Eosinophil Cationic Protein (ECP), a predictive marker of bullous pemphigoid severity and outcome

Delphine Giusti,Delphine Giusti,Gregory Gatouillat,Philippe Bernard,Philippe Bernard,Bach Nga Pham,Bach Nga Pham,Frank Antonicelli,Julie Plée,Julie Plée,Sébastien Le Jan

doi:10.1038/s41598-017-04687-5

Abstract

Bullous Pemphigoid (BP) is an inflammatory rare autoimmune bullous dermatosis, which outcome cannot be predicted through clinical investigations. Eosinophils are the main immune infiltrated cells in BP. However, the release of Major Basic Protein (MBP), Eosinophil Derived Neurotoxin (EDN), and Eosinophil Cationic Protein (ECP) upon eosinophil activation has still not been evaluated with respect to BP development. MBP, EDN and ECP were measured by ELISA in serum (n = 61) and blister fluid (n = 20) of patients with BP at baseline, and in serum after 2 months of treatment (n = 41). Eosinophil activation in BP patients was illustrated at baseline by significantly higher MBP, EDN and ECP serum concentrations as compared with control subjects (n = 20), but without distinction according to disease severity or outcome. EDN and ECP values were even higher in the blister fluids (P < 0.01 and P < 0.05, respectively), whereas MBP values were lower (P < 0.001). ECP serum concentration decreased after 60 days of treatment in BP patients with ongoing remission but not in patients who later relapsed (P < 0.05). A reduction of at least 12.8 ng/mL in ECP concentrations provided a positive predictive value for remission of 81%, showing that ECP serum variation could be a useful biomarker stratifying BP patients at risk of relapse.

Highlights

Bullous pemphigoid (BP) is a rare autoimmune blistering skin disease, with autoantibodies targeting the hemidesmosome proteins BP180 and BP2301–3
Variations of Major Basic Protein (MBP), Eosinophil Derived Neurotoxin (EDN) and Eosinophil Cationic Protein (ECP) serum concentrations between baseline and after 2 months of treatment were analyzed according to both disease extent at the time of diagnosis and disease outcome during the first year of follow-up
Highlighting the importance of eosinophils activation in the pathogenesis of Bullous Pemphigoid (BP), we showed in this study that each of the 3 granule proteins MBP, EDN and ECP displayed specific profile pattern according to either body distribution, to disease extent at the time of diagnosis and to disease outcome, suggesting that these proteins should endow specific roles during BP disease development

Summary

Introduction

Bullous pemphigoid (BP) is a rare autoimmune blistering skin disease, with autoantibodies targeting the hemidesmosome proteins BP180 and BP2301–3. In patients with BP, variations in inflammatory cytokine expression has been shown to play a critical role in the pathological processes related to the outcome of the disease[9, 10] In this line, BP is clinically characterized by the presence of tense blisters along with intense pruritus, occurring preferentially on inflammatory, erythematous plaques. Eosinophils are endowed with a potent army of proinflammatory mediators including basic proteins stored in eosinophil granules, as well as cytokines, chemokines, lipid mediators, various proteases and components of the oxygen burst[15, 16] This cytotoxic capacity is considered important in the immune response to infection with bacteria, parasites, viruses and tumor cells, their inappropriate accumulation can cause severe tissue damage in a wide variety of diseases affecting the skin and the lungs, the heart, or the gastrointestinal tract[16]. Variations of MBP, EDN and ECP serum concentrations between baseline and after 2 months of treatment were analyzed according to both disease extent at the time of diagnosis and disease outcome during the first year of follow-up

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