CD40 Ligand Deficiency
Main Article Content
Keywords
Immunologic deficiency syndromes, CD40 ligand, Hyper-IgM immunodeficiency syndrome, Immune system diseases, Immunoglobulins
Abstract
CD40 ligand deficiency (CD40L), currently classified as an inborn error of immunity affecting cellular and humoral immunity, prevalently emerges in boys within the first two years of life. It manifests itself as a decrease in serum IgG, IgA and IgE, with normal or high IgM, defects in T cell proliferation, and decrease in soluble CD40L. These accompany sinopulmonary and/or gastrointestinal infections, and there may be infections caused by pyogenic bacteria, opportunistic infections, autoimmune diseases, and neoplasms. Mild and moderate cases of this deficiency may respond well to prophylactic antibiotic therapy or to human immunoglobulin replacement therapy, in addition to the early treatment of infections. Severe cases can be treated with hematopoietic stem cell transplantation, which allows the healing of such patients, rather than sequelae and a poor progression. Thus, its differential diagnosis with other inborn errors of immunity is essential, especially CD40 deficiency and variable common immunodeficiency; the reason why we have proposed the present literature review.
References
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5. Burtin P. An example of atypical agammaglobulinemia (a case of severe hypogammaglobulinemia with increase of the beta-2 macroglobulin). Rev Fr Etud Clin Biol. 1961;6:286-9.
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7. Kavanaugh AF, Huston DP. Variable expression of IgG2 deficiency. J Allergy Clin Immunol. 1990;86:4-10.
8. Notarangelo LD, Lanzi G, Peron S, Durandy A. Defects of class-switch recombination. J Allergy Clin Immunol. 2006;117:855-64.
9. Winkelstein JA, Marino MC, Ochs H, Fuleihan R, Scholl P, Geha R, et al. The X-linked hyper IgM syndrome. Clinical and immunologic features of 79 patients. Medicine. 2003;82:373-84.
10. Lougaris V, Badolato R, Ferrari S, Plebani A. Hyper immunoglobulin M syndrome due to CD40 deficiency: clinical, molecular, and immunological features. Immunol Rev. 2005;203:48-66.
11. Revy P, Mutto T, Levy Y, Geissmann F, Plebani A, Sanal O, et al. Activation-induced cytidine deaminase (AID) deficiency causes the autosomal recessive form of the Hyper-IgM syndrome (HIGM2). Cell. 2000;102:565-75.
12. Meyers G, Ng YS, Bannock JM, Lavoie A, Walter JE, Notarangelo JD, et al. Activation-induced cytidine deaminase (AID) is required for B-cell tolerance in humans. Proc Nat Acad Sci USA. 2011;108:11554-9.
13. Maul R, Gearhart P. AID and somatic hypermutation. Adv Immunol. 2010;105:159-91.
14. Wang LL, Zhou W, Zhao W, Tian Z, Wang WF, Wang XF, et al. Clinical features and genetic analysis of 20 Chinese patients with X-linked hyper-IgM syndrome. J Immunol Res. 2014;2014:683160, http://dx.doi.org/10.1155/2014/683160.
15. de la Morena MT. Clinical phenotypes of hyper-IgM syndromes. J Allergy Clin Immunol Pract. 2016;4:1023-36.
16. Lee W, Huang J, Yeh K, Yang M, Lai M, Chen L, et al. Clinical features and genetic analysis of Taiwanese patients with the hyper IgM syndrome phenotype. Pediatr Infect Dis J. 2013;32:1010-6.
17. Rezaei N, Aghamohammadi A, Ramyar A, Pan-Hammarstrom Q, Hammarstron L. Severe congenital neutropenia or hyper-IgM syndrome? A novel mutation of CD40 ligand in a patient with severe neutropenia. Int Arch Allergy Immunol. 2008;147:255-9.
18. Kracker S, Cardes P, Mazerolles F, Durandy A. Immunoglobulin class switch recombination deficiencies. Clin Immunol. 2010;135:193-203.
