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

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.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1

Serum concentrations of Eosinophil granule proteins at baseline. Major Basic Protein (MBP) (A), Eosinophil Derived Neurotoxin (EDN) (B) and Eosinophil Cationic Protein (ECP) (C) serum levels from 61 patients with active bullous pemphigoid and 24 healthy control subjects were measured by specific ELISA at the time of diagnosis. Results are expressed as ng/mL. (**P < 0.01; ***P < 0.001). Lines correspond to median and interquartile ranges.

Figure 2

MBP, EDN and ECP serum variations between baseline and day 60. Variations in the serum concentrations of MBP (A), EDN (B) and ECP (C) were measured by mean of specific ELISAs between days 0 and 60. (MD: Mild disease; R0: Remission). (*P < 0.05).

Figure 3

Prognostic value of the decrease in ECP serum concentrations between days 0 and 60. The prognostic properties of the decrease of ECP serum concentrations measured by means of ELISA between baseline and day 60 with respect of the occurrence of a clinical remission in patients with BP are depicted as a receiver operating characteristic (ROC) curve.

Figure 4

Comparison of serum and blister fluid concentrations for MBP, ECP and EDN in 20 patients with active bullous pemphigoid. The serum blister fluids concentrations of MPB (A), EDN (B) and ECP (C) were measured by means of specific ELISAs. Variations between serum and blister fluids were analyzed by means of Wilcoxon test for MBP and EDN and paired t test for ECP. Correlation between EDN concentrations in the serum and in the blister fluids was performed by means of Spearman’s correlation coefficient analysis. Statistical significance was as follow: (*P < 0.05, **P < 0.01; ***P < 0.001). Lines define median and interquartile ranges.