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TACI Deficiency

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Book cover Humoral Primary Immunodeficiencies

Part of the book series: Rare Diseases of the Immune System ((RDIS))

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Abstract

The tumor necrosis factor (TNF) superfamily member transmembrane activator and CAML interactor (TACI, encoded by TNFRSF13B) belongs to a group of molecules which regulate B cell homeostasis, differentiation, and function. Heterozygous, compound heterozygous, or homozygous alterations in the TNFRSF13B gene are associated with various forms of antibody deficiency including IgA deficiency and CVID. These genetic alterations have a low penetrance and are generally not regarded as disease causing, but may be important genetic cofactors affecting especially the T cell-independent antibody responses and increasing risks for autoimmunity and lymphoproliferation. Therefore TACI deficiency is currently viewed as a disease-modifying factor in various forms of antibody deficiency. The management of CVID patients carrying a TACI mutation does not differ from conventional CVID. However, one should take into account the higher rates of autoimmune and lymphoproliferative complications seen in these individuals.

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References

  1. Hoffmann FS, Kuhn PH, Laurent SA, Hauck SM, Berer K, Wendlinger SA, Krumbholz M, Khademi M, Olsson T, Dreyling M, Pfister HW, Alexander T, Hiepe F, Kümpfel T, Crawford HC, Wekerle H, Hohlfeld R, Lichtenthaler SF, Meinl E. The immunoregulator soluble TACI is released by ADAM10 and reflects B cell activation in autoimmunity. J Immunol. 2015;194:542–52.

    Article  CAS  Google Scholar 

  2. Roschke V, Sosnovtseva S, Ward CD, Hong JS, Smith R, Albert V, Stohl W, Baker KP, Ullrich S, Nardelli B, Hilbert DM, Migone TS. BLyS and APRIL form biologically active heterotrimers that are expressed in patients with systemic immune-based rheumatic diseases. J Immunol. 2002;169:4314–21.

    Article  CAS  Google Scholar 

  3. Bischof D, Elsawa SF, Mantchev G, Yoon J, Michels GE, Nilson A, Sutor SL, Platt JL, Ansell SM, von Bulow G, Bram RJ. Selective activation of TACI by syndecan-2. Blood. 2006;107:3235–42.

    Article  CAS  Google Scholar 

  4. Ingold K, Zumsteg A, Tardivel A, Huard B, Steiner QG, Cachero TG, Qiang F, Gorelik L, Kalled SL, Acha-Orbea H, Rennert PD, Tschopp J, Schneider P. Identification of proteoglycans as the APRIL-specific binding partners. J Exp Med. 2005;201:1375–83.

    Article  CAS  Google Scholar 

  5. Ng LG, Sutherland AP, Newton R, Qian F, Cachero TG, Scott ML, Thompson JS, Wheway J, Chtanova T, Groom J, Sutton IJ, Xin C, Tangye SG, Kalled SL, Mackay F, Mackay CR. B cell-activating factor belonging to the TNF family (BAFF)-R is the principal BAFF receptor facilitating BAFF costimulation of circulating T and B cells. J Immunol. 2004;173:807–17.

    Article  CAS  Google Scholar 

  6. Sasaki Y, Casola S, Kutok JL, Rajewsky K, Schmidt-Supprian M. TNF family member B cell-activating factor (BAFF) receptor-dependent and -independent roles for BAFF in B cell physiology. J Immunol. 2004;173:2245–52.

    Article  CAS  Google Scholar 

  7. Schneider P, Takatsuka H, Wilson A, Mackay F, Tardivel A, Lens S, Cachero TG, Finke D, Beermann F, Tschopp J. Maturation of marginal zone and follicular B cells requires B cell activating factor of the tumor necrosis factor family and is independent of B cell maturation antigen. J Exp Med. 2001;194:1691–7.

    Article  CAS  Google Scholar 

  8. Avery DT, Kalled SL, Ellyard JI, Ambrose C, Bixler SA, Thien M, Brink R, Mackay F, Hodgkin PD, Tangye SG. BAFF selectively enhances the survival of plasmablasts generated from human memory B cells. J Clin Invest. 2003;112:286–97.

