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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.

Keywords

Systemic lupus erythematosus interferon α IFN-producing cells

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References

Dzionek

Fuchs

Schmidt

. BDCA-2, BDCA-3, and BDCA-4: Three markers for distinct subsets of dendric cells in human peripheral blood. J Immunol 2000; 165: 6037–6046.

Dzionek

Soma

Nagafune

. BDCA-2, a novel plasmacytoid dendric cell-specific type lectin, mediates antigen capture and is a potent inhibitor of interferon α/β induction. J Exp Med 2001; 194: 1823–1834.

Cao

Zhang

Rosen

. BDCA2/FCεRIγ complex signals through a novel BCR-like pathway in human plasmacytoid dendric cells. PLoS Biol 2007; 5: e248–e248.

WIPO: World intellectual property organization. International patent number: WO2006008886, http://www.wipo.int/patentscope/en/ (1 December 2011)..

Wilson

Widman

Dikman

Gorevic

. Autoimmune disease complicating antiviral therapy for hepatitis C virus infection. Semin Arthritis Rheum 2002; 32: 163–173.

Brassard

Grace

Bordens

. Interferon-α as an immunotherapeutic protein. J Leukoc Biol 2002; 71: 565–581.

Kirou

Lee

George

Louca

Peterson

MGE

Crow

. Activation of the interferon-α pathway identifies a subgroup of systemic lupus erythematosus patients with distinct serologic features and active disease. Arthritis Rheum 2005; 52: 1491–1503.

Robak

Smolewski

Wozniacka

Sysa-Jedrzejowska

Stepien

Robak

. Relationship between peripheral blood dendric cells and cytokines involved in the pathogenesis of systemic lupus erythematosus. Eur Cyt Netw 2004; 15: 222–230.

Blomberg

Eloranta

Cederblad

Nordlind

Alm

Ronnblom

. Presence of cutaneous interferon-α producing cells in patients with systemic lupus erythematosus. Lupus 2001; 10: 484–490.

10.

Farkas

Beiske

Lund-Johansen

Brandtzaeg

Jahnsen

. Plasmacytoid dendric cells (natural interferon-α/β-producing cells) accumulate in cutaneous lupus erythematosus regions. Am J Pathol 2001; 159: 237–243.

11.

Fiore

Castellano

Blasi

. Immature myeloid and plasmacytoid dendric cells infiltrate renal tubulointerstitium in patients with lupus nephritis. Mol Immunol 2007; 45: 259–265.

12.

Tucci

Calvani

Richards

Quatraro

Silvestris

. The interplay of chemokines and dendric cells in the pathogenesis of lupus nephritis. Ann N Y Acad Sci 2005; 1051: 421–432.

13.

Tucci

Quatraro

Lombardi

Pellegrino

Dammacco

Silvestris

. Glomerular accumulation of plasmacytoid dendric cells in active lupus nephritis. Arthritis Rheum 2008; 58: 251–262.

14.

Blomberg

Eloranta

M-J

Magnusson

Alm

Ronnblom

. Expression of the markers BDCA-2 and BDCA-4 and production of interferon-α by plasmacytoid dendric cells in systemic lupus erythematosus. Arthritis Rheum 2003; 48: 2524–2532.

15.

Tan

Cohen

Fries

. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982; 25: 1271–1277.

16.

Bombardier

Gladman

Urowitz

Caron

Chang

. Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthritis Rheum 1992; 35: 630–640.

17.

Shodell

Shahm

Siegal

. Circulating human plasmacytoid dendric cell are highly sensitive to corticosteroid administration. Lupus 2003; 12: 222–230.

18.

Cao

Bover

. Signaling and ligand interaction of ILT7: Receptor-mediated regulatory mechanisms for plasmacytoid dendritic cells. Immunol Rev 2010; 234: 163–176.

19.

Cao

Bover

Cho

. Regulation of TLR7/9 responses in plasmacytoid dendritic cells by BST2 and ILT7 receptor interaction. J Exp Med 2009; 206: 1603–1614.

20.

Blasius

Giurisato

Cella

Schreiber

Shaw

Colonna

. Bone marrow stromal cell antigen 2 is a specific marker of type I IFN-producing cells in the naïve mouse, but a promiscuous cell surface antigen following IFN stimulation. J Immunol 2006; 177: 3260–3265.

21.

Wallac

Petri

Olsen

. MEDI-545, an anti-interferon alpha monoclonal antibody, shows evidence of clinical activity in systemic lupus erythematosus. Arthritis Rheum 2007; 56: S526–S527.

22.

Pogue

Preston

Stalder

Bebbington

Cardarelli

. The receptor for type 1 IFNs is highly expressed on peripheral blood B cells and monocytes and mediates a distinct profile of differentiation and activation of these cells. J Interferon Cytokine Res 2004; 24: 131–139.

23.

Christensen

Shupe

Nickerson

Kashgarian

Flavell

Shlomchik

. Toll-like receptor 7 and TLR9 dictate autoantibody specificity and have opposing inflammatory and regulatory roles in a murine model of lupus. Immunity 2006; 25: 397–399.

24.

Pawar

Ramanjaneyulu

Kulkarni

Lech

Segerer

Anders

H-J

. Inhibition of toll-like receptor-7 (TLR-7) or TLR-7 plus TLR-9 attenuates glomerulonephritis and lung injury in experimental lupus. J Am Soc Nephrol 2007; 18: 1721–1731.

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