Systemic autoinflammatory diseases (SAIDs) are a group of immune-dysregulatory conditions caused by mutations in genes that encode proteins that play a pivotal role in the regulation of predominantly innate inflammatory immune responses. Most of these disorders have an early-onset, ranging from the first hours to the first decade of life. The clinical spectrum of these disorders is variable. SAIDs are characterized by the presence of chronic or recurrent systemic inflammation, secondary to abnormal activation of innate immunity pathways such as (i) inflammasome activation; (ii) increased intracellular stress leading to inflammation; (iii) enhanced NFkappaB-signalling or (iv) defects in IFN signaling (see below). Many patients afflicted by these diseases harbor mutations in genes that are relevant to key innate immune pathways. For example, mutations in genes affecting the pyrin or the NLRP3 inflammasomes are found in patients with periodic fever syndromes, neutrophilic urticaria or inflammatory bone diseases.
Since SAIDs are rare diseases that present complex symptoms and their only recent genetic and phenotypic characterization has only recently begun, the delayed diagnosis of SAIDs is common. Nevertheless, further characterization and classification of these diseases will allow physicians to gain a better understanding of the clinical manifestations and specific clinical features of different SAIDs, facilitating early diagnosis in affected patients.
Translational research approaches have brought major changes to the understanding and treatment options of SAIDs. Patients with common complex multifactorial diseases such as systemic-onset juvenile idiopathic arthritis (sJIA), and particularly those with rare monogenic autoinflammatory diseases such as cryopyrin-associated periodic syndromes (CAPS) or TNF receptor-associated periodic syndrome (TRAPS), have benefited clinically from investigations into the underlying patho-physiological mechanisms involved. These studies have pointed to a key role of IL-1 and IL-6 in disease pathogenesis, and a role for IL-18 in these processes is emerging. This has subsequently led to the development of new treatment options, and drug approvals for these conditions.
The characterization of novel autoinflammatory diseases that are not IL-1 mediated is ongoing and has been facilitated by the continued development of next generation sequencing tools. The registration of individual patients in international registries has enabled the classification of SAIDs, and has widened the spectrum beyond classical IL-1 mediated diseases. The appropriate management of SAIDs includes: (i) making an early diagnosis; (ii) classifying patients into clinically relevant subgroups, (iii) using targeted therapies based on these classifications; (iv) monitoring of patient response and outcome and (v) filing of this data in international registries. Further characterization of yet genetically and clinically uncharacterized SAIDs; the design of tailored treatment regimens and the identification of new therapeutic strategies, constitute future challenges in the field of autoinflammatory diseases, particularly for pediatric rheumatologists.
This Research Topic aims to discuss recent discoveries and new developments in the diagnosis and management of autoinflammatory diseases in childhood, from an immunological perspective. Groups of autoinflammatory diseases can that will be discussed in this Research Topic include, but are not limited to:
a. IL-1-mediated autoinflammatory diseases (including inflammasomopathies).
b. IFN-mediated autoinflammatory diseases (autoinflammatory interferonopathies).
c. NFkB dysregulation and autoinflammatory diseases.
d. IL-1/IL-18 dysregulation and MAS and SoJIA
e. Autoinflammation and immunodeficiency or lymphoproliferation or malignancy.
e. Complement disorders and autoinflammation.
We aim to gather Original Research, Review, Mini-Review and Classification articles focusing on clinical and translational studies that cover the following sub-topics:
1. Approaches to facilitate diagnosis of SAIDs.
2. Monitoring of disease activity and complications in SAIDs.
3. Therapeutic (including treat-to-target) concepts for SAIDs.
4. Registries and observational studies of the outcome of SAIDs.
5. Potential new therapeutic targets in SAIDs.
Research Topic Editor Prof. Dirk Holzinger receives research support from Novartis. Prof. Dirk Föll and Prof. Marco Gattorno receive research support from Novartis and SOBI. Prof. Raphaela Goldbach-Mansky receives research funding under government CRADAs to conduct clinical studies from SOBI, Regeneron, Novartis and Eli Lilly.
