The Evaluation of Neutropenia in X-Linked Agammaglobulinemia Patients
Abstract
Objectives: X-Linked Agammaglobulinemia (XLA) is a primary immunodeficiency disease, characterized by severe hypogammaglobulinemia and the low numbers of peripheral B cells. Neutropenia is a rare complication among the XLA patients, which may lead to a higher rate of infections and morbidity. The aim of the authors is to assess the correctness of this issue.
Methods: In this study, we compared demographic, clinical and laboratorial data between two groups of XLA patients, with and without neutropenia.
Results: Frequency of neutropenia was 15% in our population. Infectious complications were the most prevalent clinical manifestations, regardless of the presence of neutropenia. However, Lymphoproliferative complication was significantly higher in the neutropenic patients (p = 0.001). No significant difference in mortality rate was observed between the groups.
Conclusion: Neutropenia is a rare complication among the XLA patients, and significantly decreases the mean age of XLA diagnosis in the patients. But it is not related to the higher frequency of infectious diseases in the neutropenic patients compared to non-neutropenic ones.
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2. Lee PPW, Chen TX, Jiang LP, Chan KW, Yang W, Lee BW, et al. Clinical characteristics and genotype-phenotype correlation in 62 patients with X-linked agammaglobulinemia. J Clin Immunol. 2009;30(1):121–131.
3. El-Sayed ZA, Abramova I, Aldave JC, Al-Herz W, Bezrodnik L, Boukari, et al. X-linked agammaglobulinemia (XLA): Phenotype, diagnosis, and therapeutic challenges around the world. World Allergy Organ J. 2019;12(3):100018.
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5. Conley ME, Howard V. Clinical findings leading to the diagnosis of X-linked agammaglobulinemia. J Pediatr. 2002;141(4):566–571.
6. Suri D, Rawat A, Singh S. X-linked agammaglobulinemia. Indian J Pediatr. 2016;83(4):331–337.
7. Asghar A, Taher C, Nima R, Hirokazu K, Sina A, Mojtaba T-K, Golnaz H, et al. Neutropenia associated with X-Linked agammaglobulinemia. Iran J Allergy Asthma Immunol. 2009;8(1):43-47.
8. Kanegane H, Taneichi H, Nomura K, Futatani T, Miyawaki T. Severe Neutropenia in Japanese Patients with X-Linked agammaglobulinemia. J Clin Immunol. 2005;25(5):491–495.
9. Newburger PE, Dale DC. Evaluation and management of patients with isolated neutropenia. Semin Hematol. 2013;50 (3):198–206.
10. Lederman HM, Winkelstein JA. X-linked agammaglobulinemia. Medicine, 1985;64(3):145–156.
11. Winkelstein JA, Marino MC, Lederman HM, Jones SM, Sullivan K, Burks AW, at al. X-linked agammaglobulinemia. Medicine, 2006;85(4):193–202.
12. Plo Rodriguez F, Garcia Rodriguez MC, Ferreira Cerdan A, Fontan Casariego G. Neutropenia as early manifestation of X-linked agammaglobulinemia. Report on 4 patients. An Esp Pediatr 1999; 51(3):235-40.
13. Farrar JE, Rohrer J, Conley ME. Neutropenia in X-linked agammaglobulinemia. Clin Immunol Immunopathol. 1996;81(3):271-6.
14. Moin M, Aghamohammadi A, Farhoudi A, Pourpak Z, Rezaei N, Movahedi M, et al. X‐Linked Agammaglobulinemia: A survey of 33 iranian patients. Immunol Invest. 2004;33(1):81–93.
15. Hernandez-Trujillo VP, Scalchunes C, Cunningham-Rundles C, Ochs HD, Bonilla FA, Paris K, et al. Autoimmunity and inflammation in X-linked agammaglobulinemia. J Clin Immunol. 2014;34(6):627–632.
