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How should we approach classification of autoinflammatory diseases?


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



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.

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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).

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