Skip to content
Licensed Unlicensed Requires Authentication Published by De Gruyter November 7, 2016

Performance evaluation of ImmunoCAP® ISAC 112: a multi-site study

  • Marianne van Hage , Peter Schmid-Grendelmeier , Chrysanthi Skevaki , Mario Plebani ORCID logo , Walter Canonica , Jörg Kleine-Tebbe , Mats Nystrand , Mehrdad Jafari-Mamaghani and Thilo Jakob

Abstract

Background:

After the re-introduction of ImmunoCAP® ISAC sIgE 112 on the market, we undertook a study to evaluate the performance of this multiplex-based immunoassay for IgE measurements to allergen components.

Methods:

The study was carried out at 22 European and one South African site. Microarrays from different batches, eight specific IgE (sIgE) positive, three sIgE negative serum samples and a calibration sample were sent to participating laboratories where assays were performed according to the manufacturer’s instructions.

Results:

For both the negative and positive samples results were consistent between sites, with a very low frequency of false positive results (0.014%). A similar pattern of results for each of the samples was observed across the 23 sites. Homogeneity analysis of all measurements for each sample were well clustered, indicating good reproducibility; unsupervised hierarchical clustering and classification via random forests, showed clustering of identical samples independent of the assay site. Analysis of raw continuous data confirmed the good accuracy across the study sites; averaged standardized, site-specific ISU-E values fell close to the center of the distribution of measurements from all sites. After outlier filtering, variability across the whole study was estimated at 25.5%, with values of 22%, 27.1% and 22.4% for the ‘Low’, ‘Moderate to High’ and ‘Very High’ concentration categories, respectively.

Conclusions:

The study shows a robust performance of the ImmunoCAP® ISAC 112 immunoassay at different sites. Essentially the same results were obtained irrespective of assay site, laboratory-specific conditions and instruments, operator, or the use of microarrays from different batches.


Corresponding author: Thilo Jakob, MD, Department of Dermatology and Allergology, University Medical Center Gießen (UKGM), Justus Liebig University Gießen, Gaffkystr. 14, 35385 Giessen, Germany; and Allergy Research Group, Department of Dermatology, University Medical Center Freiburg, Germany

Acknowledgments

Anna-Britta Johansson, Lab technician, Department of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, Stockholm, Sweden. Martin Glatz, MD, Sara Micaletto, MD, Vanessa Virgini, MD and Muriel Traexler, Lab Technician, all Allergy Unit, Department of Dermatology, University Hospital of Zürich, Switzerland. Andrea Komann and Heike Neumann, Lab technician, Allergy Research Group, Department of Dermatology, University Medical Center Freiburg, Germany.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: TJ has received research grants, speakers and consultancy fees as well as travel support from Phadia/Thermo Fisher Scientific, Uppsala Sweden. MvH has received research support and speaker fees from Phadia/Thermo Fisher Scientific, Uppsala, Sweden. PSG has received research support, speaker and consultancy fees from Phadia/ Thermo Fisher Scientific, Uppsala, Sweden. MP has received research support and speaker fees from Phadia/Thermo Fisher Scientific, Uppsala, Sweden. GWC reports having received research grants as well as lecture or advisory board fees from Phadia/Thermo Fisher Scientific, Uppsala, Sweden. JK-T has received institutional research grants and lecture fees from Phadia/Thermo Fisher Scientific, Uppsala, Sweden. No direct conflict of interest exists regarding the presented work.

  3. Employment or leadership: MN and MJM are employees at Thermo Fisher Scientific, Uppsala, Sweden.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

References

1. Mari A, Iacovacci P, Afferni C, Barletta B, Tinghino R, Di Felice G, et al. Specific IgE to cross-reactive carbohydrate determinants strongly affect the in vitro diagnosis of allergic diseases. J Allergy Clin Immunol 1999;103:1005–11.10.1016/S0091-6749(99)70171-5Search in Google Scholar

2. Passalacqua G, Melioli G, Bonifazi F, Bonini S, Maggi E, Senna G, et al. The additional values of microarray allergen assay in the management of polysensitized patients with respiratory allergy. Allergy 2013;68:1029–33.10.1111/all.12194Search in Google Scholar PubMed

