-CCP2 Abs titers significantly decreased from a median of 747 AU/ml (interquartile range, IRQ 2171-278) at baseline to a median of 576 (IRQ 1914-197). A significant titer decrease was similar observed for all tested ACPA specificities. Interestingly 38 % (38 out of 101) of the patients positive for any ACPA specificities at baseline become negative for at least one specific ACPA at 3 months. In contrast only 6% (5 out of 85) of the patients negative for ACPA specificities at baseline become positive at 3 months. No correlation between ACPA titers and disease activity were observed at any time point.
RANKL concentration was significant higher (p<0.001) in anti-CCP2+ RF- patients (n=15; median 19 ng/ml, IQR 26-12) as compared to anti-CCP2-RF- patients (n=45; median 9 ng/ml, IQR 13-5). Similar RANKL concentration was significant higher in any-ACPA specificity+ RF- patients (n=13; median 20 ng/ml, IQR 26-15) as compared to any-ACPA specificity- RF- patients (n=47, median 9, IQR 13-6). Same differences were still detectable at 3 months but overall RANKL concentrations decreased (from a median of 11ng/ml, IQR 16-6 to a median of 9, IQR 13-6, p<0.05). RANKL was correlated with age (r= -0.33 p= 0.01 n=60).
Neither ACPA positivity, nor RANKL at baseline were discriminatory for EULAR treatment response.
Presence of ACPA in early-untreated RA patients is associated with increased levels of RANKL, but not disease activity and is modulated by first anti rheumatic treatment. Validation of our results in larger number of patients and investigation of potential direct effects of MTX on B cells are needed.
A. H. Hensvold,
P. J. Jakobsson,
N. A. Defranoux,
Crescendo Bioscience Inc.,
Crescendo Bioscience Inc.,
A. I. Catrina,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/autoantibodies-to-citrullinated-proteins-associate-with-bone-destruction-marker-and-are-modulated-by-first-anti-rheumatic-treatment-in-early-rheumatoid-arthritis/