Advertisement

Rheumatology International

, Volume 38, Issue 8, pp 1571–1576 | Cite as

C3 glomerulopathy in NLRP12-related autoinflammatory disorder: case-based review

  • Özge Başaran
  • Nermin Uncu
  • Nilgün Çakar
  • Eda Tahir Turanlı
  • Saba Kiremitci
  • Fatma Aydın
  • Umut Selda Bayrakcı
Cases with a Message
  • 46 Downloads

Abstract

Autoinflammatory diseases (AIDs) are a recently described group of conditions caused by mutations in multiple genes that code for proteins of the innate immune system. Cryopyrin-associated periodic syndromes (CAPS) are autoinflammatory diseases comprising three clinically overlapping disorders: familial cold urticarial syndrome (FCAS), Muckle–Wells syndrome (MWS), and neonatal-onset multisystem inflammatory disease (NOMID). CAPS have been associated with gain-of-function variations in NLRP3 (NOD-like receptor family, pyrin containing domain-3). However, a new class of autoinflammatory disease resembling FCAS or MWS has been described in patients with NLRP12 mutations. Here, we report a 6-year-old boy diagnosed with AID who developed an unexpected C3 glomerulopathy during attacks and carried a novel variation in NLRP12. Following treatment with IL (interleukin) 1 targeting agents, all symptoms and inflammation resolved. This is the first case in the literature affected by both autoinflammatory disease and C3 glomerulopathy.

Keywords

Autoinflammatory disease C3 glomerulopathy NLRP12 Pediatric 

Notes

Author contributions

All authors made substantial contributions to conception and design of the paper as well as participated in drafting the article. All authors gave the final approval of the version to be submitted and any revised version. Study concept and design: ÖB and USB, NU. Analysis and interpretation of data: ÖB, FA, ETT, and SK. Drafting of the manuscript. ÖB, FA, ETT, and SK. Critical revision of the manuscript for important intellectual content: USB and ÖB. Study supervision: NÇ, USB, and NU.

Funding

No funding received for this research.

Compliance with ethical standards

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from the patient described in the case report. Parents of our patient have also agreed on publishing the pictures included in this manuscript.

Conflict of interest

Authors declare that there is no conflict of interest.

References

  1. 1.
    Kuemmerle-Deschner JB (2015) CAPS–pathogenesis, presentation and treatment of an autoinflammatory disease. Semin Immunopathol 37:377–385CrossRefPubMedGoogle Scholar
  2. 2.
    de Torre-Minguela C, Mesa Del Castillo P, Pelegrín P (2017) The NLRP3 and pyrin inflammasomes: implications in the pathophysiology of autoinflammatory diseases. Front Immunol 8:43PubMedPubMedCentralGoogle Scholar
  3. 3.
    Jéru I, Duquesnoy P, Fernandes-Alnemri T, Cochet E, Yu JW, Lackmy-Port-Lis M et al (2008) Mutations in NALP12 cause hereditary periodic fever syndromes. Proc Natl Acad Sci USA 105:1614–1619CrossRefPubMedGoogle Scholar
  4. 4.
    Wang K, Li M, Hakonarson H (2010) ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res 38:e164CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Jéru I, Hentgen V, Normand S, Duquesnoy P, Cochet E, Delwail A et al (2011) Role of interleukin-1β in NLRP12-associated autoinflammatory disorders and resistance to anti-interleukin-1 therapy. Arthritis Rheum 63:2142–2148CrossRefPubMedGoogle Scholar
  6. 6.
    Borghini S, Tassi S, Chiesa S, Caroli F, Carta S, Caorsi R et al (2011) Clinical presentation and pathogenesis of cold-induced autoinflammatory disease in a family with recurrence of an NLRP12 mutation. Arthritis Rheum 63:830–839CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Jéru I, Le Borgne G, Cochet E, Hayrapetyan H, Duquesnoy P, Grateau G et al (2011) Identification and functional consequences of a recurrent NLRP12 missense mutation in periodic fever syndromes. Arthritis Rheum 63:1459–1464CrossRefPubMedGoogle Scholar
  8. 8.
    Xia X, Dai C, Zhu X, Liao Q, Luo X, Fu Y et al (2016) Identification of a novel NLRP12 nonsense mutation (Trp408X) in the extremely rare disease FCAS by exome sequencing. PLoS One 11:e0156981CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Kostik MM, Suspitsin EN, Guseva MN, Levina AS, Kazantseva AY, Sokolenko AP et al (2018) Multigene sequencing reveals heterogeneity of NLRP12-related autoinflammatory disorders. Rheumatol Int 38:887–893CrossRefPubMedGoogle Scholar
  10. 10.
    Vitale A, Rigante D, Maggio MC, Emmi G, Romano M, Silvestri E et al (2013) Rare NLRP12 variants associated with the NLRP12-autoinflammatory disorder phenotype: an Italian case series. Clin Exp Rheumatol 31(3 Suppl 77):155–156PubMedGoogle Scholar
  11. 11.
    De Pieri C, Vuch J, Athanasakis E, Severini GM, Crovella S, Bianco AM et al (2014) F402L variant in NLRP12 in subjects with undiagnosed periodic fevers and in healthy controls. Clin Exp Rheumatol 32(6):993–994PubMedGoogle Scholar
  12. 12.
    Ozen S (2010) The “other” vasculitis syndromes and kidney involvement. Pediatr Nephrol 25:1633–1639CrossRefPubMedGoogle Scholar
  13. 13.
    Tsimaratos M, Koné-Paut I, Daniel L, Gubler MC, Dussol B, Picon G (1999) Crescentic glomerulonephritis in hyper IgD syndrome. Pediatr Nephrol 13:132–134CrossRefPubMedGoogle Scholar
  14. 14.
    Nevyjel M, Pontillo A, Calligaris L, Tommasini A, D’Osualdo A, Waterham HR et al (2007) Diagnostics and therapeutic insights in a severe case of mevalonate kinase deficiency. Pediatrics 119:e523–e527CrossRefPubMedGoogle Scholar
  15. 15.
    Tsapenko MV, Call TG, Lust JA, Leung N (2011) Periodic fever syndrome with relapsing glomerulonephritis: a case report and teaching points. NDT Plus 4:346–351PubMedPubMedCentralGoogle Scholar
  16. 16.
    Hutton HL, Ooi JD, Holdsworth SR, Kitching AR (2016) The NLRP3 inflammasome in kidney disease and autoimmunity. Nephrology (Carlton) 21:736–744CrossRefGoogle Scholar
  17. 17.
    Alexander MP, Fervenza FC, De Vriese AS, Smith RJH, Nasr SH, Cornell LD et al (2016) C3 glomerulonephritis and autoimmune disease: more than a fortuitous association? J Nephrol 29:203–209CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Pediatric Rheumatology, Ankara Child Health and Disease Hematology Oncology Training and Research HospitalUniversity of Health SciencesAnkaraTurkey
  2. 2.Department of Pediatric RheumatologyAnkara University School of MedicineAnkaraTurkey
  3. 3.Division of Molecular Biology and Genetics, Faculty of Science and Literatureİstanbul Technical UniversityIstanbulTurkey
  4. 4.Department of PathologyAnkara University School of MedicineAnkaraTurkey
  5. 5.Department of Pediatric NephrologyYıldırım Beyazıt UniversityAnkaraTurkey

Personalised recommendations