Department of Orthopedics, Kansai Medical University, Osaka, Japan.
Eur J Endocrinol. 2013 Jul 6;169(2):203-9. doi: 10.1530/EJE-13-0170. Print 2013 Aug.
Macroprolactin primarily comprises a complex of prolactin (PRL) and IgG molecules, particularly anti-PRL autoantibodies. However, it is unknown why autoantibodies against PRL develop in certain subjects. This study aimed to elucidate post-translational modifications in the PRL molecule that may be involved in the pathogenesis of macroprolactinaemia.
Macroprolactinaemia was screened with a polyethylene glycol method in 238 patients with rheumatoid arthritis (RA) and 302 control subjects and confirmed by gel chromatography. We examined the relationship between macroprolactinaemia and several RA-related laboratory tests including matrix metalloproteinase-3 (MMP-3) and anti-cyclic citrullinated peptide (CCP) antibody titres. The effect of MMP-3 on the PRL molecule was examined by western blotting.
Patients with RA exhibited a significantly higher prevalence of macroprolactinaemia (15/238; 6.3%) than the young control subjects (5/219 subjects; 2.3%), but the prevalence was not different from that observed in the elderly control subjects (5/83 subjects; 6.0%). The prevalence of macroprolactinaemia in patients with elevated MMP-3 levels (9.68%) was significantly higher than that in those with normal MMP-3 levels (2.63%). Digestion of PRL with MMP-3 produced vasoinhibins with several molecular species. Serum total and free PRL levels in RA patients were higher than those in the age- and gender-matched control subjects. The levels of macroprolactin were not significantly correlated with those of RA-specific anti-CCP antibody.
We speculate that elevated MMP-3 levels may lead to the formation of new epitopes on the PRL molecule that might trigger an immune response to produce anti-PRL autoantibodies in some patients with RA. Such post-translational modifications may possibly contribute to the increased prevalence of macroprolactinaemia in elderly subjects.
巨泌乳素主要由催乳素 (PRL) 和 IgG 分子组成，特别是抗 PRL 自身抗体。然而，目前尚不清楚为什么某些患者会产生针对 PRL 的自身抗体。本研究旨在阐明可能参与巨泌乳素血症发病机制的 PRL 分子的翻译后修饰。
采用聚乙二醇法对 238 例类风湿关节炎 (RA) 患者和 302 例对照者进行巨泌乳素血症筛查，并通过凝胶层析法进行确认。我们研究了巨泌乳素血症与包括基质金属蛋白酶-3 (MMP-3) 和抗环瓜氨酸肽 (CCP) 抗体滴度在内的几种 RA 相关实验室检测指标之间的关系。通过 Western blot 检测 MMP-3 对 PRL 分子的影响。
RA 患者巨泌乳素血症的患病率（15/238；6.3%）明显高于年轻对照组（5/219 例；2.3%），但与老年对照组（5/83 例；6.0%）无差异。MMP-3 水平升高（9.68%）患者的巨泌乳素血症患病率明显高于 MMP-3 水平正常（2.63%）患者。MMP-3 消化 PRL 可产生具有多种分子形式的血管抑制素。RA 患者的血清总 PRL 和游离 PRL 水平均高于年龄和性别匹配的对照组。巨泌乳素水平与 RA 特异性抗 CCP 抗体无显著相关性。
我们推测，MMP-3 水平升高可能导致 PRL 分子上新表位的形成，这可能在某些 RA 患者中引发针对 PRL 的自身免疫反应，产生抗 PRL 自身抗体。这种翻译后修饰可能有助于增加老年患者巨泌乳素血症的患病率。