16. Bruele T, Mourad-Baars PEC, Claas ECJ, Plas RN, Kuijper E J, Bredius RGM. Campylobacter jejuni bacteremia and Helicobacter pylori in a patient with X-linked agammaglobulinemia. Eur J Clin Microbiol Infect Dis.. 2010;29(11):1315–1319.
17. Cuccherini B, Chua K, Gill V, Weir S, Wray B, Stewart D, et al. Bacteremia and Skin/Bone Infections in Two Patients with X-linked agammaglobulinemia Caused by an Unusual Organism Related to Flexispira/Helicobacter Species. Clin Immunol. 2000;97(2):121–129.
18. Fiedler K, Sindrilaru A, Terszowski G, Kokai E, Feyerabend TB, Bullinger L, et al. Neutrophil development and function critically depend on Bruton tyrosine kinase in a mouse model of X-linked agammaglobulinemia. Blood. 2010;117(4):1329–1339.
19. Jefferies CA, Doyle S, Brunner C, Dunne A, Brint E, Wietek C, et al. Bruton’s tyrosine kinase Is a Toll/Interleukin-1 Receptor domain-binding protein that participates in nuclear factor κB activation by Toll-like receptor 4. J Biol Chem. 2003;278(28):26258–26264.
20. Mangla A. Pleiotropic consequences of Bruton tyrosine kinase deficiency in myeloid lineages lead to poor inflammatory responses. Blood, 2004;104(4):1191–1197.
21. Alizadeh Z, Dashti P, Mazinani M, Nourizadeh M, Shakerian L, Tajik S, et al. Clinical and genetic study of X-linked agammaglobulinemia patients (The Benefit of Early Diagnosis). Iran J Allergy Asthma Immunol. 2020;19(3):305-309.
22. Ghorbani M, Fekrvand S, Shahkarami S, Yazdani R, Sohani M, Shaghaghi M, et al. The evaluation of neutropenia in common variable immune deficiency patients. Expert Rev Clin Immunol. 2019;15(11):1225-1233.
23. Guffroy A, Mourot-Cottet R, Gerard L, et al. Neutropenia in patients with common variable immunodeficiency: a rare event associated with severe outcome. J Clin Immunol. 2017;37(7):715–726.
2. Lee PPW, Chen TX, Jiang LP, Chan KW, Yang W, Lee BW, et al. Clinical characteristics and genotype-phenotype correlation in 62 patients with X-linked agammaglobulinemia. J Clin Immunol. 2009;30(1):121–131.
3. El-Sayed ZA, Abramova I, Aldave JC, Al-Herz W, Bezrodnik L, Boukari, et al. X-linked agammaglobulinemia (XLA): Phenotype, diagnosis, and therapeutic challenges around the world. World Allergy Organ J. 2019;12(3):100018.
4. López-Granados E, Pérez de Diego R, Ferreira Cerdán A, Fontán Casariego G, García Rodríguez MC. A genotype-phenotype correlation study in a group of 54 patients with X-linked agammaglobulinemia. J Allergy Clin Immunol. 2005;116(3):690–697.
5. Conley ME, Howard V. Clinical findings leading to the diagnosis of X-linked agammaglobulinemia. J Pediatr. 2002;141(4):566–571.
6. Suri D, Rawat A, Singh S. X-linked agammaglobulinemia. Indian J Pediatr. 2016;83(4):331–337.
7. Asghar A, Taher C, Nima R, Hirokazu K, Sina A, Mojtaba T-K, Golnaz H, et al. Neutropenia associated with X-Linked agammaglobulinemia. Iran J Allergy Asthma Immunol. 2009;8(1):43-47.
8. Kanegane H, Taneichi H, Nomura K, Futatani T, Miyawaki T. Severe Neutropenia in Japanese Patients with X-Linked agammaglobulinemia. J Clin Immunol. 2005;25(5):491–495.
9. Newburger PE, Dale DC. Evaluation and management of patients with isolated neutropenia. Semin Hematol. 2013;50 (3):198–206.
