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The influence of carrying MEFV gene variants on juvenile systemic lupus erythematosus

  • Genes and Disease
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Abstract

Juvenile-onset systemic lupus erythematosus (jSLE) patients typically have a more severe disease course than adults with SLE. We aimed to assess the prevalence and disease course of jSLE patients carrying MEFV variants. MEFV variant analyses were performed in 44 jSLE patients and effect of these variants on disease severity and course was analyzed by SLEDAI score and SLICC/ACR index. Ten of the patients (22.7%) had a MEFV variant. The median (min–max) SLEDAI score and SLICC/ACR index were 2(0–13) and 0(0–3), respectively. Median age at disease onset, disease duration, SLICC/ACR indexes, SLEDAI scores, clinical and laboratory findings of the patients were comparable in carriers of variants and non-carriers. Nineteen patients (43.2%) had biopsy-proven lupus nephritis and four of these patients had MEFV variants. There was no significant difference between patients with and without MEFV carriers in terms of lupus nephritis. Even though not significant statistically, renal involvement was milder in MEFV carriers than non-carriers. The presence of MEFV variants does not increase the overall susceptibility to jSLE in our cohort, while larger number of patients is required to display the protective role of MEFV variants in jSLE.

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References

  1. Anaya JM, Shoenfeld Y, Cervera R (2014) Systemic lupus erythematosus 2014. Autoimmune Dis 2014:274323. https://doi.org/10.1155/2014/274323

    Article  PubMed  PubMed Central  Google Scholar 

  2. Tucker LB, Uribe AG, Fernandez M, Vila LM, McGwin G, Apte M, Fessler BJ, Bastian HM, Reveille JD, Alarcon GS (2008) Adolescent onset of lupus results in more aggressive disease and worse outcomes: results of a nested matched case-control study within LUMINA, a multiethnic US cohort (LUMINA LVII). Lupus 17:314–322. https://doi.org/10.1177/0961203307087875

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Ozen S, Bilginer Y (2014) A clinical guide to autoinflammatory diseases: familial Mediterranean fever and next-of-kin. Nat Rev Rheumatol 10:135–147. https://doi.org/10.1038/nrrheum.2013.174

    Article  CAS  PubMed  Google Scholar 

  4. Lachmann HJ, Sengul B, Yavuzsen TU, Booth DR, Booth SE, Bybee A, Gallimore JR, Soyturk M, Akar S, Tunca M, Hawkins PN (2006) Clinical and subclinical inflammation in patients with familial Mediterranean fever and in heterozygous carriers of MEFV mutations. Rheumatology (Oxford) 45:746–750. https://doi.org/10.1093/rheumatology/kei279

    Article  CAS  Google Scholar 

  5. Ayaz NA, Ozen S, Bilginer Y, Erguven M, Taskiran E, Yilmaz E, Besbas N, Topaloglu R, Bakkaloglu A (2009) MEFV mutations in systemic onset juvenile idiopathic arthritis. Rheumatology (Oxford) 48:23–25. https://doi.org/10.1093/rheumatology/ken409

    Article  CAS  Google Scholar 

  6. Gershoni-Baruch R, Broza Y, Brik R (2003) Prevalence and significance of mutations in the familial Mediterranean fever gene in Henoch-Schonlein purpura. J Pediatr 143:658–661. https://doi.org/10.1067/S0022-3476(03)00502-X

    Article  CAS  PubMed  Google Scholar 

  7. Yalcinkaya F, Ozcakar ZB, Kasapcopur O, Ozturk A, Akar N, Bakkaloglu A, Arisoy N, Ekim M, Ozen S (2007) Prevalence of the MEFV gene mutations in childhood polyarteritis nodosa. J Pediatr 151:675–678. https://doi.org/10.1016/j.jpeds.2007.04.062

    Article  CAS  PubMed  Google Scholar 

  8. Rabinovich E, Livneh A, Langevitz P, Brezniak N, Shinar E, Pras M, Shinar Y (2005) Severe disease in patients with rheumatoid arthritis carrying a mutation in the Mediterranean fever gene. Ann Rheum Dis 64:1009–1014. https://doi.org/10.1136/ard.2004.029447

