Rheumatology Advance Access originally published online on November 17, 2003
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Rheumatology 2004; 43: 286-293
Rheumatology Vol. 43 No. 3 (c) British Society for Rheumatology 2003; all rights reserved
Basic Science |
The pathogenetic role of immunoglobulin G from patients with systemic lupus erythematosus in the development of lupus pleuritis
Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong.
Correspondence to: K. N. Lai, Department of Medicine, University of Hong Kong, Room 409, Professorial Block, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong. E-mail: knlai{at}hkucc.hku.hk
Objective. To investigate the pathophysiological effect of immunoglobulin G (IgG) from systemic lupus erythematosus (SLE) patients on pleural mesothelial cells and related mechanisms.
Methods. Serum IgG from 28 lupus patients and 13 healthy controls was purified by protein-G affinity chromatography. The concentrations of anti-dsDNA-, anti-histone- and/or anti-nucleohistone-containing IgGs were determined by enzyme-linked immunosorbent assay (ELISA). Lupus patients were divided into an active (n = 12) and an inactive group (n = 16) on the basis of the SLE Disease Activity Index (SLEDAI). The binding of IgG to a human pleural mesothelial cell line (MeT-5A) under different conditions, including pretreatment with DNase and preincubation with exogenous histone, DNA or nucleohistone, was examined using flow cytometry and cellular ELISA. The effect of IgG on MeT-5A cell proliferation was studied using an MTT assay. Gene expression and protein synthesis for interleukin 1ß (IL-1ß), monocyte chemoattractant protein 1 (MCP-1) and transforming growth factor ß1 (TGF-ß1) in MeT-5A cells were determined using reverse transcription–polymerase chain reaction and ELISA.
Results. The binding of IgG to MeT-5A cells was higher in the active lupus group than the inactive lupus group (P = 0.047) and controls (P = 0.003). The binding decreased in both lupus groups following pretreatment of MeT-5A cells with DNase. The binding of IgG to MeT-5A cells was greater by 112% in the active lupus group after preincubation with histone (P < 0.001), but not with DNA or nucleohistone. Exposure of MeT-5A cells to IgG from either lupus group induced cell proliferation when compared with IgG from healthy controls (P = 0.04). Gene expression and protein synthesis of MCP-1, TGF-ß1 and IL-1ß in MeT-5A cells were significantly increased after incubation with IgG from patients with active lupus when compared with IgG from the inactive lupus and control groups (P < 0.01). The concentration of anti-dsDNA antibodies correlated with the binding of IgG to MeT-5A cells and the synthesis of cytokines by MeT-5A cells. The serum level of anti-histone antibodies in the active lupus group was higher than that in the inactive group (P = 0.015) and the serum concentration correlated with cell binding and MCP-1 production.
Conclusions. IgG from lupus patients can bind to MeT-5A cells and the binding is modulated by DNA or histone. Binding of anti-dsDNA-containing IgG to MeT-5A cells induces the synthesis of proinflammatory cytokines. Our findings suggest that the binding of anti-dsDNA antibodies, particularly the IgG isotype, to pleural mesothelium plays a direct pathogenetic role in inducing inflammatory injury in the serositis of SLE.
KEY WORDS: Lupus pleuritis, Anti-dsDNA antibodies, Anti-histone antibodies, Anti-nucleohistone antibodies, Pleural mesothelial cells.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  K. Nugent, E. Diri, W. Tello, and W.D. Ratnoff Letter To the Editor: Infliximab-induced SLE-like syndrome involving the lung and pleura Lupus, September 1, 2007; 16(9): 764 - 766. [PDF]
|
|
|
|
 |
|
 A. Jonsen, I. Gunnarsson, B. Gullstrand, E. Svenungsson, A. A. Bengtsson, O. Nived, I. E. Lundberg, L. Truedsson, and G. Sturfelt Association between SLE nephritis and polymorphic variants of the CRP and Fc{gamma}RIIIa genes Rheumatology, September 1, 2007; 46(9): 1417 - 1421. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Yung, R. C.W. Tsang, Y. Sun, J. K.H. Leung, and T. M. Chan Effect of Human Anti-DNA Antibodies on Proximal Renal Tubular Epithelial Cell Cytokine Expression: Implications on Tubulointerstitial Inflammation in Lupus Nephritis J. Am. Soc. Nephrol., November 1, 2005; 16(11): 3281 - 3294. [Abstract] [Full Text] [PDF]
|
|