Metallopeptidase activities in hereditary angioedema: Effect of androgen prophylaxis on plasma aminopeptidase P Christian Drouet, PhD, Anik Désormeaux,

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Metallopeptidase activities in hereditary angioedema: Effect of androgen prophylaxis on plasma aminopeptidase P Christian Drouet, PhD, Anik Désormeaux, Josée Robillard, MSc, Denise Ponard, Laurence Bouillet, MD, PhD, Ludovic Martin, MD, PhD, Gisèle Kanny, MD, PhD, Denise-Anne Moneret-Vautrin, MD, Jean-Luc Bosson, MD, PhD, Jean-Louis Quesada, MSc, Margarita López- Trascasa, PhD, Albert Adam, PhD Journal of Allergy and Clinical Immunology Volume 121, Issue 2, Pages 429-433 (February 2008) DOI: 10.1016/j.jaci.2007.10.048 Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Distribution of APP activity in patients with HAE with no prophylaxis (solid columns, n = 147) and in healthy individuals used as the reference group (open columns, n = 116). Journal of Allergy and Clinical Immunology 2008 121, 429-433DOI: (10.1016/j.jaci.2007.10.048) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Plasma APP activity (A) and CI-INH serpin function (B) in patients treated with long-term androgen prophylaxis (200 mg of danazol or 4 mg of stanozolol per 1–4 days; solid symbols) or not treated (open symbols). Data are presented in box whisker plots showing the median (horizontal bars within boxes), the interquartile range (boxes), and the 5th to 95th percentiles (vertical bars). Values greater than and less than these levels were dotted separately. Data comparisons between groups of patients taking androgen or not are presented according to the Mann-Whitney or Student nonparametric tests. Journal of Allergy and Clinical Immunology 2008 121, 429-433DOI: (10.1016/j.jaci.2007.10.048) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Plasma APP activity and CI-INH serpin function of patients 1 and 2 with HAE undergoing short-term prophylaxis with danazol (400 and 600 mg/d, respectively, for 10 days). Differences between values observed in the context of danazol treatment (solid columns) or no treatment (open columns) are indicated as increasing factors. Journal of Allergy and Clinical Immunology 2008 121, 429-433DOI: (10.1016/j.jaci.2007.10.048) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 CI-INH function or APP activity versus disease severity. Box whisker plots of CI-INH function (A and B) or APP activity (C and D) represent the median (horizontal bars within boxes) and the interquartile range (boxes) with the 5th to 95th percentiles (vertical bars). Data were expressed for each disease severity class12 (1–2, severe disease; 3–5, mild to asymptomatic disease) in patients with no treatment (n = 157; Fig 4, A and C) and those with androgen prophylaxis (n = 59; Fig 4, B and D). Data comparisons for severity of disease between groups follow the equality of means with the Student t test (Fig 4, B) or the Mann-Whitney rank sum test (Fig 4, A, C, and D). Journal of Allergy and Clinical Immunology 2008 121, 429-433DOI: (10.1016/j.jaci.2007.10.048) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 5 Risk estimate for the association of the biologic parameters with disease severity. Odds ratios were calculated from plasma CI-INH function and APP, CPN, and ACE activity. A, Untreated patients (n = 98). B, Treated patients (n = 36). Dashed lines represent the 95% Cis, and vertical bars represent the median values. Journal of Allergy and Clinical Immunology 2008 121, 429-433DOI: (10.1016/j.jaci.2007.10.048) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions