Molecular genetic analysis for periodic fever syndromes: a supplemental role for the diagnosis of adult-onset Still’s disease

Abstract

Adult-onset Still's disease (AOSD) represents a systemic autoinflammatory disease (SAID), and its diagnostic criteria are clinical without genetic testing. Given shared manifestations between AOSD and hereditary SAIDs, molecular analysis may help differentiate these diseases. A PubMed literature search was conducted using key words "adult-onset Still's disease," "autoinflammatory disease," and "genetic mutation" between 1970 and February 2018. Articles on genetic mutations in the genes MEFV, TNFRSF1A, mevalonate kinase, or NOD2 for hereditary SAIDs in AOSD/systemic onset juvenile idiopathic arthritis (SJIA) patients were reviewed and analyzed. Five case series studies consisting of a total of 162 of both adult and pediatric patients were included. All patients fulfilled the Yamaguchi criteria for AOSD or the diagnostic criteria for SJIA. The results showed that 31.4% (51/162) of patients were identified to carry at least one genetic variant for periodic fever syndromes. In addition, four patients with the diagnosis of SJIA in other reports were confirmed to have FMF or TRAPS with molecular testing. These data together suggest that some patients who satisfy the clinical diagnostic criteria for AOSD/SOJIA could well be diagnosed with other SAIDs; genetic testing, particularly for those with atypical presentation can be supplementary to the accurate disease diagnosis by excluding other autoinflammatory diseases. AOSD is a diagnosis of exclusion and shares common manifestations with other SAIDs. The currently employed clinical criteria for AOSD can cause misdiagnosis. An updated set of classification criteria to integrate the molecular genetic analysis to exclude other autoinflammatory diseases is warranted.

The association of MEFV gene mutations with the disease risk and severity of systemic juvenile idiopathic arthritis

“…Although the pathogenesis of sJIA is poorly understood, it's widely believed that dysregulation of innate pro-and anti-inflammatory cytokines is important pathogenesis for sJIA, especially overexpression of pro-inflammatory cytokines, such as IL-1β, IL-6 and IL-18 [1,2,17]. As for the early onset age of sJIA, more and more attention was paid to the genetic background responsible for the occurrence of sJIA, especially genes of molecules involving in the above inflammatory pathways [18,19], such as NLRP3 [20] and TNFRSF1A [21]. Up to now whether the gene mutations have a role on the onset or the severity of sJIA remains a mystery.…”

Adult-onset Still’s disease in Poland – a nationwide population-based study

“…There are no clear-cut diagnostic, radiological or laboratory symptoms [4]. The currently applied clinical criteria for AOSD can result in misdiagnosis [5]. However, the criteria suggested by Yamaguchi are widely used in the diagnosis of the disease [6].…”

A Roadmap for Transforming Research to Invent the Batteries of the Future Designed within the European Large Scale Research Initiative BATTERY 2030+

“…Despite this well organized and efficient sequence, current approaches to accelerate the model‐based cell design [ 126,127 ] for one hand and model‐based battery manufacturing [ 128–135 ] for the other hand, still need to be adapted to meet the needs of a rapidly growing and constantly evolving battery technology landscape. Thus, modern battery manufacturing processes should be designed with the following goals in mind: Accelerate new cell designs in terms of performance, efficiency, and sustainability.…”