Session Type: ACR Concurrent Abstract Session
Session Time: 4:30PM-6:00PM
Background/Purpose: Antisynthetase syndrome (ARS) is an inflammatory myopathy (IM) commonly associated to interstitial lung disease (ILD) and different anti-tRNA-synthetase autoantibodies. The immune mechanisms leading to ARS are yet poorly understood. Recently, we have shown an infiltration of NK cells inside target tissues associated to a specific decrease of peripheral NK cells expressing the natural cytotoxicity receptor-3 (NKp30). These events resulted in a down-modulation of NK cell functions in active ARS patients, suggesting a contribution of NK cells to ARS pathogenesis. In patients with certain tumor subtypes, down-modulation of NKp30 has also been reported and correlated with an abnormal expression of NKp30 ligands, namely B7-H6 and BAT3. These two stress molecules are also expressed or secreted by monocytes/macrophages. In the present study we evaluated the possible impact of the soluble forms of B7-H6 and BAT3 in ARS.
Methods: From 2013-16, 53 treated or untreated patients with ARS were included (15 men = 28%; median age 48, range 18-77; 40 with Jo-1 auto-antibody = 75%) and grouped according to the disease activity (27 active and 26 inactive patients). Patients were compared to 17 healthy donors (2 men = 12%, median age 29, range 22-44) and to 20 patients with non-ARS active IM (8 men = 40%; median age 48, range 25-78; with 12 dermatomyositis = 60%, 7 auto-immune necrotizing myopathy = 35% and 1 overlaping myopathy = 5%). Serum IL-2 & IL-15 were quantified using Quantikine-ELISA-kits (R&D systems), as were soluble forms of NKp30 ligands sB7-H6 and sBAT3 (EIAab & Cusabio, respectively). Statistical analyses were performed using appropriate tests.
Results: Whereas sB7-H6 median concentration was similar in ARS patients and healthy donors, sBAT3 titers were significantly increased in patients with ARS (250 vs. 134 and pg/mL, p=0.0002, Figure 1). Importantly, sBAT3 strongly correlated with ARS activity: median sBAT3 concentration reached 340 pg/mL in active patients vs. 160 pg/mL in inactive patients (p<0.0001). Furthermore, in patients with increased sBAT3 who were tested twice longitudinally, sBAT3 decreased under treatment in 5/6 (83%) cases (from 472 to 259 pg/mL, p=0.06). sBAT3 increase was highly specific for ARS, as only 1/20 (5%) patients with non-ARS active IM showed a sBAT3 titer above 2 times the healthy donors range (median concentration in patients with non-ARS active IM = 178 pg/mL, p<0.0001). The mechanism of sBAT3 increase remains unknown and sBAT3 level did not correlate with inflammatory cytokine IL2 and IL15 serum concentrations.
Conclusion: The significant and specific increase of sBAT3 in patients with active ARS and its decrease under treatment suggested that this stress molecule may be involved in ARS pathogenesis and could also be considered as a new biomarker for ARS patients.
To cite this abstract in AMA style:Hervier B, Ouaras S, Gilardin L, Ouakrim H, Amelin D, Cohen F, Uzunhan Y, Allenbach Y, Bourgarit-Durand A, Benveniste O, Vieillard V. Soluble BAT-3: A New Biomarker for Antisynthetase Syndrome [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/soluble-bat-3-a-new-biomarker-for-antisynthetase-syndrome/. Accessed December 1, 2020.
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