Hostname: page-component-586b7cd67f-rdxmf Total loading time: 0 Render date: 2024-11-23T21:10:01.218Z Has data issue: false hasContentIssue false

An association between anti-hippocampal antibody concentration and lymphocyte production of IL-2 in patients with schizophrenia

Published online by Cambridge University Press:  09 July 2009

Z. W. Yang
Affiliation:
Immunopsychiatry Program, Western Psychiatric Institute and Clinic, Departments of Psychiatry and Pathology, University of Pittsburgh School of Medicine; and Brain, Behavior and Immunity Center, Pittsburgh, Pennsylvania, USA
K. N. R. Chengappa
Affiliation:
Immunopsychiatry Program, Western Psychiatric Institute and Clinic, Departments of Psychiatry and Pathology, University of Pittsburgh School of Medicine; and Brain, Behavior and Immunity Center, Pittsburgh, Pennsylvania, USA
G. Shurin
Affiliation:
Immunopsychiatry Program, Western Psychiatric Institute and Clinic, Departments of Psychiatry and Pathology, University of Pittsburgh School of Medicine; and Brain, Behavior and Immunity Center, Pittsburgh, Pennsylvania, USA
J. S. Brar
Affiliation:
Immunopsychiatry Program, Western Psychiatric Institute and Clinic, Departments of Psychiatry and Pathology, University of Pittsburgh School of Medicine; and Brain, Behavior and Immunity Center, Pittsburgh, Pennsylvania, USA
B. S. Rabin
Affiliation:
Immunopsychiatry Program, Western Psychiatric Institute and Clinic, Departments of Psychiatry and Pathology, University of Pittsburgh School of Medicine; and Brain, Behavior and Immunity Center, Pittsburgh, Pennsylvania, USA
A. V. Gubbi
Affiliation:
Immunopsychiatry Program, Western Psychiatric Institute and Clinic, Departments of Psychiatry and Pathology, University of Pittsburgh School of Medicine; and Brain, Behavior and Immunity Center, Pittsburgh, Pennsylvania, USA
R. Ganguli*
Affiliation:
Immunopsychiatry Program, Western Psychiatric Institute and Clinic, Departments of Psychiatry and Pathology, University of Pittsburgh School of Medicine; and Brain, Behavior and Immunity Center, Pittsburgh, Pennsylvania, USA
*
1 Address for correspondence: Dr Rohan Ganguli, Western Psychiatric Institute and Clinic, 3811 O'Hara Street, Pittsburgh, PA 15213–2593, USA

Synopsis

Serum concentrations of anti-hippocampal antibodies and in vitro production of the lymphokine interleukin-2 (IL-2) in response to phytohaemagglutinin (PHA) stimulation were determined using an enzyme immunoassay in 49 schizophrenic patients and 41 healthy controls. Decrease in IL-2 production, a finding frequently associated with many autoimmune diseases, was associated with an elevation in anti-hippocampal antibody optical density (AHA-OD) in schizophrenic patients. Although some control subjects had elevated antibody levels, this elevation was not associated with decreased IL-2 production. Low IL-2 production is well known to be a state marker associated with active autoimmune disease. We suggest that production of hippocampal antibody is a trait marker of vulnerability to autoimmune diseases. Thus, our finding of low IL-2 production in patients with high concentrations of hippocampal antibody is compatible with the possibility that such patients have an ongoing autoimmune process.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 1994

