Clin Chem Lab Med 2015; aop
Matthijs Oyaert, Pieter Vermeersch, Gert De Hertogh, Martin Hiele, Nathalie Vandeputte, Ilse Hoffman and Xavier Bossuyt*
Combining antibody tests and taking into account antibody levels improves serologic diagnosis of celiac disease DOI 10.1515/cclm-2013-1099 Received December 21, 2013; accepted January 9, 2015
Abstract Background: The European Society for Pediatric Gastroenterology and Nutrition states that if IgA anti-tissue transglutaminase (tTG) exceeds 10 times the upper limit of normal (ULN), there is the possibility to diagnose celiac disease (CD) without duodenal biopsy, if supported by anti-endomysium testing and human leukocyte antigen (HLA) typing. We aimed to evaluate whether combining IgA tTG and IgG anti-deamidated gliadin peptide (DGP) antibody testing and taking into account the antibody levels improves clinical interpretation. Methods: We calculated likelihood ratios for various test result combinations using data obtained from newly diagnosed CD patients (n = 156) [13 children 16 years)] and 974 disease controls. All patients and controls underwent duodenal biopsy. IgA anti-tTG and IgG anti-DGP assays were from Thermo Fisher and Inova. *Corresponding author: Xavier Bossuyt, MD, PhD, Laboratory Medicine, Immunology, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium, Phone: +32 16 347009, Fax: +32 16 347931, E-mail: [email protected]; Department of Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium; and Department of Microbiology and Immunology, KU Leuven – University of Leuven, Leuven, Belgium Matthijs Oyaert: Department of Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium Pieter Vermeersch: Department of Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium; and Department of Cardiovascular Sciences, KU Leuven – University of Leuven, Leuven, Belgium Gert De Hertogh: Department of Pathology, University Hospital Leuven, Leuven, Belgium Martin Hiele: Department of Gastroenterology, University Hospitals Leuven, Leuven, Belgium Nathalie Vandeputte: Werfen Benelux N.V./S.A, Excelsiorlaan 48-50, Bus 8, Zaventem, Belgium Ilse Hoffman: Department of Pediatrics, University Hospitals Leuven, Leuven, Belgium
Results: Likelihood ratios for CD markedly increased with double positivity and increasing antibody levels of IgA anti-tTG and IgG anti-DGP. Patients with double positivity and high antibody levels ( > 3 times, > 10 times ULN) had a high probability for having CD (likelihood ratio ≥ 649 for > 3 times ULN and ∞ for > 10 times ULN). The fraction of CD patients with double positivity and high antibody levels was 59%–67% (depending on the assay) for > 3 ULN and 33%–36% (depending on the assay) for > 10 ULN, respectively. This fraction was significantly higher in children with CD than in adults. Conclusions: Combining IgG anti-DGP with IgA anti-tTG and defining thresholds for antibody levels improves the serologic diagnosis of CD. Keywords: anti-deamidated gliadin; anti-tissue transglutaminase; celiac disease; likelihood ratio.
Introduction The diagnosis of celiac disease (CD) relies on symptoms, serology and histology. The European Society for Pediatric Gastroenterology and Nutrition (ESPGHAN) has recently put forward new criteria for the diagnosis of CD [1]. In these newly proposed guidelines, it is stated that patients with a clinical suspicion of CD should be tested for IgA antitissue transglutaminase (tTG) and total IgA (to exclude IgA deficiency) [1]. If IgA anti-tTG exceeds 10 times the upper limit of normal (ULN), there is the possibility to diagnose CD without duodenal biopsy, if supported by anti-endomysium testing and human leukocyte antigen (HLA) typing [1]. Follow-up testing by anti-endomysium antibodies (EMA) has been proposed by ESPGHAN because of the high specificity these antibodies confer for CD. However, antiEMA are directed against tTG and, therefore, test results for anti-tTG and anti-EMA should be highly agreeable. Determining antibodies to deamidated gliadin might be a theoretically attractive substitute to EMA as it might not only improve specificity but also sensitivity [2]. Moreover,
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2 Oyaert et al.: Serologic diagnosis of celiac disease
quantification of anti-deamidated gliadin peptide (DGP) antibodies can be automated and, therefore, is an appealing alternative for the more expensive (manual) EMA. A detailed analysis of combining anti-tTG and anti-DGP antibodies for the diagnosis of CD is needed [3]. In previous studies, we showed that the likelihood for CD increases 1) with increasing antibody concentration for either IgA anti-tTG or IgG anti-DGP; and 2) with the simultaneous presence of anti-tTG and anti-DGP antibodies [2, 4–6]. In the present study we illustrate the value of taking into account the combination of IgA anti-tTG and IgG anti-DGP as well as the antibody level in the diagnosis of CD. The analysis was done for automated commercial assays from two different manufacturers (Thermo Fisher and Inova).
