Petit Marie, Walet-Balieu Marie-Laure, Schapman Damien, Golinski Marie-Laure, Burel Carole, Barray Marion, Drouot Laurent, Maho-Vaillant Maud, Hébert Vivien, Boyer Olivier, Bardor Muriel, Joly Pascal, Calbo Sébastien
INSERM U1234, Normandie University, 76000 Rouen, France.
EA4358, Laboratoire Glycobiologie et Matrice Extracellulaire Végétale (Glyco-MEV), Normandie University, 76821 Rouen, France.
Biomedicines. 2021 Oct 8;9(10):1411. doi: 10.3390/biomedicines9101411.
Pemphigus vulgaris is an autoimmune disease that occurs due to pathogenic autoantibodies that recognize the following epidermal adhesion proteins: desmogleins. Systemic corticosteroids usually decrease the titers of anti-desmoglein autoantibodies and improve patients' conditions. Since modifications of IgG -glycosylation have been described in some autoimmune diseases, we hypothesized that changes in the pathogenic activity of pemphigus IgG could be related to changes in their -glycosylation profile. The purpose of this study was to assess, longitudinally, the pathogenicity of pemphigus serum IgG and their -glycosylation profile during phases of disease activity and clinical remission. The pathogenic activity of serum IgG was measured in vitro on immortalized keratinocytes, by immunofluorescence and dissociation assays, and IgG -glycans were analyzed by mass spectrometry. We showed (i) a correlation between pemphigus clinical activity and the pathogenicity of serum IgG at baseline and at month 6, while the persistence of the in vitro pathogenic activity of IgG during its evolution, even in patients in clinical remission, seemed to be predictive of relapse; (ii) that modifications of the -glycan structure were altered the in vitro pathogenicity of patients' autoantibodies; (iii) that the pathogenic properties of pemphigus IgG did not appear to be related to the disparity in IgG -glycans during the course of pemphigus.
寻常型天疱疮是一种自身免疫性疾病，由识别以下表皮黏附蛋白的致病性自身抗体引起：桥粒芯糖蛋白。全身用糖皮质激素通常会降低抗桥粒芯糖蛋白自身抗体的滴度并改善患者病情。由于在一些自身免疫性疾病中已描述了IgG糖基化的改变，我们推测天疱疮IgG致病活性的变化可能与其糖基化谱的改变有关。本研究的目的是纵向评估疾病活动期和临床缓解期天疱疮血清IgG的致病性及其糖基化谱。通过免疫荧光和解离试验在永生化角质形成细胞上体外测量血清IgG的致病活性，并通过质谱分析IgG聚糖。我们发现：（i）天疱疮临床活动与基线和第6个月时血清IgG的致病性之间存在相关性，而即使在临床缓解的患者中，IgG在其演变过程中体外致病活性的持续存在似乎可预测复发；（ii）聚糖结构的改变会改变患者自身抗体的体外致病性；（iii）天疱疮IgG的致病特性似乎与天疱疮病程中IgG聚糖的差异无关。
