Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: A delayed diagnoses and therapy of ACPA (Anti cyclic citrullinated peptide antibody)-negative RA patients might be associated with effective serum biomarkers in clinic.
Methods: In the present study, we performed protein chip analysis in 30 HC, 60 patients with RA (including 30 ACPA-positive and 30 ACPA-negative), and 30 with other Autoimmune diseases.
Results: We found that anti-pentraxin 3 autoantibodies were significantly up-regulated in both APCA negative and positive RA patients compared with healthy controls and other AIDs with high sensitivity and specificity. Enlarged samples of small protein chip confirmed the up-regulated anti-PTX3 level in APCA negative RA patients. Further ELISA analysis of anti-PTX3 and its autoantigen pentraxin 3 in serum and synovial fluid showed that both anti-PTX3 and PTX3 was significantly up-regulated in ACPA positive and negative RA patients and positively correlated with clinical manifestations of DAS28 and RF as well as serum inflammatory cytokines, IL-1β, IL-6 and TNF-α. We also showed that increased PTX3 secretion was derived from CD19+ B cells and preferentially bound to CD14+ monocytes in a C1q-dependent manner. Serum C1q level was higher in RA patients compared with HC and AIDs and positively correlated with PTX3 expression in RA patients. Moreover, PTX3 treatment of CD14+ monocytes combined with C1q in vitro could significantly up-regulated the activation marker CD40 expression and increased 7-AAD+Annexin V+ double positive late apoptotic cells in some RA patients. The induction of CD14+ monocytes apoptosis strongly inhibited RA-related inflammatory cytokine IL-1β, IL-6 and TNF-α secretion after LPS stimulation in vitro. LDH releasement and the cleaved GSDMD and capase-1 was significantly down-regulated while cleaved caspase-3 and Bcl-2 was significantly up-regulated after C1q and PTX3 combined treatment.
Conclusion: Our results demonstrated a detection of Anti-Pentraxin-3 autoantidies in ACPA-negative RA Patients and autoantigen PTX3 combined with C1q could effectively inhibit GSDMD mediated pyroptosis and inflammatory cytokine releasement.
To cite this abstract in AMA style:Zhang X, Wu X. Autoantigen Pentraxin-3 Is an Inflammatory Cytokine Storms Suppressor By Switching Monocytes Pyroptosis to Apoptosis in a Complement-Dependent Manner in Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). https://acrabstracts.org/abstract/autoantigen-pentraxin-3-is-an-inflammatory-cytokine-storms-suppressor-by-switching-monocytes-pyroptosis-to-apoptosis-in-a-complement-dependent-manner-in-rheumatoid-arthritis/. Accessed March 8, 2021.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/autoantigen-pentraxin-3-is-an-inflammatory-cytokine-storms-suppressor-by-switching-monocytes-pyroptosis-to-apoptosis-in-a-complement-dependent-manner-in-rheumatoid-arthritis/