Alteration of humoral, cellular and cytokine immune response to inactivated influenza vaccine in patients with Sickle Cell Disease


Autoři: Carole Nagant aff001;  Cyril Barbezange aff002;  Laurence Dedeken aff003;  Tatiana Besse-Hammer aff004;  Isabelle Thomas aff002;  Bhavna Mahadeb aff005;  André Efira aff004;  Alice Ferster aff003;  Francis Corazza aff001
Působiště autorů: Immunology Department, LHUB-ULB, Université libre de Bruxelles, Brussels, Belgium aff001;  National Influenza Centre, Sciensano, Brussels, Belgium aff002;  Department of Hematology Oncology, Hôpital Universitaire des Enfants Reine Fabiola, Université libre de Bruxelles, Brussels, Belgium aff003;  Department of Hematology Oncology, Centre Hospitalier Universitaire Brugmann, Brussels, Belgium aff004;  Microbiology Department, LHUB-ULB, Université libre de Bruxelles, Brussels, Belgium aff005
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: 10.1371/journal.pone.0223991

Souhrn

Introduction

Patients suffering from Sickle Cell Disease (SCD) are at increased risk for complications due to influenza virus. Annual influenza vaccination is strongly recommended but few clinical studies have assessed its immunogenicity in individuals with SCD. The aim of this study was to explore the biological efficacy of annual influenza vaccination in SCD patients by characterizing both their humoral and cell-mediated immunity against influenza antigen. We also aimed to investigate these immunological responses among SCD individuals according to their treatment (hydroxyurea (HU), chronic blood transfusions (CT), both HU and CT or none of them).

Methods

Seventy-two SCD patients (49 receiving HU, 9 on CT, 7 with both and 7 without treatment) and 30 healthy controls were included in the study. All subjects received the tetravalent influenza α-RIX-Tetra® vaccine from the 2016–2017 or 2017–2018 season.

Results

Protective anti-influenza HAI titers were obtained for the majority of SCD patients one month after vaccination but seroconversion rates in patient groups were strongly decreased compared to controls. Immune cell counts, particularly cellular memory including memory T and memory B cells, were greatly reduced in SCD individuals. Functional activation assays confirmed a poorer CD8+ T cell memory. We also document an imbalance of cytokines after influenza vaccination in SCD individuals with an INFγ/IL-10 ratio (Th1-type/Treg-type response) significantly lower in the SCD cohort.

Conclusion

SCD patients undergoing CT showed altered immune regulation as compared to other treatment subgroups. Altogether, the cytokine imbalance, the high regulatory T cell levels and the low memory lymphocyte subset levels observed in the SCD cohort, namely for those on CT, suggest a poor ability of SCD patients to fight against influenza infection. Nevertheless, our serological data support current clinical practice for annual influenza vaccination, though immunogenicity to other vaccines involving immunological memory might be hampered in SCD patients and should be further investigated.

Klíčová slova:

Cytokines – Cytotoxic T cells – Influenza – Influenza viruses – Lymphocytes – T cells – Vaccination and immunization – Vaccines


Zdroje

1. Yawn BP, Buchanan GR, Afenyi-Annan AN, Ballas SK, Hassell KL, James AH, et al. Management of sickle cell disease: Summary of the 2014 evidence-based report by expert panel members. JAMA. 2014; 312: 1033–1048. doi: 10.1001/jama.2014.10517 25203083

2. Davis BA, Allard S, Qureshi A, Porter JB, Pancham S, Win N, et al. Guidelines on red cell transfusion in sickle cell disease Part II: indications for transfusion. British Journal of Haematology. 2017; 176: 192–209. doi: 10.1111/bjh.14383 27858994

3. Wang WC, Dwan K. Blood transfusion for preventing primary and secondary stroke in people with sickle cell disease. Cochrane Database of Systematic Reviews. 2013; (11): CD003146. doi: 10.1002/14651858.CD003146.pub2 24226646

4. Hankins J, Jeng M, Harris S, Li CS, Liu T, Wang W. Chronic transfusion therapy for children with sickle cell disease and recurrent acute chest syndrome. Journal of Pediatric Hematology/Oncology. 2005; 27: 158–161. doi: 10.1097/01.mph.0000157789.73706.53 15750449

5. Sobota A, Sabharwal V, Fonebi G, Steinberg M. How we prevent and manage infection in sickle cell disease. British Journal of Haematology. 2015; 170: 757–767. doi: 10.1111/bjh.13526 26018640

6. Nickel RS, Hendrickson JE, Horan JT, Garrett AH, Robertson JM, Osunkwo I, et al. Alterations In Specific Immune Cell Subsets In Children With Sickle Cell Disease. Blood. 2013; 122: 2208.