    Article  CAS  Google Scholar 

  9. Novak AJ, Darce JR, Arendt BK, Harder B, Henderson K, Kindsvogel W, Gross JA, Greipp PR, Jelinek DF. Expression of BCMA, TACI, and BAFF-R in multiple myeloma: a mechanism for growth and survival. Blood. 2004;103:689–94.

    Article  CAS  Google Scholar 

  10. O'Connor BP, Raman VS, Erickson LD, Cook WJ, Weaver LK, Ahonen C, Lin LL, Mantchev GT, Bram RJ, Noelle RJ. BCMA is essential for the survival of long-lived bone marrow plasma cells. J Exp Med. 2004;199:91–8.

    Article  CAS  Google Scholar 

  11. Batten M, Fletcher C, Ng LG, Groom J, Wheway J, Laabi Y, Xin X, Schneider P, Tschopp J, Mackay CR, Mackay F. TNF deficiency fails to protect BAFF transgenic mice against autoimmunity and reveals a predisposition to B cell lymphoma. J Immunol. 2004;172:812–22.

    Article  CAS  Google Scholar 

  12. Sakurai D, Kanno Y, Hase H, Kojima H, Okumura K, Kobata T. TACI attenuates antibody production costimulated by BAFF-R and CD40. Eur J Immunol. 2007;37:110–8.

    Article  CAS  Google Scholar 

  13. Hymowitz SG, Patel DR, Wallweber HJ, Runyon S, Yan M, Yin J, Shriver SK, Gordon NC, Pan B, Skelton NJ, Kelley RF, Starovasnik MA. Structures of APRIL-receptor complexes: like BCMA, TACI employs only a single cysteine-rich domain for high affinity ligand binding. J Biol Chem. 2005;280:7218–27.

    Article  CAS  Google Scholar 

  14. Garcia-Carmona Y, Cols M, Ting AT, Radigan L, Yuk FJ, Zhang L, Cerutti A, Cunningham-Rundles C. Differential induction of plasma cells by isoforms of human TACI. Blood. 2015;125:1749–58.

    Article  CAS  Google Scholar 

  15. Mackay F, Schneider P. Cracking the BAFF code. Nat Rev Immunol. 2009;9:491–502.

    Article  CAS  Google Scholar 

  16. Schuepbach-Mallepell S, Das D, Willen L, Vigolo M, Tardivel A, Lebon L, Kowalczyk-Quintas C, Nys J, Smulski C, Zheng TS, Maskos K, Lammens A, Jiang X, Hess H, Tan SL, Schneider P. Stoichiometry of heteromeric BAFF and APRIL cytokines dictates their receptor binding and signaling properties. J Biol Chem. 2015;290:16330–42.

    Article  CAS  Google Scholar 

  17. Smulski CR, Kury P, Seidel LM, Staiger HS, Edinger AK, Willen L, Seidl M, Hess H, Salzer U, Rolink AG, Rizzi M, Schneider P, Eibel H. BAFF- and TACI-dependent processing of BAFFR by ADAM proteases regulates the survival of B cells. Cell Rep. 2017;18:2189–202.

    Article  CAS  Google Scholar 

  18. He B, Santamaria R, Xu W, Cols M, Chen K, Puga I, Shan M, Xiong H, Bussel JB, Chiu A, Puel A, Reichenbach J, Marodi L, Döffinger R, Vasconcelos J, Issekutz A, Krause J, Davies G, Li X, Grimbacher B, Plebani A, Meffre E, Picard C, Cunningham-Rundles C, Casanova JL, Cerutti A. The transmembrane activator TACI triggers immunoglobulin class switching by activating B cells through the adaptor MyD88. Nat Immunol. 2010;11:836–45.

    Article  CAS  Google Scholar 

  19. von Bulow GU, Bram RJ. NF-AT activation induced by a CAML-interacting member of the tumor necrosis factor receptor superfamily. Science. 1997;278:138–41.

