Background/Purpose: Idiopathic Inflammatory Myopathy (IIM) is a group of autoimmune diseases characterized by immune-mediated injury to skeletal muscle, including polymyositis (PM) and dermatomyositis (DM). Recent studies have shown that IIM patients exhibit a type I interferon (IFN) signature, which is also present in systemic lupus erythematosus (SLE) (1). Low density granulocytes (LDG) have been identified as an important source of IFN production in SLE patients (2). Given the importance of IFN in the pathogenesis of SLE, DM, and PM, we hypothesized that LDG numbers would be increased in patients with IIM.

Methods: Healthy donors (HD) and patients with undifferentiated connective tissue disease (UCTD) were enrolled in the Hospital for Special Surgery UCTD Registry. SLE patients were enrolled in the FLARE lupus registry, and all met at least 4 of 11 ACR classification criteria for SLE. Myositis subjects in the present study were enrolled in the Hospital for Special Surgery Myositis Registry. All patients with IIM either 1) met Bohan and Peter criteria for probable or definite PM or DM, or 2) met Bohan and Peter criteria for possible PM/DM and were positive for a myositis-specific or myositis-associated antibody. PBMC were isolated from whole blood using Ficoll density centrifugation, then stained and fixed with paraformaldehyde until analyzed by flow cytometry. Cells were stained with antibodies against CD16, CD15, CD14, CD64, and CD56. LDGs were identified as cells in the PBMC fraction staining CD15hi/CD14lo. Differences between groups were analyzed using 2-tailed Student’s T tests. No correction for multiple comparisons was made in this exploratory analysis.

Results: 18 patients with IIM (10 DM/8 PM), 14 healthy donors, 3 SLE patients, and 4 patients with UCTD were evaluated. The mean proportion of LDGs in IIM was numerically greater than HD, but the difference did not reach statistical significance (all presented as mean +/- standard error: 4.13% +/- 1.61 vs 0.91% +/- 0.27, p=0.104). However, when PM and DM patients were compared to HD in a subgroup analysis, DM patients had a significant elevation of LDGs (4.22% +/- 1.75, p=0.045). There was no significant correlation between strength as assessed by manual muscle testing (MMT8), or with creatine kinase levels. In accordance w/ prior studies, LDGs in SLE were elevated relative to HD (14.48% +/- 11.67, p=0.015), while the level in UCTD was closer to HD (0.61% +/- 0.14, p=0.558).

Conclusion: We did not find an increase in LDGs in PBMC of patients with IIM relative to HD, though a subgroup analysis showed DM patients exhibit a significant elevation of LDGs. Our study may not have had sufficient power to distinguish a difference in IIM patients relative to HD in the aggregate, possibly due to the heterogeneity and complexity of IIM patients. LDGs may be of importance in subgroups of IIM patients.

References:

1. Higgs BW, et al. Patients with systemic lupus erythematosus, myositis, rheumatoid arthritis, and scleroderma share activation of a common type I interferon pathway. Ann Rheum Dis. 70, 11 (2011).
2. Smith CK, Kaplan MJ. The role of neutrophils in the pathogenesis of systemic lupus erythematosus. Curr Opin Rheumatol. 27, 5, (2015).

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/low-density-granulocytes-in-idiopathic-inflammatory-myopathy/