The Role Of The B7/CD28 Costimulatory Molecules Family In The Pathogenesis Of Kawasaki Disease

The role of the B7/CD28 costimulatory molecules family in the pathogenesis of Kawasaki disease.ObjectiveA great deal of clinical evidence and epidemiologic data suggest that Kawasaki disease (KD) is correlated with an acute regulating imbalance of immunology. Many of evidences in the past suggested that Toll-like receptors and preinflammation factors were up regulated significantly in patients with Kawasaki disease. But the causative factors are still unknown. The B7/CD28 molecules family members can augment or antagonize T-cell receptor signaling, in the regulation of central and peripheral T-cell tolerance. The study was designed to investigate the role of signal transduction of B7/CD28 family members on immunological pathogenesis of Kawasaki disease.Methods48 patients with Kawasaki disease were enrolled in Kawasaki disease group, including 16 cases with coronary artery lesion (CAL) and 32 cases without coronary artery lesion (non-CAL). 30 patients treatment with IVIG were enrolled in IVIG-treatment group, including 23 cases IVIG sensitivity and 7 cases IVIG non-sensitivity .25 age-matched health children normal subjects were considered as controls. Real-time PCR were used to evaluate the levels of Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), B and T lymphocyte attenuator (BTLA) and inducible co-stimulatory molecule (ICOS) mRNA expressions in peripheral blood mononuclear cells, and expressions of co-stimulatory molecules such as CD80 and CD86 in monocyte/macrophage were analyzed by flow cytometry.Results(1) Compared with control group, the mRNA levels of ICOS in Kawasaki diseasegroup were up-regulated significantly (P＜0.01), but the mRNA levels of BTLA and CTLA-4 in Kawasaki disease group were down-regulated (P＜0.01 and P＜0.05). Expressions of co-stimulatory molecules: CD80 and CD86 in monocyte / macrophage during acute phase of Kawasaki disease were higher than those of control group (P＜0.01). (2) Compared with non-CAL in Kawasaki disease group, the mRNA levels of ICOS in CAL group were up-regulated significantly (P＜0.01). (3) Compared with Kawasaki disease group, the mRNA levels of BTLA and CTLA-4 in IVIG- treatment group were up-regulated significantly (P＜0.05) and the mRNA levels of ICOS in IVIG- treatment group were down-regulated (P＜0.05). (4) Compared with IVIG sensitivity group in IVIG- treatment group, the mRNA levels of ICOS in non-sensitivity group were up-regulated significantly, but the mRNA levels of BTLA and CTLA-4 in non-sensitivity group were down-regulated.Conclusions(1) Expressions of CTLA-4 and BTLA were down-regulated and expression of ICOS, CDS0 and CD86 were up-regulated during acute phase in Kawasaki disease, which suggesting that B7/CD28 family numbers might be one of the significant factors of immune aberrance in Kawasaki disease with coronary artery suffered. (2) As a key treatment method, IVIG might be related to regulated expression of B7/CD28 family numbers in Kawasaki disease.