Adamantiades-Behçet's disease (ABD) is characterized by starting with oral aphthous ulceration and developing of the systemic involvements. The pathogenesis of ABD is closely correlated with the genetic factors and the triggering factors which acquire delayed-type hypersensitivity reaction against oral streptococci mediated by IL-12 cytokine family. HLA-B51 is associated in more than 60% of the patients and its restricted CD8+ T cell response is clearly correlated with the target tissues. Bes-1 gene encoded partial S. sanguinis genome which is highly homologous with retinal protein, and 65 kD heat shock protein (Hsp-65) released from streptococci is playing an important role with human Hsp-60 in the pathogenesis of ABD. Although Hsp-65/60 has homologies with the respective T cell epitope, it stimulates peripheral blood mononuclear cells (PBMCs) from ABD patients. On the other hand, some peptides of Hsp-65 were found to reduce IL-8 and IL-12 production from PBMCs of ABD patients in active stage.
Behcet's disease (BD) is a mysterious multisystemic disorder characterized by recurrent involvement of mucocutaneous (including recurrent aphthous stomatitis; RAS), ocular, intestinal, vascular, and/or nervous system organs. Previously, the positivity of “pathergy test”, which is one of the diagnostic examinations, was reported to be related to the possession of HLA-B51 gene in BD patients, even though the positivity is low and different from the countries. Here, instead of the ordinal pathergy test, we would like to propose the prick with self-saliva as a new diagnostic way for patients with RAS of BD based on the genetic intrinsic factors including HLA-B51 and extrinsic triggering factors. BD patients are considered to acquire the hypersensitivity against oral streptococci through the innate immune mechanism in the oral cavity. Bes-1 gene and 65 kD of heat shock protein (HSP-65) derived from oral S. sanguinis are supposed to play important roles as extrinsic factors in BD pathogenesis. Although the prick positivity was not related to the possession of HLA-B51 gene, the method is suggested to be a significant way for BD diagnosis. The results also suggest that BD symptoms are due to the vascular immune responses by monocytes expressed oral streptococcal agents of the patients.
There may be some difficulties to differentiate Behcet’s disease (BD), recurrent aphthosis (RA), and herpetic aphthous ulceration, from other mimicking oral disorders. Despite of unexpected sensitivity and responsiveness, the skin pathergy test regarding a non-specific hypersensitivity has long been thought as one of auxiliary diagnostic benefits for BD.To determine the potential usefulness and disease specificity of the prick reaction with saliva, a skin prick test with neat and filter-sterilized saliva was performed on the forearm skin of 26 individuals; 10 patients with BD (8 incomplete type without uveitis, 1 complete type, and 1 neurological type), 5 with RA, 3 with herpetic oral aphthosis, 2 with erythema nodosum alone, and 6 healthy controls. We assessed the skin reaction at 48 hours after pricking, and the pricked skin lesions were biopsied and analyzed immunohistologically.Nine of 10 BD patients (90 %) exhibited an indurative erythema at the skin site pricked with self-saliva, whereas 3 of 5 RA patients (60%) were relatively weak reaction. Pricking with filter-sterilized saliva failed to recapitulate any of positive skin reactions, albeit a faint erythematous dot appeared in a few BD patients, implicating the involvement of causative microorganism(s) in oral bacterial flora. Culture of saliva from 3 randomly chosen BD patients revealed numerous streptococcal colonies on Mitis-Salivarius agar. Histology of the pricked skin sites showed perivasucular inflammatory infiltrates, composed of CD4+ T cells and CD68+ monocyte/macrophage lineage, a feature consistent with a delayed type hypersensitive reaction.Our results suggested that skin prick test using self-saliva (a new diagnostic pathergy) can be a simple and valuable in vivo diagnostic approach for differentiating BD and RA from other mimicking mucocutaneous diseases. The positive skin prick may be triggered by resident intra-oral microflora, particularly streptococci, and may in part address the underlying immunopathology in BD.
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