biopsy and in patients with Marsh I or II lesions on intestinal biopsy that responded to a gluten-free diet serologically or on intestinal biopsy. The diagnosis of non-CD was considered confirmed when intestinal biopsy showed Marsh 0 or Marsh I/Marsh II and the morphologic lesion could be explained by another disease, such as Helicobacter pylori gastritis or giardiasis. Patients who were diagnosed previously with CD or who were on a gluten-free diet were excluded. Selective IgA deficiency (IgA 10 × ULN
12/0/1 2/0/0 1/1/0 3/4/0
2/0/0 3/0/0 1/0/0 0/1/0
0/0/0 3/2/0 8/2/0 3/0/0
2/1/0 11/2/0 23/10/2 24/22/10
C EliA IgG anti-DGP Neg 1–3 × ULN 3–10 × ULN > 10 × ULN
543/202/190 11/8/4 1/0/2 0/0/0
7/2/1b 0/1c/0 0/0/0 0/0/0
1/0/0 0/0/0 0/0/0 0/0/0
0/0/0 1a/0/0 0/0/0 0/0/0
D Quanta Flash IgG anti-DGP Neg 1–3 × ULN 3–10 × ULN > 10 × ULN
557/202/189 3/4/5 0/0/2 0/0/0
2/2/1b 0/0/0 0/0/0 0/0/0
1/2e/0 0/4c,d/0 0/0/0 0/0/0
0/0/0 0/0/0 1a/0/0 0/0/0
(A and B) Distribution of IgA anti-tTG and IgG anti-DGP in CD patients with biopsy proven CD (n = 156). Panel A shows the data for EliA, whereas panel B shows the data for QUANTA FLASH. (C and D). Distribution of IgA anti-tTG and IgG anti-DGP in disease controls (verified by biopsy) (n = 974). Panel C shows the data for EliA, whereas panel D shows the data for QUANTA FLASH. Three values are given, respectively, for the three age groups, ≥ 16 years old, between 2 and 15 years old and ≤ 2 years old. ULN, upper limit of normal. Patient history [only patients with anti-endomysium antibodies (EMA) and positive serology for one or both anti-tTG assays]: aanti-EMA +++, patient diagnosed with auto-immune hepatitis, Gilbert’s syndrome and Graves thyroiditis; banti-EMA ++, initial biopsy indicated hyperemic gastritis, follow-up biopsy revealed no arguments for CD; canti-EMA +, no arguments for CD were found on initial and follow-up duodenal biopsy; danti-EMA +, patient with congenital spherocytosis, no arguments for CD on initial and followup duodenal biopsies; eanti-EMA +, patient diagnosed with reflux esophagitis grade A, no arguments for CD on biopsy.
and likelihood ratios (Table 3). For IgG anti-DGP, specificity was 100% for values exceeding 10 times ULN for both assays (Table 3).
A total of 7.7% and 8.3% (EliA and QUANTA FLASH, respectively) of the patients with CD tested negative for both IgA anti-tTG and IgG anti-DGP (Table 3). These patients tested negative for anti-EMA. A total of 14.1% and 10.3% (EliA and QUANTA FLASH, respectively) of the patients tested single positive (i.e., positive for one test and negative for the other test) (Table 3). Double positivity for IgA anti-tTG and IgG anti-DGP was found in 78.2% and 81.4% of the patients (EliA and QUANTA FLASH, respectively) and in 10 and double positivity with antibody levels > 10 times ULN had a likelihood ratio of ∞.