    Article  Google Scholar 

  20. von Bulow GU, Russell H, Copeland NG, Gilbert DJ, Jenkins NA, Bram RJ. Molecular cloning and functional characterization of murine transmembrane activator and CAML interactor (TACI) with chromosomal localization in human and mouse. Mamm Genome. 2000;11:628–32.

    Article  Google Scholar 

  21. Romberg N, Chamberlain N, Saadoun D, Gentile M, Kinnunen T, Ng YS, Virdee M, Menard L, Cantaert T, Morbach H, Rachid R, Martinez-Pomar N, Matamoros N, Geha R, Grimbacher B, Cerutti A, Cunningham-Rundles C, Meffre E. CVID-associated TACI mutations affect autoreactive B cell selection and activation. J Clin Invest. 2013;123:4283–93.

    Article  CAS  Google Scholar 

  22. Castigli E, Wilson SA, Scott S, Dedeoglu F, Xu S, Lam KP, Bram RJ, Jabara H, Geha RS. TACI and BAFF-R mediate isotype switching in B cells. J Exp Med. 2005;201:35–9.

    Article  CAS  Google Scholar 

  23. Castigli E, Wilson SA, Garibyan L, Rachid R, Bonilla F, Schneider L, Geha RS. TACI is mutant in common variable immunodeficiency and IgA deficiency. Nat Genet. 2005;37:829–34.

    Article  CAS  Google Scholar 

  24. Litinskiy MB, Nardelli B, Hilbert DM, He B, Schaffer A, Casali P, Cerutti A. DCs induce CD40-independent immunoglobulin class switching through BLyS and APRIL. Nat Immunol. 2002;3:822–9.

    Article  CAS  Google Scholar 

  25. Castigli E, Scott S, Dedeoglu F, Bryce P, Jabara H, Bhan AK, Mizoguchi E, Geha RS. Impaired IgA class switching in APRIL-deficient mice. PNAS. 2004;101:3903–8.

    Article  CAS  Google Scholar 

  26. Seshasayee D, Valdez P, Yan M, Dixit VM, Tumas D, Grewal IS. Loss of TACI causes fatal lymphoproliferation and autoimmunity, establishing TACI as an inhibitory BLyS receptor. Immunity. 2003;18:279–88.

    Article  CAS  Google Scholar 

  27. von Bulow GU, van Deursen JM, Bram RJ. Regulation of the T-independent humoral response by TACI. Immunity. 2001;14:573–82.

    Article  Google Scholar 

  28. Yan M, Wang H, Chan B, Roose-Girma M, Erickson S, Baker T, Tumas D, Grewal IS, Dixit VM. Activation and accumulation of B cells in TACI-deficient mice. Nat Immunol. 2001;2:638–43.

    Article  CAS  Google Scholar 

  29. Jabara HH, Lee JJ, Janssen E, Ullas S, Liadaki K, Garibyan L, Benson H, Sannikova T, Bram R, Hammarstrom L, Cruz AC, Siegel R, Manis J, Malley R, Geha RS. Heterozygosity for transmembrane activator and calcium modulator ligand interactor A144E causes haploinsufficiency and pneumococcal susceptibility in mice. J Allergy Clin Immunol. 2017;139:1293–1301.e4.

    Article  CAS  Google Scholar 

  30. Lee JJ, Jabara HH, Garibyan L, Rauter I, Sannikova T, Dillon SR, Bram R, Geha RS. The C104R mutant impairs the function of transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) through haploinsufficiency. J Allergy Clin Immunol. 2010;126:1234–41.e2.

    Article  CAS  Google Scholar 

  31. Lee JJ, Rauter I, Garibyan L, Ozcan E, Sannikova T, Dillon SR, Cruz AC, Siegel RM, Bram R, Jabara H, Geha RS. The murine equivalent of the A181E TACI mutation associated with common variable immunodeficiency severely impairs B-cell function. Blood. 2009;114:2254–62.

