Interpretative cut-off for alpha-1-antitrypsin concentration in detection of alpha-1-antitrypsin deficiency among pediatric patients - A pilot study
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2019
Authors
Beletić, AnđeloLeković, Z.
Zivković, Z.
Radlović, N.
Perisić, V.
Ljujić, Mila
Radojković, Dragica
Đorđević, Valentina
Stanković, S.
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Show full item recordAbstract
Background-aim
Alpha-1-antitrypsin deficiency (AATD) is an autosomal recessive
disorder characterized by the reduced alpha-1-antitrypsin (AAT)
level in blood. In pediatric patients, it is dominantly tested as a cause
of liver disease, while specific lung diseases might be potentially
regarded as additional indications. Measurement of AAT concentration is useful as a first-line test, although decreased level may be also
encountered in certain acquired conditions. Our aim was to
determine the interpretative cut-off for AAT concentration i.e. level
below which the presence of common AATD-associated alleles might
be suspected.
Methods
We included 37 subjects with clinical indications or familiar
history of AATD: 19 males and 18 females, aged between 2 months
and 19 years. Immunonephelometry was used for measurement of
AAT concentration in serum and PCR-reverse allele specific hybridization assay for detection of Z and S alleles, which are considered as
the common AATD-associ...ated alleles. Kruskal-Wallis test and ROC
analysis were applied in statistical evaluation.
Results
Three cases of AATD (ZZ genotype) and 14 carriers (13
heterozygous for Z and one for S allele) were detected. AAT
concentration (median (min-max)) measured in AATD cases (0.35
(0.31–0.39) g/L), carriers (0.81 (0.56–1.41) g/L) and patients with
no Z and S allele (1.20 (0.91–2.24) g/L) were significantly different
(P b .001). Four carriers (three heterozygous for Z and one for S
allele) had AAT concentration in the reference range (0.9–2.0 g/L).
We identified the level 1.03 g/L as the most appropriate cut-off to
distinguish group comprising both cases of AATD and carriers from
patients in whom no common AATD-associated allele was present.
Corresponding AUC value (95% Confidence interval (CI)) was 0.929
(0.795–0.987) (P b .001). Sensitivity and specificity (95% CI) reached
94.1 (71.3–99.9)% and 90.0 (68.3–98.8)% respectively.
Conclusions
In pediatric patients AAT concentration below 1.03 g/L may be
regarded as a potential cut-off indicating the presence of common
AATD-associated alleles in homo-or heterozygous form. Nevertheless, this preliminary finding needs confirmation in a larger study.
Source:
Clinica Chimica Acta, 2019, 493, S455-S455Publisher:
- Elsevier, Amsterdam
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Institution/Community
Institut za molekularnu genetiku i genetičko inženjerstvoTY - CONF AU - Beletić, Anđelo AU - Leković, Z. AU - Zivković, Z. AU - Radlović, N. AU - Perisić, V. AU - Ljujić, Mila AU - Radojković, Dragica AU - Đorđević, Valentina AU - Stanković, S. PY - 2019 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/1226 AB - Background-aim Alpha-1-antitrypsin deficiency (AATD) is an autosomal recessive disorder characterized by the reduced alpha-1-antitrypsin (AAT) level in blood. In pediatric patients, it is dominantly tested as a cause of liver disease, while specific lung diseases might be potentially regarded as additional indications. Measurement of AAT concentration is useful as a first-line test, although decreased level may be also encountered in certain acquired conditions. Our aim was to determine the interpretative cut-off for AAT concentration i.e. level below which the presence of common AATD-associated alleles might be suspected. Methods We included 37 subjects with clinical indications or familiar history of AATD: 19 males and 18 females, aged between 2 months and 19 years. Immunonephelometry was used for measurement of AAT concentration in serum and PCR-reverse allele specific hybridization assay for detection of Z and S alleles, which are considered as the common AATD-associated alleles. Kruskal-Wallis test and ROC analysis were applied in statistical evaluation. Results Three cases of AATD (ZZ genotype) and 14 carriers (13 heterozygous for Z and one for S allele) were detected. AAT concentration (median (min-max)) measured in AATD cases (0.35 (0.31–0.39) g/L), carriers (0.81 (0.56–1.41) g/L) and patients with no Z and S allele (1.20 (0.91–2.24) g/L) were significantly different (P b .001). Four carriers (three heterozygous for Z and one for S allele) had AAT concentration in the reference range (0.9–2.0 g/L). We identified the level 1.03 g/L as the most appropriate