Top

Published in:

Open Access 01-07-2015 | Review

Hyper-IgD syndrome/mevalonate kinase deficiency: what is new?

Authors: C. M. Mulders-Manders, A. Simon

Published in: Seminars in Immunopathology | Issue 4/2015

Abstract

Mevalonate kinase deficiency or hyper-IgD syndrome is a hereditary autoinflammatory syndrome caused by mutations in the mevalonate kinase gene. In this review, we will discuss new findings in this disorder that have been published in the last 2 years. This includes new insights into pathophysiology, treatment, and the clinical phenotype linked to the genetic defect.

van der Meer JW, Vossen JM, Radl J, van Nieuwkoop JA, Meyer CJ, Lobatto S, van Furth R (1984) Hyperimmunoglobulinaemia D and periodic fever: a new syndrome. Lancet 1(8386):1087–1090PubMedCrossRef

Drenth JP, Cuisset L, Grateau G, Vasseur C, van de Velde-Visser SD, de Jong JG, Beckmann JS, van der Meer JW, Delpech M (1999) Mutations in the gene encoding mevalonate kinase cause hyper-IgD and periodic fever syndrome. International Hyper-IgD Study Group. Nat Genet 22(2):178–181. doi:10.1038/9696 PubMedCrossRef

Drenth JP, Goertz J, Daha MR, van der Meer JW (1996) Immunoglobulin D enhances the release of tumor necrosis factor-alpha, and interleukin-1 beta as well as interleukin-1 receptor antagonist from human mononuclear cells. Immunology 88(3):355–362PubMedCentralPubMedCrossRef

Frenkel J, Rijkers GT, Mandey SH, Buurman SW, Houten SM, Wanders RJ, Waterham HR, Kuis W (2002) Lack of isoprenoid products raises ex vivo interleukin-1beta secretion in hyperimmunoglobulinemia D and periodic fever syndrome. Arthritis Rheum 46(10):2794–2803. doi:10.1002/art.10550 PubMedCrossRef

Kuijk LM, Beekman JM, Koster J, Waterham HR, Frenkel J, Coffer PJ (2008) HMG-CoA reductase inhibition induces IL-1beta release through Rac1/PI3K/PKB-dependent caspase-1 activation. Blood 112(9):3563–3573. doi:10.1182/blood-2008-03-144667 PubMedCrossRef

Kuijk LM, Mandey SH, Schellens I, Waterham HR, Rijkers GT, Coffer PJ, Frenkel J (2008) Statin synergizes with LPS to induce IL-1beta release by THP-1 cells through activation of caspase-1. Mol Immunol 45(8):2158–2165. doi:10.1016/j.molimm.2007.12.008 PubMedCrossRef

Pontillo A, Paoluzzi E, Crovella S (2010) The inhibition of mevalonate pathway induces upregulation of NALP3 expression: new insight in the pathogenesis of mevalonate kinase deficiency. Eur J Human Genet : EJHG 18(7):844–847. doi:10.1038/ejhg.2010.9 PubMedCentralPubMedCrossRef

Bodar EJ, Kuijk LM, Drenth JP, van der Meer JW, Simon A, Frenkel J (2011) On-demand anakinra treatment is effective in mevalonate kinase deficiency. Ann Rheum Dis 70(12):2155–2158. doi:10.1136/ard.2011.149922 PubMedCrossRef

Bodar EJ, van der Hilst JC, Drenth JP, van der Meer JW, Simon A (2005) Effect of etanercept and anakinra on inflammatory attacks in the hyper-IgD syndrome: introducing a vaccination provocation model. Neth J Med 63(7):260–264PubMed

10.

