[Retracted] Bone Marrow Plasma Cytokine Signature Profiles in Severe Aplastic Anemia

Abstract

Objective. We studied bone marrow plasma (BMP) cytokines in severe aplastic anemia (SAA) patients and healthy volunteers to investigate differences in the cytokine profiles between them and propose a cytokine signature of SAA. Methods. A Bio-Plex suspension array system was used to measure 27 analytes in BMP samples from 47 SAA patients and 30 healthy donors. Results. Compared to healthy people, SAA patients had higher levels of tumor necrosis factor α (TNF-α), interferon-γ (IFN-γ), interleukin-2 (IL-2), monocyte chemoattractant protein 1 (MCP-1), and granulocyte colony-stimulating factor (G-CSF). They also had lower levels of interleukin-1 receptor antagonist (IL-1ra), interleukin-9 (IL-9), regulated upon activation normal T cell expressed and secreted (RANTES) factor, platelet-derived growth factor-BB (PDGF-BB), and macrophage inflammatory protein 1β (MIP-1β). Levels of interleukin-4 (IL-4), IL-1ra, macrophage inflammatory protein 1α (MIP-1α), and eotaxin were significantly higher in recovering SAA (RSAA) patients. Levels of IL-5, IL-6, IL-10, IL-12, IL-13, IL-15, granulocyte-macrophage colony-stimulating factor (GM-CSF), and vascular endothelial growth factor (VEGF) were undetectable. There were no significant differences in the levels of IL-1β, IL-4, IL-7, IL-8, IL-17, basic fibroblast growth factor (FGF-β), and IFN inducible protein-10 (IP-10) between patients and healthy controls (HCs). Eotaxin, IL-1ra, MCP-1, MIP-1β, and RANTES levels increased after IST, whereas IFN-γ, G-CSF, IL-2, IL-7, and TNF-α levels decreased after IST. Conclusions. The current study demonstrated distinct cytokine profiles among untreated SAA patients, recovering SAA (RSAA) patients, and healthy people. The cytokines of RSAA patients showed similar characteristics to those of untreated SAA patients and healthy people, respectively, which may reflect that the immune status of RSAA patients is in different stages of recovery after IST; thus, it may provide an important tool in diagnosing and evaluating or predicting curative effects in clinics.

Upregulated Expression of Profilin1 on Dendritic Cells in Patients With Severe Aplastic Anemia

“…The number of Th1 cells in treatment-naive SAA patients increased significantly, and the cytokines (e.g. INF-γ, TNF-α and IL-2) associated with Th1 cells increased significantly ( 7 ). The above factors together lead to excessive activation of cytotoxic T lymphocytes (CTLs).…”

Upregulated expression of leukocyte immunoglobulin‑like receptor A3 in patients with severe aplastic anemia

“…To date, the etiology and pathogenesis of SAA have remained to be fully elucidated. Previous studies by our group have confirmed that various immune cells and cytokines constitute an abnormal immune status in patients with SAA (20,21), including the involvement of Th1/Th2 subset imbalances, hyperfunctional CTLs, insufficiencies in the regulatory T and NK cell populations and negative hematopoietic cytokines (22,23). These subsequently induce excessive apoptosis of CD34 + HSCs and inhibit hematopoietic colony formation through the perforin, granzyme B, Fas/FasL and the TNF-related apoptosis-inducing ligand pathways (13).…”

Bone Marrow Failure Syndromes, Overlapping Diseases with a Common Cytokine Signature

“…BM mesenchymal stem cells (BM-MSCs) might be involved in the pathogenesis of AA, because MSCs can differentiate in distinct types of stromal cells that support hematopoiesis and regulate immune cells in the BM niche [ 52 , 53 , 54 , 55 , 56 ]. BM-MSCs have reduced ability to suppress proliferation and differentiation of CD4 + cells, and TNF-α and IFN-γ production in AA while inducing Treg polarization without affecting IL-4, IL-10, or IL-17 production.…”

“…Other highly expressed genes are Th1, Th2, and Th17 differentiation-associated and inflammation-related genes. In addition, abnormal splicing is also documented and involved genes are related to oncogenesis, metabolism, and other signaling pathways such as mTOR (mammalian target or rapamycin) and Wnt [ 52 , 53 , 54 , 55 , 56 , 57 , 58 ].…”