Abstract
Autoinflammatory diseases (AIDs) are disorders characterised by recurrent inflammatory episodes in charge of different organs with no apparent involvement of autoantibodies or antigen-specific T lymphocytes. Few common clinical features have been identified among all monogenic AIDs (mAIDs), while the search for a common molecular pattern is still ongoing. The aim of this study was to increase knowledge on the inflammatory pathways in the development of mAIDs in order to identify possible predictive or diagnostic biomarkers for each disease and to develop future preventive and therapeutic strategies. Using protein array-based systems, we evaluated two signalling pathways known to be involved in inflammation and a wide range of inflammatory mediators (pro-inflammatory cytokines and chemokines) in a cohort of 23 patients affected by different mAIDs, as FMF, TRAPS, MKD, Blau syndrome (BS), and NLRP12D. Overall, we observed upregulation of multiple signalling pathway intermediates at protein levels in mAIDs patients’ PBMCs, compared with healthy controls, with significant differences also between patients. FMF, TRAPS, and BS presented also peculiar activations of inflammatory pathways that can distinguish them. MAPK pathway activation, however, seems to be a common feature. The serum level of cytokines and chemokines produced clear differences between patients with distinct diseases, which can help distinguish each autoinflammatory disease. The FMF cytokine production profile appears broader than that of TRAPS, which, in turn, has higher cytokine levels than BS. Our findings suggest an ongoing subclinical inflammation related to the abnormal and constitutive signalling pathways and define an elevated inflammatory cytokine signature. Moreover, the upregulation of Th17-related cytokines emphasises the important role for Th17 and/or Th17-like cells also in monogenic AIDs.
Highlights
Autoinflammatory diseases (AIDs) are a heterogeneous group of disorders characterised by immune antigen-independent dysregulation conditions typically presented in childhood with fever and sterile inflammation [1]
Most of these studies underline the prominence of the IL1β-activating inflammasome and its regulation in a large number of AIDs
The majority of them presented mild genetic mutations associated with their diseases; the diagnosis was strongly based on clinical criteria
Summary
Autoinflammatory diseases (AIDs) are a heterogeneous group of disorders characterised by immune antigen-independent dysregulation conditions typically presented in childhood with fever and sterile inflammation [1]. Some common clinical features have been identified between all inherited AIDs, such as recurrent inflammatory episodes, the presence of fever, and frequent involvement of skin, joints, gastrointestinal tract, nervous system, and other tissues. Each syndrome may have more or less severe inflammatory manifestations [2]. The rarity of these disorders often leads to their misunderstanding, with delayed diagnosis and treatments. The genetic cause of some familial autoinflammatory syndromes was identified more than 20 years ago [3,4]. The number of new monogenic autoinflammatory disthan 20 years ago [3,4]. The number of new monogenic autoinflammatory diseases (mAIDs) has been increasing every year. Tchoeminpflleaxmmmeacshoamneisrmecsepartoers asisnotceiraatcetdwiwthitthhe tahdeapdteervperlootpemineAntSCo, fleaddiifnfegretontthemaActIiDvast.ioMn oofrecoasvpear,se t1h,iws hmicholceocnuvlaerrts hepteroro-IgLe-n1eaintydcporuol-dILb-1e8dtioretchtelyir rbeiloaatectdivteoftohremtsy.pTehoisf ipsaotnheogoefnthicevkaeryiasnigt.nNalulilnlgalplealtehswoarys mtuhtaatticoonnstrionl tfhuenicntinoantaelliymmcruitnicearlesrpesoindsuee.sFucarnthecramuosere,sPevAeMrePsmaarneisfeesntsaetidonbsy, Twolhl-illieke porleycmepotroprhsi(sTmLsRos)r, hmyapionmlyoTrLpRhi-c4 moruNtaOtiDon2srleecaedpttoorsa, amnidldaoctrivlaattee-othneseNt Ffo-krmB poafthmwAaIyD, sen[6]h.anWciitnhg tNhLe RiPnc3rteraasninscgrikpntioown laenddgepraobmouottinggenaoptyopseit–ivpehefneeodtybpaeckceofrfreecltat[i5o]n. sA, lgteernaettioicns heatterdoigffeenreenittyleavnedlsdoifgtehneisceicnohmerpitlaenxcme eccohualndisbmesianrceluadsesodciianteodvweriltahppthinegdepvheelonpotmypenest,of whdicffherheanvtembAeeInDds.eMscroirbeeodvefor,rtAhiIsDms oplaetcieunlatsr [h8e]t.erogeneity could be directly related to the typAelothf opuagthhocgoemnimc ovnarcilaintic. aNl ufelal taullreelseosfomr mAIuDtasthioanvseianlrfeuandcytiboeneanllyidcerniticfiaeldr,easigdeuneesraclan mcoaleucsuelaservpearettmernantifheasttactaionnsc,hwarhaicletepriosleymthoerpshpiescmtrsumor hoyf ptohme omrpAhIiDcsmruetmataioinnss lpeoaodrltyo a unmdielrdstoorolda.teT-hoensmetecfhoramnisomf mofAaIcDtison[6]o.f Weaicth gtheeneinacsrseoacsiiantgedknwoiwthlecdlagsesiacablomutAgIeDnsothyapse– bepehneenxotteynpseivceolryredlaesticornibse, dgeinneaticrehceetnetroregvenieewity[9a]n. d digenic inheritance could be included in overlapping phenotypes, which have been described for AIDs patients [8]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
