nach oben

Rheumatology International

Erschienen in:

20.11.2017 | Genes and Disease

Evidence for genetic overlap between adult onset Still’s disease and hereditary periodic fever syndromes

verfasst von: R. Sighart, J. Rech, A. Hueber, N. Blank, S. Löhr, A. Reis, H. Sticht, U. Hüffmeier

Erschienen in: Rheumatology International | Ausgabe 1/2018

Einloggen, um Zugang zu erhalten

Abstract

Objective

Adult onset Still’s disease (AOSD) is a severe, autoimmune disease that can be challenging to treat with conventional therapeutics and biologicals in a considerable number of cases. Therefore, there is a high need to understand its pathogenesis better. As major clinical symptoms overlap between AOSD and hereditary periodic fever syndromes (HPFS), we analysed four known HPFS genes in AOSD.

Methods

We performed Sanger sequencing and quantitative analysis of all coding regions of MEFV, TNFRSF1A, MVK and NLRP3 in 40 AOSD patients. All rare coding variants (n = 6) were evaluated for several aspects to classify them as benign to pathogenic variants. Statistical analysis was performed to analyse whether variants classified as (likely) pathogenic were associated with AOSD.

Results

We identified three rare variants in MEFV, one previously not described. Association to the three likely pathogenic MEFV variants was significant (p _c = 2.34E− 03), and two of the three carriers had a severe course of disease. We observed strong evidence for significant association to mutations in TNFRSF1A (p _c = 2.40E− 04), as 5% of patients (2/40) carried a (likely) pathogenic variant in this gene. Both of them received a biological for treatment.

Conclusion

Our results indicate TNFRSF1A as a relevant gene in AOSD, especially in patients with a more challenging course of disease, while causal variants remain to be identified in the majority of patients.

Nur mit Berechtigung zugänglich

Bywaters EG (1971) Still’s disease in the adult. Ann Rheum Dis 30(2):121–133CrossRefPubMedPubMedCentral

Stabile A, Avallone L, Compagnone A et al (2006) Focus on juvenile idiopathic arthritis according to the 2001 Edmonton revised classification from the International League of Associations for Rheumatology: an Italian experience. Eur Rev Med Pharmacol Sci 10(5):229–234PubMed

Yamaguchi M, Ohta A, Tsunematsu T et al (1992) Preliminary criteria for classification of adult Still’s disease. J Rheumatol 19(3):424–430PubMed

van de Putte LB, Wouters JM (1991) Adult-onset Still’s disease. Bailliere’s Clin Rheumatol 5(2):263–275CrossRef

Efthimiou P, Georgy S (2006) Pathogenesis and management of adult-onset Still’s disease. Semin Arthritis Rheum 36(3):144–152CrossRefPubMed

de Boysson H, Fevrier J, Nicolle A et al (2013) Tocilizumab in the treatment of the adult-onset Still’s disease: current clinical evidence. Clinical Rheumatol 32(1):141–147CrossRef

Ortiz-Sanjuan F, Blanco R, Calvo-Rio V et al (2014) Efficacy of tocilizumab in conventional treatment-refractory adult-onset Still’s disease: multicenter retrospective open-label study of thirty-four patients. Arthritis Rheumatol 66(6):1659–1665CrossRefPubMed

Yao Q, Furst DE (2008) Autoinflammatory diseases: an update of clinical and genetic aspects. Rheumatology 47(7):946–51CrossRefPubMed

Kawaguchi Y, Terajima H, Harigai M et al (2001) Interleukin-18 as a novel diagnostic marker and indicator of disease severity in adult-onset Still’s disease. Arthritis Rheum 44(7):1716–1717CrossRefPubMed

10.

Mehta B, Efthimiou P (2012) Ferritin in adult-onset Still’s disease: just a useful innocent bystander? Int J Inflam 2012:298405PubMedPubMedCentral

11.

Mitrovic S, Fautrel B (2017) New Markers for Adult-Onset Still’s Disease. Joint Bone Spine

12.

