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AB0225 Results of Molecular Analysis of NLRP3, MVK and Tnfrsf1A in Patients with Systemic Juvenile Arthritis
  1. S.O. Salugina1,
  2. E. Fedorov1,
  3. M. Kaleda1,
  4. E. Kamenets2,
  5. E. Zaharova2
  1. 1Children, Nasonova Research Institute of Rheumatology
  2. 2Laboratory of metabolic disorders, Research Centre for Medical Genetics of RAMS, Moscow, Russian Federation


Background Human autoinflammatory diseases (HAIDS) are a group of rare heterogeneous genetically determined disorders characterized by periodic fever, attacks of inflammatory and rheumatic-like symptoms without autoimmune marks or infection. Clinical features of the systemic onset juvenile arthritis (soJA) has similar features so it's belonging to HAIDS is discussed. In addition, a large number of evidence indicates the pathogenesis of soJA to be closely associated with abnormalities in the innate immune system. HAIDS caused by mutations in genes encoding components of innate immunity. The studies on the genetics and molecular pathophysiology of soJA and autoinflammatory diseases are not too much.

Objectives To define presence of the same defects in patients with soJA

Methods We recruited 39 patients (M/F-21/18) with soJA aged between 1,5 and 18 years on an average 10,5±4,9 years old. Diagnosis was based on ILAR criteria for soJIA. Selection criteria were persistent fever, maculopapular rash, arthralgia/arthritis, acute-phase markers. DNA samples extracted from whole blood. We investigated three genes whose mutations are the most frequent cause of HAIDS: NLRP3, MVK and TNFRSF1A. Coding sequences of the genes were analyzed by direct automatic sequencing.

Results Among 39 pts 4 individuals showed genetic defects (10,3%): 2 of them were heterozygous for mutations in NLRP3, 1 - in TNFRSF1A (autosomal dominant mode of inheritance) and 1 is compound heterozygote for mutations in MVK (autosomal recessive mode of inheritance). Genetic diagnoses were made: CAPS-MWS in 2 pts, TRAPS-syndrome in 1 and HIDS in 1 accordingly

Conclusions Thus 10,3% of examined arthritis patients had HAIDS defects. Our findings demonstrate that patients with clinical diagnosis of soJA may suffer from various autoinflammatory diseases missed because of similar symptoms. So these conditions required differential diagnostics. We recommend genetic screening of mutations in NLRP3, MVK and TNFRSF1A genes for such patients with deficient or inadequate response to standard therapy for uncovering HAIDS and more targeted treatment.

Disclosure of Interest None declared

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