Session Type: Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose: Avascular necrosis (AVN) is a musculoskeletal condition that can result in significant pain and compromised quality of life. The diverse etiologies of AVN have been described; glucocorticoid (GC) use is the most common cause for non-traumatic AVN. However, the pathogenesis of GC-induced AVN has yet to be fully elucidated. While a wide range of the immunomodulatory effects of GC has been reported, little is known of the changes in circulating cellular phenotype for patients with GC-induced AVN. This study investigated the linkage between GC-induced AVN and altered immune homeostasis. We hypothesized that GC may differentially affect the phenotype of immune cells in AVN patients, which may serve as a measure for the systemic status of AVN patients.
Methods: Fifty-four AVN patients (47.7 ± 14.5 yr [mean ± SD]; female 26 and male 29) were enrolled for the study. Twenty-nine patients had received GC therapy and 41.3% of GC-induced AVN patients had SLE. The maximum dose of glucocorticoid in the GC-induced AVN group was 56.8 ± 22.5 mg/day. Average cumulative glucocorticoid was 42.8 ± 54.5 g. The non-GC AVN group included twenty-five patients with idiopathic AVN (40.0%), heavy alcohol use (36.0%), osteoarthritis (16.0%), and trauma (8.0%). There were no significant differences in mean age and BMI between the two groups. The GC-induced AVN group had a higher female-to-male ratio. Serum cytokines were measured by multiplex assay. Circulating immune cells were defined by cell surface markers and measured by flow cytometric analysis. Gene expression profiles from macrophages and T cells were also measured and analyzed.
Results: As the composition of innate and adaptive immune cells reflects the systemic status of the host, we measured CD14+ macrophages, myeloid dendritic cells (DCs), plasmacytoid DCs, B cells, and T cells (CD4+ and CD8+ T cells) in blood from the GC-induced AVN and non-GC-induced AVN groups. There was no difference in the number of macrophages, dendritic cells (DCs), pDCs, and B cells between the two groups. There was also no difference in the number of CD4+ T cells between the two groups, but we found the number of CD8+ cells in the GC-induced AVN group to be significantly higher than that of the non-GC AVN group (p = 0.0252). To determine if the increased count of CD8+ T cells in the GC-induced AVN group resulted from GC therapy, we also compared the number of CD8+ T cells in the GC-induced AVN group to that of the GC-treated patients who did not have AVN. The number of CD8+ T cells was higher for GC-induced AVN patients (p = 0.0008). Accordingly, a CD4/CD8 T cell ratio was significantly lower for this group (p = 0.0063). In addition to the cellular phenotype, we also found that serum TNF-α and CXCL10 were significantly higher in the GC-induced AVN group compared to those of the non-GC induced AVN group.
Conclusion: Our findings revealed the status of circulating immune cells in GC-induced AVN patients and found that the subset of lymphocytes significantly increased in the GC-induced AVN group. Our study suggests that lymphocytes in the GC-induced AVN group may escape the immunosuppressive effect of GC, and we believe further study is needed to identify the mechanism of altered immune profiles in GC-induced AVN.
To cite this abstract in AMA style:Kaneko K, Chen H, Krez A, Zeng S, Park P, Lee Y, Fujii T, Kim H, Mun S, Bae S, Pannellini T, Lane J, Hansen D, Mintz D, Bockman R, Stein E, Park-Min K. Immunophenotyping of Peripheral Blood Highlights an Association of Dysregulated Lymphocytes with Patients with Glucocorticoid-induced Osteonecrosis [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/immunophenotyping-of-peripheral-blood-highlights-an-association-of-dysregulated-lymphocytes-with-patients-with-glucocorticoid-induced-osteonecrosis/. Accessed August 1, 2021.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/immunophenotyping-of-peripheral-blood-highlights-an-association-of-dysregulated-lymphocytes-with-patients-with-glucocorticoid-induced-osteonecrosis/