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


CONCLUSIONS
These results suggest a mechanism involving LTA from streptococci in the pathogenesis of BD.
Cuchacovich
M
M
Department of Medicine, Division of Rheumatology, Clinical Hospital University of Chile, Santiago, Chile.
Merino
G
G
Yamamoto
J H
JH
Villarroel
F
F
Saavedra
T
T
Jofre
S
S
Gatica
H
H
Velasquez
V
V
Pizzo
S V
SV
Gonzalez-Gronow
M
M
D000328:Adult; D000936:Antigen-Antibody Complex / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D001528:Behcet Syndrome / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D003167:Complement Activation / Q000187:drug effects; D003182:Complement C5 / Q000276:immunology / Q000378:metabolism; D005260:Female; D006031:Glycosylation; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D016209:Interleukin-8 / Q000097:blood*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology*; D008297:Male; D037601:Mannose-Binding Lectin / Q000276:immunology / Q000378:metabolism; D013682:Teichoic Acids / Q000276:immunology*
D000936:Antigen-Antibody Complex; D003182:Complement C5; D007074:Immunoglobulin G; D016209:Interleukin-8; D008070:Lipopolysaccharides; D037601:Mannose-Binding Lectin; D013682:Teichoic Acids; C009900:lipoteichoic acid