Advertisement

Monogenic Autoinflammatory Diseases Associated with Immunodeficiency

  • Michael J. OmbrelloEmail author
Chapter

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.

Keywords

Immune deficiency Immune dysregulation PLCG2-associated antibody deficiency and immune dysregulation (PLAID) Autoinflammatory PLAID (APLAID) Deficiency of linear ubiquitination assembly complex (LUBAC) Sideroblastic anemia with B cell immunodeficiency, periodic fevers and developmental delay WDR1 deficiency 

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. 1.
    Ombrello MJ, Kastner DL, Milner JD. HOIL and water: the two faces of HOIL-1 deficiency. Nat Immunol. 2012;13(12):1133–5.PubMedCrossRefGoogle Scholar
  2. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  4. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  5. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 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.PubMedCrossRefGoogle Scholar
  7. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Milner JD. PLAID: a syndrome of complex patterns of disease and unique phenotypes. J Clin Immunol. 2015;35(6):527–30.PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Yau R, Rape M. The increasing complexity of the ubiquitin code. Nat Cell Biol. 2016;18(6):579–86.PubMedCrossRefGoogle Scholar
  13. 13.
    Gerlach B, Cordier SM, Schmukle AC, et al. Linear ubiquitination prevents inflammation and regulates immune signalling. Nature. 2011;471(7340):591–6.PubMedCrossRefGoogle Scholar
  14. 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.PubMedCrossRefGoogle Scholar
  15. 15.
    Shimizu Y, Taraborrelli L, Walczak H. Linear ubiquitination in immunity. Immunol Rev. 2015;266(1):190–207.PubMedPubMedCentralCrossRefGoogle Scholar
  16. 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.PubMedCrossRefGoogle Scholar
  17. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  18. 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.PubMedCrossRefGoogle Scholar
  19. 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.PubMedCrossRefGoogle Scholar
  20. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 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.PubMedPubMedCentralGoogle Scholar
  22. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  25. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 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.PubMedCrossRefGoogle Scholar
  27. 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.PubMedCrossRefGoogle Scholar
  28. 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.PubMedCrossRefGoogle Scholar
  29. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  30. 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.PubMedCrossRefGoogle Scholar
  31. 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.PubMedCrossRefGoogle Scholar
  32. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  33. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Kuhns DB, Fink DL, Choi U, et al. Cytoskeletal abnormalities and neutrophil dysfunction in WDR1 deficiency. Blood. 2016;128(17):2135–43.PubMedPubMedCentralCrossRefGoogle Scholar
  35. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 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.PubMedCrossRefGoogle Scholar
  37. 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.PubMedCrossRefGoogle Scholar
  38. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 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.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Intramural Research Program, Translational Genetics and Genomics UnitNational Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of HealthBethesdaUSA

Personalised recommendations