Serum angiotensin-converting enzyme activity in normal children and in those with sarcoidosis

doi:10.1016/S0022-3476(81)80959-6

The Journal of Pediatrics

Volume 99, Issue 1, July 1981, Pages 68-72

https://doi.org/10.1016/S0022-3476(81)80959-6 Get rights and content

Serum angiotensin-converting enzyme was measured in 185 children of different ages, in 32 normal adults, in 21 children with sarcoidosis, and in 36 children with other diseases. Children had higher serum ACE values than did adults; an intermediate level was observed in adolescents. Serum ACE values did not vary according to sex. Children with sarcoidosis had significantly elevated serum ACE levels that closely reflected the activity of the disease. Our results indicate that serum ACE is useful in confirming the diagnosis of sarcoidosis in childhood, and is of greater value as a sensitive indicator for following the course of the disease and the effectiveness of steroid therapy.

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Cited by (83)

Immune response to SARS-CoV-2 variants: A focus on severity, susceptibility, and preexisting immunity
2022, Journal of Infection and Public Health
The heterogeneous phenotypes among patients with coronavirus disease 2019 (COVID-19) has drawn worldwide attention, especially those with severe symptoms without comorbid conditions. Immune responses to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative virus of COVID-19, occur mainly by the innate immune response via the interferon (IFN)-mediated pathways, and the adaptive immunity via the T lymphocyte and the antibody mediated pathways. The ability of the original Wuhan SARS-CoV-2 strain, and possibly more so with new emerging variants, to antagonize IFN-mediated antiviral responses can be behind the higher early viral load, higher transmissibility, and milder symptoms compared to SARS-CoV and are part of the continued clinical evolution of COVID-19. Since it first emerged, several variants of SARS-CoV-2 have been circulating worldwide. Variants that have the potential to elude natural or vaccine-mediated immunity are variants of concern. This review focuses on the main host factors that may explain the immune responses to SARS-CoV-2 and its variants in the context of susceptibility, severity, and preexisting immunity.
Current scenario of COVID-19 in pediatric age group and physiology of immune and thymus response
2020, Saudi Journal of Biological Sciences
Citation Excerpt :
While adolescents had higher concentrations of blood ACE than adults and is interesting to observe that COVID-19 in the age group 10–19 years is only found in 1% in the Chinese group. Epidemiological proofs show that SARS-CoV-2 in children is less intense than adults (Rodriguez et al., 1981; Skarstein, 2020; Wan et al., 2020) One of the most common parameters for the severity of the COVID-19 is the chronic illness, like high blood pressure, diabetes, and cardiovascular disease (Mizumoto et al., 2015).
COVID-19 pandemic caused by SARS-CoV-2, continues to manifest with severe acute respiratory syndrome among the adults, however, it offers a convincing indication of less severity and fatality in pediatric age group (0–18 years). The current trend suggests that children may get infected but are less symptomatic with less fatality, which is concordant to earlier epidemic outbreaks of SARS-CoV and MERS-CoV, in 2002 and 2012, respectively. According to the available data, children appear to be at lower risk for COVID-19, as adults constitute for maximum number of the confirmed cases (308,592) and deaths (13,069) as on 22nd March (https://www.worldometers.info/coronavirus). However, rapid publications and information of the adult patients with COVID-19 is in progress and published, on the contrary, almost no comprehensive data or discussion about the COVID-19 in children is available. Therefore, in this review, we outline the epidemiology, clinical symptoms, diagnosis, treatment, prevention, possible immune response and role of thymus in children to combat the COVID-19 outbreak.
Serial investigation of Angiotensin-Converting Enzyme in sarcoidosis patients treated with Angiotensin-Converting Enzyme Inhibitor
2020, European Journal of Internal Medicine
Citation Excerpt :
It is elevated in serum and BAL of sarcoidosis patients and its concentrations are correlated with radiological stages [11, 12]. The International Guidelines for the diagnosis of sarcoidosis proposed ACE as a diagnostic and prognostic marker, however its sensitivity (41.4%, 95% CI 35.3-47.8%) [11] and specificity are poor (false positives are frequent and about 50% of sarcoidosis patients have normal levels of this protein at onset) [13, 14]. ACE may be elevated in certain granulomatous disorders (e.g. tuberculosis, berylliosis, silicosis).
Angiotensin-converting enzyme (ACE) is an acid glycoprotein that converts angiotensin I into angiotensin II. It is produced mainly by activated alveolar macrophages and it resulted elevated in sarcoidosis patients. ACE is the only biomarker mentioned in WASOG international guidelines for the diagnosis and follow-up of sarcoidosis patients but its sensitivity and specificity are low. This study aimed to analyze serial measurements of ACE levels in sarcoidosis patients stratified according to concomitant ACE-inhibitor therapies (ACEIs).
136 serum samples from sarcoidosis patients were retrospectively enrolled in the study. Serial ACE concentrations were measured once year for each patient. Population were divided according to radiogical stages and ACEIs.
ACE concentrations resulted higher in non-ACEIs than ACEIs group (p<E-04). This result was confirmed also stratifying population according to radiological stages particularly in stage 3 (p=2E-03) or stage 2 of the disease (p<1E-04). Considering ACEIs, serum ACE levels proved to be higher in sarcoidosis patients treated with zofenopril than in those treated with perindopril (p=2E-02), enalapril (p=2E-03) or ramipril (p=2E-04). Patients treated with ACEIs showed a progressive reduction in ACE levels to five years of follow-up (p=1.3E-02) and the zofenopril group recorded the highest ACE levels (p<1E-04).
This retrospective study investigated changes in ACE levels in patients with sarcoidosis treated or not treated with ACEIs. Considering the overall low sensitivity and specificity of this biomarker, we suggest systematically investigating medical drugs prescribed for patients with sarcoidosis, in order to optimize the interpretation of ACE in clinical management.
ACE2, COVID19 and serum ACE as a possible biomarker to predict severity of disease
2020, Journal of Clinical Virology
Serum Angiotensin-Converting Enzyme Has a High Negative Predictive Value in the Investigation for Systemic Sarcoidosis
2018, American Journal of Ophthalmology
Citation Excerpt :
Serum ACE performed less well as a screening test in the pediatric population, with high false positives; however, it still had a high NPV in this cohort. ACE levels are higher in normal children compared to adults, with 1 study reporting a mean of 32.1 ± 8.5 in adults and 46.7 in children,22 and within our study, ACE levels were 44% higher in normal children compared to adult values. Rodriguez and associates observed elevated ACE in 40% of normal children, compared to 80% of children with systemic sarcoidosis.22
To examine whether measurement of serum angiotensin-converting enzyme (ACE) is useful in diagnosing sarcoidosis in undifferentiated uveitis.
Evaluation of a diagnostic test.
Data collection was performed from 1035 consecutive subjects presenting with uveitis to Moorfields Eye Hospital undergoing measurement of serum ACE as part of baseline investigations for underlying systemic disease. The main outcome measures were sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of elevated serum ACE.
Mean age of the sample was 41.7 years and 56.1% of subjects were female. Sarcoidosis was the underlying cause for the uveitis in 110 subjects (10.6%) and was more common in adults, female subjects, black subjects, and subjects with intermediate uveitis or panuveitis. ACE was elevated in 196 subjects (18.9%) and elevated levels were observed in 85 subjects eventually diagnosed with underlying sarcoidosis (true positive 77.3%) and in 111 subjects with an alternate diagnosis (false positive 12.0%). In adult subjects, sensitivity of serum ACE was 78.1%, specificity 90.0%, and PPV 43.6%, but the NPV was 97.0%. The test performed well, with area under curve (AUC) 0.897 (95% confidence interval [CI] 0.854–0.941). Serum ACE performed less well in distinguishing sarcoid uveitis in pediatric subjects, with sensitivity 60.0%, specificity 78.5%, and PPV 10.0%, but again NPV was high at 96.9% and AUC was 0.828 (95% CI 0.571–1.000).
Serum ACE had a very high negative predictive value for sarcoid uveitis, eliminating the need for further screening tests in subjects with normal serum ACE, unless clinical suspicion was high.
Ordering of the serum angiotensin-converting enzyme test in patients receiving angiotensin-converting enzyme inhibitor th erapy an avoidable but common error
2015, Chest
Serum angiotensin-converting enzyme (ACE) levels may be decreased by use of ACE inhibitor (ACEI) medication. In this study, we determined how often ACE levels were measured in patients receiving ACEI therapy.
ACE levels analyzed over a 54-month preintervention time period at an academic medical center were reviewed retrospectively for tests performed during ACEI therapy. These data were compared with a large, deidentified dataset of ACE levels measured at a national reference laboratory; in vitro studies of ACEI inhibition; and liquid chromatography time-of-flight mass spectrometry detection of lisinopril in a subset of clinical specimens.
Over a 54-month period, 1,292 patients had ACE levels measured, with 108 patients (8.4%) receiving ACEI therapy at the time of testing. ACE levels measured for patients receiving ACEI therapy were substantially lower. In general, clinical teams did not recognize a medication effect on ACE levels. Introduction of a warning prompt in the electronic health record reduced the ordering of ACE levels in patients receiving ACEIs by > 60% in a 17-month postintervention time period. The deidentified dataset of ACE levels at a reference laboratory showed a bimodal distribution, with a peak of very low ACE levels. Using liquid chromatography time-of-flight mass spectrometry, the presence of lisinopril was confirmed in a subset of specimens with low ACE activity. In vitro studies of two different ACE assays showed significant inhibition of activity at clinically relevant concentrations.
Assessment of ACE activity is often measured for patients receiving ACEIs, potentially leading to low ACE concentrations and inaccurate interpretations.