10. Lederman HM, Winkelstein JA. X-linked agammaglobulinemia. Medicine, 1985;64(3):145–156.
11. Winkelstein JA, Marino MC, Lederman HM, Jones SM, Sullivan K, Burks AW, at al. X-linked agammaglobulinemia. Medicine, 2006;85(4):193–202.
12. Plo Rodriguez F, Garcia Rodriguez MC, Ferreira Cerdan A, Fontan Casariego G. Neutropenia as early manifestation of X-linked agammaglobulinemia. Report on 4 patients. An Esp Pediatr 1999; 51(3):235-40.
13. Farrar JE, Rohrer J, Conley ME. Neutropenia in X-linked agammaglobulinemia. Clin Immunol Immunopathol. 1996;81(3):271-6.
14. Moin M, Aghamohammadi A, Farhoudi A, Pourpak Z, Rezaei N, Movahedi M, et al. X‐Linked Agammaglobulinemia: A survey of 33 iranian patients. Immunol Invest. 2004;33(1):81–93.
15. Hernandez-Trujillo VP, Scalchunes C, Cunningham-Rundles C, Ochs HD, Bonilla FA, Paris K, et al. Autoimmunity and inflammation in X-linked agammaglobulinemia. J Clin Immunol. 2014;34(6):627–632.
16. Bruele T, Mourad-Baars PEC, Claas ECJ, Plas RN, Kuijper E J, Bredius RGM. Campylobacter jejuni bacteremia and Helicobacter pylori in a patient with X-linked agammaglobulinemia. Eur J Clin Microbiol Infect Dis.. 2010;29(11):1315–1319.
17. Cuccherini B, Chua K, Gill V, Weir S, Wray B, Stewart D, et al. Bacteremia and Skin/Bone Infections in Two Patients with X-linked agammaglobulinemia Caused by an Unusual Organism Related to Flexispira/Helicobacter Species. Clin Immunol. 2000;97(2):121–129.
18. Fiedler K, Sindrilaru A, Terszowski G, Kokai E, Feyerabend TB, Bullinger L, et al. Neutrophil development and function critically depend on Bruton tyrosine kinase in a mouse model of X-linked agammaglobulinemia. Blood. 2010;117(4):1329–1339.
19. Jefferies CA, Doyle S, Brunner C, Dunne A, Brint E, Wietek C, et al. Bruton’s tyrosine kinase Is a Toll/Interleukin-1 Receptor domain-binding protein that participates in nuclear factor κB activation by Toll-like receptor 4. J Biol Chem. 2003;278(28):26258–26264.
20. Mangla A. Pleiotropic consequences of Bruton tyrosine kinase deficiency in myeloid lineages lead to poor inflammatory responses. Blood, 2004;104(4):1191–1197.
21. Alizadeh Z, Dashti P, Mazinani M, Nourizadeh M, Shakerian L, Tajik S, et al. Clinical and genetic study of X-linked agammaglobulinemia patients (The Benefit of Early Diagnosis). Iran J Allergy Asthma Immunol. 2020;19(3):305-309.
22. Ghorbani M, Fekrvand S, Shahkarami S, Yazdani R, Sohani M, Shaghaghi M, et al. The evaluation of neutropenia in common variable immune deficiency patients. Expert Rev Clin Immunol. 2019;15(11):1225-1233.
23. Guffroy A, Mourot-Cottet R, Gerard L, et al. Neutropenia in patients with common variable immunodeficiency: a rare event associated with severe outcome. J Clin Immunol. 2017;37(7):715–726.
| Files | ||
| Issue | Vol 3, No 4 (2020) | |
| Section | Original Article | |
| DOI | https://doi.org/10.18502/igj.v3i4.7459 | |
| Keywords | ||
| X-Linked Agammaglobulinemia Neutropenia Bruton’s Tyrosine Kinase Immunodeficiency | ||
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How to Cite
1.
Safarirad M, Abbaszadeh Ganji A, Vosughi Motlagh A. The Evaluation of Neutropenia in X-Linked Agammaglobulinemia Patients. Immunol Genet J. 2020;3(4):214-221.
