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7 - Measuring immune function: markers of cell-mediated immunity and inflammation in dried blood spots

Published online by Cambridge University Press:  11 September 2009

Gillian H. Ice
Affiliation:
Ohio University
Gary D. James
Affiliation:
State University of New York, Binghamton
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Summary

Introduction

Stress is an important determinant of human immune function, but population-level research on the social ecology of immunity has lagged behind other areas of investigation. In large part this is due to methodological constraints associated with the assessment of immune function: venipuncture is a relatively invasive blood sampling procedure that requires the skills of a trained medical professional and, once collected, blood samples must be immediately assayed, or centrifuged, separated, and frozen. Obviously, these are serious impediments to field-based research, and they have hindered the exploration of stress–immunity relationships in large, representative, community-based studies.

Dried blood spots – samples of whole blood collected on filter paper following a simple finger prick – provide an alternative, minimally invasive sampling procedure. Several community-based applications have shown this to be a convenient and reliable means to facilitate sample collection, storage, and transportation, and laboratory methods have been validated for a growing number of analytes (Worthman and Stallings, 1994, 1997; Cook et al., 1998; McDade et al., 2000a; Erhardt et al., 2002; McDade and Shell-Duncan, 2002; McDade et al., 2004). Also referred to as “Guthrie papers,” filter papers have been a core component of US hospital-based newborn screening programs since the 1960s, with all newborns providing a blood spot sample to screen for congenital metabolic disorders (Mei et al., 2001).

In this chapter, detailed information is provided on the collection, handling, and analysis of dried blood-spot samples for two measures of immune activity: Epstein-Barr virus antibodies and C-reactive protein.

Type
Chapter
Information
Measuring Stress in Humans
A Practical Guide for the Field
, pp. 181 - 208
Publisher: Cambridge University Press
Print publication year: 2006

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References

Adam, B. W., Alexander, J. R., Smith, S. J.et al. (2000). Recoveries of phenylalanine from two sets of dried-blood-spot reference materials: prediction from hematocrits, spot volume, and paper matrix. Clinical Chemistry, 46, 126–8.Google ScholarPubMed
Affleck, G., Urrows, S., Tenne, H.et al. (1997). A dual pathway model of daily stressors effects on rheumatoid arthritis. Annals of Behavioral Medicine, 19, 161–70.CrossRefGoogle ScholarPubMed
Ballou, S. P. and Kushner, I. (1992). C-reactive protein and the acute phase response. Advances in Internal Medicine, 37, 313–36.Google ScholarPubMed
Baumann, H. J. and Gauldie, J. (1994). The acute phase response. Immunology Today, 15(2), 74–80.CrossRefGoogle ScholarPubMed
Bellisario, R., Colinas, R. J. and Pass, K. A. (2000). Simultaneous measurement of thyroxine and thyrotropin from newborn dried blood-spot specimens using a multiplexed fluorescent microsphere immunoassay. Clinical Chemistry, 46(9), 1422–4.Google ScholarPubMed
Biondi, M. (2001). Effects of stress on immune functions: an overview. In Psychoneuroimmunology, 3rd edn, eds. Ader, R., Felten, D. L. and Cohen, N.. San Diego CA: Academic Press, pp. 189–226.CrossRefGoogle Scholar
