Behet's disease: infectious aetiology, new autoantigens, and HLA-B51

Both innate and adaptive immune systems are activated in BD, with a proinflammatory and Th1-type of cytokine profile. BD may be linked to a specific, primary immune abnormality with a genetic mutation affecting an adhesion molecule or a proinflammatory cytokine, which predisposes to early or more intense neutrophil and T cell responses. Alternatively, a broad intracellular signalling abnormality of a transcription factor, which lowers the threshold of inflammatory responses to external stimuli, as proposed for familial Mediterranean fever with decreased pyrine expression of neutrophils, may be present (hyperreactivity model). However, an adaptive immune system is also crucial in BD, with possibly both external (streptococcal, superantigens) and internal (heat shock or organ-specific proteins) antigens driving the pathogenic tissue T cell infiltrations. Better characterisation of pathogenic immune cell subsets, systemic and local antigens, and abnormal cell-activation mechanisms may help in the future to develop more specific and less toxic immunotherapeutic approaches to the still unsatisfactorily treated BD.