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AB0983 Mefv mutations in armenian patients with systemic autoimmune diseases
  1. K Ginosyan,
  2. A Beglaryan1 1,
  3. V Vardanyan
  1. Internal Medicine, Yerevan State Medical University, Yerevan, Armenia

Abstract

Background The systemic diseases of connective tissue have autoimmune mechanism in development. While autoimmunity involves adaptive immune activation, autoinflammation involves innate immune activation. The prototype of autoinflammatory diseases is familial Mediterranean fever (FMF), which is the global medical problem for Armenian ethnos on the whole, affecting 1–2% of population.

Objectives The aim of this study was investigation of MEFV mutations and their possible influence on the systemic diseases in Armenian patients.

Methods We have examined 183 patients with FMF. All patients with FMF fulfilled Tel-Hashomer FMF diagnostic criteria. Molecular-genetic detection of 12 MEFV mutations common for Armenians carried out in Medical Genetic Centre of Armenia. In 49 patients one of autoimmune systemic diseases was diagnosed: in 24 patients- seronegative spondyloarthropathy (SNSA), in 23 - systemic lupus erythematosus (SLE), 1 patient developed Sjogren's disease and 1- systemic sclerosis.

Results In the SNSA group from 24 patients 16 were male, 8 were female, the mean age of patients was 35,4±12,2.The mean age at the beginning of the disease was 14,91±12,6. In all cases the symptoms of FMF were preceded symptoms of arthritis. Unilateral sacroiliitis was revealed in 6 patients, bilateral sacroiliitis-in 18 patients. The limitation of lumbar motion was assessed by Schober's test. 7 patients with Schober's test 1–2 cm had bilateral sacroiliits grade III-IV and fulfilled the modified New York criteria for ankylosing spondylitis. HLA B-27 was examined in 7 patients. In 5 cases it was negative, and in 2 cases –positive. MEFV gene analyses were carried out in 21 cases: 7 patients had one heterozygote mutations: 6-M694,1-M680I; 5 patients -M694V/M694V, 9 patients had compound heterozygote mutations: 5- M694V/V726A, 3 - M694V/E148Q, 1 - M680I/E148Q. So, the prevalent mutation was M694V.

In SLE group from 23 patients female were 21 (91.3%), male – 2 (8.7%). Mean age of patients was 37.4±2.5 years. The beginning of FMF was earlier than SLE. The activity of SLE estimated by SLEDAI index was significant lower than in SLE without FMF. SLE co-occurring with FMF had mild duration than classic lupus according to both clinical and laboratory findings including serological markers of SLE -ANA, anti-dsDNA. The prevalent mutation was M694V - 44.6%; V726A composed 21.7%, M680I-9.8%. Most common variations with M694V were followings:M694V/M694V,M694V/V726A,M694V/N.

Conclusions A remarkable overlap was highlighted between FMF and SLE: both diseases have such common features as arthralgia, myalgia, arthritis, fever, skin involvement, serositis and renal involvement. It is likely, that the moderation in disease phenotype and peculiar disease characteristics observed in patients with both SLE and FMF are related to MEFV. MEFV mutations appear to modify SLE phenotype. Sacroilitis may be seen more frequently in FMF patients than expected. On the other hand, FMF must be kept in mind if patients not responding to the usual therapeutic interventions for sacroiliitis.

References

  1. Doria Z., Zen M., Bettio S., et al. Autoinflammation and autoimmunity:bridging the divide. Autoimmune Rev.2012 Nov;12 (1): 22–30.

  2. Cattan D. MEFV Mutation Carriers and Diseases other than FMF;Proved and Non-proved Associations; Putative Biological Advantage. Curr. Drug Targets-Inflam.&Allergy, 2005;4:105–112.

References

Disclosure of Interest None declared

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