19. Stavnezer J. Molecular processes that regulate class switching. Curr Top Microbiol Immunol. 2000;245:127-68.
20. Grumach AS. Imunodeficiências predominantemente humorais. In: Grumach AS, editor. Alergia e imunologia na infância e na adolescência. 2 ed. São Paulo: Editora Atheneu; 2009. p.
533-55.
21. Buchbinder D, Park S, Nugent D. X-linked hyper IgM syndrome: a novel sequence variant associated with an atypical mild phenotype. J Pediat Hematol Onc. 2012;34:e212-4.
22. Xu Z, Zan H, Pone EJ, Mai T, Casali P. Immunoglobulin class-witch DNA recombination: induction, targeting and beyond. Nat Rev Immunol. 2012;12:517---31.
23. Kiani-Alikan S, Yong PF, Gilmour KC, Grosse-Kreul D, Davies EG, Ibrahim MA. Phenotypic heterogeneity in a family with a CD40 ligand intracellular domain mutation. J Clin Immunol.
2012;32:70-7.
24. Notarangelo LD, Peitsch MC. CD40lbase: a database of CD40L gene mutations causing X linked hyper IgM syndrome. Immunol Today. 1996;17:511-6.
25. Ara A, Ahmed KA, Xiang J. Multiple effects of CD40-CD40L axis in immunity against infection and cancer. Immunotargets Ther. 2018;7:55-61.
26. Forte WCN. Imunoglobulinas. In: Forte WCN, editor. Imunologia do básico ao aplicado. 3 ed. São Paulo: Editora Atheneu; 2015. p. 51-65.
27. Chatzigeorgiou A, Lyberi M, Chatzilymperis G, Nezos A, Kamper E. CD40/CD40L signaling and its implication in health and disease. Biofactors. 2009;35:474-83.
28. Okuno Y, Hoshino A, Muramatsu H, Kawashima N, Wang X, Yoshida K, et al. Late-onset combined immunodeficiency with novel IL2RG mutation and probable revertant somatic mosaicism. J Clin Immunol. 2015;35:610-4.
29. Cabral-Marques O, Ramos RN, Schimke LF, Khan TA, Amaral EP, Bonfim CCB, et al. Human CD40 ligand deficiency dysregulates the macrophage transcriptome causing functional defects that are improved by exogenous IFN-y. J Allergy Clin Immunol. 2017;139:900-12.
30. BRAGID. Brazilian Group for Immunodeficiencies. Acessado em 8/setembro/2018. In: http://www.imunopediatria.org.br.
31. Jain A, Kovacs JA, Nelson DL, Migueles SA, Pittaluga S, Fanslow W, et al. Partial immune reconstitution of X-linked hyper IgM syndrome with recombinant CD40 ligand. Blood. 2011;118:3811-7.
33. Kutukculer N, Moratto D, Aydinok Y, Lougaris V, Aksoylar S, Plebani A, et al. Disseminated cryptosporidium infection in an infant with hyper-IgM syndrome caused by CD40 deficiency. J Pediatr. 2003;142:194-6.
34. Franc¸a TT, Leite LFB, Maximo TA, Lambert CG, Zurro NB, Forte WCN, et al. A novel de novo mutation in the CD40 ligand gene in a patient with a mild X-Linked hyper-IgM phenotype initially diagnosed as CIVD: New aspects of old diseases. Front Pediatr. 2018;6:1-8.
35. Elgueta R, Benson MJ, de Vries VC, Wasiuk A, Guo Y, Noelle R. Molecular mechanism and function of CD40/CD40L engagement in the immune system. Immunol Rev. 2009;229:152-72.
36. Cabral-Marques O, Klaver S, Schimke LF, Ascendino EH, Khan TA, Pereira PV, et al. First report of the Hyper-IgM syndrome registry of the Latin America Society for Immunodeficiencies: Novel mutations, unique infections and outcomes. J Clin Immunol. 2014;34:146-56.
