AB1005 SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS EXHIBIT DYNAMIC CHANGES IN TYPE I INTERFERON- AND B CELL-ASSOCIATED TRANSCRIPTS, BUT NOT SOLUBLE CELL ADHESION MOLECULES FOLLOWING TOTAL KNEE OR TOTAL HIP ARTHROPLASTY
Authors: D. R. Fernandez, S. Batter, D. Jannat-Khah, M. Olferiev, I. Mannstadt, M. Figgie, P. Sculco, J. Blevins, C. Siegel, D. Greenman, K. Kirou, S. Goodman
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Patients with systemic lupus erythematosus (SLE) undergoing total hip arthroplasty and total knee arthroplasty (THA and TKA) experience higher complication rates than osteoarthritis (OA) patients. There are several molecular processes in SLE patients that may affect the response to the physiologic stresses of arthroplasty. Patients with SLE have been described to exhibit endothelial dysfunction, with excess secretion of soluble cell adhesion molecules, including intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), and these molecules are known to increase in plasma following arthroplasty. Excess Type 1 interferon (IFN) is a critical driver of SLE pathogenesis, and it may similarly affect the response to surgery as well as the postoperative healing process. We conducted a prospective study of SLE patients undergoing THA/TKA to investigate the role of these processes, performing comprehensive assessment of patients clinical and laboratory data, as well as biosample collection for assessment of endothelial cell dysfunction and IFN activity. <h3>Objectives:</h3> To characterize the degree of endothelial cell activation at baseline in SLE patients, as well as changes in this following THA/TKA by measuring plasma levels of soluble cell adhesion molecules ICAM-1 and VCAM-1. To characterize the difference in IFN activity in OA and SLE patients prior to and following THA/TKA. <h3>Methods:</h3> This prospective study enrolled 30 SLE patients with SLE satisfying either 2019 ACR/EULAR SLE classification criteria, or the 1997 modification of 1982 ACR SLE classification criteria. Additionally, 26 age-, sex-, and procedure-matched OA controls undergoing THA/TKA were enrolled. Demographics and risk stratification information was collected from all patients (BMI, medications, comorbidities, etc.). A rheumatologist (D.R.F., C.S.) evaluated SLE-specific disease activity on postoperative day 1 (POD1). Standard laboratory tests, as well as plasma and whole blood samples were collected from subjects at baseline, POD1, and six weeks postoperatively (6W). Plasma levels of soluble ICAM-1and VCAM-1 were measured, and whole blood RNA sequencing was performed from a subset of samples obtained at baseline, POD1, and 6W. Adverse events (AEs) were assessed at baseline, 1-, 6-, 12-, and 24-weeks. Descriptive statistics were performed and comparisons were made using Fisher's exact test, Chi-square and Wilcoxon rank-sum test. <h3>Results:</h3> The SLE patients in our cohort generally had low disease activity, with an average Systemic Lupus Erythematosus Disease Activity Index-2K score of 4, in keeping with a population undergoing elective surgery. SLE patients experienced significantly more postoperative anemia, and were seen in the emergency department more often in the 24 weeks postoperatively, compared with OA patients (Table 1). There were no significant differences in plasma levels of soluble ICAM-1 or VCAM-1 between OA and SLE patients (Table 2) at baseline or during the postoperative period. The IFN score and the IFN module identified on weighted correlation network analysis were significantly elevated in SLE patients at all time points. The IFN score and IFN module expression fell in all groups on POD1, before returning to levels comparable to baseline by 6W. A module with transcripts associated with B cells was identified, and was significantly lower in SLE patients versus OA controls at all time points. <h3>Conclusion:</h3> This is the first prospective analysis of SLE patients undergoing arthroplasty, proving the feasibility of such studies. No significant difference was observed in soluble cell adhesion molecules at any time point. Differential expression in B Cell and IFN modules was seen between OA and SLE patients, with dynamic shifts occurring in the immediate perioperative period. Larger prospective studies may allow for better assessment of factors associated with adverse events in SLE patients after THA/TKA. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> We would like to thank and acknowledge the support of the HSS Surgeon-in-Chief research grant. <h3>Disclosure of Interests:</h3> David R. Fernandez: None declared, Stephen Batter: None declared, Deanna Jannat-Khah AstraZeneca, Cytodyn, Pfizer, Wallgreens, Mikhail Olferiev: None declared, Insa Mannstadt: None declared, Mark Figgie HS2, Joint Effort ASO, Mekanika, Wishbone, Lima, Wishbone, Peter Sculco DePuy, EOS Imaging, Intellijoint, Intellijoint, Parvizi Surgical Innovation, DePuy, EOS Imaging, Intellijoint, Lima Corporate, Zimmer, Intellijoint, Jason Blevins Globus Medical, KCI, Lima Corporate, Caroline Siegel: None declared, Dina Greenman: None declared, Kyriakos Kirou: None declared, Susan Goodman UCB, Norvartis.