The Effects of Influenza Vaccination on Immune Function in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

DOI: 10.4236/ijcm.2012.36098   PDF   HTML   XML   5,508 Downloads   7,992 Views   Citations


Immune dysfunction is a hallmark of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). The purpose of this pilot study was to identify the effects of influenza vaccination on immune function in patients with CFS/ME. We included 7 patients meeting the Centre for Disease Control and Prevention criteria (CDC 1994) for ME/CFS and 8 control subjects. Bloods were collected from all participants prior to vaccination with Influvac, a trivalent inactivated influenza vaccine (TIV), 14 and 28 days following vaccination. The immune parameters examined include Natural Killer (NK) phenotypes, NK cytotoxic activity, FOXP3 and Th1/Th2/Th17 related cytokines. Flow cytometric protocols were employed. There was no significant difference in NK phenotypes and Tregs numbers between CFS/ME patients and healthy controls. However, NK activity was significantly decreased at baseline and at 28 days, while at 14 days it significantly increased in the CFS/ME patients compared to the healthy controls. Th1 pro-inflammatory cytokines increased considerably in the CFS/ME patients at 28 days compared to the non-fatigued controls. Only one Th2 cytokine, IL-4, increased in the CFS/ME participants. FOXP3 expressing Tregs only increased significantly at day 28 post vaccination in the CFS/ME patients compared to the healthy controls. Self-rated wellbeing was lower for patients at day 28 while at baseline and day 14 no differences were observed. In this pilot study immunization with influenza vaccine is accompanied by a degree of immune dysregulation in CFS/ME patients compared with controls. While vaccination may protect CFS/ME patients against influenza, it has the ability to increase cytotoxic activity and pro-inflammatory reactions post vaccination. The role of Tregs in promoting a toxic effect at 28 days post-vaccination in our patient group cannot be ruled out. The benefits of influenza vaccine still likely outweigh the risks CFS/ME patients experience following vaccination.

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E. Brenu, M. van Driel, D. Staines, S. Kreijkamp-Kaspers, S. Hardcastle and S. Marshall-Gradisnik, "The Effects of Influenza Vaccination on Immune Function in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis," International Journal of Clinical Medicine, Vol. 3 No. 6, 2012, pp. 544-551. doi: 10.4236/ijcm.2012.36098.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] P. Magnus, O. Brubakk, H. Nyland, B. H. Wold, H. K. Gjessing, I. Brandt, T. Eidem, H. Nokleby and G. Stene-Larsen, “Vaccination as Teenagers against Menin-Gococcal Disease and the Risk of the Chronic Fatigue Syndrome,” Vaccine, Vol. 27, No. 1, 2009, pp. 23-27. doi:10.1016/j.vaccine.2008.10.043
[2] S. S. Diebold, T. Kaisho, H. Hemmi, S. Akira and C. Reis e Sousa, “Innate Antiviral Responses by Means of TLR7-Mediated Recognition of Single-Stranded RNA,” Science, Vol. 303, No. 5663, 2004, pp. 1529-1531. doi:10.1126/science.1093616
[3] H. Kato, S. Sato, M. Yoneyama, M. Yamamoto, S. Uematsu, K. Matsui, T. Tsujimura, K. Takeda, T. Fujita, O. Takeuchi and S. Akira, “Cell Type-Specific Involvement of RIG-I in Antiviral Response,” Immunity, Vol. 23, No. 1, 2005, pp. 19-28.
[4] J. M. Lund, L. Alexopoulou, A. Sato, M. Karow, N. C. Adams, N. W. Gale, A. Iwasaki and R. A. Flavell, “Recognition of Single-Stranded RNA Viruses by Toll-Like Receptor 7,” Proceedings of National Academy of Sciences of the United States of America, Vol. 101, No. 15, 2004, pp. 5598-5603.
[5] A. Garcia-Sastre and C. A. Biron, “Type 1 Interferons and the Virus-Host Relationship: A Lesson in Detente,” Science, Vol. 312, No. 5775, 2006, pp. 879-882. doi:10.1126/science.1125676
[6] J. Pirhonen, T. Sareneva, M. Kurimoto, I. Julkunen and S. Matikainen, “Virus Infection Activates IL-1 Beta and IL-18 Production in Human Macrophages by a Caspase-1-Dependent Pathway,” Journal of Immunology, Vol. 162, No. 12, 1999, pp. 7322-7329.