Sensitivities, specificities and likelihood ratios for children and adults IgA anti-tTG and IgG anti-DGP double positivity ( > 10 ULN) was found in 24.5% (24/98) of the patients older
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Oyaert et al.: Serologic diagnosis of celiac disease 5
Table 3 Sensitivity, specificity and likelihood ratio (with 95% confidence intervals): 1) for various test combinations of IgA-anti-tTG and IgG anti-DGP; 2) for IgA anti-tTG; and 3) for IgG anti-DGP. IgA anti-tTG/IgG anti-DGP
Sensitivity, %
Specificity, %
Likelihood ratio
96.0 (94.6–97.1) 97.3 (96.1–98.3)
0.08 (0.05–0.14) 0.09 (0.05–0.14)
96.2 (94.8–97.3) 97.8 (96.7–98.7)
3.7 (2.3–6.1) 4.8 (2.5–8.9)
99.8 (99.3–100.0) 99.5 (98.8–99.8)
381 (95–1524) 159 (66–381)
100.0 (99.6–100.0) 99.9 (99.4–100.0)
∞ 649 (91–4620)
100.0 (99.6–100.0) 100.0 (99.6–100.0)
∞ ∞
80.8 (73.7–86.6) 84.6 (78.0–89.9)
98.7 (97.7–99.3) 98.8 (97.9–99.4)
61 (35–104) 69 (39–121)
72.4 (64.7–79.3) 80.1 (73.0–86.1)
99.8 (99.3–100.0) 99.2 (98.4–99.6)
353 (88–1413) 98 (49–195)
51.9 (43.8–60.0) 68.6 (60.5–75.0)
99.9 (99.4–100.0) 99.9 (99.4–100.0)
506 (71–3608) 668 (94–4752)
89.7 (83.9–94.0) 88.5 (82.4–93.0)
97.1 (95.9–98.1) 98.1 (97.0–98.8)
31 (22–45) 45 (29–71)
71.8 (64.0–78.7) 73.7 (66.1–80.4)
99.7 (99.1–99.9) 99.7 (99.1–99.9)
233 (75–725) 239 (77–744)
46.8 (38.8–54.9) 43.0 (35.1–51.1)
100.0 (99.6–100.0) 100.0 (99.6–100.0)
∞ ∞
Double negative Thermo Fisher EliA 7.7 (4.04–13.1) Inova Quanta Flash 8.3 (4.51–13.8) Positive for one test and negative for the other test Thermo Fisher EliA 14.1 (9.4–20.6) Inova Quanta Flash 10.3 (6.0–16.1) Double positivity 1 × ULN Thermo Fisher EliA 78.2 (70.9–84.4) Inova Quanta Flash 81.4 (74.3–96.7) Double positivity 3 × ULN Thermo Fisher EliA 59.0 (50.8–66.1) Inova Quanta Flash 66.7 (58.7–74.0) Double positivity 10 × ULN Thermo Fisher EliA 32.7 (25.6–40.2) Inova Quanta Flash 35.9 (28.4–44.0) IgA anti-tTG 1 × ULN Thermo Fisher EliA Inova Quanta Flash 3 × ULN Thermo Fisher EliA Inova Quanta Flash 10 × ULN Thermo Fisher EliA Inova Quanta Flash IgG anti-DGP 1 × ULN Thermo Fisher EliA Inova Quanta Flash 3 × ULN Thermo Fisher EliA Inova Quanta Flash 10 × ULN Thermo Fisher EliA Inova Quanta Flash ULN, upper limit of normal.
than 16 years, in 40.0% (18/45) of the patients aged between 2 and 15 years and in 69.2% (9/13) of the patients younger than 2 years of age. These differences are statistically significant (Fisher’s exact) for comparison of the ≥ 16 years group and the 2–15 years group (p 10 × ULN
Negative
1–3 × ULN
3–10 × ULN
> 10 × ULN
0.08 (0.05–0.14) 1.6 (0.7–3.9) 6.2 (1.3–30.6) ∞
1.3 (0.3–5.7) 18 (2–179) ∞ ∞
12 (1–137) ∞ ∞ ∞
∞ 56.2 (7–440) ∞ ∞
0.19 (0.14–0.27)
7.4 (3.4–16.2)
200 (28–1452)
506 (71–3608)
0.09 (0.05–0.14) 1.0 (0.2–4.6) 6.2 (0.9–44.0) ∞
3.1 (0.6–17) ∞ ∞ ∞
7.8 (2.1–28.8) ∞ ∞
∞ ∞ 219 (30–1584) ∞
0.16 (0.11–0.23)
11 (3–37)
16 (7–38)
668 (94–4752)
0.11 (0.07–0.17) 7.0 (4.2–11.7) 81 (25–259) ∞
0.12 (0.08–0.19) 9.0 (4.9–16.6) 100 (32–317) ∞
The upper panel shows the data for Thermo Fisher EliA, whereas the lower panel shows the data for Inova QUANTA FLASH. ULN, upper limit of normal. Bold values represent likelihood ratios and the 95% confidence interval (in parenthesis).
