van Venrooij Walther J, Pruijn Ger J M
Radboud Universiteit, afd. Biomoleculaire Chemie, Institute for Molecules and Materials (IMM) en het Nijmegen Centre for Molecular Life Sciences (NCMLS), Nijmegen, The Netherlands.
Ned Tijdschr Geneeskd. 2009;153:B232.
Rheumatoid arthritis (RA) is characterized by chronic inflammation of the joints and the presence of anti-citrullinated protein autoantibodies (ACPA). ACPA are very specific for RA and are involved in its pathophysiology. Five steps, all of which are supported by experimental evidence, can be distinguished during the development of the chronic inflammation in RA. Step 1: During inflammation a large influx of inflammatory cells takes place. These cells will ultimately die via apoptosis. When the dying cells are not cleared efficiently, citrullinated proteins and citrullinating enzymes are released into the extracellular space. Step 2: Extracellular proteins are citrullinated by these enzymes. Step 3: Only individuals with a certain genetic background produce ACPA. Step 4: Arthritis is induced by the formation of immune complexes of ACPA and citrullinated proteins. Step 5: These immune complexes stimulate the inflammation, which leads to the recruitment of new inflammatory cells. This establishes a vicious cycle, the RA cycle.
类风湿关节炎（RA）的特征是关节的慢性炎症以及抗瓜氨酸化蛋白自身抗体（ACPA）的存在。ACPA对RA具有高度特异性，并参与其病理生理过程。在RA慢性炎症的发展过程中，可以区分出五个步骤，所有这些步骤都有实验证据支持。步骤1：在炎症过程中，大量炎性细胞涌入。这些细胞最终会通过凋亡死亡。当死亡细胞没有被有效清除时，瓜氨酸化蛋白和瓜氨酸化酶会释放到细胞外空间。步骤2：细胞外蛋白质被这些酶瓜氨酸化。步骤3：只有具有特定遗传背景的个体才会产生ACPA。步骤4：ACPA与瓜氨酸化蛋白形成免疫复合物，从而诱发关节炎。步骤5：这些免疫复合物刺激炎症，导致新的炎性细胞募集。这就建立了一个恶性循环，即RA循环。
