Behcet’s disease (BD) is a systemic, chronic inflammatory disorder with both innate and adaptive immune responses. Heat shock proteins (HSP) are highly conserved molecules in different species with scavenger activity and involved in correct folding of newly synthesized proteins. T and B cell responses against HSPs are observed in BD patients in both and T-cell populations. 60-kD HSP (HSP60) is also shown to be recognized by pattern recognition receptors such as toll-like receptors (TLR) and is suggested to be an endogenous “danger” signal to the immune system with rapid inflammatory cytokine releases and enhancement of adaptive Th1-type responses. Elucidating the exact role of HSPs in BD pathogenesis might pave the way to less toxic therapeutic approaches to BD, such as antibacterial therapies and immunomodulation. 1. Introduction Behcet’s disease (BD) is a systemic, chronic inflammatory disorder with a diverse spectrum of clinical manifestations including mucocutaneous, ocular, vascular, gastrointestinal, musculoskeletal, and central nervous system involvement [1, 2]. A complex genetic background leading to a proinflammatory, innate-immune system derived activation perpetuated by adaptive immune responses against environmental and autoantigens is accepted as the main pathogenic mechanism in BD [3, 4]. Microbial infection has been implicated in the development of BD since its initial description in 1937 by Hulusi Behcet. Four principal hypotheses have been suggested: (i) bacterial, with Streptococci in the foreground, (ii) viral, (iii) indirectly via heat shock proteins (HSP), and (iv) crossreactive or molecular mimicry etiologies [5]. Clinical observations such as increased oral manifestations after dental manipulations, streptococcal hypersensitivity in skin tests, dominance of atypical streptococcus species in BD patients’ oral flora, and recent reports of beneficial antibacterial therapy put forward the role of Streptococcia in BD [2, 6–8]. As a wide variety of Streptococcia (sanguis, salivarius, etc.) are implicated, antigens common to various species are logical candidates of immune stimuli in BD [9]. 2. Heat Shock Proteins: Adaptive Responses Heat-shock proteins are a group of intracellular proteins which have scavenger roles for other intracellular proteins under denaturating stress conditions such as infections, hypoxia, trauma, and toxic drugs [10, 11]. Significant sequence homology exists between the mammalian and microbial HSPs (mycobacterial and streptococcal HSP65s have over 90% and human HSP60 over 50% homology) [6], shown recently also
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