ABSTRACT
OBJECTIVES: Elevated expression of Siglec-1 on circulating monocytes has been reported in some inflammatory and autoimmune diseases, but its expression and role in RA has not been elucidated. The aims of this study were to determine the expression of Siglec-1 in peripheral blood and to explore its role in mononuclear cell reactivity to autoantigen in RA. METHODS: Siglec-1 protein and mRNA levels in 42 RA patients, 39 OA patients, 28 SLE patients and 42 normal controls were determined by flow cytometry and quantitative RT-PCR, respectively. In addition, 10 patients with active RA received DMARDs for 12 weeks and the frequencies of Siglec-1-positive cells and the 28-joint DAS (DAS28) were assessed before and after therapy. Furthermore, TNF-α, IFN-γ and type II collagen were used to up-regulate Siglec-1. Peripheral blood mononuclear cells (PBMCs) from different groups were stimulated with mitogens or antigens and cell proliferation and cytokine production were determined. RESULTS: The protein and mRNA levels of Siglec-1 on PBMCs and monocytes in RA patients were significantly higher than those in OA patients and healthy controls. Moreover, the expression of Siglec-1 protein on PBMCs was positively correlated with DAS28, ESR, high-sensitivity CRP and IgM-RF, but not with anti-CCP antibody. Interestingly, Siglec-1 expression was decreased in parallel with the decrease in the DAS28 after 12 weeks of anti-rheumatic treatment. Furthermore, TNF-α, IFN-γ and type II collagen can up-regulate Siglec-1 in PBMCs. Elevated PBMC proliferation and proinflammatory cytokine production to collagen stimulation in RA patients decreased when Siglec-1 was inhibited by anti-Siglec-1 antibodies. CONCLUSION: Elevated Siglec-1 expression in PBMCs and monocytes can potentially serve as a biomarker for monitoring disease activity in RA. Siglec-1 may also play a proinflammatory role in stimulating lymphocyte proliferation and activation in RA.
Subject(s)
Arthritis, Rheumatoid/immunology , Autoantigens/immunology , Leukocytes, Mononuclear/immunology , Monocytes/immunology , Sialic Acid Binding Ig-like Lectin 1/metabolism , Adult , Arthritis, Rheumatoid/pathology , C-Reactive Protein/metabolism , Case-Control Studies , Cell Proliferation/drug effects , Cells, Cultured , Collagen Type II/pharmacology , Cytokines/metabolism , Female , Humans , Immunoglobulin M/metabolism , Interferon-gamma/pharmacology , Leukocytes, Mononuclear/drug effects , Lupus Erythematosus, Systemic/immunology , Lupus Erythematosus, Systemic/pathology , Male , Middle Aged , Monocytes/drug effects , Osteoarthritis/immunology , Osteoarthritis/pathology , RNA, Messenger/metabolism , Tumor Necrosis Factor-alpha/pharmacologyABSTRACT
OBJECTIVE: Atherosclerosis (AS) is widely accepted as an inflammatory disease and monocytes are particularly important in inflammatory immune responses. As an important biomarker of monocytes activation, Siglec-1 is highly expressed on circulating monocytes and atherosclerotic plaques of coronary artery disease (CAD) patients, but the exact role of Siglec-1 has not been elucidated. METHODS: M-CSF, INF-α, IFN-γ, TNF-α and ox-LDL alone or in combination were used to stimulate Siglec-1 expression on monocytes, whereas small interfering RNA (si-RNA) or blocking antibody was used to down-regulate Siglec-1. Meanwhile, the role of Siglec-1 in chemokines secretion was determined. Then monocytes from CAD patients or healthy controls were cocultured with CD4+ or CD8+ T cells from a third healthy individual, and lymphocyte proliferation and activation were determined. RESULTS: All the stimuluses could enhance Siglec-1 expression on monocytes in a dose-dependent manner, and M-CSF could synergistically stimulate Siglec-1 expression with ox-LDL. Moreover, the secretion of MCP-1, MIP-1α and MIP-2 were enhanced when Siglec-1 was up-regulated and down to normal level when Siglec-1 was blocked. More importantly, increased Siglec-1 expression on monocytes was related to the increased T cell proliferation and pro-inflammatory cytokines secretion in CAD patients. However, down-regulation of Siglec-1 could attenuate proliferation and activation of cocultured CD4+ and CD8+ T cells. CONCLUSION: Siglec-1 can promote chemokines and pro-inflammatory cytokines secretion and influence the inflammatory process of AS.
Subject(s)
Monocytes/immunology , Sialic Acid Binding Ig-like Lectin 1/physiology , Animals , Atherosclerosis/immunology , Cell Proliferation , Coronary Artery Disease/immunology , Humans , Mice , T-Lymphocytes/immunology , T-Lymphocytes/metabolismABSTRACT
STUDY DESIGN: Case report. OBJECTIVE: To report a case of a 19-year-old boy with intervertebral disc calcification (IDC) at C7-T1, who presented with paresis and aconuresis. Surgical outcome was assessed. SUMMARY OF BACKGROUND DATA: IDC, commonly seen in the cervical spine region in children, is well-known as a self-limiting disorder with no or little symptoms. Surgical intervention is usually not required. METHODS: A 19-year-old boy presented with acute back pain, progressive numbness, and weakness of both lower extremities and aconuresis for 1 week. There was no traumatic history or signs of infection. Radiograph, computed tomography with reconstruction, and magnetic resonance imaging revealed C7-T1 IDC with severe spinal cord compression. Decompression with anterior cervical corpectomy and fusion was performed. RESULTS: Follow-up showed complete resolution of the back pain and complete recovery of motor power and sensory function in both lower extremities and return of normal micturition function. The patient had full recovery with no complications. CONCLUSION: Serious neurologic deficit, especially a bladder dysfunction, caused by calcified intervertebral disc is rare. However, favorable outcome can be achieved in those cases where rapid diagnosis is made and followed by spinal cord decompression.
