Abstract
Historically, pediatric inflammatory diseases were viewed as autoimmune but developments in genetics of monogenic disease have supported our proposal that “inflammation against self” be viewed as an immunologic disease continuum (IDC), with genetic disorders of adaptive and innate immunity at either end. Innate immune-mediated diseases may be associated with significant tissue destruction without evident adaptive immune responses and are designated as autoinflammatory due to distinct immunopathologic features. However, the majority of pediatric inflammatory disorders are situated along this IDC. Innate immunity has been demonstrated in polygenic disorders, particularly Crohn's disease (CD). A genetic overlap exists between CD and some major histocompatability complex (MHC) class I-associated diseases, including psoriasis; these diseases seem to represent a true intermediate between autoinflammation and autoimmunity. Conversely, classical autoimmune diseases, with autoantibody and MHC class II associations, including celiac disease and rheumatoid arthritis (RA), have adaptive immune genetic associations, including Cytotoxic T-Lymphocyte Antigen-4 (CTLA4) and PTPN22. This proposed classification is clinically relevant, because innate immune-mediated disorders may respond to cytokine antagonism whereas autoimmune-mediated diseases respond better to anti-T and B cell therapies. Furthermore, the etiopathogenesis of poorly defined “autoimmune” diseases, such as juvenile idiopathic arthritis, may be inferred to have substantial innate immune involvement, based on response to IL-1 antagonism.
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Abbreviations
- ALPS:
-
autoimmune lymphoproliferative syndrome
- BD:
-
Behçet's disease
- BS:
-
Blau syndrome
- CD:
-
Crohn's disease
- CINCA:
-
chronic infantile neurological cutaneous and articular syndrome
- FMF:
-
familial Mediterranean fever
- HPFS:
-
hereditary periodic fever syndrome
- IBD:
-
inflammatory bowel disease
- IDC:
-
immunological disease continuum
- MHC:
-
major histocompatability complex
- MWS:
-
Muckle-Wells syndrome
- NALP3:
-
nacht domain-, leucine rich repeat-, and pyrin domain-containing protein 3, NOD2, nucleotide-binding oligomerisation domain 2
- NOMID:
-
neonatal onset multisystem inflammatory disease
- PAPA:
-
pyogenic arthritis, pyoderma gangrenosum and acne syndrome
- PSTPIP1:
-
proline-serine-threonine phosphatase-interacting protein 1
- RA:
-
rheumatoid arthritis
- SLE:
-
systemic lupus erythematosus
- T1D:
-
type 1 diabetes
- UC:
-
ulcerative colitis
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McGonagle, D., Aziz, A., Dickie, L. et al. An Integrated Classification of Pediatric Inflammatory Diseases, Based on the Concepts of Autoinflammation and the Immunological Disease Continuum. Pediatr Res 65, 38–45 (2009). https://doi.org/10.1203/PDR.0b013e31819dbd0a
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