Characterization of 5C11-positive activated interferon-producing cells in patients with systemic lupus erythematosus.

Abstract

OBJECTIVE:

5C11 antibody is a novel monoclonal antibody against human BST2 and can be used to detect activation of interferon-producing cells (IPCs). Activated IPCs, which produce large amounts of interferon-α (IFNα), are considered to play an important role in the pathogenesis of systemic lupus erythematosus (SLE). We investigated the characterization of 5C11-positive cells in patients with SLE.

METHODS:

The proportions of 5C11-positive cells among blood dendritic cell antigen 2 (BDCA-2)-, CD3-, CD19- and CD14-positive cells in peripheral blood from SLE patients (SLE-PBMCs) and healthy controls (control-PBMCs) were analyzed by flow cytometry. The effect of 5C11 antibody on IFNα production from SLE-PBMCs under stimulation with cytosine-phosphate-guanosine (CpG2216, bacterial oligonucleotide motif) was also examined by enzyme-linked immunosorbent assay (ELISA).

RESULTS:

The proportions of 5C11-positive cells among BDCA-2-, CD3- and CD19-, but not CD14-positive cells in SLE-PBMCs were significantly increased compared to those in control-PBMCs (p < 0.0001, all). Especially, the number of 5C11-positive cells among BDCA-2-positive cells was significantly increased in SLE-PBMCs by about six-fold compared to that in control-PBMCs (p < 0.0001). 5C11 antibody inhibited IFNα production by SLE-PBMCs induced by CpG and the inhibition rates was 27% (p < 0.001).

CONCLUSION:

SLE patients had a significantly higher proportion of 5C11-positive cells among CD3 and CD19 cells, and especially BDCA-2 positive cells. The ability of 5C11 antibody to inhibit IFNα production from SLE-PBMCs warrants further investigation for its possible clinical application for the treatment of SLE.

• Authors: M Ohshima, H Kanda, K Kubo, A Yonezumi-Hayashi, S Tateishi, K Yamamoto
• Journal: Lupus (Lupus) Vol. 22 Issue 1 Pg. 44-51 (Jan 2013) ISSN: 1477-0962 [Electronic] England
• PMID: 23087259 (Publication Type: Journal Article)

Chemical References

• Antibodies, Monoclonal
• Antigens, CD
• Antigens, CD19
• BST2 protein, human
• Biomarkers
• CD3 Complex
• CLEC4C protein, human
• CpG ODN 2216
• GPI-Linked Proteins
• Interferon-alpha
• Lectins, C-Type
• Lipopolysaccharide Receptors
• Membrane Glycoproteins
• Oligodeoxyribonucleotides
• Receptors, Immunologic
• Toll-Like Receptor 9

Topics

• Adult
• Aged
• Antibodies, Monoclonal (pharmacology)
• Antigens, CD (immunology, metabolism)
• Antigens, CD19 (metabolism)
• Biomarkers (metabolism)
• CD3 Complex (metabolism)
• Case-Control Studies
• Cell Separation (methods)
• Cells, Cultured
• Enzyme-Linked Immunosorbent Assay
• Female
• Flow Cytometry
• GPI-Linked Proteins (immunology, metabolism)
• Humans
• Interferon-alpha (metabolism)
• Lectins, C-Type (metabolism)
• Leukocytes, Mononuclear (drug effects, immunology)
• Lipopolysaccharide Receptors (metabolism)
• Lupus Erythematosus, Systemic (blood, immunology)
• Male
• Membrane Glycoproteins (metabolism)
• Middle Aged
• Oligodeoxyribonucleotides (immunology)
• Receptors, Immunologic (metabolism)
• Toll-Like Receptor 9 (agonists)
• Young Adult