الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
Autoinflammatory diseases are a group of monogenic and
polygenic disorders characterised by recurrent inflammatory episodes
whose heterogeneous symptoms are frequently associated with fever.
The key pathogenetic moment in autoinflammatory diseases is the
direct and indirect dysregulation of inflammasomes, the multiprotein
cytoplasmic complexes characteristic of innate immunity and
inflammatory responses. The main components of inflammasomes are
members of the nucleotide-binding oligomerisation domain (NOD)-
like receptor (NLR) family, a class of pattern recognition receptors
(PRR). When induced to do so by pro-inflammatory triggers such as
the stimuli transmitted by pathogens or damaged cells, NLRs
respectively detect pathogen-associated or damage-associated
molecular patterns ((PAMPs or DAMPs) and begin inflammasome
assembly, which generates the proteolytic activation of caspases and
the conversion of pro-interleukin (IL)-1β into active IL-1β, a key
molecule of inflammation and innate immunity (Davidson and
Diamond, 2020).
The term “autoimmunity” used to be referred to a condition
associated with the dysregulation of adaptive immunity alone,
whereas “autoinflammatory” was initially defined solely as a
consequence of dysregulated innate immunityConsequently, the
pathogenetic mechanisms of autoimmune diseases (ADs) were
considered to be exclusively mediated by B and T lymphocytes whose
B and T cell receptors (BCRs and TCRs) recognised specific antigens,
started the inflammatory response against autoantigens, and activated
B cell-mediated autoantibody production, Although ADs are still
considered adaptive immunity-mediated disorders, there is increasing
Summary & Conclusion
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evidence that innate immunity and inflammasomes are also involved.
It seems clear that despite the differences in the system primarly
involved, autoinflammatory and autoimmune disease share common
characteristics as the activation
against self, with subsequent systemic inflammation, and the
absence of an external causal trigger clearly identified. The main
difference between the two pathogenetic mechanisms is that in
autoinflammatory diseases, the innate immune system is the one
directly causing inflammation, while in ADs, it subsequently activates
the adaptive system that is the one to activate the inflammatory
process (Davidson et al., 2018).
Autoimmune diseases and autoinflammatory diseases share
similar etiopathogenetic and clinical characteristics, including genetic
predisposition and recurrent systemic inflammatory flares. The first
phase of ADs involves innate immunity: by means of TLRs, DCs
recognise and internalise autoantigens arising from the process of
apoptosis, which leads to IFN-α production, DC maturation,
autoantigen presentation, B and T cell recruitment, and autoantibody
synthesis. The second phase involves adaptive immunity, a selfsustaining
process in which immune complexes containing nucleic
acids and autoantibodies are internalised by DC by means of Fcγ-
receptors (FcγRs), thus leading to IFN-α synthesis, additional DC and
T cell activation, and autoantibody production (McGonagle and
Watad, 2019).
Various data indicate that innate and adaptive immunity
represents two strictly interconnected phases in the development of
Autoimmune diseases. The protracted or increased activation of PRRs
plays a key role in autoimmune mechanisms, and the strict link