Behçet's disease: from innate to adaptive immunity

Both innate and adaptive immune systems are activated in Behçet's disease (BD) with a proinflammatory and Th1 type cytokine profile. BD might be linked to a specific, primary immune abnormality with a genetic mutation effecting an adhesion molecule, a proinflammatory cytokine/chemokine or a transcription or regulatory factor, which predisposes to early or more intense neutrophil and T cell responses. Increased neutrophil responses to urate crystals and fMLP or superantigen-drived interferon-γ response of T cells suggest a model with these characteristics, which also explains the 'pathergy' or 'skin urate' tests. MEFV gene mutations, suggested to be specific for familial mediterranean fever, which decrease the expression of an anti-inflammatory protein 'pyrine' from neutrophils, are also described in BD from Turkey.

However, adaptive immune system is also crucial in BD with possibly both external (streptococcal, HSV) and internal antigens driving the pathogenic tissue T cell infiltrations. Heat shock proteins 60 and 70 can also activate innate immune system directly with Toll-like receptors 2 and 4 and provide both an early innate activation and prolonged T cell response. The diverse manifestations of BD responding to different therapeutical agents also suggest the role of organ-specific antigens (retinal-S antigen in uveitis) or genetic predispositions (factor V Leiden in thrombosis) in different BD clinical subsets.

Better characterization of pathogenic immune cell subsets, systemic and local antigens, and abnormal cell activation mechanisms may help to develop more specific and less toxic immunotherapeutic approaches to still unsatisfactorily treated BD in the future.