cut-off to distinguish group comprising both cases of AATD and carriers from patients in whom no common AATD-associated allele was present. Corresponding AUC value (95% Confidence interval (CI)) was 0.929 (0.795–0.987) (P b .001). Sensitivity and specificity (95% CI) reached 94.1 (71.3–99.9)% and 90.0 (68.3–98.8)% respectively. Conclusions In pediatric patients AAT concentration below 1.03 g/L may be regarded as a potential cut-off indicating the presence of common AATD-associated alleles in homo-or heterozygous form. Nevertheless, this preliminary finding needs confirmation in a larger study. PB - Elsevier, Amsterdam C3 - Clinica Chimica Acta T1 - Interpretative cut-off for alpha-1-antitrypsin concentration in detection of alpha-1-antitrypsin deficiency among pediatric patients - A pilot study EP - S455 SP - S455 VL - 493 DO - 10.1016/j.cca.2019.03.964 ER -
@conference{ author = "Beletić, Anđelo and Leković, Z. and Zivković, Z. and Radlović, N. and Perisić, V. and Ljujić, Mila and Radojković, Dragica and Đorđević, Valentina and Stanković, S.", year = "2019", abstract = "Background-aim Alpha-1-antitrypsin deficiency (AATD) is an autosomal recessive disorder characterized by the reduced alpha-1-antitrypsin (AAT) level in blood. In pediatric patients, it is dominantly tested as a cause of liver disease, while specific lung diseases might be potentially regarded as additional indications. Measurement of AAT concentration is useful as a first-line test, although decreased level may be also encountered in certain acquired conditions. Our aim was to determine the interpretative cut-off for AAT concentration i.e. level below which the presence of common AATD-associated alleles might be suspected. Methods We included 37 subjects with clinical indications or familiar history of AATD: 19 males and 18 females, aged between 2 months and 19 years. Immunonephelometry was used for measurement of AAT concentration in serum and PCR-reverse allele specific hybridization assay for detection of Z and S alleles, which are considered as the common AATD-associated alleles. Kruskal-Wallis test and ROC analysis were applied in statistical evaluation. Results Three cases of AATD (ZZ genotype) and 14 carriers (13 heterozygous for Z and one for S allele) were detected. AAT concentration (median (min-max)) measured in AATD cases (0.35 (0.31–0.39) g/L), carriers (0.81 (0.56–1.41) g/L) and patients with no Z and S allele (1.20 (0.91–2.24) g/L) were significantly different (P b .001). Four carriers (three heterozygous for Z and one for S allele) had AAT concentration in the reference range (0.9–2.0 g/L). We identified the level 1.03 g/L as the most appropriate cut-off to distinguish group comprising both cases of AATD and carriers from patients in whom no common AATD-associated allele was present. Corresponding AUC value (95% Confidence interval (CI)) was 0.929 (0.795–0.987) (P b .001). Sensitivity and specificity (95% CI) reached 94.1 (71.3–99.9)% and 90.0 (68.3–98.8)% respectively. Conclusions In pediatric patients AAT concentration below 1.03 g/L may be regarded as a potential cut-off indicating the presence of common AATD-associated alleles in homo-or heterozygous form. Nevertheless, this preliminary finding needs confirmation in a larger study.", publisher = "Elsevier, Amsterdam", journal = "Clinica Chimica Acta", title = "Interpretative cut-off for alpha-1-antitrypsin concentration in detection of alpha-1-antitrypsin deficiency among pediatric patients - A pilot study", pages = "S455-S455", volume = "493", doi = "10.1016/j.cca.2019.03.964" }
Beletić, A., Leković, Z., Zivković, Z., Radlović, N., Perisić, V., Ljujić, M., Radojković, D., Đorđević, V.,& Stanković, S.. (2019). Interpretative cut-off for alpha-1-antitrypsin concentration in detection of alpha-1-antitrypsin deficiency among pediatric patients - A pilot study. in Clinica Chimica Acta Elsevier, Amsterdam., 493, S455-S455. https://doi.org/10.1016/j.cca.2019.03.964
Beletić A, Leković Z, Zivković Z, Radlović N, Perisić V, Ljujić M, Radojković D, Đorđević V, Stanković S. Interpretative cut-off for alpha-1-antitrypsin concentration in detection of alpha-1-antitrypsin deficiency among pediatric patients - A pilot study. in Clinica Chimica Acta. 2019;493:S455-S455. doi:10.1016/j.cca.2019.03.964 .
Beletić, Anđelo, Leković, Z., Zivković, Z., Radlović, N., Perisić, V., Ljujić, Mila, Radojković, Dragica, Đorđević, Valentina, Stanković, S., "Interpretative cut-off for alpha-1-antitrypsin concentration in detection of alpha-1-antitrypsin deficiency among pediatric patients - A pilot study" in Clinica Chimica Acta, 493 (2019):S455-S455, https://doi.org/10.1016/j.cca.2019.03.964 . .