Skip to main content
SpringerLink
Log in

Monogenic Autoinflammatory Diseases Associated with Immunodeficiency

  • Chapter
  • First Online:
Textbook of Autoinflammation

  • 1744 Accesses

Abstract

Despite the presence of accentuated inflammation, a subset of monogenic autoinflammatory disorders is also associated with increased susceptibility to infection. Mutations in PLCG2 cause autoinflammation in the context of immune dysregulation with antibody deficiency. Deficiency of components of the linear ubiquitin chain assembly complex (LUBAC) leads to severe autoinflammation with immunodeficiency in association with polyglucosan myopathy. Mutations in TRNT1 produce a syndrome of siderblastic anemia with B cell immunodeficiency, periodic fevers and developmental delay. Finally, patients with deficiency in WDR1 manifest autoinflammatory periodic fever, immunodeficiency and thrombocytopenia.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

AIP:

Actin interacting protein

ANA:

Anti-nuclear antibody

APLAID:

Autoinflammatory PLAID

CCA:

Cytosine-cytosine-adenosine

CRP:

C-reactive protein

cSH2:

Carboxy-terminal Src homology 2

DAG:

Diacylglycerol

ESR:

Erythrocyte sedimentation rate

FAMIN:

Fatty acid metabolic-immune nexus

HOIL-1:

Heme-oxidized IRP2 ubiquitin ligase 1

HOIP:

HOIL-1 interacting protein

Ig:

Immunoglobulin

IL:

Interleukin

IP3:

Inositol triphosphate

LPS:

Lipopolysaccharide

LUBAC:

Linear ubiquitination chain assembly complex

MAPK:

Mitogen-activated protein kinase

MYD88:

Myeloid differentiation primary response 88

NF-κB:

Nuclear factor kappa-light-chain-enhancer of activated B cells

NK:

Natural killer

NLRP3:

Nucleotide binding and oligomerization domain, leucine rich repeat, pyrin 3

PBMC:

Peripheral blood mononuclear cells

PFIT:

Periodic fever, immunodeficiency and thrombocytopenia

PIP2:

Phosphatidylinositol bisphosphate

PLAID:

PLCγ2-associated antibody deficiency and immune dysregulation

PLCγ2:

Phospholipase Cγ2

RIP1:

Receptor interacting protein 1

ROS:

Reactive oxygen species

RSC:

Receptor signaling complexes

SHARPIN:

 SHANK-associated RH domain-interacting protein like 1

SIFD:

Sideroblastic anemia with B cell immunodeficiency, periodic fevers and developmental delay

TNF:

Tumor necrosis factor

TRNT:

tRNA nucleotidyltransferase

WDR1:

WD domain repeat containing protein 1

References

  1. Ombrello MJ, Kastner DL, Milner JD. HOIL and water: the two faces of HOIL-1 deficiency. Nat Immunol. 2012;13(12):1133–5.

    Article  CAS  PubMed  Google Scholar 

  2. Boisson B, Laplantine E, Dobbs K, et al. Human HOIP and LUBAC deficiency underlies autoinflammation, immunodeficiency, amylopectinosis, and lymphangiectasia. J Exp Med. 2015;212(6):939–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Boisson B, Laplantine E, Prando C, et al. Immunodeficiency, autoinflammation and amylopectinosis in humans with inherited HOIL-1 and LUBAC deficiency. Nat Immunol. 2012;13(12):1178–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Chae JJ, Park YH, Park C, et al. Connecting two pathways through Ca 2+ signaling: NLRP3 inflammasome activation induced by a hypermorphic PLCG2 mutation. Arthritis Rheumatol. 2015;67(2):563–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Zhou Q, Lee GS, Brady J, et al. A hypermorphic missense mutation in PLCG2, encoding phospholipase Cgamma2, causes a dominantly inherited autoinflammatory disease with immunodeficiency. Am J Hum Genet. 2012;91(4):713–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Cader MZ, Boroviak K, Zhang Q, et al. C13orf31 (FAMIN) is a central regulator of immunometabolic function. Nat Immunol. 2016;17(9):1046–56.