Systemic autoinflammatory diseases (SAIDs) are a group of immune-dysregulatory conditions caused by mutations in genes that encode proteins that play a pivotal role in the regulation of predominantly innate inflammatory immune responses. Most of these disorders have an early-onset, ranging from the first hours to the first decade of life. The clinical spectrum of these disorders is variable. SAIDs are characterized by the presence of chronic or recurrent systemic inflammation, secondary to abnormal activation of innate immunity pathways such as (i) inflammasome activation; (ii) increased intracellular stress leading to inflammation; (iii) enhanced NFkappaB-signalling or (iv) defects in IFN signaling (see below). Many patients afflicted by these diseases harbor mutations in genes that are relevant to key innate immune pathways. For example, mutations in genes affecting the pyrin or the NLRP3 inflammasomes are found in patients with periodic fever syndromes, neutrophilic urticaria or inflammatory bone diseases.
Since SAIDs are rare diseases that present complex symptoms and their only recent genetic and phenotypic characterization has only recently begun, the delayed diagnosis of SAIDs is common. Nevertheless, further characterization and classification of these diseases will allow physicians to gain a better understanding of the clinical manifestations and specific clinical features of different SAIDs, facilitating early diagnosis in affected patients.
Translational research approaches have brought major changes to the understanding and treatment options of SAIDs. Patients with common complex multifactorial diseases such as systemic-onset juvenile idiopathic arthritis (sJIA), and particularly those with rare monogenic autoinflammatory diseases such as cryopyrin-associated periodic syndromes (CAPS) or TNF receptor-associated periodic syndrome (TRAPS), have benefited clinically from investigations into the underlying patho-physiological mechanisms involved. These studies have pointed to a key role of IL-1 and IL-6 in disease pathogenesis, and a role for IL-18 in these processes is emerging. This has subsequently led to the development of new treatment options, and drug approvals for these conditions.
The characterization of novel autoinflammatory diseases that are not IL-1 mediated is ongoing and has been facilitated by the continued development of next generation sequencing tools. The registration of individual patients in international registries has enabled the classification of SAIDs, and has widened the spectrum beyond classical IL-1 mediated diseases. The appropriate management of SAIDs includes: (i) making an early diagnosis; (ii) classifying patients into clinically relevant subgroups, (iii) using targeted therapies based on these classifications; (iv) monitoring of patient response and outcome and (v) filing of this data in international registries. Further characterization of yet genetically and clinically uncharacterized SAIDs; the design of tailored treatment regimens and the identification of new therapeutic strategies, constitute future challenges in the field of autoinflammatory diseases, particularly for pediatric rheumatologists.
This Research Topic aims to discuss recent discoveries and new developments in the diagnosis and management of autoinflammatory diseases in childhood, from an immunological perspective. Groups of autoinflammatory diseases can that will be discussed in this Research Topic include, but are not limited to:
a. IL-1-mediated autoinflammatory diseases (including inflammasomopathies).
b. IFN-mediated autoinflammatory diseases (autoinflammatory interferonopathies).
c. NFkB dysregulation and autoinflammatory diseases.
d. IL-1/IL-18 dysregulation and MAS and SoJIA
e. Autoinflammation and immunodeficiency or lymphoproliferation or malignancy.
e. Complement disorders and autoinflammation.
We aim to gather Original Research, Review, Mini-Review and Classification articles focusing on clinical and translational studies that cover the following sub-topics:
1. Approaches to facilitate diagnosis of SAIDs.
2. Monitoring of disease activity and complications in SAIDs.
3. Therapeutic (including treat-to-target) concepts for SAIDs.
4. Registries and observational studies of the outcome of SAIDs.
5. Potential new therapeutic targets in SAIDs.
Research Topic Editor Prof. Dirk Holzinger receives research support from Novartis. Prof. Dirk Föll and Prof. Marco Gattorno receive research support from Novartis and SOBI. Prof. Raphaela Goldbach-Mansky receives research funding under government CRADAs to conduct clinical studies from SOBI, Regeneron, Novartis and Eli Lilly.