    Article  CAS  Google Scholar 

  32. Bacchelli C, Buckland KF, Buckridge S, Salzer U, Schneider P, Thrasher AJ, Gaspar HB. The C76R transmembrane activator and calcium modulator cyclophilin ligand interactor mutation disrupts antibody production and B-cell homeostasis in heterozygous and homozygous mice. J Allergy Clin Immunol. 2011;127:1253–9.e13.

    Article  CAS  Google Scholar 

  33. Salzer U, Chapel HM, Webster AD, Pan-Hammarstrom Q, Schmitt-Graeff A, Schlesier M, Peter HH, Rockstroh JK, Schneider P, Schaffer AA, Hammarstrom L, Grimbacher B. Mutations in TNFRSF13B encoding TACI are associated with common variable immunodeficiency in humans. Nat Genet. 2005;37:820–8.

    Article  CAS  Google Scholar 

  34. Salzer U, Bacchelli C, Buckridge S, Pan-Hammarström Q, Jennings S, Lougaris V, Bergbreiter A, Hagena T, Birmelin J, Plebani A, Webster AD, Peter HH, Suez D, Chapel H, McLean-Tooke A, Spickett GP, Anover-Sombke S, Ochs HD, Urschel S, Belohradsky BH, Ugrinovic S, Kumararatne DS, Lawrence TC, Holm AM, Franco JL, Schulze I, Schneider P, Gertz EM, Schäffer AA, Hammarström L, Thrasher AJ, Gaspar HB, Grimbacher B. Relevance of biallelic versus monoallelic TNFRSF13B mutations in distinguishing disease-causing from risk-increasing TNFRSF13B variants in antibody deficiency syndromes. Blood. 2009;113:1967–76.

    Article  CAS  Google Scholar 

  35. Garibyan L, Lobito AA, Siegel RM, Call ME, Wucherpfennig KW, Geha RS. Dominant-negative effect of the heterozygous C104R TACI mutation in common variable immunodeficiency (CVID). J Clin Invest. 2007;117:1550–7.

    Article  CAS  Google Scholar 

  36. Chinen J, Martinez-Gallo M, Gu W, Cols M, Cerutti A, Radigan L, Zhang L, Potocki L, Withers M, Lupski JR, Cunningham-Rundles C. Transmembrane activator and CAML interactor (TACI) haploinsufficiency results in B-cell dysfunction in patients with Smith-Magenis syndrome. J Allergy Clin Immunol. 2011;127:1579–86.

    Article  CAS  Google Scholar 

  37. Romberg N, Virdee M, Chamberlain N, Oe T, Schickel JN, Perkins T, Cantaert T, Rachid R, Rosengren S, Palazzo R, Geha R, Cunningham-Rundles C, Meffre E. TNF receptor superfamily member 13b (TNFRSF13B) hemizygosity reveals transmembrane activator and CAML interactor haploinsufficiency at later stages of B-cell development. J Allergy Clin Immunol. 2015;136:1315–25.

    Article  CAS  Google Scholar 

  38. Warnatz K, Denz A, Dräger R, Braun M, Groth C, Wolff-Vorbeck G, Eibel H, Schlesier M, Peter HH. Severe deficiency of switched memory B cells (CD27(+)IgM(−)IgD(−)) in subgroups of patients with common variable immunodeficiency: a new approach to classify a heterogeneous disease. Blood. 2002;99:1544–51.

    Article  CAS  Google Scholar 

  39. Endo T, Nishio M, Enzler T, Cottam HB, Fukuda T, James DF, Karin M, Kipps TJ. BAFF and APRIL support chronic lymphocytic leukemia B-cell survival through activation of the canonical NF-kappaB pathway. Blood. 2007;109:703–10.

    Article  CAS  Google Scholar 

  40. Margraf RL, Coonrod EM, Durtschi JD, Augustine NH, Voelkerding KV, Hill HR, Kumánovics A. TACI mutation p.Lys154Ter identified in Good Syndrome. Clin Immunol. 2013;146:10–2.