3. Canonica GW, Ansotegui IJ, Pawankar R, Schmid-Grendelmeier P, van Hage M, Baena-Cagnani CE, et al. A WAO – ARIA – GA(2)LEN consensus document on molecular-based allergy diagnostics. World Allergy Organ J 2013;6:17.10.1186/1939-4551-6-17Search in Google Scholar PubMed PubMed Central

4. Valenta R, Lidholm J, Niederberger V, Hayek B, Kraft D, Gronlund H. The recombinant allergen-based concept of component-resolved diagnostics and immunotherapy (CRD and CRIT). Clin Exp Allergy 1999;29:896–904.10.1046/j.1365-2222.1999.00653.xSearch in Google Scholar PubMed

5. Incorvaia C, Fuiano N, Canonica GW. Seeking allergy when it hides: which are the best fitting tests? World Allergy Organ J 2013;6:11.10.1186/1939-4551-6-11Search in Google Scholar PubMed PubMed Central

6. Kleine-Tebbe PD, Jakob T. Molecular allergy diagnostics using IgE singleplex determinations: methodological and practical considerations for use in clinical routine. Allergo J Int 2015;24:185–97.10.1007/s40629-015-0067-zSearch in Google Scholar PubMed PubMed Central

7. Hiller R, Laffer S, Harwanegg C, Huber M, Schmidt WM, Twardosz A, et al. Microarrayed allergen molecules: diagnostic gatekeepers for allergy treatment. FASEB J 2002;16:414–6.10.1096/fj.01-0711fjeSearch in Google Scholar PubMed

8. Harwanegg C, Hiller R. Protein microarrays for the diagnosis of allergic diseases: state-of-the-art and future development. Clin Chem Lab Med 2005;43:1321–6.10.1515/CCLM.2005.226Search in Google Scholar PubMed

9. Jakob T, Forstenlechner P, Matricardi P, Kleine-Tebbe J. Molecular allergy diagnostics using multiplex assays: methodological and practical considerations for use in research and clinical routine. Allergo J Int 2015;24:320–32.10.1007/s40629-015-0087-8Search in Google Scholar PubMed PubMed Central

10. Gadisseur R, Chapelle JP, Cavalier E. A new tool in the field of in-vitro diagnosis of allergy: preliminary results in the comparison of ImmunoCAP® 250 with the ImmunoCAP® ISAC. Clin Chem Lab Med 2011;49:277–80.10.1515/CCLM.2011.052Search in Google Scholar PubMed

11. Martinez-Aranguren R, Lizaso MT, Goikoetxea MJ, Garcia BE, Cabrera-Freitag P, Trellez O, et al. Is the determination of specific IgE against components using ISAC 112 a reproducible technique? PLoS One 2014;9:e88394.10.1371/journal.pone.0088394Search in Google Scholar PubMed PubMed Central

12. Cabrera-Freitag P, Goikoetxea MJ, Gamboa PM, Martinez-Aranguren R, Beorlegui C, Fernandez J, et al. A study of the variability of the in vitro component-based microarray ISAC CDR 103 technique. J Investig Allergol Clin Immunol 2011;21:414–5.Search in Google Scholar

13. Choi JS, Roh JY, Lee JR. Clinical availability of component-resolved diagnosis using microarray technology in atopic dermatitis. Ann Dermatol 2014;26:437–46.10.5021/ad.2014.26.4.437Search in Google Scholar PubMed PubMed Central

14. Lizaso MT, Garcia BE, Tabar AI, Lasa E, Echechipia S, Alvarez MJ, et al. Comparison of conventional and component-resolved diagnostics by two different methods (Advia-Centaur/Microarray-ISAC) in pollen allergy. Ann Allergy Asthma Immunol 2011;107:35–41.10.1016/j.anai.2011.03.017Search in Google Scholar PubMed

15. Huss-Marp PD, Gutermuth J, Schäffner I, Darsow U, Pfab F, Brockow K, et al. Comparison of molecular and extract-based allergy diagnostics with multiplex and singleplex analysis. Allergo J Int 2015;24:46–53.10.1007/s40629-015-0046-4Search in Google Scholar PubMed PubMed Central

