Dolcino Marzia, Lunardi Claudio, Ottria Andrea, Tinazzi Elisa, Patuzzo Giuseppe, Puccetti Antonio
Institute Giannina Gaslini, Genova, Italy.
Department of Medicine, University of Verona, Verona, Italy.
PLoS One. 2014 Dec 16;9(12):e115424. doi: 10.1371/journal.pone.0115424. eCollection 2014.
Psoriatic arthritis (PsA) is a chronic inflammatory disease of unknown origin, characterized by erosions and new bone formation. Diagnosis of PsA is mainly clinical and there are no biomarkers available. Moreover in PsA autoantibodies have not been described so far. Indeed an autoimmune origin has been suggested but never proven. Aim of the study was to investigate the possible presence of autoantibodies typically associated with PsA.
We used pooled IgG immunoglobulins derived from 30 patients with PsA to screen a random peptide library in order to identify disease relevant autoantigen peptides.
Among the selected peptides, one was recognised by nearly all the patients' sera. The identified peptide (PsA peptide: TNRRGRGSPGAL) shows sequence similarities with skin autoantigens, such as fibrillin 3, a constituent of actin microfibrils, desmocollin 3, a constituent of the desmosomes and keratin 78, a component of epithelial cytoskeleton. Interestingly the PsA peptide shares homology with the nebulin-related anchoring protein (N-RAP), a protein localized in the enthesis (point of insertion of a tendon or ligament to the bone), which represents the first affected site during early PsA. Antibodies affinity purified against the PsA peptide recognize fibrillin, desmocollin, keratin and N-RAP. Moreover antibodies directed against the PsA peptide are detectable in 85% of PsA patients. Such antibodies are not present in healthy donors and are present in 13/100 patients with seroposive rheumatoid arthritis (RA). In seronegative RA these antibodies are detectable only in 3/100 patients.
Our results indicate that PsA is characterized by the presence of serum autoantibodies crossreacting with an epitope shared by skin and joint antigens.
银屑病关节炎(PsA)是一种病因不明的慢性炎症性疾病,其特征为侵蚀和新骨形成。PsA的诊断主要依靠临床症状,目前尚无生物标志物。此外,迄今为止尚未发现PsA患者存在自身抗体。确实有人提出PsA可能源于自身免疫,但从未得到证实。本研究的目的是调查PsA患者中是否可能存在典型的自身抗体。
我们使用从30例PsA患者中提取的混合IgG免疫球蛋白来筛选随机肽库,以鉴定与疾病相关的自身抗原肽。
在所选肽段中,有一种几乎被所有患者血清识别。鉴定出的肽段(PsA肽段:TNRRGRGSPGAL)与皮肤自身抗原具有序列相似性,如肌动蛋白微原纤维的组成成分原纤蛋白3、桥粒的组成成分桥粒芯胶蛋白3以及上皮细胞骨架的组成成分角蛋白78。有趣的是,PsA肽段与伴肌动蛋白相关锚定蛋白(N-RAP)具有同源性,N-RAP是一种位于肌腱附着点(肌腱或韧带与骨的插入点)的蛋白质,而肌腱附着点是PsA早期首先受累的部位。针对PsA肽段亲和纯化的抗体可识别原纤蛋白、桥粒芯胶蛋白、角蛋白和N-RAP。此外,85%的PsA患者可检测到针对PsA肽段的抗体。健康供体中不存在此类抗体,在100例血清阳性类风湿关节炎(RA)患者中有13例存在此类抗体。在血清阴性RA患者中,仅100例中有3例可检测到此类抗体。
我们的结果表明,PsA的特征是存在与皮肤和关节抗原共有的表位发生交叉反应的血清自身抗体。