Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: Autoinflammatory disorders (AD) are characterized by recurrent fevers associated with systemic symptoms involving joints, skin, muscles, and eyes in the absence of adaptive immune responses. Profound dysregulations in various innate immune pathways including the inflammasome-mediated IL-1 signaling are characteristic of these syndromes. While previous studies have revealed that neutrophils may play critical roles in driving the inflammatory process in AD, whether specific neutrophil subsets and neutrophil processes play distinct pathogenic roles in these diseases remains to be characterized.
Methods: We examined the presence of distinct proinflammatory neutrophil subsets in AD and assessed their pathogenic potential. Blood was obtained from healthy controls and from patients with Familial Mediterranean Fever (FMF), Pyogenic Arthritis, Pyoderma gangrenosum, and Acne (PAPA) syndrome, Cryopyrin Associated Periodic Syndromes (CAPS), Tumor necrosis factor receptor-associated periodic syndrome (TRAPS), Autoinflammation-PLCG2-associated antibody deficiency-immune dysregulation (APLAID), and mutation negative AD. Normal density granulocytes (NDGs) were isolated by dextran sedimentation and PBMCs were isolated by Ficoll gradient. Presence of low-density granulocytes (LDGs) was assessed by a negative selection magnetic bead procedure from the PBMC fraction. The capacity of NDGs and LDGs to synthesize neutrophil extracellular traps (NETs) spontaneously was assessed by fluorescence microscopy.
Results: LDGs were classified as CD15+/CD14lo or CD10+/CD14lo and were detected, to varying extents, in all auto-inflammatory samples tested. Compared to healthy control NDGs and autologous NDGs, LDGs from AD patients displayed an enhanced ability to spontaneously form NETs. The proinflammatory cytokine IL-1β was externalized in NETs from NDGs and LDGs from AD patients. NDGs and LDGs from AD patients displayed distinct mRNA expression profile for inflammasome-related proteins and nucleic acid-sensing TLRs.
Conclusion: Collectively, these preliminary results suggest that LDGs are present in AD, may represent a potential source for IL-1β production and contribute to tissue damage and disease manifestations.
To cite this abstract in AMA style:Mistry P, Purmalek M, Jones A, Ombrello AK, Kastner DL, Aksentijevich I, Kaplan M. Characterization of Low-Density Granulocytes in Autoinflammatory Disorders [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/characterization-of-low-density-granulocytes-in-autoinflammatory-disorders/. Accessed October 28, 2020.
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