Bohm B, Burkhardt H, Uebe S et al (2012) Identification of low-frequency TRAF3IP2 coding variants in psoriatic arthritis patients and functional characterization. Arthritis Res Ther 14(2):R84CrossRefPubMedPubMedCentral

13.

Sherry ST, Ward MH, Kholodov M et al (2001) dbSNP: the NCBI database of genetic variation. Nucleic Acids Res 29(1):308–311CrossRefPubMedPubMedCentral

14.

Lek M, Karczewski KJ, Minikel EV et al (2016) Analysis of protein-coding genetic variation in 60,706 humans. Nature 536(7616):285–291CrossRefPubMedPubMedCentral

15.

Yang H, Wang K (2015) Genomic variant annotation and prioritization with ANNOVAR and wANNOVAR. Nat Protoc 10(10):1556–1566CrossRefPubMedPubMedCentral

16.

Vajjhala PR, Kaiser S, Smith SJ et al (2014) Identification of multifaceted binding modes for pyrin and ASC pyrin domains gives insights into pyrin inflammasome assembly. J Biol Chem 289(34):23504–23519CrossRefPubMedPubMedCentral

17.

Weinert C, Morger D, Djekic A et al (2015) Crystal structure of TRIM20 C-terminal coiled-coil/B30.2 fragment: implications for the recognition of higher order oligomers. Sci Rep 5:10819CrossRefPubMedPubMedCentral

18.

Naismith JH, Devine TQ, Kohno T et al (1996) Structures of the extracellular domain of the type I tumour necrosis factor receptor. Structure 4(11):1251–1262CrossRefPubMed

19.

Guex N, Peitsch MC (1997) SWISS-MODEL and the Swiss-PdbViewer: an environment for comparative protein modeling. Electrophoresis 18(15):2714–2723CrossRefPubMed

20.

Sayle RA, Milner-White EJ (1995) RASMOL: biomolecular graphics for all. Trends Biochem Sci 20(9):374CrossRefPubMed

21.

Richards S, Aziz N, Bale S et al. (2015) Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 17(5):405–424CrossRefPubMedPubMedCentral

22.

Kleinberger J, Maloney KA, Pollin TI et al (2016) An openly available online tool for implementing the ACMG/AMP standards and guidelines for the interpretation of sequence variants. Genet Med 18(11):1165CrossRefPubMedPubMedCentral

23.

Schouten JP, McElgunn CJ, Waaijer R et al (2002) Relative quantification of 40 nucleic acid sequences by multiplex ligation-dependent probe amplification. Nucleic Acids Res 30(12):e57CrossRefPubMedPubMedCentral

24.

Korber A, Mossner R, Renner R et al (2013) Mutations in IL36RN in patients with generalized pustular psoriasis. J Invest Dermatol 133(11):2634–2637CrossRefPubMed

25.

Reese MG, Eeckman FH, Kulp D et al (1997) Improved splice site detection in Genie. J Comput Biol 4(3):311–323CrossRefPubMed

26.

Desmet FO, Hamroun D, Lalande M et al (2009) Human splicing finder: an online bioinformatics tool to predict splicing signals. Nucleic Acids Res 37(9):e67CrossRefPubMedPubMedCentral

27.

R CT (2012) R: a language and environment for statistical computing. http://wwwR-projectorg/. ISBN 3–900051-07-0

28.

Mossner R, Frambach Y, Wilsmann-Theis D et al (2015) Palmoplantar pustular psoriasis is associated with missense variants in CARD14, but not with loss-of-function mutations in IL36RN in European patients. J Invest Dermatol 135(10):2538–2541CrossRefPubMed

29.

Papin S, Cuenin S, Agostini L et al (2007) The SPRY domain of Pyrin, mutated in familial Mediterranean fever patients, interacts with inflammasome components and inhibits proIL-1beta processing. Cell Death Differ 14(8):1457–1466CrossRefPubMed

30.

Dode C, Pecheux C, Cazeneuve C et al (2000) Mutations in the MEFV gene in a large series of patients with a clinical diagnosis of familial Mediterranean fever. Am J Med Genet 92(4):241–246CrossRefPubMed

31.