16. Lupinek C, Wollmann E, Baar A, Banerjee S, Breiteneder H, Broecker BM, et al. Advances in allergen-microarray technology for diagnosis and monitoring of allergy: the MeDALL allergen-chip. Methods 2014;66:106–19.10.1016/j.ymeth.2013.10.008Search in Google Scholar PubMed PubMed Central

17. Melioli G, Bonifazi F, Bonini S, Maggi E, Mussap M, Passalacqua G, et al. The ImmunoCAP ISAC molecular allergology approach in adult multi-sensitized Italian patients with respiratory symptoms. Clin Biochem 2011;44:1005–11.10.1016/j.clinbiochem.2011.05.007Search in Google Scholar PubMed

18. Ahlgrim C, Gutermuth J, Onell A, Borres MP, Schaffner I, Darsow U, et al. Comparison of molecular multiplex and singleplex analysis of ige to grass pollen allergens in untreated german grass pollen-allergic patients. J Investig Allergol Clin Immunol 2015;25:190–5.Search in Google Scholar

19. Williams P, Onell A, Baldracchini F, Hui V, Jolles S, El-Shanawany T. Evaluation of a novel automated allergy microarray platform compared with three other allergy test methods. Clin Exp Immunol 2016;184:1–10.10.1111/cei.12721Search in Google Scholar PubMed PubMed Central

20. Ott H, Weissmantel S, Kennes LN, Merk HF, Baron JM, Folster-Holst R. Molecular microarray analysis reveals allergen- and exotoxin-specific IgE repertoires in children with atopic dermatitis. J Eur Acad Dermatol Venereol 2014;28:100–7.10.1111/jdv.12083Search in Google Scholar PubMed

21. Carter S, Heaps A, Boswijk K, Jolles S, Kaminski E. Identification of clinically relevant allergens using the Phadia ISAC microarray in patients with idiopathic anaphylaxis. Clin Exp Allergy 2012;42:1829–30.Search in Google Scholar

22. Heaps A, Carter S, Selwood C, Moody M, Unsworth J, Deacock S, et al. The utility of the ISAC allergen array in the investigation of idiopathic anaphylaxis. Clin Exp Immunol 2014;177:483–90.10.1111/cei.12334Search in Google Scholar PubMed PubMed Central

23. Nordlund B, Konradsen JR, Kull I, Borres MP, Onell A, Hedlin G, et al. IgE antibodies to animal-derived lipocalin, kallikrein and secretoglobin are markers of bronchial inflammation in severe childhood asthma. Allergy 2012;67:661–9.10.1111/j.1398-9995.2012.02797.xSearch in Google Scholar PubMed

24. Ackerbauer D, Bublin M, Radauer C, Varga EM, Hafner C, Ebner C, et al. Component-resolved IgE profiles in Austrian patients with a convincing history of peanut allergy. Int Arch Allergy Immunol 2015;166:13–24.10.1159/000371422Search in Google Scholar PubMed

25. Schuler S, Ferrari G, Schmid-Grendelmeier P, Harr T. Microarray-based component-resolved diagnosis of latex allergy: isolated IgE-mediated sensitization to latexprofilin Hev b8 may act as confounder. Clin Transl Allergy 2013;3:11.10.1186/2045-7022-3-11Search in Google Scholar PubMed PubMed Central

26. Letran A, Espinazo M, Moreno F. Measurement of IgE to pollen allergen components is helpful in selecting patients for immunotherapy. Ann Allergy Asthma Immunol 2013;111:295–7.10.1016/j.anai.2013.07.005Search in Google Scholar PubMed

27. Sastre J, Landivar ME, Ruiz-Garcia M, Andregnette-Rosigno MV, Mahillo I. How molecular diagnosis can change allergen-specific immunotherapy prescription in a complex pollen area. Allergy 2012;67:709–11.10.1111/j.1398-9995.2012.02808.xSearch in Google Scholar PubMed

28. Asero R. Component-resolved diagnosis-assisted prescription of allergen-specific immunotherapy: a practical guide. Eur Ann Allergy Clin Immunol 2012;44:183–7.Search in Google Scholar