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Fidder H, Chowers Y, Ackerman Z, Pollak RD, Crusius JB, Livneh A, Bar-Meir S, Avidan B, Shinhar Y (2005) The familial Mediterranean fever (MEVF) gene as a modifier of Crohnʼs disease. Am J Gastroenterol 100:338–343. https://doi.org/10.1111/j.1572-0241.2005.40810.x

    Article  CAS  PubMed  Google Scholar 

  10. Atagunduz P, Ergun T, Direskeneli H (2003) MEFV mutations are increased in Behcet’s disease (BD) and are associated with vascular involvement. Clin Exp Rheumatol 21:S35–S37

    CAS  PubMed  Google Scholar 

  11. Erer B, Cosan F, Oku B, Ustek D, Inanc M, Aral O, Gul A (2014) MEFV gene variations in patients with systemic lupus erythematosus. Mod Rheumatol 24:93–96. https://doi.org/10.3109/14397595.2013.854049

    Article  CAS  PubMed  Google Scholar 

  12. Shinar Y, Kosach E, Langevitz P, Zandman-Goddard G, Pauzner R, Rabinovich E, Livneh A, Lidar M (2012) Familial Mediterranean FeVer gene (MEFV) mutations as a modifier of systemic lupus erythematosus. Lupus 21:993–998. https://doi.org/10.1177/0961203312441048

    Article  CAS  PubMed  Google Scholar 

  13. Deniz R, Ozen G, Yilmaz-Oner S, Alibaz-Oner F, Erzik C, Aydin SZ, Inanc N, Eren F, Bayalan F, Direskeneli H, Atagunduz P (2015) Familial Mediterranean fever gene (MEFV) mutations and disease severity in systemic lupus erythematosus (SLE): implications for the role of the E148Q MEFV allele in inflammation. Lupus 24:705–711. https://doi.org/10.1177/0961203314560203

    Article  CAS  PubMed  Google Scholar 

  14. Ozen S, Bakkaloglu A (2005) C reactive protein: protecting from lupus in familial Mediterranean fever. Ann Rheum Dis 64:786–787. https://doi.org/10.1136/ard.2004.027037

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Petri M, Orbai AM, Alarcon GS, Gordon C, Merrill JT, Fortin PR, Bruce IN, Isenberg D, Wallace DJ, Nived O, Sturfelt G, Ramsey-Goldman R, Bae SC, Hanly JG, Sanchez-Guerrero J, Clarke A, Aranow C, Manzi S, Urowitz M, Gladman D, Kalunian K, Costner M, Werth VP, Zoma A, Bernatsky S, Ruiz-Irastorza G, Khamashta MA, Jacobsen S, Buyon JP, Maddison P, Dooley MA, van Vollenhoven RF, Ginzler E, Stoll T, Peschken C, Jorizzo JL, Callen JP, Lim SS, Fessler BJ, Inanc M, Kamen DL, Rahman A, Steinsson K, Franks AG Jr, Sigler L, Hameed S, Fang H, Pham N, Brey R, Weisman MH, McGwin G Jr, Magder LS (2012) Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum 64:2677–2686. https://doi.org/10.1002/art.34473

    Article  PubMed  PubMed Central  Google Scholar 

  16. Sohar E, Gafni J, Pras M, Heller H (1967) Familial Mediterranean fever. A survey of 470 cases and review of the literature. Am J Med 43:227–253. https://doi.org/10.1016/0002-9343(67)90167-2

    Article  CAS  PubMed  Google Scholar 

  17. Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang CH (1992) Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthritis Rheum 35:630–640

    Article  CAS  Google Scholar 

  18. Gladman DD, Urowitz MB, Goldsmith CH, Fortin P, Ginzler E, Gordon C, Hanly JG, Isenberg DA, Kalunian K, Nived O, Petri M, Sanchez-Guerrero J, Snaith M, Sturfelt G (1997) The reliability of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index in patients with systemic lupus erythematosus. Arthritis Rheum 40:809–813. https://doi.org/10.1002/1529-0131(199705)40:5%3c809:AID-ART5%3e3.0.CO;2-X