    Article  CAS  PubMed  Google Scholar 

  7. Ombrello MJ, Remmers EF, Sun G, et al. Cold urticaria, immunodeficiency, and autoimmunity related to PLCG2 deletions. N Engl J Med. 2012;366(4):330–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Aderibigbe OM, Priel DL, Lee CC, et al. Distinct cutaneous manifestations and cold-induced leukocyte activation associated with PLCG2 mutations. JAMA Dermatol. 2015;151(6):627–34.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Gandhi C, Healy C, Wanderer AA, Hoffman HM. Familial atypical cold urticaria: description of a new hereditary disease. J Allergy Clin Immunol. 2009;124(6):1245–50.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Gresset A, Hicks SN, Harden TK, Sondek J. Mechanism of phosphorylation-induced activation of phospholipase C-gamma isozymes. J Biol Chem. 2010;285(46):35836–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Milner JD. PLAID: a syndrome of complex patterns of disease and unique phenotypes. J Clin Immunol. 2015;35(6):527–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Yau R, Rape M. The increasing complexity of the ubiquitin code. Nat Cell Biol. 2016;18(6):579–86.

    Article  CAS  PubMed  Google Scholar 

  13. Gerlach B, Cordier SM, Schmukle AC, et al. Linear ubiquitination prevents inflammation and regulates immune signalling. Nature. 2011;471(7340):591–6.

    Article  CAS  PubMed  Google Scholar 

  14. Iwai K, Fujita H, Sasaki Y. Linear ubiquitin chains: NF-kappaB signalling, cell death and beyond. Nat Rev Mol Cell Biol. 2014;15(8):503–8.

    Article  CAS  PubMed  Google Scholar 

  15. Shimizu Y, Taraborrelli L, Walczak H. Linear ubiquitination in immunity. Immunol Rev. 2015;266(1):190–207.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Nilsson J, Schoser B, Laforet P, et al. Polyglucosan body myopathy caused by defective ubiquitin ligase RBCK1. Ann Neurol. 2013;74(6):914–9.

    Article  CAS  PubMed  Google Scholar 

  17. Wang K, Kim C, Bradfield J, et al. Whole-genome DNA/RNA sequencing identifies truncating mutations in RBCK1 in a novel Mendelian disease with neuromuscular and cardiac involvement. Genome Med. 2013;5(7):67.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Rahighi S, Ikeda F, Kawasaki M, et al. Specific recognition of linear ubiquitin chains by NEMO is important for NF-kappaB activation. Cell. 2009;136(6):1098–109.

    Article  CAS  PubMed  Google Scholar 

  19. Tokunaga F, Sakata S, Saeki Y, et al. Involvement of linear polyubiquitylation of NEMO in NF-kappaB activation. Nat Cell Biol. 2009;11(2):123–32.

    Article  CAS  PubMed  Google Scholar 

  20. Emmerich CH, Ordureau A, Strickson S, et al. Activation of the canonical IKK complex by K63/M1-linked hybrid ubiquitin chains. Proc Natl Acad Sci U S A. 2013;110(38):15247–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. HogenEsch H, Gijbels MJ, Offerman E, van Hooft J, van Bekkum DW, Zurcher C. A spontaneous mutation characterized by chronic proliferative dermatitis in C57BL mice. Am J Pathol. 1993;143(3):972–82.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Chakraborty PK, Schmitz-Abe K, Kennedy EK, et al. Mutations in TRNT1 cause congenital sideroblastic anemia with immunodeficiency, fevers, and developmental delay (SIFD). Blood. 2014;124(18):2867–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Wiseman DH, May A, Jolles S, et al. A novel syndrome of congenital sideroblastic anemia, B-cell immunodeficiency, periodic fevers, and developmental delay (SIFD). Blood. 2013;122(1):112–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Sasarman F, Thiffault I, Weraarpachai W, et al. The 3′ addition of CCA to mitochondrial tRNASer(AGY) is specifically impaired in patients with mutations in the tRNA nucleotidyl transferase TRNT1. Hum Mol Genet. 2015;24(10):2841–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Wedatilake Y, Niazi R, Fassone E, et al. TRNT1 deficiency: clinical, biochemical and molecular genetic features. Orphanet J Rare Dis. 2016;11(1):90.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Frans G, Moens L, Schaballie H, et al. Homozygous N-terminal missense mutation in TRNT1 leads to progressive B-cell immunodeficiency in adulthood. J Allergy Clin Immunol. 2017;139(1):360–363.e6.

    Article  CAS  PubMed  Google Scholar 

  27. Barton C, Kausar S, Kerr D, Bitetti S, Wynn R. SIFD as a novel cause of severe fetal hydrops and neonatal anaemia with iron loading and marked extramedullary haemopoiesis. J Clin Pathol. 2018;71(3):275–8.

