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How should we approach classification of autoinflammatory diseases?

Abstract

The notion of 'autoinflammatory' disease was introduced at the end of the 1990s, and, since then, this concept has rapidly evolved. As a result, multiple definitions of autoinflammatory disease, and classifications of conditions encompassed by these definitions, have been proposed; this succession highlights advances that have been made in understanding of the innate immune system, and especially the roles of IL-1β and the inflammasome in autoinflammtory conditions. However, the definitions and classifications that have been suggested to date face a number of structure and content issues. We therefore propose another, more clinically-oriented, definition: autoinflammatory diseases are diseases with clinical signs of inflammation, associated with elevated levels of acute-phase reactants, which are attributable to dysfunction of the innate immune system, genetically-determined or triggered by an endogenous factor. From this foundation, we propose a clinically-based classification of autoinflammatory diseases, and go on to discuss how immunological diseases as a whole, including autoimmune diseases, can be appropriately located within a continuum only if the classification process is multidimensional. For this purpose, we appeal to the philosophical concepts of family resemblance and signature.

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Figure 1: Incorporating dysfunction of the innate and adaptive immune systems in disease classifications.

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Authors and Affiliations

Authors

Contributions

G. Grateau and O. Steichen researched the data for the article. G. Grateau, S. Amselem and O. Steichen contributed equally to writing the article. All authors provided a substantial contribution to discussion of the content and to review and/or editing of the manuscript before submission.

Corresponding author

Correspondence to Gilles Grateau.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Table 1

Proposed categories of autoinflammatory diseases from selected classifications (PDF 94 kb)

Supplementary Table 2

Classification of autoinflammatory diseases according to their main pathological features* (DOC 41 kb)

Supplementary Figure 1

The immune disease continuum. Schematic representation of the continuum of inflammatory diseases proposed by McGonagle and McDermott.4 (PDF 149 kb)

Supplementary Figure 2

The continuum of immune diseases along the gradient of amyloidosis prevalence. (PDF 130 kb)

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Grateau, G., Hentgen, V., Stojanovic, K. et al. How should we approach classification of autoinflammatory diseases?. Nat Rev Rheumatol 9, 624–629 (2013). https://doi.org/10.1038/nrrheum.2013.101

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