Biondi, M., Costantini, A. and Parisi, A. M. (1996). Can loss and grief activate latent neoplasia?Psychotherapy and Psychosomatics, 65, 102–5.CrossRefGoogle ScholarPubMed
Black, P. H. (2002). Stress and the inflammatory response: a review of neurogenic inflammation. Brain, Behavior, and Immunity, 16, 622–53.CrossRefGoogle ScholarPubMed
Boyce, W. T., Chesney, M., Alkon, A.et al. (1995). Psychobiologic reactivity to stress and childhood respiratory illnesses: results of two prospective studies. Psychosomatic Medicine, 57, 411–22.CrossRefGoogle ScholarPubMed
Boyce, W. T., Chesterman, E. A., Martin, N.et al. (1993). Immunologic changes occurring at kindergarten entry predict respiratory illnesses after the Loma Prieta earthquake. Journal of Developmental and Behavioral Pediatrics, 14, 296–303.CrossRefGoogle ScholarPubMed
Boyce, W. T., Jensen, E. W., Cassel, J. C.et al. (1977). Influence of life events and family routines on childhood respiratory tract illness. Pediatrics, 60(4), 609–15.Google ScholarPubMed
Carson, R. T. and Vignali, D. A. A. (1999). Simultaneous quantitation of 15 cytokines using a multiplexed flow cytometric assay. Journal of Immunological Methods, 227, 41–52.CrossRefGoogle ScholarPubMed
Cohen, S. (1995). Psychological stress and susceptibility to upper respiratory infections. American Journal of Respiratory Critical Care Medicine, 152(Supplement), 53–8.CrossRefGoogle ScholarPubMed
Cohen, S., Frank, E., Doyle, W. J.et al. (1998). Types of stressors that increase susceptibility to the common cold in healthy adults. Health Psychology, 17(3), 214–23.CrossRefGoogle ScholarPubMed
Cook, E. B., Stahl, J. L., Lowe, L.et al. (2001). Simultaneous measurement of six cytokines in a single sample of human tears using microparticle-based flow cytometry: allergics vs. non-allergics. Journal of Immunological Methods, 254, 109–18.CrossRefGoogle Scholar
Cook, J. D., Flowers, C. H. and Skikne, B. S. (1998). An assessment of dried blood-spot technology for identifying iron deficiency. Blood, 92, 1807–13.Google ScholarPubMed
Danesh, J., Wheeler, J. G., Hirschfield, G.M.et al. (2004). C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease. New England Journal of Medicine, 350, 1387–97.CrossRefGoogle ScholarPubMed
Danner, M., Kasl, S. V., Abramson, J. L. and Vaccarino, V. (2003). Association between depression and elevated C-reactive protein. Psychosomatic Medicine, 65, 347–56.CrossRefGoogle ScholarPubMed
Dentino, A. N., Pieper, C. F., Rao, K. M. K.et al. (1999). Association of interleukin-6 and other biologic variables with depression in older people living in the community. Journal of the American Geriatrics Society, 47, 6–11.CrossRefGoogle ScholarPubMed
Erhardt, J. G., Craft, N. E., Heinrich, F. and Bielaski, H. K. (2002). Rapid and simple measurement of retinol in dried whole blood spots. Journal of Nutrition, 132(2), 318–21.CrossRefGoogle ScholarPubMed
Esterling, B. A., Antoni, M. H., Kumar, M. and Schneiderman, N. (1993). Defensiveness, trait anxiety, and Epstein-Barr viral capsid antigen antibody titers in healthy college students. Health Psychology, 12(2), 132–9.CrossRefGoogle ScholarPubMed
Esterling, B. A., Antoni, M. H., Schneiderman, N.et al. (1992). Psychosocial modulation of antibody to Epstein-Barr viral capsid antigen and human Herpesvirus Type-6 in HIV-1-infected and at-risk gay men. Psychosomatic Medicine, 54, 354–71.CrossRefGoogle ScholarPubMed
Fleck, A. (1989). Clinical and nutritional aspects of changes in acute-phase proteins during inflammation. Proceedings of the Nutrition Society, 48, 347–54.CrossRefGoogle ScholarPubMed
