Missing links in high quality diagnostics of inflammatory systemic rheumatic diseases: It is all about the patient!

The aim of this review is to focus attention on high quality diagnostics of systemic inflammatory rheumatic diseases. Though many steps in the diagnostic process from the first visit in a doctor's office till a final diagnosis have been established a lot of things still must be done to improve quality assurance and secure fast and safe transmission of data from one step to the next. Some procedures inherent in early high quality diagnostics need to be worked out. A number of elements can be improved, some stumble stones can be removed, and a tighter collaboration between actors at different levels in the line of action in clinical and laboratory medicine can be organized. Several proposals have been made by international working groups such as the IUIS International Autoantibody Standardization Committee, and the EASI steering group in collaboration with their national EASI teams. Practical exercises carried out for more than three decades by the European Consensus Finding Study Group have proven to very useful. The review points at several principles worked out by these international expert groups can be useful in actual daily practice also in rheumatology. The hope is that the presentation will give rise to a continued discussion on how to link different parts of the diagnostic process together and strengthen collaboration between all teams involved in the diagnostic chain. The ultimate measure of success will be better clinical outcomes for patients and increased satisfaction in their families.

All you wanted to know about anti-CCP but were afraid to ask.

The most specific biomarker associated with the diagnosis of rheumatoid arthritis (RA) is autoantibodies to citrullinated peptides/proteins (ACPA). Though recognized as an important marker of progressive erosive disease its use has been hampered by doubt about what is a positive versus a negative reaction in the several assays that have become available commercially. This review intends to indicate that the CCP2 assay has the highest specificity and sensitivity in stratified studies that encompass sera from RA patients and non-RA inflammatory controls compared to other ACPA tests. Still, larger and strictly stratified studies are highly warranted to substantiate this conclusion.

Autoantibodies in ANCA-associated vasculitis.

Antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides are systemic or more limited conditions characterized by necrotizing destruction of small and medium-sized vessels (eg, capillaries, venules, and arterioles). ANCAs are the most predominant autoantibodies in patients affected by vasculitis, but other autoantibodies may also occur, probably reflecting pathogenetic events in affected tissue. These autoantibodies are assumed to play a role in the initiation and propagation of chronic inflammation. ANCAs are valuable for clinical diagnosis, follow-up, and guidance in therapy.

Antinuclear antibodies: a contemporary nomenclature using HEp-2 cells.

The choice of terms used to describe indirect immunofluorescence (IIF) staining patterns of autoantibodies binding to HEp-2 cells is at present quite varied and disordered because no accurate consensus on names and descriptions exist. The aim of our study was to propose a logical and ordered IIF classification taxonomy based on 29 different selected IIF patterns. In a preliminary project carried out at Statens Serum Institut it was first shown by use of a software programme named DOORS developed by Percepton Ltd, that reading of digitized images of HEp-2 patterns on an LCD monitor could be used instead of traditional microscopy. Digitized images of HEp-2 patterns were then used in the EU supported project named CANTOR (June 1998-July 2000) aiming to reach consensus among three clinical immunology expert centres and collaborating to attain a classification version that could be used to qualitatively and quantitatively test and train image recognitions skills of laboratory technicians against expert consensus. The usability of this classification version was then tested in a course consisting of training and certification. The conclusion was that participants in the training programme clearly increased their perceptive skills using images, terms, descriptions and the graphic and statistic tools in the self-administered DOORS programme and that software-assisted training could achieve a common and accurate level of visual pattern interpretation. All results from this project were reported to the European Commission but have not previously been published in scientific literature. This communication presents the final results of agreed image classifications.

The immune response to citrullinated proteins in patients with rheumatoid arthritis: genetic, clinical, technical, and epidemiological aspects.

This article reviews data concerning the applicability of anti-citrullinated peptide antibodies in the diagnosis, estimation of prognosis, and follow-up of patients with rheumatoid arthritis (RA). The production of anti-citrullinated peptide antibodies is closely associated with the presence of the HLA-DRB1 shared epitope, a known risk factor for development of RA, and the production may be influenced by environmental factors such as tobacco smoking. Patients who harbor this antibody from the early stage of their disease develop more severe erosive disease than patients with RA who lack the antibody. The anti-citrullinated peptide antibody level may be a reflection of disease activity, at least in the early phase of the disease. The antibody can sometimes be found several years before the onset of clinical symptoms of RA, which may represent an open window for preventive measures to be taken.

Appropriateness of autoantibody testing in clinical medicine.

BACKGROUND: Pathologically expressed autoantibodies reflect ongoing immune-mediated inflammation in patients and may even be regarded as surrogate markers of disease prognosis and clinical outcome in certain clinical settings. MATERIALS AND METHODS: The most appropriate way to decide about autoantibody testing is to set a tentative diagnosis before ordering a few clinically relevant autoantibody screening tests and then follow locally agreed rules for continued testing. RESULTS: Different algorithms were applied considering both the possibility to obtain an initial tentative diagnosis by the clinician and another strategy to be adopted when the clinical information cannot be obtained. CONCLUSIONS: Guidelines can only be formulated by close collaboration between clinical and laboratory experts that reach agreement on testing and reporting strategies and thereby ensure the highest possible compliance with both local and international recommendations for diagnostics.