ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 0590

Association of Lipid Mediator Profiles and Development of Future Incident Inflammatory Arthritis in a High Risk, Anti-citrullinated Protein Antibody Positive Population

Lauren Vanderlinden1, Elizabeth Bemis2, Kristen Polinski3, Kristen Demoruelle4, Marie Feser5, Jennifer Seifert6, Ted Mikuls7, Michael Weisman8, Jane Buckner9, Kevin Deane10, Michael Clare-Salzler11, V. Michael Holers12 and Jill Norris13, 1Colorado School of Public Health, Monument, CO, 2Colorado School of Public Health Anschutz Medical Campus, Aurora, CO, 3CSPH, Gaithersburg, CO, 4University of Colorado Anschutz Medical Campus, Aurora, CO, 5University of Colorado Denver, Aurora, CO, 6University of Colorado School of Medicine, Littleton, CO, 7University of Nebraska Medical Center, Omaha, NE, 8Adjunct Professor of Medicine, Stanford University; Distinguished Professor of Medicine Emeritus, David Geffen School of Medicine at UCLA, Los Angeles, CA, 9Benaroya Research Institute at Virginia Mason, Seattle, WA, 10University of Colorado Denver, Denver, CO, 11Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL, 12University of Colorado, Denver, CO, 13Colorado School of Public Health, Aurora, CO

Meeting: ACR Convergence 2021

Keywords: , , , ,

Session Information

Date: Sunday, November 7, 2021

Title: Epidemiology & Public Health Poster II: Inflammatory Arthritis – RA, SpA, & Gout (0560–0593)

Session Type: Poster Session B

Session Time: 8:30AM-10:30AM

Background/Purpose: Lipid mediators are endogenously derived from the metabolism of omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) and have important roles in promoting and resolving inflammation. As such PUFAs have been implicated in the pathogenesis of systemic inflammatory and autoimmune diseases including rheumatoid arthritis (RA). As lipid mediators share common pathways and enzymes, individual lipid mediators do not act in isolation and therefore must be analyzed in combination as a profile. The goal of this study was to determine the association of polyunsaturated fatty acid (PUFA)-derived lipid mediator profiles with progression from pre-diagnosis RA-related autoimmunity to clinically apparent inflammatory arthritis (IA).

Methods: Using the Studies of the Etiologies of Rheumatoid Arthritis (SERA), we examined a prospective cohort that includes first-degree relatives (FDRs) of individuals with RA (FDR cohort) and individuals who screened positive for RA-related autoantibodies at health fairs (screened cohort). We followed 133 anti-CCP3.1 positive participants, of which 29 participants subsequently developed IA during follow-up (mean time to IA development = 1.15 years). Exposures included concentrations (pg/ml) of lipid mediators quantified from baseline plasma samples via liquid chromatography tandem mass spectrometry with profiles identified via principal component analysis (PCA). Multivariable Cox proportional hazard models were then developed for each lipid mediator profile, either stratified by or adjusted for HLA-DRB1 shared epitope status (dependent on presence of effect modification between lipid mediator profile and shared epitope).

Results: Baseline characteristics of the study population is shown in Table 1. The top 5 PCA components (PC) explained >50% of all variance among the lipid mediators, with the factor loadings of each lipid mediator shown in Table 2. Of these lipid mediator profiles, PC2 had a significant protective effect on IA risk (HR 0.79, 95% CI: 0.66-0.96, p-value = 0.018) in the total study population (Table 3). For profile PC2, the important lipid mediators had a mix of positive and negative loadings for lipid mediators in the cytochrome P450 soluble epoxide hydrolase (CYP sEH) and 15-lipoxygenase (15-LOX) enzymatic pathways. PC4 also demonstrated a significant protective effect on IA risk, but only within the shared epitope positive study population (HR 0.53, 95% CI: 0.32-0.87, p-value = 0.012). For profile PC4, the vast majority of important lipid mediators had negative loading factors and are downstream products from omega-3 parent fatty acids. Other lipid profiles identified showed no association with the risk of IA.

Conclusion: Our study revealed two lipid mediator profiles to be significantly associated with incident IA in a high-risk pre-diagnosis cohort characterized by ACPA positivity. These findings suggest specific PUFA metabolite profiles impact on the early evolution of RA and ultimately the development of IA, some working solely within the SE positive population.

Table 1: Characteristics of the ACPA-positive study participants (n = 133) at baseline visit. Except where indicated otherwise, values are the number (%); IA = inflammatory arthritis.

Table 2: PC Factor Loadings. Factor loadings are shown for each lipid mediator for the 5 profiles of interest. Lipid mediators with large impact loadings are highlighted either red (negative loading) or green (positive loading). Negative loadings means the individual lipid mediator is negatively correlated with the PC, while positive loadings means the individual lipid mediator is positively correlated. The precursor fatty acid and omega fatty acid type (either omega3 or omega6) are shown for each lipid mediator.

Table 3: Cox proportional hazard results for the outcome of Inflammatory Arthritis (IA) for each lipid mediator profile (PC). All models were adjusted for age at baseline and recruitment type (FDR or health fair). For total population models, SE status was adjusted for as well.

Disclosures: L. Vanderlinden, None; E. Bemis, None; K. Polinski, None; K. Demoruelle, Pfizer, 5; M. Feser, None; J. Seifert, None; T. Mikuls, Gilead Sciences, 2, Horizon, 2, 5, Pfizer Inc, 2, Sanofi, 2, Bristol-Myers Squibb, 2; M. Weisman, Novartis, 2, Gilead, 2, GSK, 2, UCB, 2; J. Buckner, Janssen R&D, 5; K. Deane, Inova Diagnostics, Inc, 5, Bristol Meyers Squibb, 1, 5, Janssen Research and Development, LLC, 5, imaware, 2, ThermoFisher, 2, 5, Medscape, 6; M. Clare-Salzler, None; V. Holers, Jansson, 5; J. Norris, None.

To cite this abstract in AMA style:

Vanderlinden L, Bemis E, Polinski K, Demoruelle K, Feser M, Seifert J, Mikuls T, Weisman M, Buckner J, Deane K, Clare-Salzler M, Holers V, Norris J. Association of Lipid Mediator Profiles and Development of Future Incident Inflammatory Arthritis in a High Risk, Anti-citrullinated Protein Antibody Positive Population [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 9). https://acrabstracts.org/abstract/association-of-lipid-mediator-profiles-and-development-of-future-incident-inflammatory-arthritis-in-a-high-risk-anti-citrullinated-protein-antibody-positive-population/. Accessed .

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/association-of-lipid-mediator-profiles-and-development-of-future-incident-inflammatory-arthritis-in-a-high-risk-anti-citrullinated-protein-antibody-positive-population/