anti-tTG (p
Matthijs Oyaert, Pieter Vermeersch, Gert De Hertogh, Martin Hiele, Nathalie Vandeputte, Ilse Hoffman and Xavier Bossuyt*
Combining antibody tests and taking into account antibody levels improves serologic diagnosis of celiac disease DOI 10.1515/cclm-2013-1099 Received December 21, 2013; accepted January 9, 2015
Abstract Background: The European Society for Pediatric Gastroenterology and Nutrition states that if IgA anti-tissue transglutaminase (tTG) exceeds 10 times the upper limit of normal (ULN), there is the possibility to diagnose celiac disease (CD) without duodenal biopsy, if supported by anti-endomysium testing and human leukocyte antigen (HLA) typing. We aimed to evaluate whether combining IgA tTG and IgG anti-deamidated gliadin peptide (DGP) antibody testing and taking into account the antibody levels improves clinical interpretation. Methods: We calculated likelihood ratios for various test result combinations using data obtained from newly diagnosed CD patients (n = 156) [13 children 16 years)] and 974 disease controls. All patients and controls underwent duodenal biopsy. IgA anti-tTG and IgG anti-DGP assays were from Thermo Fisher and Inova. *Corresponding author: Xavier Bossuyt, MD, PhD, Laboratory Medicine, Immunology, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium, Phone: +32 16 347009, Fax: +32 16 347931, E-mail: [email protected]; Department of Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium; and Department of Microbiology and Immunology, KU Leuven – University of Leuven, Leuven, Belgium Matthijs Oyaert: Department of Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium Pieter Vermeersch: Department of Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium; and Department of Cardiovascular Sciences, KU Leuven – University of Leuven, Leuven, Belgium Gert De Hertogh: Department of Pathology, University Hospital Leuven, Leuven, Belgium Martin Hiele: Department of Gastroenterology, University Hospitals Leuven, Leuven, Belgium Nathalie Vandeputte: Werfen Benelux N.V./S.A, Excelsiorlaan 48-50, Bus 8, Zaventem, Belgium Ilse Hoffman: Department of Pediatrics, University Hospitals Leuven, Leuven, Belgium
Results: Likelihood ratios for CD markedly increased with double positivity and increasing antibody levels of IgA anti-tTG and IgG anti-DGP. Patients with double positivity and high antibody levels ( > 3 times, > 10 times ULN) had a high probability for having CD (likelihood ratio ≥ 649 for > 3 times ULN and ∞ for > 10 times ULN). The fraction of CD patients with double positivity and high antibody levels was 59%–67% (depending on the assay) for > 3 ULN and 33%–36% (depending on the assay) for > 10 ULN, respectively. This fraction was significantly higher in children with CD than in adults. Conclusions: Combining IgG anti-DGP with IgA anti-tTG and defining thresholds for antibody levels improves the serologic diagnosis of CD. Keywords: anti-deamidated gliadin; anti-tissue transglutaminase; celiac disease; likelihood ratio.
Introduction The diagnosis of celiac disease (CD) relies on symptoms, serology and histology. The European Society for Pediatric Gastroenterology and Nutrition (ESPGHAN) has recently put forward new criteria for the diagnosis of CD [1]. In these newly proposed guidelines, it is stated that patients with a clinical suspicion of CD should be tested for IgA antitissue transglutaminase (tTG) and total IgA (to exclude IgA deficiency) [1]. If IgA anti-tTG exceeds 10 times the upper limit of normal (ULN), there is the possibility to diagnose CD without duodenal biopsy, if supported by anti-endomysium testing and human leukocyte antigen (HLA) typing [1]. Follow-up testing by anti-endomysium antibodies (EMA) has been proposed by ESPGHAN because of the high specificity these antibodies confer for CD. However, antiEMA are directed against tTG and, therefore, test results for anti-tTG and anti-EMA should be highly agreeable. Determining antibodies to deamidated gliadin might be a theoretically attractive substitute to EMA as it might not only improve specificity but also sensitivity [2]. Moreover,
Brought to you by | University of California - San Francisco Authenticated Download Date | 3/2/15 11:27 PM
2 Oyaert et al.: Serologic diagnosis of celiac disease
quantification of anti-deamidated gliadin peptide (DGP) antibodies can be automated and, therefore, is an appealing alternative for the more expensive (manual) EMA. A detailed analysis of combining anti-tTG and anti-DGP antibodies for the diagnosis of CD is needed [3]. In previous studies, we showed that the likelihood for CD increases 1) with increasing antibody concentration for either IgA anti-tTG or IgG anti-DGP; and 2) with the simultaneous presence of anti-tTG and anti-DGP antibodies [2, 4–6]. In the present study we illustrate the value of taking into account the combination of IgA anti-tTG and IgG anti-DGP as well as the antibody level in the diagnosis of CD. The analysis was done for automated commercial assays from two different manufacturers (Thermo Fisher and Inova).