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Baron, M., Stern, M., Auavi, R. & Witz, I. P. (1977). Tissue-binding factor in schizophrenic sera: a clinical and genetic study. Biological Psychiatry 12, 199216.Google Scholar
Boehme, D. H., Cottrell, J. C., Dohan, F. C. & Hillegass, L. M. (1973). Fluorescent antibody studies of immunoglobulin binding by brain tissue. Archives of General Psychiatry, 28, 202207.Google Scholar
Boitard, C. & Bach, J. S. (1991). Immunogenetics of IDDM. In Molecular Autoimmunity (ed. Talal, N.), pp. 273318. Academic Press: London.Google Scholar
Chengappa, K. N. R., Ganguli, R., Yang, Z. W., Shurin, G., Cochran, J., Brar, J. S. & Rabin, B. (1992). Non-right sidedness; an association with lower IL-2 production. Life Sciences 51, 18431849.Google Scholar
Cross, R. J., Brooks, W. H., Roszman, T. L. & Markesbery, W. R. (1982). Hypothalamic-immune interaction: effect of hypophy-sectomy on neuroimmuno-modulation. Journal of Neurological Sciences 53, 557566.Google Scholar
DeLisi, L. E. & Wyatt, R. J. (1982). Abnormal immune regulation in schizophrenic patients. Psychopharmacology Bulletin 18, 158163.Google Scholar
DeLisi, L. E., King, A. C. & Targum, S. (1985). Serum immunoglobulin concentration in patients admitted to an acute psychiatric inpatient service. British Journal of Psychiatry 145, 661666.CrossRefGoogle Scholar
Dixon, W. J. (1988). Univariate and multivariate analysis of variance and covariance, including repeated measures. In BMDP Statistical Software Manual, vol. 2 (ed. Dixon, W. J.), pp. 10451080. University of California Press, Berkeley, CA.Google Scholar
Fessel, W. J. (1963). The ‘antibrain’ factors in psychiatric patients sera. Archives of General Psychiatry 8, 614621.Google Scholar
Ganguli, R. & Rabin, B. S. (1989). Increased IL-2 receptor concentration in schizophrenic and brain damaged patients. Archives of General Psychiatry 46, 292.Google Scholar
Ganguli, R., Rabin, B. S., Kelly, R. H., Lyte, M. & Raghu, U. (1987). Clinical and laboratory evidence of autoimmunity in acute schizophrenia. Annals of the New York Academy of Sciences 496, 676685.Google Scholar
Ganguli, R., Rabin, B. S. & Belle, S. H. (1989 a). Decreased IL-2 production in schizophrenic patients. Biological Psychiatry 26, 427430.CrossRefGoogle ScholarPubMed
Ganguli, R., Rabin, B. S. & Kelly, R. H. (1989 b). Multiple autoantibodies and autoimmune disease in schizophrenic patients: evidence for an autoimmune pathogenesis. In Interactions Among CNS, Neuroendocrine and Immune Systems (ed. Hadden, J. W., Masek, K. and Nistico, G.), pp. 365384. Pythagora Press: Rome, Milan.Google Scholar
Ganguli, R., McAllister, C. G., Rabin, B. S., Solomon, W., Brar, J. S. & Rehn, T. (1991). Alterations in interleukins and in Tlymphocyte subsets in a subgroup of schizophrenics. Biological Psychiatry 29, 109A.Google Scholar
Gillis, S., Ferm, M. M., Ou, W. & Smith, K. A. (1978). T cell growth factor: parameters of production and a quantitative microassay for activity. Journal of Immunology 120, 20272032.Google Scholar
Heath, R. G. & Krupp, I. M. (1967). Schizophrenia as an immunologic disorder. Archives of General Psychiatry 16, 19.Google Scholar
Heath, R. G., McCarron, K. L. & O'Neil, C. E. (1989). Antiseptal brain antibody in IgG of schizophrenic patients. Biological Psychiatry 25, 725733.Google Scholar
Kaye, W. A., Adri, M. N., Soeldner, J. S., Rabinowe, S. L., Kaldany, A., Kahn, C. R., Bistrian, B., Srikanta, S., Gander, O. P. & Eisenbarth, G. S. (1986). Acquired defect in interleukin-2 production in patients with type I diabetes mellitus. New England Journal of Medicine 315, 920924.CrossRefGoogle ScholarPubMed
