Lessons from characterization and treatment of the autoinflammatory syndromes

Aksentijevich, Ivona; McDermott, Michael F.

doi:10.1097/bor.0000000000000362

Cited by 44 publications

(29 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Mutations in either the N-or C-terminus of the TNFAIP3 gene result in loss of A20 function. HA20 is a novel single-gene auto-in ammatory disease rst reported in 2016 by Zhou et al (12), who found that its primary phenotype is Behçet's disease-like symptoms (13), including recurrent oral ulcers, genital ulcers, and gastrointestinal symptoms (14). However, numerous studies have shown that some patients exhibit not only the characteristics of auto-in ammatory diseases, but also those of various autoimmune diseases.…”

Section: Resultsmentioning

confidence: 99%

Analysis of the Clinical and Genetic Characteristics of 3 Cases of A20 Haploinsufficiency

Zhang

Zhou

Lai

et al. 2020

Preprint

View full text Add to dashboard Cite

Background To evaluate the clinical and genetic characteristics of 3 children with HA20. Methods The clinical and genetic testing data of 3 children with HA20 treated at CIP between August 2016 and October 2019 were retrospectively analysed. Results Patient 1 presented with arthritis and inflammatory bowel disease, patient 2 presented with axial spinal arthritis and lupus-like syndrome, and patient 3 presented with recurrent oral ulcers, gastrointestinal ulcers, and perianal abscesses. For laboratory examination, In patient 1, the WBC,CRP and AESR showed high. In patient 2, the WBC was normal, but CRP and AESR showed high. In patient 3, the WBC, CRP, and AESR showed high. Patient 2 was positive for antinuclear antibodies, anti-Sjögren’s syndrome antigen A, dsDNA, rheumatoid factor and Coombs test. Genetic testing showed that the 3 patients were heterozygous for mutations in the TNFAIP3 gene. For treatment, patient 1 used TNFα antagonist and thalidomide, patient 2 used TNFαantagonist and sulfasalazine, and patient 3 used hormones and thalidomide. Patients 1 and 2 were followed up for 4 and 3 months, respectively. There was improvement in joint and gastrointestinal symptoms, inflammatory indices and RF were normal, dsDNA and Coombs test became negative. Patient 3 was treated at an outside hospital and showed gradual improvement in oral ulcers and perianal abscesses. Conclusion HA20 is a single-gene auto-inflammatory disease caused by mutation in the TNFAIP3 gene. It presents clinically as a Behçet-like syndrome and can present as various other autoimmune diseases as well. Hormones and immunosuppressive agents are effective treatments, and cytokine antagonists can be used in refractory cases. Whole-exome genetic testing should be proactively performed for children with an early age of onset or Behçet-like presentation to achieve early diagnosis and accurate treatment.

show abstract

Section: Resultsmentioning

confidence: 99%

Analysis of the Clinical and Genetic Characteristics of 3 Cases of A20 Haploinsufficiency

Zhang

Zhou

Lai

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Autoinflammatory diseases affect the innate immune system, and some of them are characterized by inflammasome activation and subsequent IL-1β production [ 15 ]. The clinical manifestations of autoinflammatory diseases are similar to those of AOSD, and a dramatic response to IL-1β blockade was reported in Western countries [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

Adding colchicine to immunosuppressive treatments; a potential option for biologics-refractory adult-onset Still’s disease

et al. 2018

View full text Add to dashboard Cite

BackgroundAdult-onset Still’s disease (AOSD) is a rare inflammatory disorder characterized by the classical triad of daily spiking fever, arthritis, and typical salmon-colored rash. Resistance to first-line corticosteroids and second-line disease modified anti-rheumatic-drugs defines refractory AOSD, which mostly includes the polycyclic or chronic courses of the disease. Anti-cytokine therapies are recommended in AOSD patients who are refractory to traditional treatments. This is the first report on the efficacy of colchicine in a patient with AOSD which was refractory to immunosuppressive treatments including biologics.Case presentationA 24-years Japanese female patient was referred to our hospital for the flare-up of AOSD under the combined treatments with steroid, immunosuppressants, and biologics. She was diagnosed with AOSD according to the Yamaguchi criteria, based on the presence of spiking fever, polyarthralgia, skin rash, and hyperferritinemia. Interleukin-6 or tumor necrosis factor-α blockade treatments were not effective, the oral administration of colchicine was stared under the immunosuppressive treatments with steroid and cyclosporine A (CyA). Colchicine treatment silenced the disease activity of AOSD. The dose of prednisolone was successfully tapered, and the elevated levels of C-reactive protein were normalized. Remission has been maintained for 13 months with the start of oral administration of colchicine.ConclusionWe concluded that colchicine is an alternative treatment in patients with refractory AOSD, particularly in those with impaired therapeutic effects against anti-cytokines therapies.

show abstract

“…Secondly, a large association study performed in 982 SoJIA children and 8010 healthy controls identified a strong association between SoJIA and different HLA-DRB1 * 11 haplotypes which all contain glutamate 58 [55]. This finding is more challenging since it would involve adaptive immunity in the AoSD pathogenesis which was not expected [56].…”

Section: A Role For a Genetic Backgroundmentioning

confidence: 97%