Metallopeptidase activities in hereditary angioedema:: Effect of androgen prophylaxis on plasma aminopeptidase P

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:121

Article

Drouet, Christian^1,2,3  Desormeaux, Anik⁴  Robillard, Josee⁴  Ponard, Denise³  Bouillet, Laurence³  Martin, Ludovic⁵  Kanny, Gisele⁶  Moneret-Vautrin, Denise-Anne⁶  Bosson, Jean-Luc³  Quesada, Jean-Louis⁷  Lopez-Trascasa, Margarita⁸  Adam, Albert⁴ 

[1] GREPI, CNRS, UMR 5525, F-38043 Grenoble, France

[2] Univ Grenoble 1, F-38043 Grenoble, France

[3] Natl Reference Ctr Angiodema, F-38043 Grenoble, France

[4] Univ Montreal, Fac Pharm, Montreal, PQ H3C 3J7, Canada

[5] CHU Angers, Serv Dermatol, Angers, France

[6] CHU Nancy, EA Maladies Allergiques Diagnost & Therapeut Med, Nancy, France

[7] CHU Grenoble, INSERM, CIC, Grenoble, France

[8] Hosp Univ La Paz, Unidad Immunol, Madrid, Spain

关键词: hereditary angioedema;    aminopeptidase P;    C1 inhibitor;    androgen;    danazol;    stanozolol;    bradykinin;    des-Arg(9)-bradykinin;   

DOI  :  10.1016/j.jaci.2007.10.048

来源: Elsevier

【 摘 要 】

Background: Aminopeptidase P (APP) plays an important role in the catabolism of kinins in human plasma, mostly for des-Arg(9)-bradykinin. Impaired degradation of this active bradykinin metabolite was found to be associated with a decreased APP activity in hypertensive patients who experienced angioedema while being treated with angiotensin I-converting enzyme inhibitors. The pathophysiology of hereditary angioedema is presently attributed only to a quantitative/qualitative C1 inhibitor (CI-INH) defect with increased bradykinin release. Objectives: In the context of androgen prophylaxis, increased CI-INH function cannot fully explain protection from angioedema attacks alone because of the limited reversion of the CI-INH defects. Therefore we hypothesized that androgen prophylaxis could enhance plasma APP activity. Methods: Patients with hereditary angioedema were investigated for plasma metallopeptidase activities responsible for kinin catabolism (APP, angiotensin I-converting enzyme, and carboxypeptidase N) and for CI-INH function in treated and untreated patients. Results: APP activity was asymmetrically distributed in untreated patients (n = 147): the mean value was significantly lower than the value in a reference healthy and unmedicated population (n = 116; P <= .001). Prophylaxis with androgen induced a significant increase in APP activity (P <= .001), whereas it did not affect the other metallopeptidase activities. In both patient groups, APP activity showed a significant inverse relationship to disease severity (P <= .001). Conclusion: In addition to the effect on circulating CI-INH levels, the increase in APP levels brought on by androgens could contribute to a more effective control of the kinin accumulation considered to be responsible for the symptoms of angioedema.

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