[7] G. T. Belz, S. Bedoui, F. Kupresanin, F. R. Carbone and W. R. Heath, “Minimal Activation of Memory CD8+ T Cell by Tissue-Derived Dendritic Cells Favors the Stimulation of Naive CD8+ T Cells,” Nature Immunology, Vol. 8, 2007, pp. 1060-1066. doi:10.1038/ni1505
[8] J. F. Fonteneau, M. Gilliet, M. Larsson, I. Dasilva, C. Munz, Y. J. Liu and N. Bhardwaj, “Activation of Influenza Virus-Specific CD4+ and CD8+ T Cells: A New Role for Plasmacytoid Dendritic Cells in Adaptive Immunity,” Blood, Vol. 101, No. 9, 2003, pp. 3520-3526. doi:10.1182/blood-2002-10-3063
[9] L. D. Devanur and J. R. Kerr, “Chronic Fatigue Syndrome,” Journal of Clinical Virology, Vol. 37, No. 3, 2006, pp. 139-150. doi:10.1016/j.jcv.2006.08.013
[10] S. B. Harvey, M. Wadsworth, S. Wessely and M. Hotopf, “Etiology of Chronic Fatigue Syndrome: Testing Popular Hypotheses Using a National Birth Cohort Study,” Psychosomatic Medicine, Vol. 70, No. 4, 2008, pp. 488-495. doi:10.1097/PSY.0b013e31816a8dbc
[11] D. V. Ablashi, H. B. Eastman, C. B. Owen, M. M. Roman, J. Friedman, J. B. Zabriskie, D. L. Peterson, G. R. Pearson and J. E. Whitman, “Frequent HHV-6 Reactivation in Multiple Sclerosis (MS) and Chronic Fatigue Syndrome (CFS) Patients,” Journal of Clinical Virology, Vol. 16, No. 3, 2000, pp. 179-191. doi:10.1016/S1386-6532(99)00079-7
[12] S. H. Beqaj, A. M. Lerner and J. T. Fitzgerald, “Immunoassay with Cytomegalovirus Early Antigens from Gene Products p52 and CM2 (UL44 and UL57) Detects Active Infection in Patients with Chronic Fatigue Syndrome,” Journal of Clinical Pathology, Vol. 61, No. 5, 2008, pp. 623-626. doi:10.1136/jcp.2007.050633
[13] D. Buchwald, M. H. Wener, T. Pearlman and P. Kith, “Markers of Inflammation and Immune Activation in Chronic Fatigue and Chronic Fatigue Syndrome,” Journal of Rheumatology, Vol. 24, No. 2, 1997, pp. 372-376.
[14] E. DeFreitas, B. Hilliard, P. R. Cheney, D. S. Bell, E. Kiggundu, D. Sankey, Z. Wroblewska, M. Palladino, J. P. Woodward and H. Koprowski, “Retroviral Sequences Related to Human T-Lymphotropic Virus Type II in Patients with Chronic Fatigue Immune Dysfunction Syndrome,” Proceedings of National Academy of Sciences of the United States of America, Vol. 88, No. 7, 1991, pp. 2922-2926. doi:10.1073/pnas.88.7.2922
[15] D. Gold, R. Bowden, J. Sixbey, R. Riggs, W. J. Katon, R. Ashley, R. M. Obrigewitch and L. Corey, “Chronic Fatigue. A Prospective Clinical and Virologic Study,” Journal of the American Medical Association, Vol. 264, 1990, pp. 48-53. doi:10.1001/jama.264.1.48
[16] B. Grinde, “Is Chronic Fatigue Syndrome Caused by a Rare Brain Infection of a Common, Normally Benign Virus?” Medical Hypotheses, Vol. 71, No. 2, 2008, pp. 270-274. doi:10.1016/j.mehy.2008.03.014
[17] J. F. Jones, “Epstein-Barr Virus and the Chronic Fatigue Syndrome: A Short Review,” Microbiological Sciences, Vol. 5, No. 12, 1988, pp. 366-369.