37. Kokron CM, Barros MT. Imunodeficiências primárias. In: Kalil J, Motta A, Agondi R, editors. Alergia e Imunologia clínica: aplicac¸ão clínica. São Paulo: Editora Atheneu; 2015. p. 294-325.
38. Goudouris ES, Silva AMR, Ouricuri AL, Grumach AS, CondinoNeto A, Costa-Carvalho BT, et al. II Consenso Brasileiro sobre o uso de imunoglobulina humana em pacientes com imunodeficiências primárias. Rev Einstein. 2017;15:1-16.
39. Kanegae MPP, dos Santos AMN, Cavalcanti CM, Condino-Neto A. Triagem neonatal para imunodeficiência combinada grave. Rev Bras Alerg Imunopatol. 2011;34:7-11.
40. Bayrakci B, Ersoy F, Sanal O, Kilic S, Metin A, Tezcan I. The efficacy of immunoglobulin replacement therapy in the longterm follow-up of the B-cell deficiencies (XLA, HIM, CVID). Turk J Ped. 2005;47:239-46.
41. Tomizawa D, Imai K, Ito S, Kajiwara M, Minegishi Y, Nagasawa M, et al. Allogeneic hematopoietic stem cell transplantation for seven children With X-linked hyper-IgM syndrome: a single center experience. Am J Hematol. 2004;76:33-9.
42. Tseng M, Ge S, Roberts R, Kuo C, Choi J, Nissen NN, et al. Liver transplantation in a patient with CD40 ligand deficiency and hyper-IgM syndrome: clinical and immunological assessments. Am J Transplant. 2016;16:1626-32.
43. Lobo FM, Scholl PR, Fuleihan RL. CD40 ligand-deficient t cells from X-linked hyper-IgM syndrome carriers have intrinsic priming capability. J Immunol. 2002;168:1473-8.
44. Ziegner UH, Ochs HD, Schanen C, Feig SA, Seyama K, Futatani T, et al. Unrelated umbilical cord stem cell transplantation for X-linked immunodeficiencies. J Pediatr. 2001;138:570-3.
45. Gennery AR, Slatter MA, Grandin L, Taupin P, Cant AJ, Veys P, et al. Transplantation of hematopoietic stem cells and long-term survival for primary immunodeficiencies in Europe: entering a new century, do we do better? J Allergy Clin Immunol. 2010;126:602-10.
46. Leven EA, Maffuci P, Ochs HD, Scholl PR, Buckley RH, Fuleihan RL, et al. HyperIgM syndrome: A report from the USIDNET regist. J Clin Immunol. 2016;36:490-501.
47. Hoeyveld EV, Zhang PX, Boeck KD, Fuleihan R, Bossuyt X. Hyper-immunoglobulin M syndrome caused by a mutation in the promotor for CD40L. Blackwell Publishing Ltd. Immunology. 2007;120:497-501.
48. Santos LFM, Mukai AO, Bertoli CJ, Fernandes TA, Suetugo CP, Santos LFM, et al. Relato de um caso de neutropenia congênita grave em um lactente jovem. Rev Paul Pediatr. 2011;29: 680-4.
49. Cabral-Marques O, Franc¸a TT, Al-Sbiei A, Schimke LF, Khan TA, Feriotti C, et al. CD40 ligand deficiency causes functional defects of peripheral neutrophils that are improved by exogenous IFN-. J Allergy Clin Immunol. 2018;142:1571-88.
50. Shearer WT, Fleisher TA, Buckley RH, Ballas Z, Ballow M, Blaese MR, et al. Recommendations for live viral and bacterial vaccines in immunodeficient patients and their close contacts. J Allergy Clin Immunol. 2014;133:961-6.
51. Bonilla FA. Update: vaccines in primary immunodeficiency. J Allergy Clin Immunol. 2018;141:474-81.
2. Etzioni A, Ochs HD. The hyper IgM syndrome - an evolving story. Pediatr Res. 2004;56:519-25.
3. Rawat A, Mathew B, Pandiarajan V, Jindal A, Sharma M, Suri D, et al. Clinical and molecular features of X-linked hyper IgM syndrome- an experience from North India. Clin Immunol. 2018;195:59-66.
