The Role of Immune Regulatory Cells in Nontraumatic Osteonecrosis of the Femoral Head: A Retrospective Clinical Study

Abstract

The immunologic factors have been implicated in the pathogenesis of osteonecrosis. We aimed to investigate the potential role of immune regulatory cells in the development of osteonecrosis of femoral head (ONFH). Sixty-seven patients diagnosed with ONFH and fifty-eight age-, height-, and weight-matched healthy subjects were included in this retrospective study between September 2015 and September 2018. The flow cytometry was used to test the count, percentage, and ratio of T and B lymphocyte subsets in peripheral blood. The T and B lymphocyte levels were compared among different ARCO stages, CJFH types, and etiology groups. The total lymphocyte count, CD3+T cells, Ts cells (CD3+CD8+), B-1 cell count, and B-1 cells (CD5+CD19+) were significantly higher in the patients with ONFH than those in the control subjects. The percentage of T lymphocytes in the patients with ARCO IV stage was significantly smaller than that in the ONFH patients with ARCO II and III stages. The percentage of inhibitory T lymphocytes in patients with CJFH type L3 was significantly smaller than that in the patients with types L1 and L2. In terms of the different ONFH etiologies, the total lymphocyte count and Ts cells (CD3+CD8+) were significantly lower in the ONFH patients induced by excessive alcohol intake than those in the idiopathic ONFH patients. Our results seem to indicate that immune regulatory cells, such as T and B lymphocytes, play an important role in the pathogenesis of ONFH. The development and progression of ONFH may be associated with immune system imbalance.

CD4+ T Cell Profile and Activation Response in Sickle Cell Disease Patients with Osteonecrosis

“…Recent studies have demonstrated that inflammatory processes are associated with the development and progression of osteonecrosis. Abnormal immune response, imbalanced immune cell subpopulations, and higher plasma levels of inflammatory cytokines in patients with osteonecrosis suggest that inflammation plays a crucial role in this disorder [ 12 – 14 ]. Moreover, chemokines and cytokines released by necrotic cells recruit inflammatory cells, inducing local and systemic immune response in patients with osteonecrosis [ 15 – 17 ].…”

ARG2, MAP4K5 and TSTA3 as Diagnostic Markers of Steroid-Induced Osteonecrosis of the Femoral Head and Their Correlation With Immune Infiltration

“…Clinically, for the lack of typical symptoms and sensitive diagnostic indicators, it is sometimes difficult to predict and diagnose cases with SONFH and thus lose the optimal treatment opportunity. Moreover, as indicated from existing studies, immune cells primarily impact the development of SONFH (Ma et al, 2019). For this reason, there is profound significance in finding specific diagnostic markers and analyzing the pattern of infiltration of immune cells for improving the prognosis of SONFH cases.…”

Osteoimmunology and osteonecrosis of the femoral head

“…Increasing evidence points to inflammatory osteoimmunology playing an indispensable role in the pathogenesis of ONFH. 4 - 8 …”

“…While immune cells such as macrophages are important for resolving inflammation and promote subsequent tissue repair, they also contribute to ONFH, suggesting that the disease arises as a result of immune system dysfunction. 5 , 8 Bone biology and immunology have recently been combined in the field of osteoimmunology to become an important focus of ONFH research. 9 We will summarize the current understanding of the osteoimmunology of ONFH, focusing on the important roles of macrophages, T and B cells, and neutrophils, as well as related signalling molecules.…”

“… 20 Treg cells secrete the anti-inflammatory cytokines IL-4, IL-10, and transforming growth factor beta (TGF-β), which inhibit osteoclast activity, thereby preventing bone damage. 8 Via cytotoxic T lymphocyte associated protein (CTLA-4), a kind of transmembrane receptor, inhibitory T cells can bind to osteoclast precursors to suppress the osteoclast activity. The reduction in the number of inhibitory T cells is shown to be associated with ONFH progression.…”