Ter Haar N, Lachmann H, Ozen S, Woo P, Uziel Y, Modesto C, Kone-Paut I, Cantarini L, Insalaco A, Neven B, Hofer M, Rigante D, Al-Mayouf S, Touitou I, Gallizzi R, Papadopoulou-Alataki E, Martino S, Kuemmerle-Deschner J, Obici L, Iagaru N, Simon A, Nielsen S, Martini A, Ruperto N, Gattorno M, Frenkel J, Paediatric Rheumatology International Trials O, The Eurofever/Eurotraps Project (2013) Treatment of autoinflammatory diseases: results from the Eurofever Registry and a literature review. Ann Rheum Dis 72(5):678–685. doi:10.1136/annrheumdis-2011-201268 PubMedCrossRef

11.

Stoffels M, Jongekrijg J, Remijn T, Kok N, van der Meer JW, Simon A (2015) TLR2/TLR4-dependent exaggerated cytokine production in hyperimmunoglobulinaemia D and periodic fever syndrome. Rheumatology 54(2):363–368. doi:10.1093/rheumatology/keu341 PubMedCrossRef

12.

Marcuzzi A, Tommasini A, Crovella S, Pontillo A (2010) Natural isoprenoids inhibit LPS-induced-production of cytokines and nitric oxide in aminobisphosphonate-treated monocytes. Int Immunopharmacol 10(6):639–642. doi:10.1016/j.intimp.2010.03.008 PubMedCrossRef

13.

Marcuzzi A, Piscianz E, Girardelli M, Crovella S, Pontillo A (2011) Defect in mevalonate pathway induces pyroptosis in Raw 264.7 murine monocytes. Apoptosis : Int J Programmed Cell Death 16(9):882–888. doi:10.1007/s10495-011-0621-1 CrossRef

14.

Tricarico PM, Kleiner G, Valencic E, Campisciano G, Girardelli M, Crovella S, Knowles A, Marcuzzi A (2014) Block of the mevalonate pathway triggers oxidative and inflammatory molecular mechanisms modulated by exogenous isoprenoid compounds. Int J Mol Sci 15(4):6843–6856. doi:10.3390/ijms15046843 PubMedCentralPubMedCrossRef

15.

Kleiner G, Celsi F, Tricarico PM, Zacchigna S, Crovella S, Marcuzzi A (2013) Systemic and neuronal inflammatory markers in a mouse model of mevalonate kinase deficiency: a strain-comparative study. In Vivo 27(6):715–722PubMed

16.

Hager EJ, Tse HM, Piganelli JD, Gupta M, Baetscher M, Tse TE, Pappu AS, Steiner RD, Hoffmann GF, Gibson KM (2007) Deletion of a single mevalonate kinase (Mvk) allele yields a murine model of hyper-IgD syndrome. J Inherit Metab Dis 30(6):888–895. doi:10.1007/s10545-007-0776-7 PubMedCrossRef

17.

Hager EJ, Piganelli JD, Tse HM, Gibson KM (2012) Aberrant expression of costimulatory molecules in splenocytes of the mevalonate kinase-deficient mouse model of human hyper-IgD syndrome (HIDS). J Inherit Metab Dis 35(1):159–168. doi:10.1007/s10545-011-9349-x PubMedCentralPubMedCrossRef

18.

Marcuzzi A, Pontillo A, De Leo L, Tommasini A, Decorti G, Not T, Ventura A (2008) Natural isoprenoids are able to reduce inflammation in a mouse model of mevalonate kinase deficiency. Pediatr Res 64(2):177–182. doi:10.1203/PDR.0b013e3181761870 PubMedCrossRef

19.

Marcuzzi A, Crovella S, Pontillo A (2011) Geraniol rescues inflammation in cellular and animal models of mevalonate kinase deficiency. In vivo 25(1):87–92PubMed

20.

Marcuzzi A, Zanin V, Kleiner G, Monasta L, Crovella S (2013) Mouse model of mevalonate kinase deficiency: comparison of cytokine and chemokine profile with that of human patients. Pediatr Res 74(3):266–271. doi:10.1038/pr.2013.96 PubMedCrossRef

21.

