1485: Characterization of Regulatory Receptors on Plasmacytoid Dendritic Cells in Lupus

Mark Jensen¹, Ilona Nln¹, Taro Iwamoto², Jessica Dorschner³, Danielle Vsetecka³, Jacqueline Paredes¹, Ruth Fernandez Ruiz⁴, Theresa Wampler Muskardin⁵ and Timothy Niewold¹, ¹Hospital for Special Surgery, New York, NY, ²Chiba University, New York, NY, ³Mayo Clinic, Rochester, ⁴Hospital for Special Surgery/Weill Cornell Medicine, New York, NY, ⁵Colton Center for Autoimmunity, NYU School of Medicine, New York, NY

Background/Purpose: To characterize regulatory surface receptors on blood plasmacytoid dendritic cells (PDCs) of lupus patients and controls to determine if receptor expression and function associates with disease activity or clinical characteristics in SLE.

Methods: Quantitative multicolor flow cytometry was used to measure immunoglobulin like transcript 7 (ILT7), bone marrow derived antigen 2 (BDCA2), ILT3, Fc epsilon receptor I (FcεRI), leukocyte-associated immunoglobulin-receptor 1 (LAIR1), natural killer cell P44-related protein (NKp44), bone marrow stromal cell antigen 2 (BST2), dendritic cell (DC) immunoreceptor (DCIR), and Fc gamma receptor IIa (FcγRII) on PDCs of peripheral blood mononuclear cells (PBMC) from 65 SLE patients and 15 controls. For functional studies, PBMC from 9 SLE and 9 controls were treated with ILT7 and BDCA2 crosslinking antibodies followed by TLR9 agonists.

Results: Significant associations were found between multiple receptors, IFN levels, SLEDAI scores, and autoreactive antibody titers. ILT7 expression correlated inversely with SLEDAI, and ANA titers. High IFN SLE patients had increased levels of the ILT7 ligand BST2 and at the same time reduced ILT7 expression. BDCA2 levels were 5-fold higher than ILT7 levels, and were also inversely correlated with SLEDAI. Crosslinking ILT7 only weakly inhibited IFN secretion. Crosslinking BDCA2 significantly reduced IFN production in SLE patient cells, but this was much greater in patients with low SLEDAI scores than those with high SLEDAI scores.

Conclusion: We identify associations between PDC regulatory receptors and clinical disease in lupus patients, and dominant inhibitory function of BDCA2 over ILT7 in pDC type I IFN secretion with dependency upon disease activity.

Disclosures: M. Jensen, None; I. Nln, None; T. Iwamoto, None; J. Dorschner, None; D. Vsetecka, None; J. Paredes, None; R. Fernandez Ruiz, None; T. Wampler Muskardin, None; T. Niewold, None.