Gillespie, S. H., Dow, C., Raynes, J. G.et al. (1991). Measurement of acute phase proteins for assessing severity of Plasmodium falciparum malaria. Journal of Clinical Pathology, 44, 228–31.CrossRefGoogle ScholarPubMed
Glaser, R., MacCallum, R. C.,Laskowski, B. F.et al. (2001). Evidence for a shift in the Th1 to Th2 cytokine response associated with chronic stress and aging. Journal of Gerontology A. Biological Sciences and Medical Sciences, 56, M477–82.CrossRefGoogle Scholar
Glaser, R., Kiecolt-Glaser, J. K., Bonneau, R. G.et al. (1992). Stress-induced modulation of the immune response to recombinant hepatitis B vaccine. Psychosomatic Medicine, 54, 22–9.CrossRefGoogle ScholarPubMed
Glaser, R., Kiecolt-Glaser, J. K., Speicher, C. E. and Holliday, J. E. (1985). Stress, loneliness, and changes in herpesvirus latency. Journal of Behavioral Medicine, 8(3), 249–60.CrossRefGoogle ScholarPubMed
Glaser, R., Pearl, D. K., Kiecolt-Glaser, J. K. and Malarkey, W. B. (1994). Plasma cortisol levels and reactivation of latent Epstein-Barr virus in response to examination stress. Psychoneuroendocrinology, 19(8), 765–72.CrossRefGoogle ScholarPubMed
Glaser, R., Pearson, G. R., Bonneau, R. H.et al. (1993). Stress and the memory T-cell response to the Epstein-Barr virus in healthy medical students. Health Psychology, 12(6), 435–42.CrossRefGoogle ScholarPubMed
Glaser, R., Pearson, G. R., Jones, J. F.et al. (1991). Stress-related activation of Epstein-Barr virus. Brain, Behavior, and Immunity, 5, 219–32.CrossRefGoogle ScholarPubMed
Glaser, R., Rice, J., Sheridan, J.et al. (1987). Stress-related immune suppression: health implications. Brain, Behavior and Immunity, 1, 7–20.CrossRefGoogle ScholarPubMed
Glaser, R., Friedman, S. B., Smyth, F.et al. (1999). The differential impact of training stress and final examination stress on herpesvirus latency at the United States Military Academy at West Point. Brain, Behavior and Immunity, 13, 240–51.CrossRefGoogle ScholarPubMed
Glaser, R., Robles, T. F., Sheridan, J., Malarkey, W. B. and Kiecolt-Glaser, J. K. (2003). Mild depressive symptoms are associated with amplified and prolonged inflammatory responses after influenza virus vaccination in older adults. Archives of General Psychiatry, 60, 1009–14.CrossRefGoogle ScholarPubMed
Grossi, G., Perski, A., Evangard, B., Blomkvist, V. and Orth-Gomer, K. (2003). Physiological correlates of burnout among women. Journal of Psychosomatic Research, 55, 309–16.CrossRefGoogle ScholarPubMed
Hall, M., Baum, A., Buysse, D. J.et al. (1998). Sleep as a mediator of the stress-immune relationship. Psychosomatic Medicine, 60, 48–51.CrossRefGoogle ScholarPubMed
Henle, W. and Henle, G. (1982). Epstein-Barr virus and infectious mononucleosis. In Human Herpesvirus Infections: Clinical Aspects, ed. Glaser, R. and Gottleib-Stematsky, T.. New York: Marcel Dekker, 151–62.Google Scholar
Herbert, T. B. and Cohen, S. (1993). Stress and immunity in humans: a meta-analytic review. Psychosomatic Medicine, 55, 364–79.CrossRefGoogle ScholarPubMed
Ironson, G., Wynings, C., Schneiderman, N.et al. (1997). Posttraumatic stress symptoms, intrusive thoughts, loss, and immune function after Hurricane Andrew. Psychosomatic Medicine, 59, 128–41.CrossRefGoogle ScholarPubMed
Irwin, M., Daniels, M., Smith, T. L., Bloom, E. and Weiner, H. (1987). Impaired natural killer cell activity during bereavement. Brain, Behavior, and Immunity, 1, 98–104.CrossRefGoogle ScholarPubMed
Jemmott, J. G. and Magloire, K. (1988). Academic stress, social support, and secretory immunoglobulin A. Journal of Personality and Social Psychology, 55(5), 802–10.CrossRefGoogle ScholarPubMed
