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.

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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/