Janka Caroline, Selmi Carlo, Gershwin M Eric, Will Hans, Sternsdorf Thomas
Heinrich-Pette-Institut für experimentelle Virologie und Immunologie and the Universität Hamburg, Hamburg, Germany.
Hepatology. 2005 Mar;41(3):609-16. doi: 10.1002/hep.20619.
Serum autoantibodies against components of nuclear dots (anti-NDs), namely PML and Sp100, are specifically detected in 20% to 30% of patients with primary biliary cirrhosis (PBC). Although anti-ND antibodies are nonpathogenic, the mechanisms that lead to this unique reactivity are critical to understanding the loss of immune tolerance in PBC. Importantly, Sp100 and PML are both covalently linked to small ubiquitin-related modifiers (SUMOs). Therefore, we investigated whether SUMO proteins are independent autoantigens in PBC and studied 99 PBC sera samples for reactivity against NDs, PML, and Sp100, as well as against SUMO-2 and SUMO-1 recombinant proteins. Autoantibodies against SUMO-2 and SUMO-1 were found in 42% and 15% of anti-ND-positive PBC sera, respectively. Anti-SUMO reactivity was not observed in anti-ND-negative sera. Anti-SUMO-2 autoantibodies were found in 58% of sera containing autoantibodies against both PML and Sp100 and were detected exclusively in sera containing anti-Sp100 autoantibodies. In conclusion, SUMO proteins constitute a novel and independent class of autoantigens in PBC. Furthermore, we believe our data emphasize the post-translational modification of lysine by either lipoylation in the case of AMA or SUMOylation in the case of specific anti-ND autoantibodies as the pivotal site for autoantibody generation in PBC.
在20%至30%的原发性胆汁性肝硬化（PBC）患者中可特异性检测到针对核点成分（抗核点，即抗PML和抗Sp100）的血清自身抗体。尽管抗核点抗体无致病性，但导致这种独特反应性的机制对于理解PBC中免疫耐受的丧失至关重要。重要的是，Sp100和PML均与小泛素相关修饰物（SUMO）共价连接。因此，我们研究了SUMO蛋白是否为PBC中的独立自身抗原，并对99份PBC血清样本进行检测，以观察其对核点、PML、Sp100以及SUMO-2和SUMO-1重组蛋白的反应性。分别在42%的抗核点阳性PBC血清和15%的此类血清中发现了针对SUMO-2和SUMO-1的自身抗体。在抗核点阴性血清中未观察到抗SUMO反应性。在58%同时含有抗PML和抗Sp100自身抗体的血清中发现了抗SUMO-2自身抗体，且仅在含有抗Sp100自身抗体的血清中检测到。总之，SUMO蛋白构成了PBC中一类新的独立自身抗原。此外，我们认为我们的数据强调了在PBC中，赖氨酸的翻译后修饰，如抗线粒体抗体（AMA）情况下的硫辛酸化或特定抗核点自身抗体情况下的SUMO化，是自身抗体产生的关键位点。