Keller, S. E., Shiflett, S. C., Schleifer, S. J. and Bartlett, J. A. (1994). Stress, immunity, and health. In Handbook of Human Stress and Immunity, ed. Glaser, R. and Kiecolt-Glaser, J.. San Diego, CA: Academic Press, 217–44.Google Scholar
Kiecolt-Glaser, J. K., Fisher, L. D., Ogrocki, P.et al. (1987a). Marital quality, marital disruption, and immune function. Psychosomatic Medicine, 49(1), 13–34.CrossRefGoogle Scholar
Kiecolt-Glaser, J. K. and Glaser, R. (1988). Methodological issues in behavioral immunology research with humans. Brain, Behavior, and Immunity, 2, 67–78.CrossRefGoogle ScholarPubMed
Kiecolt-Glaser, J. K. and Glaser, R. (1995). Psychoneuroimmunology and health consequences: Data and shared mechanisms. Psychosomatic Medicine, 57, 269–74.CrossRefGoogle ScholarPubMed
Kiecolt-Glaser, J. K. and Glaser, R. (1997). Measurement of immune response. In Measuring Stress: A Guide for Health and Social Scientists, ed. Cohen, S., Kessler, R. C. and Gordon, L. U.. New York: Oxford University Press, 213–29.Google Scholar
Kiecolt-Glaser, J. K., Glaser, R., Gravenstein, S., Malarkey, W. B. and Sheridan, J. (1996). Chronic stress alters the immune response to influenza virus vaccine in older adults. Proceedings of the National Academy of Sciences, 93, 3043–7.CrossRefGoogle ScholarPubMed
Kiecolt-Glaser, J. K., Glaser, R., Shuttleworth, E. C.et al. (1987b). Chronic stress and immunity in family caregivers of Alzheimer's disease victims. Psychosomatic Medicine, 49, 523–35.CrossRefGoogle Scholar
Kiecolt-Glaser, J. K., Kennedy, S., Malkoff, S.et al. (1988). Marital discord and immunity in males. Psychosomatic Medicine, 50, 213–29.CrossRefGoogle ScholarPubMed
Kiecolt-Glaser, J. K., Malarkey, W. B., Cacioppo, J. T. and Glaser, R. (1994). Stressful personal relationships: immune and endocrine function. In Handbook of Human Stress and Immunity, ed. Glaser, R. and Kiecolt-Glaser, J. K.. San Diego, CA: Academic Press, 321–39.Google Scholar
Kiecolt-Glaser, J. K., Marucha, P. T., Malarkey, W. B., Mercado, A. M. and Glaser, R. (1995). Slowing of wound healing by psychological stress. Lancet, 346, 1194–6.CrossRefGoogle ScholarPubMed
Kiecolt-Glaser, J. K., Glaser, R., Gravenstein, S., Malarkey, W. B. and Sheridian, J. (1996). Chronic stress alters the immune response to influenza virus vaccine in older adults. Proceedings of the National Academy of Sciences, 93, 3043–7.CrossRefGoogle ScholarPubMed
Kiecolt-Glaser, J. K., Glaser, R., Cacioppo, J. T. and Malarkey, W. B. (1998). Marital Stress: immunologic, neuroendocrine, and autonomic correlates. Annals of the New York Academy of Sciences, 840, 656–63.CrossRefGoogle ScholarPubMed
Kiecolt-Glaser, J. K., Preacher, K. J., MacCallum, R. C.et al. (2003). Chronic stress and age-related increases in the proinflammatory cytokine IL-6. Proceedings of the National Academy of Sciences, 100, 9090–5.CrossRefGoogle ScholarPubMed
Kuby, J. (1994). Immunology, 2nd edn. New York: W.H. Freeman.Google Scholar
Lagrand, W. K., Visser, C. A., Hermens, W. T.et al. (1999). C-reactive protein as a cardiovascular risk factor: more than a epiphenomenon?Circulation, 100, 96–102.CrossRefGoogle ScholarPubMed
Libby, P., Ridker, P. M. and Maseri, A. (2002). Inflammation and atherosclerosis. Circulation, 105, 1135–43.CrossRefGoogle ScholarPubMed
Lutgendorf, S. K., Antoni, M. H., Kumar, M. and Schneiderman, N. (1994). Changes in cognitive coping strategies predict EBV-antibody titre change following a stressor disclosure induction. Journal of Psychosomatic Medicine, 38(1), 63–78.CrossRefGoogle ScholarPubMed
