Expression of OX40 and Bcl-2 in the Lesions and Peripheral Blood Lymphocytes from Patients with Lupus Erythematosus and Its Significance

Objective:The pathogenesis of lupus erythematosus(LE)is complex and still unclear.It was believed that dysregulation of apoptosis may play an important role in the pathogenesis of lupus LE.OX40(CD134)is a kind of transmembrane protein expressed in exterior of activated T cell and is a superfamily member of tumor necrosis factor receptor.OX40 has the ability of transmitting co-stimulating signal,in addition to promote the proliferation and polarization of T cell as well as the generation of cell factor.OX40 plays crucial roles in the inflammation and immunoreaction as a kind of transcription factor.It may be concerned with the pathology process of some autoimmunity disease.Bcl-2(B-cell lymphoma leukemia-2),whose gene-expression was adjusted by OX40 is an foremost apoptosis suppressive gene.Overexpression of Bcl-2 may participate in the development of autoimmunity disease by apoptosis-dysregulation of auto-reactive T/B lymphocyte and breakdown of self-tolerance.In this study,our purpose is to approach the pathogenesis and mechanism of lupus erythematosus(LE)by detecting the expression of OX40 and Bcl-2 in the lesions and peripheral blood lymphocytes from patients with LE by ABC immunohistochemical method and RT-PCR.Methods:52 paraffin imbedding tissue specimens of the lesions from patients with LE(SLE 10,SCLE 15,DLE 27)kept in our department as experimental group were collected with 10 subjects of normal person's skin speciments as control group. ABC immunohistochemistry was used to exanmine the expression of OX40 and Bcl-2 among these groups.Strictly according to SLE's selected condition,30 subjects with SLE as experimental group were collected with 10 subjects of normal persons as control group.OX40 and Bcl-2 mRNA in peripheral blood lymphocytes from the two groups were detected by means of RT-PCR.The experimental data were expressed with((?)±s)and analysed by SAS 9.13 statistic software.Results:Immunohistochemistry:OX40 and Bcl-2 were expressed in all groups. Both OX40 and Bcl-2 were strongly expressed in LE groups.OX40 mainly existed in cell membrane and cytoplasm.Bcl-2 mainly existed in cytoplasm.While OX40 and Bcl-2 were stained a little in control group,the difference expression of OX40 and Bcl-2 between LE groups and control group were significantly(P＜0.05,P＜0.05). The expression of OX40 and Bcl-2 in the lesions from patients with,SCLE and DLE showed no statistically significant difference.Correlation analysis showed that the expression of OX40 was significantly correlated with that of Bcl-2(spearman: r=0.86982,P＜0.0001).There were positive staining in keratinocytes(atratum basale,atratum apinosum and stratum granulosum),glandular epithelium cell(hair follicle,sebaceous gland and eccrine gland),vascular endothelial cell and a great deal of lymphocytes permeating all aroud.RT-PCR:OX40 and Bcl-2 mRNA were more strongly expressed in activity SLE group while feebly expressed in control group.There was significant deviation between activity SLE group and control group (p＜0.05).Conclusions:OX40 and Bcl-2 play a key role in the pathogenesis of LE. OX40/OX40L may result in the immunity pathology damage of LE by promoting inflammatory CD4~+ T cell's soakage to tissues,increasing memory T cell's generation,promting APC's maturity,as well as excreting more autoantibody and cytokine(IL-2、IL-4、IL-5)needed by immunity responsion.The expression of OX40 may promote the generation of some antiapoptosis factors named Bcl-2. Overexpression of Bcl-2 may induce the development of LE by apoptosis-dysregulation of auto-reactive T/B lymphocyte and breakdown of self-tolerance.It may also promote apoptosis restrain of inflammation cell,which induced the persistence of inflammation.Inflammation cell may excrete various cytokine,which morely induced immunity pathology damage of LE.This study validated that the abnormal expression of OX40 and Bcl-2 is well evidenced in LE patients.We can presume the reciprocity of the two factors in anti-apoptosis,and it may play an important role in the pathogenesis of LE.