Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: Systemic lupus erythematous (SLE) is a complex autoimmune disease often involving multiple organs. In SLE, immune complexes containing autoreactive antibody and nuclear material activate plasmacytoid dendritic cells (PDCs). Activated PDCs are thought to contribute to disease pathogenesis by secreting IFN-alpha and through presentation of autoantigen to T cells. PDC activation is regulated by numerous inhibitory surface receptors including ILT7 which serves as a negative feedback pathway to limit PDC IFN production. We and others have linked numerous gene polymorphisms with blood IFN levels, disease severity, and clinical characteristics.
Methods: We studied expression of 12 inhibitory surface receptors on PDCs from a cohort of patients (n>60) and controls (n>20) by quantitative flow cytometry and correlated them with IFN levels, clinical characteristics, and disease severity. ILT7 function was studied by measuring the impact of ILT7 crosslinking on IFN and cytokine output using blood mononuclear cells and purified PDCs from patients and controls. A second inhibitory receptor, CD303, was studied as a comparator.
Results: We find selective downregulation of surface ILT7 expression and decreased ILT7 function by PDCs of patients with high ANA titers (p<.0001 for SLE with high vs low ANA titers).
Conclusion: These data suggest that decreased function of the ILT7 pathway leads to chronic PDC activation in SLE patients. The association with higher ANA titers suggests that dysfunction in this pathway may contribute to the formation of autoreactive antibodies and may contribute to disease pathogenesis in SLE via an impact on the IFN pathway as well as humoral autoimmunity.
To cite this abstract in AMA style:Jensen MA, Dorschner JM, Vsetecka D, Amin S, Makol A, Ernste FC, Osborn T, Moder K, Chowdhary V, Niewold TB. Expression Levels and Function of the Inhibitory Molecule, Immunoglobulin like Transcript 7 (ILT7), Are Decreased on Circulating Plasmacytoid Dendritic Cells in SLE Patients with High ANA Titers [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/expression-levels-and-function-of-the-inhibitory-molecule-immunoglobulin-like-transcript-7-ilt7-are-decreased-on-circulating-plasmacytoid-dendritic-cells-in-sle-patients-with-high-ana-titers/. Accessed December 2, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/expression-levels-and-function-of-the-inhibitory-molecule-immunoglobulin-like-transcript-7-ilt7-are-decreased-on-circulating-plasmacytoid-dendritic-cells-in-sle-patients-with-high-ana-titers/