Increased expression of Siglec-1 on peripheral blood monocytes and its role in mononuclear cell reactivity to autoantigen in rheumatoid arthritis.

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.

• Authors: Yi-Song Xiong, Yue Cheng, Qiu-Shui Lin, Ai-Lin Wu, Juan Yu, Chang Li, Yi Sun, Ren-Qian Zhong, Li-Juan Wu
• Journal: Rheumatology (Oxford, England) (Rheumatology (Oxford)) Vol. 53 Issue 2 Pg. 250-9 (Feb 2014) ISSN: 1462-0332 [Electronic] England
• PMID: 24196391 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Autoantigens
• Collagen Type II
• Cytokines
• Immunoglobulin M
• RNA, Messenger
• SIGLEC1 protein, human
• Sialic Acid Binding Ig-like Lectin 1
• Tumor Necrosis Factor-alpha
• Interferon-gamma
• C-Reactive Protein

Topics

• Adult
• Arthritis, Rheumatoid (immunology, pathology)
• Autoantigens (immunology)
• 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, immunology)
• Lupus Erythematosus, Systemic (immunology, pathology)
• Male
• Middle Aged
• Monocytes (drug effects, immunology)
• Osteoarthritis (immunology, pathology)
• RNA, Messenger (metabolism)
• Sialic Acid Binding Ig-like Lectin 1 (metabolism)
• Tumor Necrosis Factor-alpha (pharmacology)