Lutgendorf, S. K., Garand, L., Buckwalter, K. C.et al. (1999). Life stress, mood disturbance, and elevated interleukin-6 in healthy older women. Journal of Gerontology: Medical Sciences, 54A, M434–9.Google Scholar
Maes, M., Lin, A., Delmeire, L.et al. (1999). Elevated serum interleukin-6 (IL-6) and IL-6 receptor concentrations in posttraumatic stress disorder following accidental man-made traumatic events. Biological Psychiatry, 45, 833–9.CrossRefGoogle ScholarPubMed
Marshall, G. D., Agarwal, S. K., Lloyd, C. (1998). Cytokine dysregulation associated with exam stress in healthy medical students. Brain, Behavior, and Immunity, 12, 297–307.CrossRefGoogle ScholarPubMed
Marucha, P. T., Kiecolt-Glaser, J. K. and Favagchi, M. (1998). Mucosal wound healing is impaired by examination stress. Psychosomatic Medicine, 60, 362–5.CrossRefGoogle ScholarPubMed
McDade, T. W. (2001). Lifestyle incongruity, social integration, and immune function in Samoan adolescents. Social Science and Medicine, 53, 103–14.CrossRefGoogle ScholarPubMed
McDade, T. W. (2002). Status incongruity in Samoan youth: a biocultural analysis of culture change, stress, and immune function. Medical Anthropology Quarterly, 16, 123–50.CrossRefGoogle ScholarPubMed
McDade, T. W. (2003). Life event stress and immune function in Samoan adolescents: toward a cross-cultural psychoneuroimmunology. In Social and Cultural Lives of Immune Systems, ed. Wilce, J.. New York: Routledge, 170–88.Google Scholar
McDade, T. W., Burhop, J. and Dohnal, J. (2004). High sensitivity enzyme immunoassay for C-reactive protein in dried blood spots. Clinical Chemistry, 50, 652–4.CrossRefGoogle ScholarPubMed
McDade, T. W. and Shell-Duncan, B. (2002). Whole blood collected on filter paper provides a minimally-invasive method for assessing transferrin receptor level. Journal of Nutrition, 132, 3760–3.CrossRefGoogle ScholarPubMed
McDade, T. W., Stallings, J. F., Angold, A.et al. (2000a). Epstein-Barr virus antibodies in whole blood spots: A minimally-invasive method for assessing an aspect of cell-mediated immunity. Psychosomatic Medicine, 62, 560–67.CrossRefGoogle Scholar
McDade, T. W., Stallings, J. F. and Worthman, C. M. (2000b). Culture change and stress in Western Samoan youth: methodological issues in the cross-cultural study of stress and immune function. American Journal of Human Biology, 12, 792–802.3.0.CO;2-F>CrossRefGoogle Scholar
McDade, T. W. and Worthman, C. M. (2004). Socialization ambiguity in Samoan adolescents: a new model for research in human development and stress in the context of culture change. Journal of Research in Adolescence, 14, 49–72.CrossRefGoogle Scholar
McDade, T. W., Hawkley, L. C. and Cacioppo, J. T. (2006). Psychosocial and behavioral predictors of inflamation in middle-age and older adults: the Chicago health, aging, and social relations study. Psychosomatic Medicine, 68, 376–81.CrossRefGoogle Scholar
Mei, J. V., Alexander, J. R., Adam, B. W. and Hannon, W. H. (2001). Use of filter paper for the collection and analysis of human whole blood specimens. Journal of Nutrition, 131, 1631–6S.CrossRef
Meyer, R. J. and Haggerty, R. J. (1962). Streptococcal infections in families: Factors altering individual susceptibility. Pediatrics, 29, 539–49.Google ScholarPubMed
Mortensen, R. F. (1994). Macrophages and acute-phase proteins. Immunology Series, 60, 143–58.Google ScholarPubMed
Moynihan, J. A., Kruszeska, B., Brenner, G. J. and Cohen, N. (1998). Neural, endocrine, and immune system interactions. Relevance for health and disease. Advances in Experimental Medicine and Biology, 438, 541–9.CrossRefGoogle ScholarPubMed