    Article  PubMed  Google Scholar 

  28. Lougaris V, Chou J, Baronio M, et al. Novel biallelic TRNT1 mutations resulting in sideroblastic anemia, combined B and T cell defects, hypogammaglobulinemia, recurrent infections, hypertrophic cardiomyopathy and developmental delay. Clin Immunol. 2018;188:20–2.

    Article  CAS  PubMed  Google Scholar 

  29. Giannelou A, Wang H, Zhou Q, et al. Aberrant tRNA processing causes an autoinflammatory syndrome responsive to TNF inhibitors. Ann Rheum Dis. 2018;77(4):612–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. DeLuca AP, Whitmore SS, Barnes J, et al. Hypomorphic mutations in TRNT1 cause retinitis pigmentosa with erythrocytic microcytosis. Hum Mol Genet. 2016;25(1):44–56.

    Article  CAS  PubMed  Google Scholar 

  31. Hull S, Malik AN, Arno G, et al. Expanding the phenotype of TRNT1-related immunodeficiency to include childhood cataract and inner retinal dysfunction. JAMA Ophthalmol. 2016;134(9):1049–53.

    Article  PubMed  Google Scholar 

  32. Liwak-Muir U, Mamady H, Naas T, et al. Impaired activity of CCA-adding enzyme TRNT1 impacts OXPHOS complexes and cellular respiration in SIFD patient-derived fibroblasts. Orphanet J Rare Dis. 2016;11(1):79.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Facecchia K, Fochesato LA, Ray SD, Stohs SJ, Pandey S. Oxidative toxicity in neurodegenerative diseases: role of mitochondrial dysfunction and therapeutic strategies. J Toxicol. 2011;2011:683728.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Kuhns DB, Fink DL, Choi U, et al. Cytoskeletal abnormalities and neutrophil dysfunction in WDR1 deficiency. Blood. 2016;128(17):2135–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Standing AS, Malinova D, Hong Y, et al. Autoinflammatory periodic fever, immunodeficiency, and thrombocytopenia (PFIT) caused by mutation in actin-regulatory gene WDR1. J Exp Med. 2017;214(1):59–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Kato A, Kurita S, Hayashi A, Kaji N, Ohashi K, Mizuno K. Critical roles of actin-interacting protein 1 in cytokinesis and chemotactic migration of mammalian cells. Biochem J. 2008;414(2):261–70.

    Article  CAS  PubMed  Google Scholar 

  37. Gressin L, Guillotin A, Guerin C, Blanchoin L, Michelot A. Architecture dependence of actin filament network disassembly. Curr Biol. 2015;25(11):1437–47.

    Article  CAS  PubMed  Google Scholar 

  38. Kile BT, Panopoulos AD, Stirzaker RA, et al. Mutations in the cofilin partner Aip1/Wdr1 cause autoinflammatory disease and macrothrombocytopenia. Blood. 2007;110(7):2371–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Kim ML, Chae JJ, Park YH, et al. Aberrant actin depolymerization triggers the pyrin inflammasome and autoinflammatory disease that is dependent on IL-18, not IL-1beta. J Exp Med. 2015;212(6):927–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Intramural Research Program, Translational Genetics and Genomics Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA

    Michael J. Ombrello

Authors
  1. Michael J. Ombrello
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michael J. Ombrello .

Editor information

Editors and Affiliations

  1. Pediatric Rheumatology Unit, Shaare Zedek Medical Center and Hebrew University, Jerusalem, Israel

    Philip J. Hashkes

  2. Department Paediatrics, Division of Rheumatology, The Hospital for Sick Children and University of Toronto, Toronto, ON, Canada

    Ronald M. Laxer

  3. Department of Internal Medicine, Radboudumc Expertisecenter for Immunodeficiency and Autoinflammation, Radboud University Medical Center, Nijmegen, The Netherlands

    Anna Simon

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Ombrello, M.J. (2019). Monogenic Autoinflammatory Diseases Associated with Immunodeficiency. In: Hashkes, P., Laxer, R., Simon, A. (eds) Textbook of Autoinflammation. Springer, Cham. https://doi.org/10.1007/978-3-319-98605-0_28

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-98605-0_28

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-98604-3

  • Online ISBN: 978-3-319-98605-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation