Differential expression of beta 2 integrins in Korean Behcet’s disease patients

Abstract

Background and objectives: Beta 2 integrins (CD11/CD18) are cell adhesion molecules that play a major role in cell migration to inflammatory sites. They also induce cellular signaling, subsequently leading to cytokine production. On our preliminary strudy, we demonstrated possible alteration in susceptibility to Behcet’s disease (BD) according to single nucleotide polymorphisms of CD11a, CD11c and CD18.Thus, our aim was to investigate the possible relationship between beta 2 integrins expression and BD.

Materials and methods: BD patients (n=51) consisting of 22 active patients and 29 inactive patients, 20 recurrent aphthous ulcer (RAU) patients and 23 healthy controls (HC) were included. The expression of CD11a, CD11b, CD11c, as well as CD4, CD8, CD18 and CD56 in peripheral blood mononuclear cells was assessed by flow cytometry. The transcriptional level expression of CD11a and CD11c was assessed by reverse transcription polymerase charin reaction.Western blot analysis was performed to evaluate CD11a and CD11c protein. Immunohistochemical analysis of CD11a and CD11c was done on erythema nodosum like lesions of 13 BD patients and 14 idiopathic erythema nodosum lesions.

Results: On flow cytometry, the surface expression of CD3 was significantly increased whereas CD4 expression was significantly decreased in BD patients. Expression of CD11a was significanty increased, in contrast to decreased expression of CD11b. RAU patients showed significant decrease in mRNA level of CD11a whereas BD patients did not, compared to the HC. CD11c expression was significantly higher in active BD group compared to the inactive group. CD11c mRNA expression was decreased in BD patients but showed increased CD11c expression by Western blotting compared to the healthy controls. Immunohistochemisty did not show any significant difference between BD patients and classical erythema nosodum.

Discussion: In contrast to previous reports, our study showed decreased CD11a surface expression on peripheral blood. The decrease is likely to have caused from active transmigration of CD11a+ cells in to the tissues, as relative mRNA level and western blot results suggest. CD11c did not show significant difference of surface expression among other groups except the active and the inactive group. Based on the relative low mRNA expression and higher expression in western blot, we suggest that the CD11c might have an immunomodulatory role.

Conclusion: Thus, our study implies that the differential expression of beta 2 integrins in BD patients, especially CD11a and CD11c is likely to be involved in the pathogenesis of BD.Further studies on the functional effect of CD11/CD18 in immunologic abnormalities are needed to elucidate the exact role of CD11/CD18 in BD