Cantarini L, Vitale A, Magnotti F, Lucherini OM, Caso F, Frediani B, Galeazzi M, Rigante D (2013) Weekly oral alendronate in mevalonate kinase deficiency. Orphanet J Rare Dis 8:196. doi:10.1186/1750-1172-8-196 PubMedCentralPubMedCrossRef

22.

Mandey SH, Kuijk LM, Frenkel J, Waterham HR (2006) A role for geranylgeranylation in interleukin-1beta secretion. Arthritis Rheum 54(11):3690–3695. doi:10.1002/art.22194 PubMedCrossRef

23.

Liao Y-H, Lin Y-C, Tsao S-T, Lin Y-C, Yang A-J, Huang C-T, Huang K-C, Lin WW (2013) HMG-CoA reductase inhibitors activate caspase-1 in human monocytes depending on ATP release and P2X7 activation. J Leukoc Biol 93(2):289–299PubMedCrossRef

24.

van der Burgh R, Pervolaraki K, Turkenburg M, Waterham HR, Frenkel J, Boes M (2014) Unprenylated RhoA contributes to IL-1beta hypersecretion in mevalonate kinase deficiency model through stimulation of Rac1 activity. J Biol Chem 289(40):27757–27765. doi:10.1074/jbc.M114.571810 PubMedCrossRef

25.

Marcuzzi A, Zanin V, Piscianz E, Tricarico PM, Vuch J, Girardelli M, Monasta L, Bianco AM, Crovella S (2012) Lovastatin-induced apoptosis is modulated by geranylgeraniol in a neuroblastoma cell line. Int J Dev Neurosci : Off J Int Soc Developmental Neurosci 30(6):451–456. doi:10.1016/j.ijdevneu.2012.06.002 CrossRef

26.

van der Burgh R, Nijhuis L, Pervolaraki K, Compeer EB, Jongeneel LH, van Gijn M, Coffer PJ, Murphy MP, Mastroberardino PG, Frenkel J, Boes M (2014) Defects in mitochondrial clearance predispose human monocytes to interleukin-1beta hypersecretion. J Biol Chem 289(8):5000–5012. doi:10.1074/jbc.M113.536920 PubMedCentralPubMedCrossRef

27.

Shendi HM, Walsh D, Edgar JD (2012) Etanercept and anakinra can prolong febrile episodes in patients with hyperimmunoglobulin D and periodic fever syndrome. Rheumatol Int 32(1):249–251. doi:10.1007/s00296-009-1322-8 PubMedCrossRef

28.

Galeotti C, Meinzer U, Quartier P, Rossi-Semerano L, Bader-Meunier B, Pillet P, Kone-Paut I (2012) Efficacy of interleukin-1-targeting drugs in mevalonate kinase deficiency. Rheumatology 51(10):1855–1859. doi:10.1093/rheumatology/kes097 PubMedCrossRef

29.

Tsitsami E, Papadopoulou C, Speletas M (2013) A case of hyperimmunoglobulinemia d syndrome successfully treated with canakinumab. Case Rep Rheumatol 2013:795027. doi:10.1155/2013/795027 PubMedCentralPubMed

30.

Shendi HM, Devlin LA, Edgar JD (2014) Interleukin 6 blockade for hyperimmunoglobulin D and periodic fever syndrome. J Clin Rheumatol : Pract Rep Rheum Musculoskelet Dis 20(2):103–105. doi:10.1097/01.RHU.0000442576.41537.de

31.

Di Gangi M, Amato G, Converso G, Benenati A, Leonetti C, Borella E, Doria A, Foti R (2014) Long-term efficacy of adalimumab in hyperimmunoglobulin D and periodic fever syndrome. Isr Med Assoc J 16(10):605–607

32.

Chaudhury S, Hormaza L, Mohammad S, Lokar J, Ekong U, Alonso EM, Wainwright MS, Kletzel M, Whitington PF (2012) Liver transplantation followed by allogeneic hematopoietic stem cell transplantation for atypical mevalonic aciduria. Am J Transplant : Off J Am Soc Transplant Am Soc Transplant Surg 12(6):1627–1631. doi:10.1111/j.1600-6143.2011.03989.x CrossRef

33.