biopsy and in patients with Marsh I or II lesions on intestinal biopsy that responded to a gluten-free diet serologically or on intestinal biopsy. The diagnosis of non-CD was considered confirmed when intestinal biopsy showed Marsh 0 or Marsh I/Marsh II and the morphologic lesion could be explained by another disease, such as Helicobacter pylori gastritis or giardiasis. Patients who were diagnosed previously with CD or who were on a gluten-free diet were excluded. Selective IgA deficiency (IgA 10 × ULN
12/0/1 2/0/0 1/1/0 3/4/0
2/0/0 3/0/0 1/0/0 0/1/0
0/0/0 3/2/0 8/2/0 3/0/0
2/1/0 11/2/0 23/10/2 24/22/10
C EliA IgG anti-DGP Neg 1–3 × ULN 3–10 × ULN > 10 × ULN
543/202/190 11/8/4 1/0/2 0/0/0
7/2/1b 0/1c/0 0/0/0 0/0/0
1/0/0 0/0/0 0/0/0 0/0/0
0/0/0 1a/0/0 0/0/0 0/0/0
D Quanta Flash IgG anti-DGP Neg 1–3 × ULN 3–10 × ULN > 10 × ULN
557/202/189 3/4/5 0/0/2 0/0/0
2/2/1b 0/0/0 0/0/0 0/0/0
1/2e/0 0/4c,d/0 0/0/0 0/0/0
0/0/0 0/0/0 1a/0/0 0/0/0
(A and B) Distribution of IgA anti-tTG and IgG anti-DGP in CD patients with biopsy proven CD (n = 156). Panel A shows the data for EliA, whereas panel B shows the data for QUANTA FLASH. (C and D). Distribution of IgA anti-tTG and IgG anti-DGP in disease controls (verified by biopsy) (n = 974). Panel C shows the data for EliA, whereas panel D shows the data for QUANTA FLASH. Three values are given, respectively, for the three age groups, ≥ 16 years old, between 2 and 15 years old and ≤ 2 years old. ULN, upper limit of normal. Patient history [only patients with anti-endomysium antibodies (EMA) and positive serology for one or both anti-tTG assays]: aanti-EMA +++, patient diagnosed with auto-immune hepatitis, Gilbert’s syndrome and Graves thyroiditis; banti-EMA ++, initial biopsy indicated hyperemic gastritis, follow-up biopsy revealed no arguments for CD; canti-EMA +, no arguments for CD were found on initial and follow-up duodenal biopsy; danti-EMA +, patient with congenital spherocytosis, no arguments for CD on initial and followup duodenal biopsies; eanti-EMA +, patient diagnosed with reflux esophagitis grade A, no arguments for CD on biopsy.
and likelihood ratios (Table 3). For IgG anti-DGP, specificity was 100% for values exceeding 10 times ULN for both assays (Table 3).
A total of 7.7% and 8.3% (EliA and QUANTA FLASH, respectively) of the patients with CD tested negative for both IgA anti-tTG and IgG anti-DGP (Table 3). These patients tested negative for anti-EMA. A total of 14.1% and 10.3% (EliA and QUANTA FLASH, respectively) of the patients tested single positive (i.e., positive for one test and negative for the other test) (Table 3). Double positivity for IgA anti-tTG and IgG anti-DGP was found in 78.2% and 81.4% of the patients (EliA and QUANTA FLASH, respectively) and in 10 and double positivity with antibody levels > 10 times ULN had a likelihood ratio of ∞.