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^*: Presented in part at the Annual Meetings of the American Academy of Allergy, New Orleans, March, 1979, and of the Society of Pediatric Research, Atlanta, May, 1979.

^**: Recipient of an American Lung Association training fellowship (1979–1980).

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Original articleSerum angiotensin-converting enzyme activity in normal children and in those with sarcoidosis*

Am J Med

Tissue Cell

Lancet

Biochem Biophys Res Comm

The specificity and nature of serum angiotensin-converting enzyme (Serum ACE) elevations in sarcoidosis

Ann NY Acad Sci

Elevation of serum angiotensinconverting enzyme in Gaucher's disease

N Engl J Med

Serum angiotensin-converting enzyme in leprosy and coccidioidomycosis

Ann Intern Med

Serum angiotensin-converting enzyme for diagnosis and therapeutic evaluation of sarcoidosis

Am Rev Respir Dis

Elevation of angiotensin-converting enzyme in granulomatous lymph nodes and serum in sarcoidosis

Ann NY Acad Sci

Marked elevation of serum angiotensin-converting enzyme and hepatic fibrosis containing long spacing collagen fibrils in type 2 acute neuropathic Gaucher's disease

J Clin Pathol

Angiotensin-conventing enzyme, I. Activity and correlation with serum lysozyme in sarcoidosis, other chest or lymph node diseases and healthy persons

Scand J Respir Dis

Serum angiotensin-converting enzyme activity in sarcoidosis in children and adults

The clinical picture of sarcoidosis in children

Pediatrics

Original article
Serum angiotensin-converting enzyme activity in normal children and in those with sarcoidosis*