O'Meara, J. T. (1990). Samoan Planters: Tradition and Economic Development in Polynesia. Fort Worth, TX: Holt, Rinehart and Winston.Google Scholar
Owen, N., Poulton, T., Hay, F. C., Mohamed-Ali, V. and Steptoe, A. (2003). Socioeconomic status, C-reactive protein, immune factors, and responses to acute mental stress. Brain, Behavior, and Immunity, 17, 286–95.CrossRefGoogle ScholarPubMed
Pearson, T. A., Mensah, G. A., Alexander, R. W.et al. (2003). Markers of inflammation and cardiovascular disease: application to clinical and public health practice. Circulation, 107, 499–511.CrossRefGoogle ScholarPubMed
Pepys, M. B. (1995). The acute phase response and C-reactive protein. In Oxford Textbook of Medicine Vol. 2, 3rd edn, ed. Weatherall, D. J., Ledingham, J. G. G. and Warrell, D. A.. Oxford: Oxford University Press, 1527–33.Google Scholar
Petrie, K. J., Booth, R. J., Pennebaker, J. W. and Davison, K. P. (1995). Disclosure of trauma and immune response to a Hepatitis B vaccination program. Journal of Consulting and Clinical Psychology, 63(5), 787–92.CrossRefGoogle ScholarPubMed
Pike, J. L., Smith, T. L., Hauger, R. L.et al. (1997). Chronic life stress alters sympathetic, neuroendocrine, and immune responsitivity to an acute psychological stressor in humans. Psychosomatic Medicine, 59(4), 447–57.CrossRefGoogle Scholar
Ridker, P. M., Buring, J. E., Shih, J., Matias, M. and Hennekens, C. H. (1998). Prospective study of C-reactive protein and the risk of future cardiovascular events among apparently healthy women. Circulation, 98, 731–3.CrossRefGoogle ScholarPubMed
Ross, R. (1999). Atherosclerosis: An inflammatory disease. New England Journal of Medicine, 340, 115–26.CrossRefGoogle Scholar
Schleifer, S. J., Scott, B., Stein, M. and Keller, S. E. (1986). Behavioral and developmental aspects of immunity. Journal of the American Academy of Child Psychiatry, 26(6), 751–63.CrossRefGoogle Scholar
Segerstrom, S. C., Kemeny, M. E. and Laudenslager, M. L. (2001). Individual difference factors in psychoneuroimmunology. In Psychoneuroimmunology, 3rd edn, eds. Ader, R., Felten, D. L. and Cohen, N.. San Diego, CA: Academic Press, 87–109.CrossRefGoogle Scholar
Shore, B. (1982). Sala'ilua: A Samoan Mystery. New York: Columbia University Press.Google Scholar
Solomon, G. F., Segerstrom, S. C., Grohr, P., Kemeny, M. and Fahey, J. (1997). Shaking up immunity: Psychological and immunologic changes after a natural disaster. Psychosomatic Medicine, 59, 114–27.CrossRefGoogle ScholarPubMed
Tracy, R. P. (1998). Inflammation in cardiovascular disease. Circulation, 97, 2000–2.CrossRefGoogle ScholarPubMed
Uchino, B. N., Cacioppo, J. T. and Kiecolt-Glaser, J. K. (1996). The relationship between social support and physiological processes: a review with emphasis on underlying mechanisms and implications for health. Psychological Bulletin, 119(3), 488–531.CrossRefGoogle Scholar
Worthman, C. M. and Stallings, J. F. (1994). Measurement of gonadotrophins in dried blood spots. Clinical Chemistry, 40(3), 448–53.Google Scholar
Worthman, C. M. and Stallings, J. F. (1997). Hormone measures in finger-prick blood spot samples: New field methods for reproductive endocrinology. American Journal of Physical Anthropology, 104(1), 1–22.3.0.CO;2-V>CrossRefGoogle ScholarPubMed
Zautra, A. J., Hoffman, J., Potter, P.et al. (1997). Examination of changes in interpersonal stress as a factor in disease exacerbations among women with rheumatoid arthritis. Annals of Behavioral Medicine, 19, 279–86.CrossRefGoogle ScholarPubMed

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