Behçet's disease (Adamantiades-Behçet's disease)

Abstract

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.

Figure 1

Streptococcal colonies appeared from saliva of an ABD patient in MS agar dish. According to the instruction of the MS agar (Difco Lab.), mainly 3 kinds of bacterial colonies are differentiated as blue crystal (probably S. mitis, etc.), gum-drop (S. salivarius, etc.), and dip (micrococcus species, etc.) shapes at 3–5 day culture.

Figure 2

(a) 33-year-old female ABD patient showed erythema reaction exhibiting more than 10 mm in diameter by self-saliva (salivary prick: S-prick) 48 hours after prick. A tinny spot by sterilized self-saliva (sterilized salivary prick: SS-prick) and control saline (control saline prick: CS-prick) were observed. (b) Histology of the skin reaction by S-prick from 27-year-old male ABD patient. Edema in the upper dermis and many mononuculear cell infiltration around the dilated vessels in the middle dermis were found (HE, 100x). The magnified view of the vascular change with infiltrate (200x). (c) Immunochemical histology of the skin reaction by S-prick. (avidin-biotin complex peroxydase method: ABC method, 200x). Infiltration of CD3+/CD4+ cells is mainly found around vessels and the proportion of infiltrate was CD3+/4+ > CD68+ > CD8+ cells. No CD20+ and CD56+ cells were found.

Figure 3

IL-8 production from MONO cells activated by S. sanguinis antigen was suppressed by LO1 and UK in a dose-dependent manner.

Figure 4

(a) and (b) Hypothesis of oral immune reaction developing the systemic manifestation in ABD. The local vascular reaction may be caused by the antigen presenting cells immunized by S. sanguinis in the oral cavity [32].