[18] A. Linde, B. Andersson, S. B. Svenson, H. Ahrne, M. Carlsson, P. Forsberg, H. Hugo, A. Karstorp, R. Lenkei, A. Lindwall, et al., “Serum Levels of Lymphokines and Soluble Cellular Receptors in Primary Epstein-Barr Virus Infection and in Patients with Chronic Fatigue Syndrome,” Journal of Infectious Diseases, Vol. 165, No. 6, 1992, pp. 994-1000. doi:10.1093/infdis/165.6.994
[19] E. W. Brenu, D. R. Staines, O. K. Baskurt, K. J. Ashton, S. B. Ramos, R. M. Christy and S. M. Marshall-Gradisnik, “Immune and Hemorheological Changes in Chronic Fatigue Syndrome,” Journal of Translational Medicine, Vol. 8, 2010, p. 1. doi:10.1186/1479-5876-8-1
[20] N. G. Klimas and A. O. Koneru, “Chronic Fatigue Syndrome: Inflammation, Immune Function, and Neuroendocrine Interactions,” Current Rheumatology Reports, Vol. 9, No. 6, 2007, pp. 482-487. doi:10.1007/s11926-007-0078-y
[21] M. Maes, I. Mihaylova and J. C. Leunis, “Chronic Fatigue Syndrome Is Accompanied by an IgM-Related Immune Response Directed against Neopitopes Formed by Oxidative or Nitrosative Damage to Lipids and Proteins,” Neuroendocrinology Letters, Vol. 27, 2006, pp. 615-21.
[22] Racciatti, M. Dalessandro, L. Delle Donne, K. Falasca, P. Zingariello, R. Paganelli, E. Pizzigallo, and J. Vecchiet, “Study of immune alterations in patients with chronic fatigue syndrome with different etiologies,” International Journal of Immunopathology and Pharmacology, Vol. 17, No. 2, 2004, pp. 57-62.
[23] F. Friedberg, L. Dechene, M. J. McKenzie II and R. Fontanetta, “Symptom Patterns in Long-Duration Chronic Fatigue Syndrome,” Journal of Psychosomatic Research, Vol. 48, No. 1, 2000, pp. 59-68. doi:10.1016/S0022-3999(99)00077-X
[24] “Report of the Working Group on the Possible Relationship between Hepatitis B Vaccination and the Chronic Fatigue Syndrome,” Canadian Medical Association Journal, Vol. 149, 1993, pp. 314-319.
[25] S. Appel, J. Chapman and Y. Shoenfeld, “Infection and Vaccination in Chronic Fatigue Syndrome: Myth or Reality?” Autoimmunity, Vol. 40, No. 1, 2007, pp. 48-53. doi:10.1080/08916930701197273
[26] G. Delage, I. Salit, R. Pennie, M. Alary, B. Duval and B. Ward, “The Possible Relation between Hepatitis B Vaccination and Chronic Fatigue Syndrome,” Union Medical Canada, Vol. 122, 1993, pp. 278-279.
[27] D. Ortega-Hernandez and Y. Shoenfeld, “Infection, Vaccination, and Autoantibodies in Chronic Fatigue Syndrome, Cause or Coincidence?” Annals of the New York Academy Sciences, Vol. 1173, 2009, pp. 600-609. doi:10.1111/j.1749-6632.2009.04799.x
[28] K. M. Sleigh, D. G. Danforth, R. T. Hall, J. A. Fleming and H. G. Stiver, “Double-Blind, Randomized Study of the Effects of Influenza Vaccination on the Specific Antibody Response and Clinical Course of Patients with Chronic Fatigue Syndrome,” Canadian Journal of Infectious Diseases, Vol. 11, No. 5, 2000, pp. 267-273.
[29] K. M. Sleigh, F. H. Marra and H. G. Stiver, “Influenza Vaccination: Is It Appropriate in Chronic Fatigue Syndrome?” American Journal of Respiratory Medicine, Vol. 1, 2002, pp. 3-9. doi:10.1007/BF03257157
[30] W. Brenu, M. L. van Driel, D. R. Staines, K. J. Ashton, S. B. Ramos, J. Keane, N. G. Klimas and S. M. Marshall-Gradisnik, “Immunological Abnormalities as Potential Biomarkers in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis,” Journal of Translational Medicine, Vol. 9, 2011, p. 81. doi:10.1186/1479-5876-9-81
[31] K. Fukuda, S. E. Straus, I. Hickie, M. C. Sharpe, J. G. Dobbins and A. Komaroff, “The Chronic Fatigue Syndrome: A Comprehensive Approach to Its Definition and Study. International Chronic Fatigue Syndrome Study Group,” Annals of Internal Medicine, Vol. 121, No. 12, 1994, pp. 953-959.
[32] "3.9 Influenza,” The Australian Immunisation Handbook, 9th Edition, 2012.
