Predictive potential of ACE phenotyping in extrapulmonary sarcoidosis

• Published in: Respiratory research Vol. 23; no. 1; pp. 1 - 211
• Main Authors: Danilov, Sergei M, Kurilova, Olga V, Sinitsyn, Valentin E, Kamalov, Armais A, Garcia, Joe G. N, Dudek, Steven M
• Format: Journal Article
• Language: English
• Published: London BioMed Central Ltd 22.08.2022; BioMed Central; BMC
• Subjects: Angiotensin converting enzyme; Angiotensin I-converting enzyme; Blood; Blood levels; Blood vessels; Cardiovascular diseases; Complications and side effects; Conformational changes; Dendritic cells; Diagnosis; Disease; Enzymes; Epitopes; Genetic aspects; Granulomas; Health aspects; Health risks; Immunoreactivity; Lung diseases; Macrophages; Medical imaging; Monoclonal antibodies; Mutation; Parameter identification; Parameter sensitivity; Phenotyping; Plasma; Plasma ACE; Polymorphism; Positron emission; Proteins; Risk factors; Sarcoidosis; Screening; Systemic sarcoidosis; Tomography; United States; St Louis Missouri; United States > US
• ISSN: 1465-993X; 1465-9921; 1465-993X; 1465-9921
• DOI: 10.1186/s12931-022-02145-z

Abstract Elevated ACE expression in tissues (reflected by blood ACE levels) is associated with increased risk of cardiovascular diseases and is also a marker for granulomatous diseases. We developed a new approach for characterization of ACE status in the blood—ACE phenotyping and established normal values of ACE levels 50–150% of control pooled plasma. ACE phenotyping was performed in citrated plasma of 120 patients with known interstitial lung diseases. In the 1st set of 100 patients we found 22 patients with ACE levels > 150%; ACE phenotyping also objectively identified the presence of ACE inhibitors in the plasma of 15 patients. After excluding these patients and patient with ACE mutation that increases ACE shedding, 17 patients were identified as a suspicious for systemic sarcoidosis based on elevation of blood ACE (> 150% of mean). A new parameter that we have established–ACE immunoreactivity (with mAb 9B9)—allowed us to detect 22 patients with decreased values (< 80%) of this parameter, which may indicate the presence of ACE in the blood that originates from macrophages/dendritic cells of granulomas. In the remaining 20 patients, this new parameter (mAbs binding/activity ratio) was calculated using 3 mAbs (9B9, 3A5 and i1A8—having overlapping epitopes), and 8 patients were identified as having decreases in this parameter, thus increasing dramatically the sensitivity for detection of patients with systemic sarcoidosis. Whole body PET scan confirmed extrapulmonary granulomas in some patients with lower immunoreactivity towards anti-ACE mAbs. ACE phenotyping has novel potential to noninvasively detect patients with systemic sarcoidosis.