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Behçet’s disease patients present high levels of deglycosylated anti-lipoteichoic acid IgG and high IL-8 production after lipoteichoic acid stimulation

M. Cuchacovich¹, G. Merino², J.H. Yamamoto³, F. Villarroel⁴, T. Saavedra⁵, S. Jofre⁶, H. Gatica¹, V. Velasquez⁷, S.V. Pizzo⁸, M. Gonzalez-Gronow⁸

¹Department of Medicine, Division of Rheumatology, Clinical Hospital University of Chile, Santiago, Chile; ²Department of Ophthalmology, Catholic University of Chile, Santiago; ³Department of Ophthalmology, Sao Pauolo University, Brazil; ⁴Los Andes Ophtalmological Foundation, Santiago, Chile; ⁵Department of Dermatology; ⁶Department of Odontology and Oral Surgery, and ⁷Department of Ophthalmology, University of Chile Clinical Hospital, Santiago, Chile; ⁸Department of Pathology, Duke University Medical Center, Durham, North Carolina, USA.
Miguel Cuchacovich M.D. Professor of Medicine; Guillermo Merino M.D. Assistant Professor;

ABSTRACTJoyce H. Yamamoto M.D. Professor of Ophthalmology; Francisco Villarroel M.D. Professor of Ophthalmology; Tirsa Saavedra M.D. Assistant Professor of Dermatology; Sergio Jofre Professor of Dentistry, University of Chile; Héctor Gatica M.D. Assistant Professor of Rheumatology; Victor Velasquez M.D. Profes-sor of Ophthalmology; Salvatore V. Pizzo M.D. Professor of Medicine; Mario Gonzalez-Gronow Ph.D. Assistant Research Professor.
This work was supported by Grants 1990 122 from FONDECYT-Chile and CA-86344 from the National Cancer Institute.
Please address correspondence to:
Mario Gonzalez-Gronow, PhD, Department of Pathology, Box 3712, Duke
University Medical Center, Durham,
NC 27710, USA.
E-mail: gonza002@mc.duke.edu
Received on September 6, 2004; accepted in revised form on February 9, 2005.
Clin Exp Rheumatol 2005; 23 (Suppl. 38): S27-S34.
© Copyright Clinical and Experimental Rheumatology 2005.

Key words: Behçet’s disease, lipoteichoic acid, deglycosylated IgG, MBP binding, interleukin-8 secretion.

Objectives
Lipoteichoic acid (LTA), induces some of the clinical symptoms of Behçet’s disease (BD) in a rat animal model. These results led to the hypothesis that LTA may also trigger BD in humans. We investigated the humoral and cellular immune response against LTA and lipopolysaccharide (LPS) in patients with BD, and compared these responses with those of patients with active chronic oral ulcers (OU) and normal controls.

Methods
Samples were obtained from 12 active BD, 12 inactive BD, 12 active OU and 12 normal controls. Anti-LTA, anti-LPS antibodies levels and the capacity of immune complexes anti-LTA IgG-LTA to activate complement were studied. Exposed mannose residues in anti-LTA IgG were analyzed in the four groups. The interleukin-8 (IL-8) production by peripheral blood mononuclear cells cultures after LTA and LPS stimulation was also studied in all groups.

Results
The capacity to bind mannan binding protein (MBP) of anti-LTA IgGs was significantly higher in BD and active OU patients relative to normal controls (p < 0.001). However, only active BD patients generated significantly higher levels of C5a than controls (p < 0.0001). The IgGs purified from the sera of BD patients showed a high specificity for LTA from Streptococcus sanguis or Streptococcus faecalis. LTA also stimulates the secretion of IL-8 in peripheral blood mononuclear cells isolated from active BD patients. Anti-LPS IgA and IgG titers were significantly higher only in active OU patients relative to normal controls (p < 0.0018).

Conclusion
These results suggest a mechanism involving LTA from streptococci in the pathogenesis of BD.

Key words
Behçet’s disease, lipoteichoic acid, deglycosylated IgG, MBP binding, interleukin-8 secretion.

This work was supported by Grants 1990 122 from FONDECYT-Chile and CA-86344 from the National Cancer Institute.
Please address correspondence to: Mario Gonzalez-Gronow, PhD, Department of Pathology, Box 3712, Duke University Medical Center, Durham, NC 27710, USA.
E-mail: gonza002@mc.duke.edu