Conformational Fingerprinting of the Angiotensin I-Converting Enzyme (ACE). 1. Application in Sarcoidosis

Authors:
  • IBIrina V. Balyasnikova
    Irina V. Balyasnikova
  • ADAnastasia S. Danilova
    Anastasia S. Danilova
  • INIrina A. Naperova
    Irina A. Naperova
  • NANatalia E. Arablinskaya
    Natalia E. Arablinskaya
  • RMRoman Metzger
    Roman Metzger
  • FFFolker E. Franke
    Folker E. Franke
  • DSDavid E. Schwartz
    David E. Schwartz
  • IGIrina V. Gachok
    Irina V. Gachok
  • ITIlya N. Trakht
    Ilya N. Trakht
  • OKOlga A. Kost
    Olga A. Kost
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Abstract
Fine epitope mapping of monoclonal antibodies (mAbs) to 16 epitopes on human angiotensin I-converting enzyme (ACE) revealed that the epitopes of all mAbs contained putative glycosylation sites. ACE glycosylation is both cell- and tissue-specific and, therefore, the local conformation of ACE produced by different cells could be also unique. The pattern of ACE binding by a set of mAbs to 16 epitopes of human ACE — “conformational fingerprint of ACE” — is the most sensitive marker of ACE conformation and could be cell- and tissue-specific. The recognition of ACEs by mAbs to ACE was estimated using an immune-capture enzymatic plate precipitation assay. Precipitation patterns of soluble recombinant ACE released from Chinese hamster ovary (CHO)-ACE cells was influenced by conditions that alter ACE glycosylation. This pattern was also strongly cell type specific. Patients with sarcoidosis exhibited conformational fingerprints of tissue ACE (lungs and lymph nodes), as well as blood ACE, which were distinct from controls. Conformational fingerprinting of ACE may detect ACE originated from the cells other than endothelial cells in the blood and when combined with elevated blood ACE levels in patients with sarcoidosis may potentially reflect extrapulmonary sarcoidosis involvement (bone marrow, spleen, liver). If proven true, this would serve as a biomarker of enormous potential clinical significance.

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