Coker I, Colak A, Yolcu I et al (2011) MEFV gene mutation spectrum in familial Mediterranean fever (FMF): a single center study in the Aegean region of Turkey. Z Rheumatol 70(6):511–516CrossRefPubMed

32.

(1997) Ancient missense mutations in a new member of the RoRet gene family are likely to cause familial Mediterranean fever. Int FMF Consort Cell 90(4):797–807

33.

Rieber N, Gavrilov A, Hofer L et al (2015) A functional inflammasome activation assay differentiates patients with pathogenic NLRP3 mutations and symptomatic patients with low penetrance variants. Clin Immunol 157(1):56–64CrossRefPubMed

34.

Yuksel S, Eren E, Hatemi G et al (2014) Novel NLRP3/cryopyrin mutations and pro-inflammatory cytokine profiles in Behcet’s syndrome patients. Int Immunol 26(2):71–81CrossRefPubMed

35.

Aksentijevich I, Galon J, Soares M et al. (2001) The tumour-necrosis-factor receptor-associated periodic syndrome: new mutations in TNFRSF1A, ancestral origins, genotype-phenotype studies, and evidence for further genetic heterogeneity of periodic fevers. Am J Hum Genet. 69(2):301–314CrossRefPubMedPubMedCentral

36.

McDermott MF, Aksentijevich I, Galon J et al. (1999) Germline mutations in the extracellular domains of the 55 kDa TNF receptor, TNFR1, define a family of dominantly inherited autoinflammatory syndromes. Cell. 97(1):133–144CrossRefPubMed

37.

Landrum MJ, Lee JM, Benson M et al (2016) ClinVar: public archive of interpretations of clinically relevant variants. Nucleic Acids Res 44(D1):D862–D868CrossRefPubMed

38.

Kriegel MA, Huffmeier U, Scherb E et al (2003) Tumour necrosis factor receptor-associated periodic syndrome characterized by a mutation affecting the cleavage site of the receptor: implications for pathogenesis. Arthritis Rheum 48(8):2386–2388CrossRefPubMed

39.

Cosan F, Emrence Z, Erbag G et al (2013) The association of TNFRSF1A gene and MEFV gene mutations with adult onset Still’s disease. Rheumatol Int 33(7):1675–1680CrossRefPubMed

40.

Kim JJ, Kim JK, Shim SC et al (2013) MEFV gene mutations and their clinical significance in Korean patients with adult-onset Still’s disease. Clin Exp Rheumatol 31(3 Suppl 77):60–63PubMed

41.

Nonaka F, Migita K, Jiuchi Y et al (2015) Increased prevalence of MEFV exon 10 variants in Japanese patients with adult-onset Still’s disease. Clin Exp Immunol 179(3):392–397CrossRefPubMedPubMedCentral

42.

Tanaka N, Izawa K, Saito MK et al (2011) High incidence of NLRP3 somatic mosaicism in patients with chronic infantile neurologic, cutaneous, articular syndrome: results of an International Multicenter Collaborative Study. Arthritis Rheum 63(11):3625–3632CrossRefPubMedPubMedCentral

43.

Betancur JF, Navarro EP, Echeverry A et al (2015) Hyperferritinemic syndrome: still’s disease and catastrophic antiphospholipid syndrome triggered by fulminant Chikungunya infection: a case report of two patients. Clinical Rheumatol 34(11):1989–1992CrossRef

44.

Schifter T, Lewinski UH (1998) Adult onset Still’s disease associated with Epstein-Barr virus infection in a 66-year-old woman. Scand J Rheumatol 27(6):458–460CrossRefPubMed

45.

Chen DY, Chen YM, Lan JL et al (2012) Significant association of past parvovirus B19 infection with cytopenia in both adult-onset Still’s disease and systemic lupus erythematosus patients. Clin Chim Acta 413(9–10):855–860CrossRefPubMed

46.

Brandwein SR, Salusinsky-Sternbach M (1989) Adult Still’s disease in only one of identical twins. J Rheumatol 16(12):1599–1601PubMed

47.

Ansell BM, Bywaters EG, Lawrence JS (1969) Familial aggregation and twin studies in Still’s disease. Juv Chronic Polyarthritis Rheumatol 2:37–61

48.