4. Rosen FS, Kevy SV, Merler E, Janeway CA, Gitlin D. Recurrent bacterial infections and dysgamma-globulinemia: deficiency of 7S gamma-globulins in the presence of elevated 19S gammaglobulins. Report of two cases. Pediatrics. 1961;28:182-95.
5. Burtin P. An example of atypical agammaglobulinemia (a case of severe hypogammaglobulinemia with increase of the beta-2 macroglobulin). Rev Fr Etud Clin Biol. 1961;6:286-9.
6. Klaver SG, Condino-Neto A. Defeitos genético-moleculares e aspectos clínicos de pacientes com síndrome de Hiper IgM autossômica. In: Dissertac¸ão de mestrado) Instituto de Ciências Biológicas da USP. 2011. p. 111.
7. Kavanaugh AF, Huston DP. Variable expression of IgG2 deficiency. J Allergy Clin Immunol. 1990;86:4-10.
8. Notarangelo LD, Lanzi G, Peron S, Durandy A. Defects of class-switch recombination. J Allergy Clin Immunol. 2006;117:855-64.
9. Winkelstein JA, Marino MC, Ochs H, Fuleihan R, Scholl P, Geha R, et al. The X-linked hyper IgM syndrome. Clinical and immunologic features of 79 patients. Medicine. 2003;82:373-84.
10. Lougaris V, Badolato R, Ferrari S, Plebani A. Hyper immunoglobulin M syndrome due to CD40 deficiency: clinical, molecular, and immunological features. Immunol Rev. 2005;203:48-66.
11. Revy P, Mutto T, Levy Y, Geissmann F, Plebani A, Sanal O, et al. Activation-induced cytidine deaminase (AID) deficiency causes the autosomal recessive form of the Hyper-IgM syndrome (HIGM2). Cell. 2000;102:565-75.
12. Meyers G, Ng YS, Bannock JM, Lavoie A, Walter JE, Notarangelo JD, et al. Activation-induced cytidine deaminase (AID) is required for B-cell tolerance in humans. Proc Nat Acad Sci USA. 2011;108:11554-9.
13. Maul R, Gearhart P. AID and somatic hypermutation. Adv Immunol. 2010;105:159-91.
14. Wang LL, Zhou W, Zhao W, Tian Z, Wang WF, Wang XF, et al. Clinical features and genetic analysis of 20 Chinese patients with X-linked hyper-IgM syndrome. J Immunol Res. 2014;2014:683160, http://dx.doi.org/10.1155/2014/683160.
15. de la Morena MT. Clinical phenotypes of hyper-IgM syndromes. J Allergy Clin Immunol Pract. 2016;4:1023-36.
16. Lee W, Huang J, Yeh K, Yang M, Lai M, Chen L, et al. Clinical features and genetic analysis of Taiwanese patients with the hyper IgM syndrome phenotype. Pediatr Infect Dis J. 2013;32:1010-6.
17. Rezaei N, Aghamohammadi A, Ramyar A, Pan-Hammarstrom Q, Hammarstron L. Severe congenital neutropenia or hyper-IgM syndrome? A novel mutation of CD40 ligand in a patient with severe neutropenia. Int Arch Allergy Immunol. 2008;147:255-9.
18. Kracker S, Cardes P, Mazerolles F, Durandy A. Immunoglobulin class switch recombination deficiencies. Clin Immunol. 2010;135:193-203.
19. Stavnezer J. Molecular processes that regulate class switching. Curr Top Microbiol Immunol. 2000;245:127-68.
20. Grumach AS. Imunodeficiências predominantemente humorais. In: Grumach AS, editor. Alergia e imunologia na infância e na adolescência. 2 ed. São Paulo: Editora Atheneu; 2009. p.