7. Nickel RS, Osunkwo I, Garrett A, Robertson J, Archer DR, Promislow DE, et al. Immune parameter analysis of children with sickle cell disease on hydroxycarbamide or chronic transfusion therapy. British Journal of Haematology. 2015; 169: 574–83. doi: 10.1111/bjh.13326 25753210

8. Balandya E, Reynolds T, Obaro S, Makani J. Alteration of lymphocyte phenotype and function in sickle cell anemia: Implications for vaccine responses. American Journal of Hematology. 2016; 91: 938–946. doi: 10.1002/ajh.24438 27237467

9. Strouse JJ, Reller ME, Bundy DG, Amoako M, Cancio M, Han RN, et al. Severe pandemic H1N1 and seasonal influenza in children and young adults with sickle cell disease. Blood. 2010; 116: 3431–3434. doi: 10.1182/blood-2010-05-282194 20656929

10. Bundy DG, Strouse JJ, Casella JF, Miller MR. Burden of influenza-related hospitalizations among children with sickle cell disease. Pediatrics. 2010; 125: 234–243. doi: 10.1542/peds.2009-1465 20100764

11. Inusa B, Zuckerman M, Gadong N, Afif M, Arnott S, Heath P, et al. Pandemic influenza A (H1N1) virus infections in children with sickle cell disease. Blood. 2010; 115: 2329–2330. doi: 10.1182/blood-2009-12-260836 20299522

12. American Academy of Pediatrics Committee on Infectious diseases. Recommandations for Prevention and Control of Influenza in Children, 2013–2014. Pediatrics. 2013; 132/4

13. De Montalembert M, Abboud MR, Fiquet A, Inati A, Lebensburger JD, Kaddah N, et al. 13-valent pneumococcal conjugate vaccine (PCV13) is immunogenic and safe in children 6–17 years of age with sickle cell disease previously vaccinated with 23-valent pneumococcal polysaccharide vaccine (PPSV23): Results of a phase 3 study. Pediatric Blood Cancer. 2015; 62: 1427–1436. doi: 10.1002/pbc.25502 25810327

14. Purohit S, Alvarez O, O’Brien R, Andreansky S. Durable immune response to inactivated H1N1 vaccine is less likely in children with sickle cell anemia receiving chronic transfusions. Pediatric Blood Cancer. 2012; 59: 1280–1283. doi: 10.1002/pbc.24206 22628221

15. World Medical Association. DECLARATION OF HELSINKI 2008: Ethical Principles for Medical Research Involving Human Subjects. 2016. https://www.aix-scientifics.com/en/_helsinki08.html.

16. Ainsworth MA. New drugs and European procedures of approval. The European Agency for the Evaluation of Medicinal Products’role. Ugeskr Laeger. 2003; 165: 1648–1649. 12756819

17. Simms PE, Ellis TM. Utility of flow cytometric detection of CD69 expression as a rapid method for determining poly- and oligoclonal lymphocyte activation. Clinical and Diagnostic Laboratory Immunology. 1996; 3: 301–304. 8705673

18. Mardiney M, Brown MR, Fleisher TA. Measurement of T-cell CD69 expression: a rapid and efficient means to assess mitogen- or antigen-induced proliferative capacity in normals. Cytometry. 1996; 26: 305–310. doi: 10.1002/(SICI)1097-0320(19961215)26:4<305::AID-CYTO11>3.0.CO;2-V 8979031

19. Schatorjé EJH, Gemen EFA, Driessen GJA, Leuvenink J, van Hout RWNM, de Vries E. Paediatric reference values for the peripheral T cell compartment. Scandinavian Journal of Immunology. 2012; 75: 436–444. doi: 10.1111/j.1365-3083.2012.02671.x 22420532

20. Smet J, Mascart F, Schandené L. Are the reference values of B cell subpopulations used in adults for classification of common variable immunodeficiencies appropriate for children? Clinical Immunology. 2011; 138: 266–273. doi: 10.1016/j.clim.2010.12.001 21215701

21. Piqueras B, Lavenu-Bombled C, Galicier L, Bergeron-van der Cruyssen F, Mouthon L, Chevret S, et al. Common variable immunodeficiency patient classification based on impaired B cell memory differentiation correlates with clinical aspects. Journal of Clinical Immunology. 2003; 23: 385–400. doi: 10.1023/a:1025373601374 14601647

22. Remy KE, Hall MW, Cholette J, Juffermans NP, Nicol K, Doctor A, et al. Mechanisms of red blood cell transfusion-related immunomodulation. 2018; 58: 804–815.

