Session Information
Date: Sunday, November 10, 2019
Session Title: RA – Treatments Poster I: Novel Treatments
Session Type: Poster Session (Sunday)
Session Time: 9:00AM-11:00AM
Background/Purpose:
CXCL13 chemokine, by interacting with CXCR5 receptor, attracts B-lymphocytes and CD4+CXCR5+ICOS+ follicular helper T-lymphocytes (THFs) in lymphoid follicles. In rheumatoid arthritis (RA) CXCL13 is expressed by synovial follicular dendritic cells and activated mature antigen-experienced T-helper cells. CXCL13 serum levels are increased in RA and associated with synovial infiltration by lymphoid aggregates, as well as with a preferential response to anti-IL-6R as compared to anti-TNFα monotherapy (1).
Abatacept (ABA), a T-cell co-stimulation blocker, reduces circulating THFs number in RA. This reduction is correlated with CXCL13 serum levels decrease in primary Sjögren’s Syndrome, but not much information is available on this issue in RA (2).
The purposes of this study were to analyze the effect of ABA on CXCL13 serum levels in RA and to verify whether they predict the response to the drug.
Methods:
32 RA patients (F/M=25/7; median (25th-75th percentile) age=62 (52-66) years; CRP- DAS28=4.6 (4.0-5.3); ACPA positive: 81%), before and after 6 months of treatment with ABA were evaluated. Serum CXCL13 levels were dosed by commercial ELISA. Circulating TFHs were identifiedby flow-cytometry in 25 subjects. Response to treatment was evaluated with the EULAR criteria.
Results: At baseline, a positive correlation between CXCL13 levels and CRP-DAS28 values was found (r=0.34; p=0.05). After therapy with ABA + methotrexate, a reduction of CXCL13 was observed (158 (109-274) vs 96 (59-154) pg/ml; p< 0.01). It was significant only in responders (n: 22: 158 (104-293) vs 96 (89-182)) pg/ml; p< 0.01; in non-responders (n:10) =164 (95-240) vs 101 (57-142) pg/ml; p=0.06). At baseline, no significant difference was found between the two subgroups (p=0.47) and among patients seropositive for ACPA if compared with the negative ones (ACPA+ vs ACPA-=174 (117-287) vs 96 (73-194) pg/ml; p=0.07). A reduction of THFs was found (0.6 (0-3) vs 0.1 (0-0.7) % of CD4+ T cells; p=0.05), without correlation with the decrease of CXCL13 levels (r=0.20; p=0.33).
Conclusion:
Our results confirmed that CXCL13 serum levels are directly correlated with disease activity and demonstrated that ABA therapy induces their reduction, as well as that of circulating THFs. These findings suggest that the co-stimulation blockade at central level and/or in the synovium lead to a reduced generation of THFs and production of CXCL13. We could not demonstrate that CXCL13 levels predict, or are correlated with, clinical response to ABA in this small cohort of patients.
1.Dennis G, Arthritis Res Ther 2014; 2. Verstappen GM, Arthritis Rheumatol 2017.
Bristol-Myers-Squibb Italy provided an unrestricted research grant for the study conduction.
To cite this abstract in AMA style:
Piantoni S, Regola F, Andreoli L, Tincani A, Airò P. CXCL13 Serum Levels and Circulating Follicular Helper T-Cells Decrease After Co-stimulation Blockade with Abatacept in Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/cxcl13-serum-levels-and-circulating-follicular-helper-t-cells-decrease-after-co-stimulation-blockade-with-abatacept-in-rheumatoid-arthritis/. Accessed May 28, 2020.« Back to 2019 ACR/ARP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/cxcl13-serum-levels-and-circulating-follicular-helper-t-cells-decrease-after-co-stimulation-blockade-with-abatacept-in-rheumatoid-arthritis/