Presence of retinal pericyte-reactive autoantibodies in diabetic retinopathy patients.
Presence of retinal pericyte-reactive autoantibodies in diabetic retinopathy patients.
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DOI：
10.1038/srep20341
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发表时间：
2016-02-03
影响因子：
4.6
通讯作者：
Lin F
中科院分区：
文献类型：
--
作者：
Zhang L;Li Y;Payne J;Srivastava S;Fan X;Fung J;Li X;Kern TS;Lin F
视网膜周细胞（RPC）的损失是早期糖尿病视网膜病变（DR）的标志，但RPC死亡的机制尚不清楚。尽管在先前使用牛RPC的研究中假设针对RPC的自身抗体可能发展并诱导RPC死亡，但尚不清楚DR患者中是否存在针对人RPC上细胞表面抗原的自身抗体，此类自身抗体是否有助于RPC损伤/丢失，以及如果是，通过何种机制。我们使用原代人RPC筛选了DR患者和对照组的血清样本，发现DR组对RPC反应的IgG水平显著高于对照组。具有较高RPC反应性IgG水平的血清样品比具有较低RPC反应性IgG水平的血清样品诱导更严重的补体介导的RPC损伤。我们还评估了这些血清样本中补体激活产物C3 a、C4 a和C5 a的水平，发现DR组的血清C3 a和C5 a水平高于对照组，但C4 a水平没有升高。这些数据首次提供了证据，表明针对RPC的自身抗体可以在DR患者中产生，并且这些自身抗体可以通过补体激活导致周细胞损伤。
The loss of retinal pericytes (RPCs) is a hallmark of early stage diabetic retinopathy (DR), but the mechanism underlying RPC death is unclear. Although it was postulated in previous studies using bovine RPCs that autoantibodies against RPCs might develop and induce RPC death, it is unknown whether autoantibodies against cell-surface antigens on human RPCs exist in DR patients, whether such autoantibodies contribute to RPC damage/loss, and if they do, through which mechanism. We screened serum samples from DR patients and controls using primary human RPCs and found that that levels of IgGs reactive to RPCs were significantly higher in the DR group than the control group. Serum samples with higher RPC-reactive IgG levels induced more severe complement-mediated RPC damage than those with lower RPC-reactive IgG levels. We also assessed levels of the complement-activation products C3a, C4a and C5a in these serum samples, and found that serum levels of C3a and C5a, but not C4a, were higher in the DR group than control group. These data provide evidence the first time showing that autoantibodies against RPCs can develop in DR patients, and that these autoantibodies could contribute to pericyte damage through complement activation.