533-55.
21. Buchbinder D, Park S, Nugent D. X-linked hyper IgM syndrome: a novel sequence variant associated with an atypical mild phenotype. J Pediat Hematol Onc. 2012;34:e212-4.
22. Xu Z, Zan H, Pone EJ, Mai T, Casali P. Immunoglobulin class-witch DNA recombination: induction, targeting and beyond. Nat Rev Immunol. 2012;12:517---31.
23. Kiani-Alikan S, Yong PF, Gilmour KC, Grosse-Kreul D, Davies EG, Ibrahim MA. Phenotypic heterogeneity in a family with a CD40 ligand intracellular domain mutation. J Clin Immunol.
2012;32:70-7.
24. Notarangelo LD, Peitsch MC. CD40lbase: a database of CD40L gene mutations causing X linked hyper IgM syndrome. Immunol Today. 1996;17:511-6.
25. Ara A, Ahmed KA, Xiang J. Multiple effects of CD40-CD40L axis in immunity against infection and cancer. Immunotargets Ther. 2018;7:55-61.
26. Forte WCN. Imunoglobulinas. In: Forte WCN, editor. Imunologia do básico ao aplicado. 3 ed. São Paulo: Editora Atheneu; 2015. p. 51-65.
27. Chatzigeorgiou A, Lyberi M, Chatzilymperis G, Nezos A, Kamper E. CD40/CD40L signaling and its implication in health and disease. Biofactors. 2009;35:474-83.
28. Okuno Y, Hoshino A, Muramatsu H, Kawashima N, Wang X, Yoshida K, et al. Late-onset combined immunodeficiency with novel IL2RG mutation and probable revertant somatic mosaicism. J Clin Immunol. 2015;35:610-4.
29. Cabral-Marques O, Ramos RN, Schimke LF, Khan TA, Amaral EP, Bonfim CCB, et al. Human CD40 ligand deficiency dysregulates the macrophage transcriptome causing functional defects that are improved by exogenous IFN-y. J Allergy Clin Immunol. 2017;139:900-12.
30. BRAGID. Brazilian Group for Immunodeficiencies. Acessado em 8/setembro/2018. In: http://www.imunopediatria.org.br.
31. Jain A, Kovacs JA, Nelson DL, Migueles SA, Pittaluga S, Fanslow W, et al. Partial immune reconstitution of X-linked hyper IgM syndrome with recombinant CD40 ligand. Blood. 2011;118:3811-7.
33. Kutukculer N, Moratto D, Aydinok Y, Lougaris V, Aksoylar S, Plebani A, et al. Disseminated cryptosporidium infection in an infant with hyper-IgM syndrome caused by CD40 deficiency. J Pediatr. 2003;142:194-6.
34. Franc¸a TT, Leite LFB, Maximo TA, Lambert CG, Zurro NB, Forte WCN, et al. A novel de novo mutation in the CD40 ligand gene in a patient with a mild X-Linked hyper-IgM phenotype initially diagnosed as CIVD: New aspects of old diseases. Front Pediatr. 2018;6:1-8.
35. Elgueta R, Benson MJ, de Vries VC, Wasiuk A, Guo Y, Noelle R. Molecular mechanism and function of CD40/CD40L engagement in the immune system. Immunol Rev. 2009;229:152-72.
36. Cabral-Marques O, Klaver S, Schimke LF, Ascendino EH, Khan TA, Pereira PV, et al. First report of the Hyper-IgM syndrome registry of the Latin America Society for Immunodeficiencies: Novel mutations, unique infections and outcomes. J Clin Immunol. 2014;34:146-56.
37. Kokron CM, Barros MT. Imunodeficiências primárias. In: Kalil J, Motta A, Agondi R, editors. Alergia e Imunologia clínica: aplicac¸ão clínica. São Paulo: Editora Atheneu; 2015. p. 294-325.