23. Long CB, Ramos I, Rastogi D, Manwani D, Janow G, Del Rio M, et al. Humoral and cell-mediated immune responses to monovalent 2009 influenza A/H1N1 and seasonal trivalent influenza vaccines in high risk children. Journal of Pediatrics. 2012; 160: 74–81. doi: 10.1016/j.jpeds.2011.06.045 21840537

24. Olafsdottir TA, Alexandersson KF, Sveinbjornsson G, Lapini G, Palladino L, Montomoli E, et al. Age and influenza-specific pre-vaccination antibodies strongly affect influenza vaccine responses in the icelandic population whereas disease and medication have small effects. Frontiers in Immunology. 2018; 8: 1872. doi: 10.3389/fimmu.2017.01872 29358933

25. McLean HQ, Caspard H, Griffin MR, Gaglani M, Peters TR, Poehling KA, et al. Association of prior vaccination with influenza vaccine effectiveness in children receiving live attenuated or inactivated vaccine. JAMA Network Open. 2018; 1: e183742. doi: 10.1001/jamanetworkopen.2018.3742 30646262

26. Liu W, de Vlas SJ, Tang F, Ma MJ, Wei MT, Liu LJ, et al. Clinical and immunological characteristics of patients with 2009 pandemic influenza 1 (H1N1) virus infection after vaccination. Clinical Infectious Diseases. 2010; 51: 1028–1032. doi: 10.1086/656588 20887209

27. Gomez Lorenzo MM, Fenton MJ. Immunobiology of influenza vaccines. Chest. 2013; 143: 502–510. doi: 10.1378/chest.12-1711 23381315

28. Strutt TM, McKinstry KK, Dibble JP, Winchell C, Kuang Y, Curtis JD, et al. Memory CD4+ T cells induce innate responses independently of pathogen. Nature Medicine. 2010; 16: 558–564. doi: 10.1038/nm.2142 20436484

29. Spitaels J, Roose K, Saelens X. Influenza and memory T cells: how to awake the force. Vaccines. 2016; 13: 4.

30. Sridhar S, Begom S, Bermingham A, Hoschler K, Adamson W, Carman W, et al. Cellular immune correlates of protection against symptomatic pandemic influenza. Nature Medicine. 2013; 19: 1305–1312. doi: 10.1038/nm.3350 24056771

31. Szczepanek S, Adami A, Louis D, Farrington N, Bracken S, Natarajan P, et al. B cell exhaustion in sickle cell disease patients is associated with inhibited memory generation after influenza vaccination (P3009). The Journal of Immunology. 2013; 190: 55.5.

32. Olenscki Gilli SC, Pericole FV, Benites BD, Sippert EA, Castilho LM, Addas-Carvalho M, et al. Cytokine polymorphisms in sickle cell disease and the relationship with cytokine expression. Experimental Hematology 2016; 44: 583–589. doi: 10.1016/j.exphem.2016.03.008 27026283

33. Bandeira IC, Rocha LB, Barbosa MC, Elias DB, Querioz JA, Freitas MV, et al. Chronic inflammatory state in sickle cell anemia patients is associated with HBB(*)S haplotype. Cytokine. 2014; 65: 217–221.

34. Zou Q, Wu B, Xue J, Fan X, Feng C, Geng S, et al. CD8+ Treg cells suppress CD8+ T cell-responses by IL-10-dependent mechanism during H5NA influenza virus infection. European Journal of Immunology. 2014; 44: 103–114. doi: 10.1002/eji.201343583 24114149

35. Shahid Z, Kleppinger A, Gentleman B, Falsey AR, McElhaney JE. Clinical and immunologoc predictors of influenza illness among vaccinated older adults. Vaccine. 2010; 28: 6145–6151. doi: 10.1016/j.vaccine.2010.07.036 20646987

36. Yazdanbakhsh K. Mechanisms of sickle cell alloimmunization. Transfusion Clinique et Biologique. 2015; 22: 178–181. doi: 10.1016/j.tracli.2015.05.005 26056038

37. Belcher JD, Mahaseth H, Welch TE, Otterbein LE, Hebbel RP, Vercellotti GM. Heme oxygenase-1 is a modulator of inflammation and vaso-occlusion in transgenic sicklemice. Journal of Clinical Investigation. 2006; 116: 808–816. doi: 10.1172/JCI26857 16485041

38. Yazdanbakhsh K. Immunoregulatory network in sickle cell alloimmunization. American Society of Hematology. 2016; (1): 457–461.


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PLOS One


2019 Číslo 10

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