Auto Inflammatory Disease Defined

Immune system
Innate immunity
Auto-inflammatory diseases Presentation of the three speakers
Pr. Isabelle TOUITOU Dr. Hal HOFFMAN Dr. Laurent DUBUQUOY
IInnate immunity
First line of defense Immediate response Non-specific
Molecules recognized :
Acquired immunity
Action after 3 days Specific – Antigen
Pathogen- and Damage Associated Molecular Patterns (PAMPs and DAMPs)
by Pattern Recognition Receptors (PRRs) In macrophages, neutrophils and dendritic cells

IInnate immunity Acquired immunity PAMPs(eg :LPS (bacteria)
DAMPs(eg : ATP PRRs
NF- B
Macrophages
TLR NLR
Inflammasome
Caspase-1 Pro-IL-1 IL-1
TLR : Toll-like receptor NLR : NOD-like receptor
IL-1 Inflammation
Fever

IInnate immunity
Auto-inflammatory diseases
Familial mediterranean fever
Mixed pattern diseases
Psoriasis
Acquired immunity
Auto-immune diseases
Rheumatoïd arthritis
Immunological disease continuum

Auto-Inflammatory diseases Common characteristics
CClinic
Seemingly unprovoked fever Severe localized Inflammation (skin, joints…) Acute-phase proteins
Molecular
Innate genes like some NLRs
Dysregulated innate immune responses
Auto-Inflammatory diseases A non-exhaustive classification
RRecurrent fevers Infections
Rheumatologic
Behçet – Gout JIA – Still – Schnitzler
Recurrent hydatiform
moles
Reproductive wastage Granulomatous
Tuberculosis Lyme
Leprosy
Hereditary Majeed angioedema
PAPA
Pyogenic
FMF – MAPS – TRAPS – CAPS NAPS12 – PFAPA
Crohn – Blau EOS
Monogenic Multifactorial disease Genetic component unknown Susceptibility
APS : Associated Periodic Syndrome – CAPS : Cryopyrin APS- EOS : Early onset sarcoidosis – FMF : Familial Mediterranean fever – JIA : Juvenile idiopathic arthritis – MAPS: Mevalonate kinase APS – NAPS12 : NLRP12 APS – PAPA : Pyogenic arthritis pyoderma gangrenosum and acne – PFAPA: Periodic fever aphtosis pharyngitis adenitis – TRAPS: TNF receptor 1 APS

Auto-Inflammatory diseases Pr. Isabelle TOUITOU MD, PhD
GGenetics of auto inflammatory diseases, Montpellier (IGH, CNRS UPR1142, CHU A. de Villeneuve)
Family Mediterranean Fever gene : MEFV the first gene French consortium, Nature genetics 1997
Molecular diagnosis – National reference centre Physiopathology of recurrent fevers and Rheumatoïd
arthritis (Pr. Jorgensen)
International Society of Auto-inflammatory diseases
Coordinator of EuroTRAPS

Auto-Inflammatory diseases Dr. Hal HOFFMAN MD
DDivision of Rheumatology, Allergy and Immunology, University of California at San Diego
CAPS = Three clinical entities = Cryopyrinopathies Cryopyrin Associated Periodic Syndrome gene : NLRP3
Hoffman H. et al, Nature genetics 2001
NLRP3 inflammasome
Mechanistic effects of monocytes patients
Treatments of CAPS : IL1- receptor antagonist Hoffman HM. et al, The lancet 2004