Reduced complement receptor 1 (CR1, CD35) transcription in systemic lupus erythematosus

被引:32
作者
Arora, V
Verma, J
Dutta, R
Marwah, V
Kumar, A
Das, N [1 ]
机构
[1] All India Inst Med Sci, Dept Biochem, New Delhi 110029, India
[2] All India Inst Med Sci, Dept Med, New Delhi 110029, India
关键词
complement receptor 1; systemic lupus erythematosus; rythematosus; RT-PCR; western blot; sCR1;
D O I
10.1016/j.molimm.2004.03.004
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease characterized by the production of a broad spectrum of autoantibodies against nuclear, cytoplasmic and cell surface antigens and immune complex overload. Complement receptor I (CRI, CD 35), a transmembrane glycoprotein found on the surface of erythrocytes, leukocytes and glomerular podocytes plays a key role in the clearance of immune complexes and regulation of complement cascade. A drastic decline in the level of cell surface CRI appears to be an important event in pathology of SLE. However, the etiology of lower than normal expression of cell surface CRI in this disease is poorly understood. We studied the level of leukocyte CRI transcription in 30 patients with active SLE and 30 controls by reverse transcriptase-polymerase chain reaction (RT-PCR) and related the same with the level of CRI protein expression monitored by Western blotting. For RT-PCR, ratio of CR1/beta-actin was considered for semiquantitation of the level of CRI transcription. Despite individual variation at the level of transcription, 70% (21 out of 30) of the patients expressed CRI transcript at the lowest range of 0-15% as compared to the controls wherein only 30% (9 out of 30 individuals) demonstrated CRI transcript in this range. Majority of the controls (70%) expressed CR1 transcript at the level above 15%. Mean level of CRI transcript in patients (mean +/-S.D. = 21.09 +/- 14.3) was significantly lower than the controls (mean+/-S.D. = 48.91 +/- 26.34) (P < 0.001). The level of CRI transcription correlated inversely with circulating immune complexes (CIC) (r = 0.52, P < 0.01). This may suggest that although erythrocyte CRI is the chief vehicle for CIC clearance, drastic decline in leukocyte CRI expression may impair the phagocyte mediated immune complex clearance and contribute to increased complement consumption in SLE. Total leukocyte CR1 protein expression was also significantly reduced in patients (P < 0.001) as compared to controls. This decline at the protein level gave a very significant positive correlation with CRI transcript (r = 0.67, P < 0.01). A marginal increase in soluble CR1 (sCR1) was observed in the plasma (ELISA) of SLE patients compared to the controls but was insignificant. This paper for the first time brings evidence to suggest that reduced synthesis of CRI contributes substantially to the low cell surface CRI expression in SLE. Our findings also suggest increased proteolytic cleavage of leukocyte cell surface CRI in these patients. However, evidence for the latter is indirect. (C) 2004 Elsevier Ltd. All fights reserved.
引用
收藏
页码:449 / 456
页数:8
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