Neven B, Valayannopoulos V, Quartier P, Blanche S, Prieur AM, Debre M, Rolland MO, Rabier D, Cuisset L, Cavazzana-Calvo M, de Lonlay P, Fischer A (2007) Allogeneic bone marrow transplantation in mevalonic aciduria. N Engl J Med 356(26):2700–2703. doi:10.1056/NEJMoa070715 PubMedCrossRef

34.

Arkwright PD, Abinun M, Cant AJ (2007) Mevalonic aciduria cured by bone marrow transplantation. N Engl J Med 357(13):1350. doi:10.1056/NEJMc072002 PubMedCrossRef

35.

Levy M, Arion A, Berrebi D, Cuisset L, Jeanne-Pasquier C, Bader-Meunier B, Jung C (2013) Severe early-onset colitis revealing mevalonate kinase deficiency. Pediatrics 132(3):e779–e783. doi:10.1542/peds.2012-3344 PubMedCrossRef

36.

Bianco AM, Girardelli M, Vozzi D, Crovella S, Kleiner G, Marcuzzi A (2014) Mevalonate kinase deficiency and IBD: shared genetic background. Gut 63(8):1367–1368. doi:10.1136/gutjnl-2013-306555 PubMedCentralPubMedCrossRef

37.

Parvaneh N, Ziaee V, Moradinejad MH, Touitou I (2014) Intermittent neutropenia as an early feature of mild mevalonate kinase deficiency. J Clin Immunol 34(1):123–126. doi:10.1007/s10875-013-9955-5 PubMedCrossRef

38.

Schulert GS, Bove K, McMasters R, Campbell K, Leslie N, Grom AA (2014) Mevalonate kinase deficiency associated with recurrent liver dysfunction, macrophage activation syndrome and perforin gene polymorphism. Arthritis Care Res. doi:10.1002/acr.22527

39.

von Linstow M-L, Rosenfeldt V (2014) Neonatal hepatitis as first manifestation of hyperimmunoglobulinemia d syndrome. Case Rep Pediatr 2014:936890

40.

Siemiatkowska AM, van den Born LI, van Hagen PM, Stoffels M, Neveling K, Henkes A, Kipping-Geertsema M, Hoefsloot LH, Hoyng CB, Simon A, den Hollander AI, Cremers FPM, Collin RWJ (2013) Mutations in the mevalonate kinase (MVK) gene cause nonsyndromic retinitis pigmentosa. Ophthalmology 120(12):2697–2705PubMedCrossRef

41.

Zhang S-Q, Jiang T, Li M, Zhang X, Ren Y-Q, Wei S-C, Sun L-D, Cheng H, Li Y, Yin X-Y, Hu Z-M, Wang Z-Y, Liu Y, Guo B-R, Tang H-Y, Tang X-F, Ding Y-T, Wang J-B, Li P, Wu B-Y, Wang W, Yuan X-F, Hou J-S, Ha W-W, Wang W-J, Zhai Y-J, Wang J, Qian F-F, Zhou F-S, Chen G, Zuo X-B, Zheng X-D, Sheng Y-J, Gao J-P, Liang B, Li P, Zhu J, Xiao F-L, Wang P-G, Cui Y, Li H, Liu S-X, Gao M, Fan X, Shen S-K, Zeng M, Sun G-Q, Xu Y, Hu J-C, He T-T, Li Y-R, Yang H-M, Wang J, Yu Z-Y, Zhang H-F, Hu X, Yang K, Wang J, Zhao S-X, Zhou Y-W, Liu J-J, Du W-D, Zhang L, Xia K, Yang S, Wang J, Zhang X-J (2012) Exome sequencing identifies MVK mutations in disseminated superficial actinic porokeratosis. Nat Genet 44(10):1156–1160PubMedCrossRef

42.

