Up-regulation of transcription factor Blimp1 in systemic lupus erythematosus

Abstract

PurposeB lymphocyte induced maturation protein 1 (Blimp1) is a transcription factor that is critical for differentiation and antibody production in plasma cells. In order to understand the mechanism of systemic lupus erythematosus (SLE), the role of Blimp1 expression was studied in patients with SLE and in healthy control subjects. And Blimp1 tissue distribution in MRL/lpr lupus mice was also investigated. MethodsThe mRNA expression level of Blimp1 was analyzed by fluorescent real time PCR and compared between the 40 SLE patients and 30 control subjects. Expression of CD138, CD27 and CD19 in peripheral blood cells was analyzed by flow cytometry. Blimp1 mRNA and protein expression levels and tissue distribution in the kidneys, spleen and lymph nodes of MRL/lpr lupus and normal mice were analyzed. ResultsBlimp1 mRNA expression level was 2.1 times greater in the SLE group as compared to the control group. The increased mRNA expression of Blimp1 seemed to be related to SLE disease activity and anti-nuclear antibody (ANA) titer. In SLE patients, the CD138+ plasma cells increased as the CD27+ cells decreased. Compared with normal mice, Blimp1 was strongly expressed in the kidneys, lymph nodes and spleen of MRL/lpr lupus mice. The expression level of Blimp1 mRNA in the kidneys, lymph nodes and spleen of MRL/lpr lupus mice was much higher than normal mice (1.76, 2.02, and 2.05 times greater, respectively, P<0.05). Similarly, protein levels in the above mentioned organs were also much higher (1.54, 1.99, and 2.21 times greater, respectively, P<0.05). ConclusionsThe elevated expression of Blimp1 in SLE patients and in the lupus mouse model is correlated with increases in plasma cells, autoantibodies and disease activity. It is closely related to differentiation of B-lymphocytes, antibody production and renal lesions. Blimp1 may play a role in SLE disease development.