29. Wollmann E, Lupinek C, Kundi M, Selb R, Niederberger V, Valenta R. Reduction in allergen-specific IgE binding as measured by microarray: a possible surrogate marker for effects of specific immunotherapy. J Allergy Clin Immunol 2015;136:806–80.10.1016/j.jaci.2015.02.034Search in Google Scholar PubMed PubMed Central

30. Asarnoj A, Hamsten C, Waden K, Lupinek C, Andersson N, Kull I, et al. Sensitization to cat and dog allergen molecules in childhood and prediction of symptoms of cat and dog allergy in adolescence: A BAMSE/MeDALL study. J Allergy Clin Immunol 2016;137:813–21 e7.10.1016/j.jaci.2015.09.052Search in Google Scholar PubMed PubMed Central

31. Scala E, Alessandri C, Bernardi ML, Ferrara R, Palazzo P, Pomponi D, et al. Cross-sectional survey on immunoglobulin E reactivity in 23,077 subjects using an allergenic molecule-based microarray detection system. Clin Exp Allergy 2010;40:911–21.10.1111/j.1365-2222.2010.03470.xSearch in Google Scholar PubMed

32. Rossi RE, Melioli G, Monasterolo G, Harwanegg C, Rossi L, Canonica GW, et al. Sensitization profiles in polysensitized patients from a restricted geographical area: further lessons from multiplexed component resolved diagnosis. Eur Ann Allergy Clin Immunol 2011;43:171–5.Search in Google Scholar

33. Burney PG, Potts J, Kummeling I, Mills EN, Clausen M, Dubakiene R, et al. The prevalence and distribution of food sensitization in European adults. Allergy 2014;69:365–71.10.1111/all.12341Search in Google Scholar PubMed

34. Panzner P, Vachova M, Vitovcova P, Brodska P, Vlas T. A comprehensive analysis of middle-European molecular sensitization profiles to pollen allergens. Int Arch Allergy Immunol 2014;164:74–82.10.1159/000362760Search in Google Scholar PubMed

35. Onell A, Hjalle L, Borres MP. Exploring the temporal development of childhood IgE profiles to allergen components. Clin Transl Allergy 2012;2:24.10.1186/2045-7022-2-24Search in Google Scholar PubMed PubMed Central

36. Hatzler L, Panetta V, Lau S, Wagner P, Bergmann RL, Illi S, et al. Molecular spreading and predictive value of preclinical IgE response to Phleum pratense in children with hay fever. J Allergy Clin Immunol 2012;130:894–901 e5.10.1016/j.jaci.2012.05.053Search in Google Scholar PubMed

37. Simpson A, Lazic N, Belgrave DC, Johnson P, Bishop C, Mills C, et al. Patterns of IgE responses to multiple allergen components and clinical symptoms at age 11 years. J Allergy Clin Immunol 2015;136:1224–31.10.1016/j.jaci.2015.03.027Search in Google Scholar PubMed PubMed Central

38. De Leeuw J, Mair P. Gifi methods for optimal scaling in R: the package homals. Stat Softw 2009;31:1–30.Search in Google Scholar

39. Friedman J, Hastie T, Tibshirani R. The elements of statistical learning: Springer series in statistics. Berlin: Springer, 2001.10.1007/978-0-387-21606-5Search in Google Scholar

40. Breunig MM, Kriegel HP, Ng RT, Sander J. LOF: identifying density-based local outliers. ACM sigmod record; 2000;29:93–104.10.1145/342009.335388Search in Google Scholar

41. Villalta D, Asero R. Is the detection of IgE to multiple Bet v 1-homologous food allergens by means of allergen microarray clinically useful? J Allergy Clin Immunol 2010;125:1158–61.10.1016/j.jaci.2010.01.043Search in Google Scholar PubMed

42. Fleiss J. Design and analysis of clinical experiments. New York: John Wiley & Sons, 1986.Search in Google Scholar


Supplemental Material:

The online version of this article (DOI: 10.1515/cclm-2016-0586) offers supplementary material, available to authorized users.


Received: 2016-7-1
Accepted: 2016-9-20
Published Online: 2016-11-7
Published in Print: 2017-3-1

©2017 Walter de Gruyter GmbH, Berlin/Boston

Downloaded on 19.3.2024 from https://www.degruyter.com/document/doi/10.1515/cclm-2016-0586/html
Scroll to top button