Dai J, Chen M, Fu X, Yu Y, Shi Z, Yu C, Wang G, Tian H, Liu H, Zhang F (2013) Mutation analysis of the MVK gene in Chinese patients with disseminated superficial actinic porokeratosis. J Dermatol Sci 72(3):320–322. doi:10.1016/j.jdermsci.2013.07.011 PubMedCrossRef

43.

Zhou Y, Liu J, Fu X, Yu Y, Shi B, Yu G, Shi Z, Wu W, Pan F, Tian H, Liu H, Zhang F (2013) Identification of three novel frameshift mutations of the MVK gene in four Chinese families with disseminated superficial actinic porokeratosis. Br J Dermatol 169(1):193–195. doi:10.1111/bjd.12224 PubMedCrossRef

44.

Lu WS, Zheng XD, Yao XH, Zhang LF, Wang MQ, Jiang FX, Zhang SP, Hu B (2014) A novel MVK missense mutation in one Chinese family with disseminated superficial actinic porokeratosis. Mol Biol Rep 41(11):7229–7233. doi:10.1007/s11033-014-3609-4 PubMedCrossRef

45.

Zhou MS, Xie HF, Chen ML, Jian D, Liu FF, Chen X, Shen N, Si N, Li J (2014) A novel mutation for disseminated superficial actinic porokeratosis in the MVK gene. Br J Dermatol 171(2):427–429. doi:10.1111/bjd.12947 PubMedCrossRef

46.

Lu WS, Zheng XD, Yao XH, Zhang LF, Hu B, Lu YJ (2014) Detection of a novel missense mutation in the mevalonate kinase gene in one Chinese family with DSAP. Int J Clin Exp Pathol 7(2):728–732PubMedCentralPubMed

47.

Zeng K, Zhang QG, Li L, Duan Y, Liang YH (2014) Splicing mutation in MVK is a cause of porokeratosis of Mibelli. Arch Dermatol Res 306(8):749–755. doi:10.1007/s00403-014-1465-7 PubMedCrossRef

48.

Rodrigues AVM, Maggs JL, McWilliam SJ, Pirmohamed M, Coen M, Wilson ID, Park BK, Antoine DJ (2014) Quantification of urinary mevalonic acid as a biomarker of HMG-CoA reductase activity by a novel translational LC-MS/MS method. Bioanalysis 6(7):919–933PubMedCrossRef

Title: Hyper-IgD syndrome/mevalonate kinase deficiency: what is new?
Authors: C. M. Mulders-Manders
A. Simon
Publication date: 01-07-2015
Publisher: Springer Berlin Heidelberg
Published in: Seminars in Immunopathology / Issue 4/2015
Print ISSN: 1863-2297
Electronic ISSN: 1863-2300
DOI: https://doi.org/10.1007/s00281-015-0492-6

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits

Illustration of figure on mountain summit/© Orapun / Stock.adobe.com, STEP AAG HeroTeaserCollection image/© Tarek / Generated with AI / Stock.adobe.com, ACC 2024 Pediatric and Congenital Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Pulmonary Vascular Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Valvular Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 HF and Cardiomyopathies: Year in Review/© 2024 American College of Cardiology, Woman out walking/© Seventyfour / stock.adobe.com (symbolic image with model), Woman checking smartwatch /© saltdium / stock.adobe.com (symbolic image with model), Cardiac catheterization/© Damian / stock.adobe.com

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 4/2015

New discoveries in CRMO: IL-1β, the neutrophil, and the microbiome implicated in disease pathogenesis in Pstpip2-deficient mice

Protein misfolding and dysregulated protein homeostasis in autoinflammatory diseases and beyond

Broadening the definition of autoinflammation

New monogenic autoinflammatory diseases—a clinical overview

The myths we believed in familial Mediterranean fever: what have we learned in the past years?

Pathogenesis of Behçet’s disease: autoinflammatory features and beyond

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

Highlights from the ACC 2024 Congress

ACC 2024 Congress Coverage