Immunoglobulin G subclasses and prolactin (PRL) isoforms in macroprolactinemia due to anti-PRL autoantibodies
Immunoglobulin G subclasses and prolactin (PRL) isoforms in macroprolactinemia due to anti-PRL autoantibodies
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DOI：
10.1210/jc.2004-1600
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发表时间：
2005-05-01
影响因子：
5.8
通讯作者：
Inagaki, C
中科院分区：
文献类型：
--
作者：
Hattori, N;Ikekubo, K;Inagaki, C
虽然抗泌乳素自身抗体引起的大泌乳素血症在高泌乳素血症患者中并不少见，但这种大泌乳素血症的发病机制尚不清楚。我们通过酶免疫分析法检测了抗PRL自身抗体的IgG亚类，并通过Western blotting、质谱和二维电泳检测了6例抗PRL自身抗体患者和29例对照者的PRL磷酸化和同工型。抗prl自身抗体患者的prl特异性IgG亚类是异质性的，但6例患者中有5例显示IgG4优势，已知这是由慢性抗原刺激产生的。Western blot和质谱分析显示，人垂体PRL在丝氨酸194和丝氨酸163位点被磷酸化，而血清PRL的丝氨酸163位点被去磷酸化。双向电泳结果显示，正常高泌乳素血症患者血清PRL主要由等电点（pI）为6.58的异构体组成，抗PRL自身抗体患者血清PRL主要由等电点（pI）为6.43和6.29的酸性异构体组成。我们的数据首先证明了人垂体PRL在血清中被丝氨酸磷酸化和部分去磷酸化，并表明酸性同工型可能在抗PRL自身抗体患者中引起慢性抗原刺激。
Although macroprolactinemia due to antiprolactin (anti-PRL) autoantibodies is not uncommon among hyperprolactinemic patients, the pathogenesis of such macroprolactinemia is still unknown. We examined IgG subclasses of anti-PRL autoantibodies by enzyme immunoassay, and PRL phosphorylation and isoforms by Western blotting, mass spectrometry, and two-dimensional electrophoresis in six patients with anti-PRL autoantibodies and in 29 controls. PRL-specific IgG subclasses in patients with anti-PRL autoantibodies were heterogeneous, but five of six patients showed IgG4 predominance, which is known to be produced by chronic antigen stimulation. Western blot and mass spectrometric analyses revealed that human pituitary PRL was phosphorylated at serine 194 and serine 163, whereas serine 163 in serum PRL was dephosphorylated. On two-dimensional electrophoresis, serum PRL mainly consisted of isoform with isoelectric point (pI) 6.58 in control hyperprolactinemic patients, whereas acidic isoforms (pIs 6.43 and 6.29) were also observed in patients with anti-PRL autoantibodies. Our data first demonstrate that human pituitary PRL is serine phosphorylated and partially dephosphorylated in serum, and suggest that the acidic isoforms may give rise to chronic antigen stimulation in patients with anti-PRL autoantibodies.