    Article  CAS  Google Scholar 

  41. Sáenz-Cuesta M, Martínez-Pomar N, de Gracia J, Echaniz P, Villegas E, Prada A, Otaegui D, Matamoros N, Cuadrado E. TACI mutation in Good’s Syndrome: in search of a genetic basis. Clin Immunol. 2012;145:27–30.

    Article  Google Scholar 

  42. Speletas M, Salzer U, Florou Z, Petinaki E, Daniil Z, Bardaka F, Gourgoulianis KI, Skoulakis C, Germenis AE. Heterozygous alterations of TNFRSF13B/TACI in tonsillar hypertrophy and sarcoidosis. Clin Dev Immunol. 2013;2013:532437.

    Article  Google Scholar 

  43. Fischer A, Provot J, Jais JP, Alcais A, Mahlaoui N, Members of the CEREDIH French PID Study Group. Autoimmune and inflammatory manifestations occur frequently in patients with primary immunodeficiencies. J Allergy Clin Immunol. 2017;140:1388–1393.e8.

    Article  CAS  Google Scholar 

  44. Mackay F, Woodcock SA, Lawton P, Ambrose C, Baetscher M, Schneider P, Tschopp J, Browning JL. Mice transgenic for BAFF develop lymphocytic disorders along with autoimmune manifestations. J Exp Med. 1999;190:1697–710.

    Article  CAS  Google Scholar 

  45. Khare SD, Sarosi I, Xia XZ, McCabe S, Miner K, Solovyev I, Hawkins N, Kelley M, Chang D, Van G, Ross L, Delaney J, Wang L, Lacey D, Boyle WJ, Hsu H. Severe B cell hyperplasia and autoimmune disease in TALL-1 transgenic mice. Proc Natl Acad Sci U S A. 2000;97:3370–5.

    Article  CAS  Google Scholar 

  46. Chu VT, Enghard P, Schürer S, Steinhauser G, Rudolph B, Riemekasten G, Berek C. Systemic activation of the immune system induces aberrant BAFF and APRIL expression in B cells in patients with systemic lupus erythematosus. Arthritis Rheum. 2009;60:2083–93.

    Article  CAS  Google Scholar 

  47. Treamtrakanpon W, Tantivitayakul P, Benjachat T, Somparn P, Kittikowit W, Eiam-ong S, Leelahavanichkul A, Hirankarn N, Avihingsanon Y. APRIL, a proliferation-inducing ligand, as a potential marker of lupus nephritis. Arthritis Res Ther. 2012;14:R252.

    Article  CAS  Google Scholar 

  48. Becker-Merok A, Nikolaisen C, Nossent HC. B-lymphocyte activating factor in systemic lupus erythematosus and rheumatoid arthritis in relation to autoantibody levels, disease measures and time. Lupus. 2006;15:570–6.

    Article  CAS  Google Scholar 

  49. Stohl W, Metyas S, Tan SM, Cheema GS, Oamar B, Roschke V, Wu Y, Baker KP, Hilbert DM. Inverse association between circulating APRIL levels and serological and clinical disease activity in patients with systemic lupus erythematosus. Ann Rheum Dis. 2004;63:1096–103.

    Article  CAS  Google Scholar 

  50. Dillon SR, Harder B, Lewis KB, Moore MD, Liu H, Bukowski TR, Hamacher NB, Lantry MM, Maurer M, Krejsa CM, Ellsworth JL, Pederson S, Elkon KB, Wener MH, Dall'Era M, Gross JA. B-lymphocyte stimulator/a proliferation-inducing ligand heterotrimers are elevated in the sera of patients with autoimmune disease and are neutralized by atacicept and B-cell maturation antigen-immunoglobulin. Arthritis Res Ther. 2010;12:R48.