Fautrel B (2008) Adult-onset Still’ disease. Best Pract Res Clin Rheumatol 22(5):773–792CrossRefPubMed

49.

Lehmann P, Salzberger B, Haerle P et al (2010) Variable intrafamilial expressivity of the rare tumour necrosis factor-receptor associated periodic syndrome-associated mutation I170N that affects the TNFR1A cleavage site. Modern Rheumatol 20(3):311–315CrossRef

50.

Rowczenio DM, Trojer H, Russell T et al (2013) Clinical characteristics in subjects with NLRP3 V198M diagnosed at a single UK center and a review of the literature. Arthritis Res Ther 15(1):R30CrossRefPubMedPubMedCentral

51.

Neven B, Callebaut I, Prieur AM et al (2004) Molecular basis of the spectral expression of CIAS1 mutations associated with phagocytic cell-mediated autoinflammatory disorders CINCA/NOMID, MWS, and FCU. Blood 103(7):2809–2815CrossRefPubMed

52.

Hoffman HM, Mueller JL, Broide DH et al (2001) Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle–Wells syndrome. Nat Genet 29(3):301–305CrossRefPubMedPubMedCentral

53.

Schaner P, Richards N, Wadhwa A et al (2001) Episodic evolution of pyrin in primates: human mutations recapitulate ancestral amino acid states. Nat Genet 27(3):318–321CrossRefPubMed

54.

Timmann C, Muntau B, Kuhne K et al (2001) Two novel mutations R653H and E230K in the Mediterranean fever gene associated with disease. Mutat Res 479(1–2):235–239CrossRefPubMed

55.

Agostini L, Martinon F, Burns K et al (2004) NALP3 forms an IL-1beta-processing inflammasome with increased activity in Muckle–Wells autoinflammatory disorder. Immunity 20(3):319–325CrossRefPubMed

Titel: Evidence for genetic overlap between adult onset Still’s disease and hereditary periodic fever syndromes
verfasst von: R. Sighart
J. Rech
A. Hueber
N. Blank
S. Löhr
A. Reis
H. Sticht
U. Hüffmeier
Publikationsdatum: 20.11.2017
Verlag: Springer Berlin Heidelberg
Erschienen in: Rheumatology International / Ausgabe 1/2018
Print ISSN: 0172-8172
Elektronische ISSN: 1437-160X
DOI: https://doi.org/10.1007/s00296-017-3885-0

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

24.04.2024 | DGIM 2024 | Kongressbericht | Nachrichten

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Evidence for genetic overlap between adult onset Still’s disease and hereditary periodic fever syndromes

Abstract

Objective

Methods

Results

Conclusion

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Metformin rückt in den Hintergrund

Myokarditis nach Infekt – richtig schwierig wird es bei Profisportlern

Thrombophiliescreening – Wenn, dann richtig und nur bei therapeutischer Konsequenz

Bei Senioren mit Prostatakarzinom auf Anämie achten!

Update Innere Medizin

Springer Medizin

Abstract

Objective

Methods

Results

Conclusion

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 1/2018

Decreased serum vitamin B12 and vitamin D levels affect sleep quality in children with familial Mediterranean fever

Pyoderma gangrenosum and pyogenic arthritis presenting as severe sepsis in a rheumatoid arthritis patient treated with golimumab

Fatigue in familial Mediterranean fever and its relations with other clinical parameters

Parenchymal neuro-Behçet disease with erectile dysfunction and micturition disturbances: case report and literature review

MMAB, a novel candidate gene to be screened in the molecular diagnosis of Mevalonate Kinase Deficiency

Biological therapies for the treatment of Behçet’s disease-related uveitis beyond TNF-alpha blockade: a narrative review

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Metformin rückt in den Hintergrund

Myokarditis nach Infekt – richtig schwierig wird es bei Profisportlern

Thrombophiliescreening – Wenn, dann richtig und nur bei therapeutischer Konsequenz

Bei Senioren mit Prostatakarzinom auf Anämie achten!

Update Innere Medizin