Several initiatives have been undertaken, independent of the European Autoantibody Standardization Initiative (EASI), to standardize autoantibodies in the Netherlands. The Dutch EASI team has made an inventory of which initiatives on autoantibody standardization are already available and what future plans for autoantibody standardization exist. This inventory will subsequently be used to define whatmay be addressed by the Dutch EASI team. The Diagnostic Compass, initiated by the association of Dutch health insurance companies, describes methods and relevance of laboratory tests, including autoantibody tests. Recently, this initiative has been taken over by an independent publisher. There is also a national organization involved in developing guidelines in medicine, including guidelines for autoantibody testing. In addition, there is a national foundation for quality assessment in clinical laboratories (SKML). The quality assessment includes a wide array of autoantibodies. Samples are collected and thoroughly investigated by reference laboratories. Interpretation of results and advice to clinicians are part of the program. Feedback on the results of this proficiency testing is given in reports and during meetings to discuss trends, technical issues, and new developments. The last initiative that we discuss is the foundation Referentie Laboratorium Reuma Serologie (RELARES),which was founded to standardize serology in rheumatic diseases by preparing standard sera. Recently, RELARES has been combined with SKML. A new SKMLworking group, Standardization Autoimmune Serology, has been initiated to continue the work of RELARES. When comparing the already available Dutch initiatives to the international EASI goals, there appears to be a lack of harmonization in testing algorithms, and this issue is the most important topic to be addressed in the near future.

Impact
This publication is mainly an overview of the network of distinct organisations, including the Dutch EASI-team, working in the field of autoimmune diagnostics. Since there is substantial overlap in the people involved, there is optimal collaboration in order to achieve the goals of EASI.

Damoiseaux J, Bakker-Jonges L, Cohen Tervaert JW, Derksen R, Hooijkaas H, Kallenberg C, Klasen I, Limburg P, Smeenk R, and Hamann D (2010). Laboratoriumdiagnostiek van ANA, anti-ds-DNA- en anti-ENA-antistoffen: aanbevelingen naar aanleiding van een enquête. Ned Tijdschr Klin Chem Labgeneesk 2010;35:234-239. (in Dutch)

Abstract
To gain insight in the laboratory diagnostics of auto-antibodies to nuclear antigens (ANA, anti-dsDNA- and anti-ENA-anti¬bodies), the Dutch EASI-team has prepared a questionnaire in collaboration with SKML. This questionnaire has been distributed to all participants of the external quality assessment program for these auto-antibodies, as organized by SKML. Due to the high response (87%), the Dutch situation has been very well documented. The results are summarized in this paper and, in addition, recommendations of the Dutch EASI-team are given. Although these recommendations are not to be used as official guidelines, they may harmonize and improve the detection of auto-antibodies to nuclear antigens.

Impact
The questionnaire has been translated in English and has been used by many other national EASI-teams. This has resulted in national publications in other countries (Van Blerk et al. Acta Clin Belgica 2014;69:83-86) as well as in an overview of the European situation as far as countries have participated (Damoiseaux et al, Clin Exp Rheum 2014;32:539-546). In collaboration with the International Society for Immunological Societies (IUIS) a set of recommendations have been published (Agmon-Levin et al, Ann Rheum Dis 2014;73:17-23).

Molen RG van der, Roozendaal C, and Damoiseaux J. Detectie van ANCA in Nederlandse laboratoria: de klinische praktijk in relatie tot de internationale consensus en nationale richtlijn. Ned Tijdschr Klin Chem Labgeneesk 2014;39:19-24. (in Dutch)

Abstract
To gain insight in the laboratory diagnostics performed in the Netherlands for anti-neutrophil cytoplasmic antibody (ANCA), a questionnaire was sent to all Dutch diagnostic laboratories (n=50) who participate in the Dutch quality assessment (SKML) ANCA-GBM program. Due to the high response (86%), the Dutch situation has been very well documented. The results are summarized in this paper and compared to the International Consensus Statement on Testing and Reporting of ANCA (1999) and the Dutch CBO guidelines on small vessel vasculitis (2010). Major conclusions resulting from the questionnaire are that international and national guidelines are not consequently applied by all labs. However, it should be noted that with the development of new test systems, current guidelines need revision.

Impact
The questionnaire has been translated in English and has been used by many other national EASI-teams. This has resulted in an overview of the European situation as far as countries have participated (Damoiseaux et al, Clin Chem Lab Med 2018; in press).

Damoiseaux J, Bossuyt X, Broeders S, Hamann D, Leeuw K de, Limper M, Otten H, Roozendaal C, Schouwers S, Schreurs M, Thurlings R, Daele P van, Molen R van der, Van Hoovels L, Vercammen M, Bonroy C. International Consensus on ANA Patterns (ICAP): inbedding in het Nederlandse taalgebied. Laboratoriumgeneeskunde 2018;1:17-26. (in Dutch)

Abstract
In order to establish harmonization in reporting results of autoimmune diagnostics, just a few years ago international consensus was reached about the nomenclature and definitions of HEp-2 patterns obtained by indirect immunofluorescence (IIF). This test is applied to detect anticellular antibodies that are generally reported as anti-nuclear antibodies (ANA). These antibodies play a crucial role in the diagnostic work-up of systemic autoimmune rheumatic diseases. In close collaboration between the Belgian and Dutch EASI-teams the consensus is made available for the Dutch-speaking areas. Starting point is the widespread use of the Dutch names for the distinct HEp-2 patterns in both the Dutch and Flemish clinical laboratories.

Impact
Translation of the ICAP nomenclature and pattern definitions enables harmonization of the reporting of test results. Importantly, also the external quality assessment as organized by the SKML currently ask for reporting according to ICAP nomenclature. The translation has come accross in close collaboration with the Belgian EASI-team.

Mulder L, Molen R van der, Koelman C, Leeuwen E van, Roos A, Damoiseaux J. Validation conform ISO-15189 of assays in the field of autoimmunity: joint efforts in The Netherlands. Autoimmun Rev 2018;17:513-517.

Abstract
ISO 15189:2012 requires validation of methods used in the medical laboratories, and lists a series of performance parameters for consideration to include. Although these performance parameters are feasible for clinical chemistry analytes, application in the validation of autoimmunity tests is a challenge. Lack of gold standards or reference methods in combination with the scarcity of well-defined diagnostic samples of patients with rare diseases make validation of new assays difficult. The present manuscript describes the initiative of Dutch medical immunology laboratory specialists to combine efforts and perform multi-center validation studies of new assays in the field of autoimmunity. Validation data and reports are made available to interested Dutch laboratory specialists.

Impact
Since the introduction of this initiative several assays have been validated according to the proposed algorithm. Although this is not an EASI-initiative, the proposed algorithm can easily be used by EASI-teams in other countries and this is also in accordance with a possible role of EASI in assisting laboratories in the process of accreditation (Bizzaro et al. Autoimmun Rev 2017;16-81-86).

Current Activities:

A follow-up questionnaire has been distributed about the ANA-dsDNA-ENA algorithm that is currently being used in the Dutch autoimmune laboratories. The goal is to find out if laboratories adhere to the Dutch recommendations. If laboratories follow the recommendation it is asked if this is the result of an adjustment; if laboratories do not adhere to the recommendation it is asked to give an argument. The responses are currently being analysed and the expectation is that the recommendations might be slightly adjusted and be included in a national guideline.
The Dutch EASI-team participates in the project of the Belgian EASI-team to explore how ICAP is anticipated on the one hand by laboratory specialists and on the other hand by rheumatologists and clinical immunologists. Results will eventually be analysed by the Belgian EASI-team.