38. Goudouris ES, Silva AMR, Ouricuri AL, Grumach AS, CondinoNeto A, Costa-Carvalho BT, et al. II Consenso Brasileiro sobre o uso de imunoglobulina humana em pacientes com imunodeficiências primárias. Rev Einstein. 2017;15:1-16.
39. Kanegae MPP, dos Santos AMN, Cavalcanti CM, Condino-Neto A. Triagem neonatal para imunodeficiência combinada grave. Rev Bras Alerg Imunopatol. 2011;34:7-11.
40. Bayrakci B, Ersoy F, Sanal O, Kilic S, Metin A, Tezcan I. The efficacy of immunoglobulin replacement therapy in the longterm follow-up of the B-cell deficiencies (XLA, HIM, CVID). Turk J Ped. 2005;47:239-46.
41. Tomizawa D, Imai K, Ito S, Kajiwara M, Minegishi Y, Nagasawa M, et al. Allogeneic hematopoietic stem cell transplantation for seven children With X-linked hyper-IgM syndrome: a single center experience. Am J Hematol. 2004;76:33-9.
42. Tseng M, Ge S, Roberts R, Kuo C, Choi J, Nissen NN, et al. Liver transplantation in a patient with CD40 ligand deficiency and hyper-IgM syndrome: clinical and immunological assessments. Am J Transplant. 2016;16:1626-32.
43. Lobo FM, Scholl PR, Fuleihan RL. CD40 ligand-deficient t cells from X-linked hyper-IgM syndrome carriers have intrinsic priming capability. J Immunol. 2002;168:1473-8.
44. Ziegner UH, Ochs HD, Schanen C, Feig SA, Seyama K, Futatani T, et al. Unrelated umbilical cord stem cell transplantation for X-linked immunodeficiencies. J Pediatr. 2001;138:570-3.
45. Gennery AR, Slatter MA, Grandin L, Taupin P, Cant AJ, Veys P, et al. Transplantation of hematopoietic stem cells and long-term survival for primary immunodeficiencies in Europe: entering a new century, do we do better? J Allergy Clin Immunol. 2010;126:602-10.
46. Leven EA, Maffuci P, Ochs HD, Scholl PR, Buckley RH, Fuleihan RL, et al. HyperIgM syndrome: A report from the USIDNET regist. J Clin Immunol. 2016;36:490-501.
47. Hoeyveld EV, Zhang PX, Boeck KD, Fuleihan R, Bossuyt X. Hyper-immunoglobulin M syndrome caused by a mutation in the promotor for CD40L. Blackwell Publishing Ltd. Immunology. 2007;120:497-501.
48. Santos LFM, Mukai AO, Bertoli CJ, Fernandes TA, Suetugo CP, Santos LFM, et al. Relato de um caso de neutropenia congênita grave em um lactente jovem. Rev Paul Pediatr. 2011;29: 680-4.
49. Cabral-Marques O, Franc¸a TT, Al-Sbiei A, Schimke LF, Khan TA, Feriotti C, et al. CD40 ligand deficiency causes functional defects of peripheral neutrophils that are improved by exogenous IFN-. J Allergy Clin Immunol. 2018;142:1571-88.
50. Shearer WT, Fleisher TA, Buckley RH, Ballas Z, Ballow M, Blaese MR, et al. Recommendations for live viral and bacterial vaccines in immunodeficient patients and their close contacts. J Allergy Clin Immunol. 2014;133:961-6.
51. Bonilla FA. Update: vaccines in primary immunodeficiency. J Allergy Clin Immunol. 2018;141:474-81.
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Jul 15, 2020
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Leite, L., Máximo, T., Mosca, T., & Forte, W. (2020). CD40 Ligand Deficiency. Allergologia Et Immunopathologia, 48(4), 409-413. https://all-imm.com/index.php/aei/article/view/166
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How to Cite
Leite, L., Máximo, T., Mosca, T., & Forte, W. (2020). CD40 Ligand Deficiency. Allergologia Et Immunopathologia, 48(4), 409-413. https://all-imm.com/index.php/aei/article/view/166