Data from: Correlation of IgG autoantibodies against acetylcholine receptors and desmogleins in patients with pemphigus treated with steroid sparing agents or rituximab

Introduction: Autoantibodies (autoAbs) against desmoglein-1 (DSG1) and desmoglein-3 (DSG3) have conventionally been studied and well accepted in the pathogenesis of pemphigus vulgaris (PV) and foliaceus (PF). Recent studies have suggested that non-DSG autoAbs may contribute to the pathogenesis of pemphigus, including autoAbs directed at acetylcholine receptors (AChR) and thyroid peroxidase (TPO). The purpose of this study is to retrospectively analyze PV and PF patient sera to better understand the relationship between anti-AChR and -TPO Abs to disease activity and DSG reactivity between patients treated with prednisone and steroid sparing agents (SSA; n=22) or prednisone and rituximab (n=21).

Methods: Patients were evaluated at 2 time points, T1 and T2, for disease activity using the Pemphigus Disease Area Index (PDAI), and sera were tested for the presence of TPO, DSG1, DSG3, muscarinic (M3) and nicotinic (n) AChR IgG autoAbs, as well as antibodies against Varicella Zoster Virus (VZV) by ELISA.

Results: Disease activity significantly decreased in patients from T1 to T2 (p < .0001). A significant difference was seen in IgG anti-DSG1 (p < .0001) and anti-DSG3 (p=.0049) levels when T1 was compared to T2 in both treatment groups. A significant increase was found between pemphigus patients and normal subjects with nAChR (p < .0001) at T1 but not with m3AChR, TPO or VZV Abs. No significant difference was seen between T1 and T2 values in patients with pemphigus for the non–desmoglein Abs TPO (p = .7559), M3AChR (p = .9003), nAChR (p = .5143) or VZV (p = .2454). These findings demonstrate that although an increase in IgG anti-nAChR autoAbs was found in PV and PF subjects, these Abs did not decrease with treatment. No other non-DSG Abs were increased or significantly changed over time in patients with pemphigus. This suggests that anti -AChR and -TPO Abs may not play a direct role in the pathogenesis of most patients with pemphigus, but does not rule out a role for non-DSG auto antibodies in distinct subsets of pemphigus patient.

引言：针对桥粒芯糖蛋白1（desmoglein-1，DSG1）和桥粒芯糖蛋白3（desmoglein-3，DSG3）的自身抗体（autoantibodies，autoAbs）在寻常型天疱疮（pemphigus vulgaris，PV）和落叶型天疱疮（pemphigus foliaceus，PF）发病机制中的作用已通过传统研究得到充分证实。近期研究提示，非DSG自身抗体可能参与天疱疮的发病，包括针对乙酰胆碱受体（acetylcholine receptors，AChR）和甲状腺过氧化物酶（thyroid peroxidase，TPO）的自身抗体。本研究旨在回顾性分析PV和PF患者血清，以更好地理解接受泼尼松联合类固醇节省剂（steroid sparing agents，SSA；n=22）或泼尼松联合利妥昔单抗（rituximab；n=21）治疗的患者中，抗AChR与抗TPO抗体、疾病活动度及DSG反应性之间的关系。

方法：在两个时间点（T1和T2）使用天疱疮疾病面积指数（Pemphigus Disease Area Index，PDAI）评估患者疾病活动度，并通过酶联免疫吸附试验（ELISA）检测血清中TPO、DSG1、DSG3、毒蕈碱型（M3）和烟碱型（n）AChR IgG自身抗体，以及水痘带状疱疹病毒（Varicella Zoster Virus，VZV）抗体的存在。

结果：从T1到T2，患者疾病活动度显著降低（p < 0.0001）。在两个治疗组中，T1与T2相比，IgG抗DSG1（p < 0.0001）和抗DSG3（p=0.0049）水平存在显著差异。T1时，天疱疮患者与正常受试者之间的烟碱型AChR（nAChR）抗体水平显著升高（p < 0.0001），但毒蕈碱型M3AChR、TPO或VZV抗体无此差异。对于非桥粒芯糖蛋白抗体（TPO、M3AChR、nAChR或VZV），天疱疮患者T1与T2之间的数值无显著差异（TPO：p=0.7559；M3AChR：p=0.9003；nAChR：p=0.5143；VZV：p=0.2454）。这些发现表明，尽管PV和PF受试者中存在IgG抗nAChR自身抗体升高，但此类抗体并未随治疗降低。其他非DSG抗体在天疱疮患者中未随时间升高或发生显著变化。这提示抗AChR和抗TPO抗体可能在大多数天疱疮患者的发病机制中不直接发挥作用，但不排除非DSG自身抗体在特定天疱疮患者亚群中的作用。