Behcet's disease.

Behcet's disease (BD) is a systemic disorder of recurrent acute inflammation, characterized by major symptoms of oral aphthous ulcers, uveitis, skin lesions and genital ulcers. Involvement of intestines, vessels, and central nervous system (CNS) sometimes leads to a poor prognosis. Patients with BD are known to distribute along the ancient Silk Road. The incidence is relatively higher from eastern Asia to the Mediterranean area as roughly 1-10 patients in 10,000 people, whereas only 1-2 patients in 1,000,000 people in UK and North America. Although etiology of the disease is still unknown, high prevalence of HLA-B51, increased expression of heat shock protein 60 and Th1 dominant immune responses in the patients are considered important in its pathogenesis. Non-infectious neutrophil activation and infection with Streptococcus sanguis and herpes simplex virus would also be associated. Because BD lacks any pathognomonic symptoms and laboratory findings, the diagnosis relies largely upon the criteria proposed by the International Study Group for Behcet's disease in 1990. In Japan, the diagnosis was also made according to the Japanese criteria revised in 1987. Recently, the Behcet's Disease Research Committee of Japan again revised the Japanese criteria in 2003 to avoid overdiagnosis. The new Japanese criteria are introduced in this review. Differential diagnosis excluding Sweet's disease, pemphigus, erythema nodosum and Crohn's disease is important, and positive laboratory data for pathergy test, prick test for dead Streptococci and HLA-B51 are emphasized to make appropriate diagnosis in these criteria. Pathological findings of the disease-affected site such as erythematous nodosum is also stressed. Treatment for the disease has been chosen according to the clinical symptoms. Non-steroidal anti-inflammatory drugs, immunosuppressants, corticosteroids and colchicine are basically introduced. Recently, effects of interferon-alpha/beta, anti-tumor necrosis factor antibody and thalidomide are encouraging, specifically in treatment for the cases with poor prognosis including eye, intestine, vessel and CNS involvement. Low dose weekly administration of methotraxate looks effective for the cases with CNS involvement. Further studies for elucidation of the etiology, improvement of the diagnostic criteria and development of new therapy are needed to conquer the disease.

Characterisation of cartilage intermediate layer protein (CILP)-induced arthropathy in mice.

OBJECTIVES: To characterise cartilage intermediate layer protein (CILP)-induced arthropathy in mice. METHODS: The first and second halves of the nucleotide triphosphate pyrophosphohydrolase (NTPPHase) non-homologous region of human CILP were prepared as recombinant proteins (C1 and C2, respectively), including three overlapping fragments of C2 (C2F1, C2F2, and C2F3). C57BL/6 mice were immunised with these proteins to induce arthritis. In addition, a separate group of mice were immunised repeatedly with the mixture of C1 and C2 to see the effect of chronic immunisation. Arthritis developed in the mice, and cellular and humoral immune responses against CILP were analysed. RESULTS: Immunisation with C2 and with the mixture C2F1/C2F2/C2F3 caused the severest arthritis to develop in mice. Immunisation with one of C1, C2F1, C2F2, or C2F3 caused milder arthritis, even though each of the fragments carried T cell epitopes. Immunisation either with C1 or C2 alone evoked cellular and humoral immune responses to both the C1 and C2 proteins. Further, the repeated immunisation with the C1/C2 mixture caused tendon calcification and bone irregularity, together with decreased NTPPH activity. CONCLUSIONS: The results show that multiple T cell epitopes are needed for the development of CILP-induced arthritis, and present the characteristic new model of mild arthropathy accompanied by extra-articular calcifications. An immune response to putative murine CILP/NTPPH may be involved in the ectopic calcifications in the arthritic mice.