Abstract
Given the lack of a serological test specific for Behçet's disease, its diagnosis rests upon clinical criteria. The clinical diagnosis is nevertheless difficult because the disease manifestations vary widely, especially at the onset of disease. The aim of this study was to identify molecules specifically recognized by serum autoantibodies in patients with Behçet's disease and to evaluate their diagnostic value. We screened a cDNA library from human microvascular endothelial cells with serum IgG from two patients with Behçet's disease and isolated a reactive clone specific to the carboxy-terminal subunit of Sip1 (Sip1 C-ter). Using ELISA, we measured IgG, IgM and IgA specific to Sip1 C-ter in patients with various autoimmune diseases characterized by the presence of serum anti-endothelial cell antibodies, such as Behçet's disease, systemic lupus erythematosus, systemic sclerosis and various forms of primary vasculitis, as well as in patients with diseases that share clinical features with Behçet's disease, such as inflammatory bowel disease and uveitis. IgM immunoreactivity to Sip1 C-ter was significantly higher in patients with Behçet's disease and in patients with primary vasculitis than in the other groups of patients and healthy subjects tested (P < 10-4 by Mann-Whitney test). ELISA detected IgG specific to Sip1 C-ter in sera from 11/56 (20%) patients with Behçet's disease, IgM in 23/56 (41%) and IgA in 9/54 (17%). No sera from patients with systemic lupus erythematosus, systemic sclerosis, inflammatory bowel disease, uveitis or healthy subjects but 45% of sera from patients with primary vasculitis contained IgM specific to Sip1 C-ter. Serum levels of soluble E-selectin, a marker of endothelial activation and inflammation, correlated with levels of serum IgM anti Sip-1 C-ter in patients with Behçet's disease (r = 0.36, P = 0.023). In conclusion, Sip1 C-ter is a novel autoantigen in Behçet's disease. IgM specific to Sip1 C-ter might be useful in clinical practice as an immunological marker of endothelial dysfunction in vasculitis.
Highlights
Behçet's disease (BD) is a systemic form of primary vasculitis characterized by recurrent oral and genital ulcers and ocular inflammation and with frequent involvement of the joints, central nervous system and gastrointestinal tract
We enrolled 32 consecutive patients with systemic lupus erythematosus (SLE) diagnosed in accordance with the American College of Rheumatology revised criteria for the classification of SLE [14], 24 consecutive patients with systemic sclerosis (SSc) diagnosed in accordance with the criteria of the American Rheumatism Association [15], 20 patients with primary vasculitis (9 patients with Wegener's granulomatosis, 4 with Churg-Strauss syndrome, 2 with Takayasu's Arteritis, 2 with Horton disease, 2 with microscopic poly-angiitis, 1 with panarteritis nodosa), 33 patients with inflammatory bowel disease (IBD), 17 patients with uveitis (12 with idiopathic diffused uveitis, 5 with idiopathic anterior uveitis) and 40 healthy subjects, matched for sex and age
Serum IgM immunoreactivity to Sip1 Cter was significantly higher in patients with BD and in patients with other primary vasculitis than in those with SLE, SSc, IBD, uveitis and healthy subjects (P < 10-4 by Mann-Whitney) (Figure 2a)
Summary
Behçet's disease (BD) is a systemic form of primary vasculitis characterized by recurrent oral and genital ulcers and ocular inflammation and with frequent involvement of the joints, central nervous system and gastrointestinal tract. The most favoured pathogenetic mechanism is a genetic susceptibility associated with HLA-B gene polymorphisms. Other evidence indicates a pathogenic role for environmental factors, including infectious agents or autoimmune mechanisms [1]. Because the low specificity and immunoreactivity of these autoantibodies prevents their use in diagnosis, no serological test specific for BD is yet available. The diagnosis is, based on clinical criteria. The clinical diagnosis of BD is difficult because the signs and symptoms vary widely, especially at the onset of disease
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