[33] J. P. Aubry, A. Blaecke, S. Lecoanet-Henchoz, P. Jeannin, N. Herbault, G. Caron, V. Moine and J. Y. Bonnefoy, “Annexin V Used for Measuring Apoptosis in the Early Events of Cellular Cytotoxicity,” Cytometry, Vol. 37, No. 3, 1991, pp. 197-204. doi:10.1002/(SICI)1097-0320(19991101)37:3<197::AID-CYTO6>3.0.CO;2-L
[34] L. Dickson and K. Finlayson, “VPAC and PAC Receptors: From Ligands to Function,” Pharmacology & Therapeutics, Vol. 121, No. 3, 2009, pp. 294-316. doi:10.1016/j.pharmthera.2008.11.006
[35] P. C. Doherty and A. Kelso, “Toward a Broadly Protective Influenza Vaccine,” The Journal of Clinical Investigation, Vol. 118, 2008, pp. 3273-3275.
[36] Y. Ghendon, S. Markushin, Y. Vasiliev, I. Akopova, I. Koptiaeva, G. Krivtsov, O. Borisova, N. Ahmatova, E. Kurbatova, S. Mazurina and V. Gervazieva, “Evaluation of Properties of Chitosan as an Adjuvant for Inactivated Influenza Vaccines Administered Parenterally,” Journal of Medical Virology, Vol. 81, No. 3, 2009, pp. 494-506. doi:10.1002/jmv.21415
[37] S. M. Hsieh and S. C. Chang, “Insufficient Perforin Expression in CD8+ T Cells in Response to Hemagglutinin from Avian Influenza (H5N1) Virus,” Journal of Immunology, Vol. 176, No. 6, 2006, pp. 4530-4533.
[38] X. S. He, T. H. Holmes, K. Mahmood, G. W. Kemble, C. L. Dekker, A. M. Arvin and H. B. Greenberg, “Phenotypic Changes in Influenza-Specific CD8+ T Cells after Immunization of Children and Adults with Influenza Vaccines,” The Journal of Infectious Diseases, Vol. 197, No. 6, 2008, pp. 803-811. doi:10.1086/528804
[39] J. Mysliwska, P. Trzonkowski, E. Szmit, L. B. Brydak, M. Machala and A. Mysliwski, “Immunomodulating Effect of Influenza Vaccination in the Elderly Differing in Health Status,” Experimental Gerontology, Vol. 39, No. 10, 2004, pp. 1447-58. doi:10.1016/j.exger.2004.08.005
[40] J. E. McElhaney, S. Gravenstein, C. M. Upshaw, J. W. Hooton, P. Krause, P. Drinka and R. C. Bleackley, “Granzyme B: A Marker of Risk for Influenza in Institutionalized Older Adults,” Vaccine, Vol. 19, No. 27, 2001, pp. 3744-3751. doi:10.1016/S0264-410X(01)00087-1
[41] J. M. Schapiro, Y. Segev, L. Rannon, M. Alkan and B. Rager-Zisman, “Natural Killer (NK) Cell Response after Vaccination of Volunteers with Killed Influenza Vaccine,” Journal of Medical Virology, Vol. 30, No. 3, 1990, pp. 196-200. doi:10.1002/jmv.1890300310
[42] R. Clark, N. B. Anderson, V. R. Clark and D. R. Williams, “Racism as a Stressor for African Americans. A Biopsy-chosocial Model,” The American Psychologist, Vol. 54, No. 10, 1999, pp. 805-816. doi:10.1037/0003-066X.54.10.805
[43] V. Demicheli, D. Rivetti, J. J. Deeks and T. O. Jefferson, “Vaccines for Preventing Influenza in Healthy Adults,” Cochrane Database of Systematic Reviews, 2000, Article ID: CD001269.
[44] I. Rosenkrands, C. Vingsbo-Lundberg, T. J. Bundgaard, T. Lindenstrom, V. Enouf, S. van der Werf, P. Andersen and E. M. Agger, “Enhanced Humoral and Cell-Mediated Immune Responses after Immunization with Trivalent Influenza Vaccine Adjuvanted with Cationic Liposomes,” Vaccine, Vol. 29, No. 37, 2011, pp. 6283-6291. doi:10.1016/j.vaccine.2011.06.040
[45] J. E. McElhaney, S. Gravenstein, P. Krause, J. W. Hooton, C. M. Upshaw and P. Drinka, “Assessment of Markers of the Cell-Mediated Immune Response after Influenza Virus Infection in Frail Older Adults,” Clinical and Vaccine Immunology, Vol. 5, No. 6, 1998, pp. 840-844.
[46] J. E. McElhaney, S. Gravenstein, C. M. Upshaw, J. W. Hooton, P. Krause and P. Drinka, “Immune Response to Influenza Vaccination in Institutionalized Elderly: Effect on Different T-Cell Subsets,” Vaccine, Vol. 16, No. 4, 1998, pp. 403-409. doi:10.1016/S0264-410X(97)80918-8

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