Overall, the relation between these two cytoplasmic HEp-2 IIFA patterns and the distinct anti-tRNA synthetase antibodies is subject to further discussion. around the clinical relevance of the 29 distinct HEp-2 IIFA patterns. This clinical relevance JNJ 303 is primarily defined within the context of the suspected disease and includes recommendations for follow-up testing. The discussion includes how this information may benefit the clinicians in daily practice and how the knowledge can be used to further improve diagnostic and classification criteria. Keywords:antinuclear antibodies, indirect immunofluorescence, clinical interpretation, ANA patterns == Introduction == Autoantibodies, as detected by the indirect immunofluorescence assay (IIFA) on HEp-2 cells (IIFA HEp-2), are recognised as important diagnostic markers in a plethora of autoimmune diseases, in particular the systemic autoimmune rheumatic diseases (SARD).1Although somewhat dated by todays standards, members of the American College of Rheumatology (ACR) prepared an evidence-based guideline for the usefulness of the HEp-2 IIFA results for diagnostic and prognostic purposes and also for meeting diagnostic criteria.2That guideline was based on reactivity with nuclear antigens as detected by IIFA on rodent tissue or HEp-2 cells. More recently, the IIFA on HEp-2 cells was reinforced as the gold standard JNJ 303 for autoantibody screening in SARD.3 Interestingly, the HEp-2 IIFA test reveals much more information than the mere absence or presence of autoantibodies, that is, the level of antibody as well as the HEp-2 IIFA pattern. Based on titration or appropriate evaluation of the fluorescence intensity, the antibody level can be determined and this information has general concordance with the clinical relevance of the test result. Indeed, higher antibody levels are better associated with SARD and have an increased likelihood to identify the autoantigen in follow-up testing.46The importance of the level of autoantibodies is also recognised in the ACR guideline as well as by the recommendations issued by the European Autoimmunity Standardization Initiative (EASI) and the International Union of Immunologic Societies (IUIS) Autoantibody Standardization Subcommittee.2 7 The HEp-2 IIFA pattern may also reveal clinically relevant information. This information is not restricted to giving direction to follow-up testing for antigen-specificity, but, for instance, the centromere pattern is included in the classification criteria for systemic sclerosis,8while the nuclear dense fine speckled pattern is usually reported to be more prevalent in apparently healthy individuals as compared with patients with SARD.9To harmonise the names and descriptions of the distinct HEp-2 IIFA patterns, an ordered classification taxonomy was proposed.10This proposal was subsequently elaborated on by the International Consensus on ANA Patterns (ICAP), initiated in parallel to the 12th International Workshop on Autoantibodies and Autoimmunity (2014) held in Sao Paulo, Brazil. During this workshop, a consensus was reached around the nomenclature and definitions of 28 HEp-2 IIFA patterns. Each HEp-2 IIFA pattern was ascribed an alphanumeric code from AC-1 to AC-28.11The consensus nomenclature for each pattern and representative images were also made available online at the ICAP website (http://www.ANApatterns.org). In addition to the nuclear patterns, important cytoplasmic and mitotic patterns may also be observed in HEp-2 IIFA analysis. Although reporting non-nuclear patterns is considered clinically relevant,7for various jurisdictional reasons there is no clear-cut consensus viewpoint on reporting non-nuclear patterns JNJ 303 as a negative or positive test.12With the understanding that the term Antinuclear antibody (ANA) test may be inappropriate to designate a test Mouse Monoclonal to Rabbit IgG (kappa L chain) that also addresses autoantibodies to antigens in the cytoplasm and mitotic apparatus, an alternative name, anticellular antibodies, was suggested in the EASI/IUIS recommendations.7Recent publications from ICAP have preferred the term HEp-2 IIFA as it covers the whole spectrum of patterns that can be observed when using the HEp-2 cells as substrate.13 14 Originally, the HEp-2 IIFA patterns were associated with diseases, but it was anticipated that many of these associations are only valid if the antigen-specificity was confirmed by follow-up testing. In subsequent ICAP workshops, it was agreed that the disease associations should be replaced by clinical relevance. In this current paper, we present the consensus around the clinical relevance of the distinct HEp-2 IIFA patterns JNJ 303 as achieved by consecutive workshops and discussions among the executive ICAP members. == Materials and methods == For discussion about the structure of clinical relevance templates were prepared for AC-2 (LECA), AC-3 (JD) and AC-5 (MS). This formed the basis of JNJ 303 a guideline for description of each AC pattern (EC). Of highest importance, it was agreed that the information should be objective and helpful for the clinician, the patternantigen associations should be put in the right clinical context and information should be evidence-based. In preparation for the third ICAP workshop in Kyoto (2016), composition of the clinical relevance files was started.