Sensitivities, specificities and likelihood ratios for children and adults IgA anti-tTG and IgG anti-DGP double positivity ( > 10 ULN) was found in 24.5% (24/98) of the patients older
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Oyaert et al.: Serologic diagnosis of celiac disease 5
Table 3 Sensitivity, specificity and likelihood ratio (with 95% confidence intervals): 1) for various test combinations of IgA-anti-tTG and IgG anti-DGP; 2) for IgA anti-tTG; and 3) for IgG anti-DGP. IgA anti-tTG/IgG anti-DGP
Sensitivity, %
Specificity, %
Likelihood ratio
96.0 (94.6–97.1) 97.3 (96.1–98.3)
0.08 (0.05–0.14) 0.09 (0.05–0.14)
96.2 (94.8–97.3) 97.8 (96.7–98.7)
3.7 (2.3–6.1) 4.8 (2.5–8.9)
99.8 (99.3–100.0) 99.5 (98.8–99.8)
381 (95–1524) 159 (66–381)
100.0 (99.6–100.0) 99.9 (99.4–100.0)
∞ 649 (91–4620)
100.0 (99.6–100.0) 100.0 (99.6–100.0)
∞ ∞
80.8 (73.7–86.6) 84.6 (78.0–89.9)
98.7 (97.7–99.3) 98.8 (97.9–99.4)
61 (35–104) 69 (39–121)
72.4 (64.7–79.3) 80.1 (73.0–86.1)
99.8 (99.3–100.0) 99.2 (98.4–99.6)
353 (88–1413) 98 (49–195)
51.9 (43.8–60.0) 68.6 (60.5–75.0)
99.9 (99.4–100.0) 99.9 (99.4–100.0)
506 (71–3608) 668 (94–4752)
89.7 (83.9–94.0) 88.5 (82.4–93.0)
97.1 (95.9–98.1) 98.1 (97.0–98.8)
31 (22–45) 45 (29–71)
71.8 (64.0–78.7) 73.7 (66.1–80.4)
99.7 (99.1–99.9) 99.7 (99.1–99.9)
233 (75–725) 239 (77–744)
46.8 (38.8–54.9) 43.0 (35.1–51.1)
100.0 (99.6–100.0) 100.0 (99.6–100.0)
∞ ∞
Double negative Thermo Fisher EliA 7.7 (4.04–13.1) Inova Quanta Flash 8.3 (4.51–13.8) Positive for one test and negative for the other test Thermo Fisher EliA 14.1 (9.4–20.6) Inova Quanta Flash 10.3 (6.0–16.1) Double positivity 1 × ULN Thermo Fisher EliA 78.2 (70.9–84.4) Inova Quanta Flash 81.4 (74.3–96.7) Double positivity 3 × ULN Thermo Fisher EliA 59.0 (50.8–66.1) Inova Quanta Flash 66.7 (58.7–74.0) Double positivity 10 × ULN Thermo Fisher EliA 32.7 (25.6–40.2) Inova Quanta Flash 35.9 (28.4–44.0) IgA anti-tTG 1 × ULN Thermo Fisher EliA Inova Quanta Flash 3 × ULN Thermo Fisher EliA Inova Quanta Flash 10 × ULN Thermo Fisher EliA Inova Quanta Flash IgG anti-DGP 1 × ULN Thermo Fisher EliA Inova Quanta Flash 3 × ULN Thermo Fisher EliA Inova Quanta Flash 10 × ULN Thermo Fisher EliA Inova Quanta Flash ULN, upper limit of normal.
than 16 years, in 40.0% (18/45) of the patients aged between 2 and 15 years and in 69.2% (9/13) of the patients younger than 2 years of age. These differences are statistically significant (Fisher’s exact) for comparison of the ≥ 16 years group and the 2–15 years group (p 10 × ULN
Negative
1–3 × ULN
3–10 × ULN
> 10 × ULN
0.08 (0.05–0.14) 1.6 (0.7–3.9) 6.2 (1.3–30.6) ∞
1.3 (0.3–5.7) 18 (2–179) ∞ ∞
12 (1–137) ∞ ∞ ∞
∞ 56.2 (7–440) ∞ ∞
0.19 (0.14–0.27)
7.4 (3.4–16.2)
200 (28–1452)
506 (71–3608)
0.09 (0.05–0.14) 1.0 (0.2–4.6) 6.2 (0.9–44.0) ∞
3.1 (0.6–17) ∞ ∞ ∞
7.8 (2.1–28.8) ∞ ∞
∞ ∞ 219 (30–1584) ∞
0.16 (0.11–0.23)
11 (3–37)
16 (7–38)
668 (94–4752)
0.11 (0.07–0.17) 7.0 (4.2–11.7) 81 (25–259) ∞
0.12 (0.08–0.19) 9.0 (4.9–16.6) 100 (32–317) ∞
The upper panel shows the data for Thermo Fisher EliA, whereas the lower panel shows the data for Inova QUANTA FLASH. ULN, upper limit of normal. Bold values represent likelihood ratios and the 95% confidence interval (in parenthesis).
anti-tTG (p
