Longitudinal Tracking of Autoantibody Levels in a Pemphigus Vulgaris Patient: Support for a Role of Anti-Desmoglein 1 Autoantibodies as Predictors of Disease Progression

February 2017 | Volume 16 | Issue 2 | Original Article | 135 | Copyright © February 2017

Nadia Y. Abidi MD, Irene Lainiotis BS, Gretchen Malikowski MD, Kristina Seiffert-Sinha MD, and Animesh A. Sinha MD PhD

University at Buffalo, Buffalo, NY

Abstract
Anti-desmoglein (Dsg) 1 and -Dsg3 antibody titers have an established role in the diagnosis of the autoimmune blistering skin disease pemphigus vulgaris (PV). However, their usefulness for disease monitoring has been controversial. A recent large-scale immunoprofiling study by our group indicated that anti-Dsg1 levels may be a better predictor of disease activity than anti-Dsg3 levels, with declining levels predicting progression from active phase of disease to early remission, irrespective of lesional subtypes. Here, we report an illustrative case of a PV patient with mucocutaneous disease that was followed longitudinally for >2.5 years clinically and by serum serology. Autoantibody levels directed against both Dsg1 and -3 showed a moderate correlation with PDAI scores, supporting a correlation of Dsg1 and 3 levels with disease severity. However, while both anti-Dsg3 and -Dsg1 antibody levels demonstrated a steady parallel decline after initiation of rituximab therapy, only anti-Dsg1 antibodies fell to levels below detectability with the progression to remission, while anti-Dsg3 levels remained elevated. This case illustrates the potential key role and clinical benefit of tracking anti-Dsg1 levels to monitor and conceivably predict disease activity in patients with PV. J Drugs Dermatol. 2017;16(2):135-139.

INTRODUCTION

Pemphigus vulgaris (PV) is characterized by the presence of autoantibodies targeting the desmosomal cadherins Dsg1 and Dsg3, leading to acantholysis and intraepidermal blistering.1 Presently, scoring systems such as the Pemphigus Disease Area Index (PDAI) are the primary methods available to monitor PV disease severity. Anti-Dsg1 and Dsg3 antibody titers have an established role in the clinical diagnosis of pemphigus.1,2 However, their usefulness for disease monitoring has been controversial.3,4 Several studies suggest that autoantibody levels correlate with disease severity and specific lesional subtypes.5-7 Others show that clinical improvement of lesions is not always accompanied by a decrease in Dsg1 and -3 autoantibody values.3,6 Anti-Dsg3, in particular, has been found to be elevated in PV patients in remission.3,8 A recent immuno-profiling study by our group, using the largest PV patient repository to date, indicated that anti-Dsg1 levels may be a better predictor of disease activity than anti-Dsg3 levels, with declining levels predicting progression from active phase of disease to early remission, irrespective of lesional subtypes.9 This study also demonstrated persistently elevated anti-Dsg3 levels in many remittent patients.9 Although large in sample size, these results were based on a snapshot of the autoantibody levels at a given time point. Here, we present a PV patient in whom we were able to follow anti-Dsg1 and -Dsg3 levels over a span of 2.5 years. This report confirms our previous findings in a longitudinal fashion.

Case Presentation

A 43-year-old Caucasian male of Ashkenazi Jewish descent with a two-year history of biopsy-confirmed PV presented with scattered mucosal and cutaneous erosions to his upper torso, scalp, and oropharynx (PDAI score of 10). On presentation, his disease was being moderately controlled with Mycophenolate mofetil (MMF) 1g twice a day. See Table 1 for corresponding anti-Dsg1, anti-Dsg3 and PDAI scores for this and subsequent visits. One month after the initial visit, he continued to have active disease with superficial erosions on his scalp and lower lip. IVIg treatment was proposed, but declined at this time by the patient. Instead, the dose of MMF was increased to 1.5g twice a day and prednisone 20 mg daily was added. At two months, he was clinically improving (persisting superficial erosions on his upper chest and back, but no new bulla or mucosal lesions). At four months, physical exam revealed a few superficial erosions on his upper chest and back and no oral lesions. His dose of MMF and prednisone were decreased to 1.5 g and 10 mg daily, respectively, and IVIg was started. At six months, there were approximately 20 cutaneous lesions on his chest and scalp and no mucosal lesions. IVIg treatment was stopped after one cycle of 2 g/kg, as the patient perceived