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

Abstract

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.