    Article  CAS  PubMed  Google Scholar 

  19. Yilmaz E, Ozen S, Balci B, Duzova A, Topaloglu R, Besbas N, Saatci U, Bakkaloglu A, Ozguc M (2001) Mutation frequency of Familial Mediterranean Fever and evidence for a high carrier rate in the Turkish population. Eur J Hum Genet 9:553–555. https://doi.org/10.1038/sj.ejhg.5200674

    Article  CAS  PubMed  Google Scholar 

  20. Lidar M, Zandman-Goddard G, Shinar Y, Zaks N, Livneh A, Langevitz P (2008) Systemic lupus erythematosus and familial Mediterranean fever: a possible negative association between the two disease entities–report of four cases and review of the literature. Lupus 17:663–669. https://doi.org/10.1177/0961203308089403

    Article  CAS  PubMed  Google Scholar 

  21. Tunca M, Akar S, Onen F, Ozdogan H, Kasapcopur O, Yalcinkaya F, Tutar E, Ozen S, Topaloglu R, Yilmaz E, Arici M, Bakkaloglu A, Besbas N, Akpolat T, Dinc A, Erken E, Turkish FMFSG (2005) Familial Mediterranean fever (FMF) in Turkey: results of a nationwide multicenter study. Medicine 84:1–11

    Article  Google Scholar 

  22. Matsuda M, Kishida D, Tsuchiya-Suzuki A, Fukushima K, Shimojima Y, Yazaki M, Ikeda S (2010) Periodic peritonitis due to familial Mediterranean fever in a patient with systemic lupus erythematosus. Intern Med 49:2259–2262

    Article  Google Scholar 

  23. Inamo Y, Hayashi R, Saito K, Hasegawa M, Nakamura A, Hashimoto K, Fuchigami T, Nishikomori R (2013) A Japanese pediatric patient with coexisting systemic lupus erythematosus and familial Mediterranean fever. Lupus 22:1056–1059. https://doi.org/10.1177/0961203313497117

    Article  CAS  PubMed  Google Scholar 

  24. Basaran O, Aydin F, Celikel BA, Uncu N, Cakar N (2016) Coexistence of systemic lupus erythematosus and familial Mediterranean fever in a pediatric patient. Lupus 25:1062–1063. https://doi.org/10.1177/0961203315627872

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pediatric Rheumatology, Kanuni Sultan Süleyman Research and Training Hospital, University of Health Sciences, No: 46/1, Kucukcekmece, 34303, Istanbul, Turkey

    Ayşe Tanatar, Mustafa Çakan, Şerife Gül Karadağ & Nuray Aktay Ayaz

  2. Department of Pediatric Rheumatology, Faculty of Medicine, Erciyes University, Kayseri, Turkey

    Ayşenur Paç Kısaarslan & Betül Sözeri

Authors
  1. Ayşe Tanatar
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  2. Mustafa Çakan
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  3. Şerife Gül Karadağ
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  4. Ayşenur Paç Kısaarslan
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  5. Betül Sözeri
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  6. Nuray Aktay Ayaz
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Contributions

NAA wrote and revised the paper and together with AT interpreted the data and formulated conclusions. MÇ, AP, BS and SGK also wrote the statistical analysis plan, cleaned and analyzed the data, and revised each draft. They also involved with study design and recruitment. All authors approved the final version of manuscript.

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Correspondence to Nuray Aktay Ayaz.

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The authors declare that they have no conflict of interest.

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The study was reviewed and approved by the ethical review committee of Kanuni Sultan Süleyman Training and Research Hospital (Ethics Approval number: 80929729-000-6874).

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All participants and parents provided written informed consent.

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Tanatar, A., Çakan, M., Karadağ, Ş.G. et al. The influence of carrying MEFV gene variants on juvenile systemic lupus erythematosus. Rheumatol Int 41, 157–161 (2021). https://doi.org/10.1007/s00296-019-04420-7

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  • DOI: https://doi.org/10.1007/s00296-019-04420-7

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