Date: Sunday, November 8, 2015
Session Type: ACR Concurrent Abstract Session
Session Time: 4:30PM-6:00PM
Background/Purpose: Increased circulatory levels of the chemokine CXCL4 have been associated with the presence of pulmonary fibrosis (PF) by HRCT in an observational study of patients with systemic sclerosis (SSc)1. In addition, higher baseline levels of CXCL4 predicted faster decline in DLCO in a subgroup of patients from this study1. No studies have evaluated whether CXCL4 can predict both extent and progression of PF in SSc patients, all of whom have well-characterized PF and all of whom are receiving aggressive therapy with either mycophenolate (MMF) or cyclophosphamide (CYC).
Methods: Between September 2009 and January 2013, 142 SSc-PF patients from 14 US centers were randomized to receive MMF (titrated as tolerated to 3.0 g/day in divided doses) for 2 years or oral CYC (titrated as tolerated to 2 mg/kg daily) for 1 year followed by 1 year on placebo. Plasma samples were obtained at baseline, 1 and 2 years. Baseline plasma samples were examined by validated, commercially available ELISA kits (Human CXCL4/PF4 Quantikine Kit – R&D Systems). CXCL4 levels were compared between SSc-PF patients (N=136) and age- and gender-matched healthy control patients (N=67) using a Student’s t test. Correlations were performed between CXCL4 levels and baseline measures of extent of PF, as well as change in DLCO (from baseline) at 12, 18, and 24 months.
Results: Among 136 participants with baseline plasma samples, 94% were ANA positive, 46% were Scl-70 positive, 13% were Anti-RNA polymerase III positive. Baseline pulmonary function was as follows (All Mean [SD]% predicted): FVC 66.5 [9.1]; TLC 65.8 [11.1]; DLCO 54.0 [12.7]. Baseline quantitative lung fibrosis (QLF) scores were 22.8 [19.6] and 8.6 [6.9], for the zone of maximum involvement (ZM) and whole lung (WL), respectively. Baseline modified Rodnan skin score (mRSS) was 14.7 [10.5] and Baseline Dyspnea Index (BDI) was 7.2 [2.2]. Baseline CXCL4 levels were higher in SSc-PF patients compared with healthy controls (Mean [SD]: 2699  versus 2233.4 [1351.1], respectively; P=0.03). There were no significant correlations between baseline CXCL4 levels and extent of PF as measured by FVC, TLC, DLCO, QLF-ZM, QLF-WL, BDI (all P-values >0.2), and extent of cutaneous sclerosis as measured by the mRSS (P=0.2). There were also no significant correlations between baseline CXCL4 levels and change in DLCO at 12 (P =0.6), 18 (P =0.4), or 24 months (P=0.6).
Conclusion: Consistent with prior studies,1 levels of CXCL4 were higher in patients with SSc-PF compared with controls. However, CXCL4 levels were not correlated with extent of PF and progression of PF as measured by change in DLCO in patients with SSc-PF.
1. van Bon L, Affandi AJ, Broen RB, et al. Proteome-wide Analysis and CXCL4 as a Biomarker in Systemic Sclerosis. NEJM 2014;370:433-43.
To cite this abstract in AMA style:Volkmann ER, Tashkin DP, Roth M, Tseng CH, LeClair H, Clements PJ, Furst DE, Mayes MD, Charles J, Khanna D, Elashoff R, Assassi S. CXCL4 Does Not Predict Extent or Progression of Interstitial Lung Disease in Systemic Sclerosis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/cxcl4-does-not-predict-extent-or-progression-of-interstitial-lung-disease-in-systemic-sclerosis/. Accessed January 27, 2022.
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