    Article  Google Scholar 

  51. Salzer U, Birmelin J, Bacchelli C, Witte T, Buchegger-Podbielski U, Buckridge S, Rzepka R, Gaspar HB, Thrasher AJ, Schmidt RE, Melchers I, Grimbacher B. Sequence analysis of TNFRSF13b, encoding TACI, in patients with systemic lupus erythematosus. J Clin Immunol. 2007;27:372–7.

    Article  CAS  Google Scholar 

  52. Groom JR, Fletcher CA, Walters SN, Grey ST, Watt SV, Sweet MJ, Smyth MJ, Mackay CR, Mackay F. BAFF and MyD88 signals promote a lupuslike disease independent of T cells. J Exp Med. 2007;204:1959–71.

    Article  CAS  Google Scholar 

  53. Figgett WA, Fairfax K, Vincent FB, Le Page MA, Katik I, Deliyanti D, Quah PS, Verma P, Grumont R, Gerondakis S, Hertzog P, O'Reilly LA, Strasser A, Mackay F. The TACI receptor regulates T-cell-independent marginal zone B cell responses through innate activation-induced cell death. Immunity. 2013;39:573–83.

    Article  CAS  Google Scholar 

  54. Figgett WA, Deliyanti D, Fairfax KA, Quah PS, Wilkinson-Berka JL, Mackay F. Deleting the BAFF receptor TACI protects against systemic lupus erythematosus without extensive reduction of B cell numbers. J Autoimmun. 2015;61:9–16.

    Article  CAS  Google Scholar 

  55. Tran NL, Schneider P, Santiago-Raber ML. TACI-dependent APRIL signaling maintains autoreactive B cells in a mouse model of systemic lupus erythematosus. Eur J Immunol. 2017;47:713–23.

    Article  CAS  Google Scholar 

  56. Pan-Hammarström Q, Salzer U, Du L, Björkander J, Cunningham-Rundles C, Nelson DL, Bacchelli C, Gaspar HB, Offer S, Behrens TW, Grimbacher B, Hammarström L. Reexamining the role of TACI coding variants in common variable immunodeficiency and selective IgA deficiency. Nat Genet. 2007;39:429–30.

    Article  Google Scholar 

  57. Tsuji S, Stein L, Kamada N, Nuñez G, Bram R, Vallance BA, Sousa AE, Platt JL, Cascalho M. TACI deficiency enhances antibody avidity and clearance of an intestinal pathogen. J Clin Invest. 2014;124:4857–66.

    Article  CAS  Google Scholar 

  58. Janzi M, Melén E, Kull I, Wickman M, Hammarström L. Rare mutations in TNFRSF13B increase the risk of asthma symptoms in Swedish children. Genes Immun. 2012;13:59–65.

    Article  CAS  Google Scholar 

  59. Ladjemi MZ, Lecocq M, Weynand B, Bowen H, Gould HJ, Van Snick J, Detry B, Pilette C. Increased IgA production by B-cells in COPD via lung epithelial interleukin-6 and TACI pathways. Eur Respir J. 2015;45:980–93.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Dermatology, University Hospital Regensburg, Regensburg, Germany

    Astrid Bergbreiter

  2. Department of Rheumatology and Clinical Immunology, Faculty of Medicine, Medical Center—University of Freiburg, Freiburg im Breisgau, Germany

    Ulrich Salzer

  3. Center for Chronic Immunodeficiency (CCI), Faculty of Medicine, Medical Center—University of Freiburg, Freiburg im Breisgau, Germany

    Ulrich Salzer

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  1. Astrid Bergbreiter
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  1. Careggi Hospital, Department of Clinical and Experimental Medicine, University of Florence, Firenze, Italy

    Mario Milco D'Elios

  2. University Medical Centre Freiburg, Department of Rheumatology and Clinical Immunology and Center for Chronic Immunodeficiency, Freiburg, Germany

    Marta Rizzi

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Bergbreiter, A., Salzer, U. (2019). TACI Deficiency. In: D'Elios, M., Rizzi, M. (eds) Humoral Primary Immunodeficiencies. Rare Diseases of the Immune System. Springer, Cham. https://doi.org/10.1007/978-3-319-91785-6_9

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