Kelly, R. H., Ganguli, R. & Rabin, B. S. (1987). Antibody to discrete area of the brain in normal individuals and patients with schizophrenia. Biological Psychiatry 22, 14881491.Google Scholar
Knight, J. G., Knight, A., Menkes, D. B. & Mullen, P. E. (1990). Autoantibodies against brain septal region antigens specific to schizophrenia? Biological Psychiatry 28, 467474.Google Scholar
Kuznetsova, N. I. & Semenov, S. F. (1961). Determining antibodies to the brain in the serum of patients with neuropsychiatric diseases. Zhurnal Nevropathologii Psikhiatrii Imeni SS Korsakova 61, 869874.Google Scholar
Logan, D. G. & Deodhar, S. D. (1970). Schizophrenia, an immunologic disorder? Journal of the American Medical Association 212, 17031704.Google Scholar
Lowry, O. H., Rosebrough, N. J., Farr, A. L. & Randall, R. J. (1951). Protein measurement with the folin phenol reagent. Journal of Biological Chemistry 193, 265275.CrossRefGoogle ScholarPubMed
Lyte, M. (1987). Generation and measurement of IL-1, IL-2 and mitogen levels in small volumes of whole blood. Journal of Clinical Laboratory Analysis 1, 8388.Google Scholar
Murray, R. M., Lewis, S. W. & Reveley, A. M. (1985). Towards an etiological classification of schizophrenia. Lancet i, 10231026.Google Scholar
Neveu, P. J., Barneoud, P., Vitiello, S., Kelley, K. W. & LeMoal, M. A. (1989). Brain neocortex modulation of mitogen induced interleukin-2, but not interleukin-1 production. Immunology Letters 21, 307310.CrossRefGoogle Scholar
Pandey, R., Gutta, A. K. & Chaturvedi, U. C. (1981). Autoimmune model of schizophrenia with special reference to antibrain antibodies. Biological Psychiatry 16, 11231136.Google Scholar
Rapaport, M. H., McAllister, C. M., Pickar, D., Nelson, D. L. & Paul, S. M. (1989). Elevated levels of interleukin-2 receptors in schizophrenia. Archives of General Psychiatry 46, 291292.Google Scholar
Rubin, R. T. (1965). Investigation of precipitins of human brain in sera of psychotic patients. British Journal of Psychiatry 111, 10031006.Google Scholar
Shima, S., Yano, K., Sugiura, M. & Tokunaga, Y. (1991). Anticerebral antibodies in functional psychoses. Biological Psychiatry 29, 322328.Google Scholar
Shintani, F., Shigenobu, K., Mauro, N., Nakaki, T., Nibuya, M., Suzuki, E., Kinoshita, N. & Yagi, G. (1991). Serum IL-6 in schizophrenic patients. Life Sciences 49, 661664.Google Scholar
Sirota, P., Schild, K., Firer, M., Tanay, A., Meytes, D. & Slor, H. (1991). Autoantibodies to DNA in multicase families with schizophrenia. Biological Psychiatry 29, 103A.Google Scholar
Solomon, G. F. & Amkraut, A. A. (1981). Psychoneuroendocrinological effects on the immune response. Annual Review of Microbiology 35, 155184.Google Scholar
Spitzer, R. L., Endicott, J. & Robins, E. (1978 a). Research Diagnostic Criteria: rationale and reliability. Archives of General Psychiatry 35, 773782.Google Scholar
Spitzer, R. L., Endicott, J. & Robins, E. (1978 b). The Schedule for Affective Disorders and Schizophrenia (SADS). New York State Psychiatric Institute: New York.Google Scholar
Stein, M., Schiavi, R. C. & Camerino, M. (1976). Influence of brain and behavior on the immune system: the effect of hypothalamic lesions on immune processes is desired. Science 191, 435440.Google Scholar
Sundin, U. & Thelander, S. (1989). Antibody reactivity to brain membrane proteins in serum from schizophrenic patients. Brain, Behavior, and Immunity 3, 345358.Google Scholar
Villemain, F., Chatenoud, L., Galinowski, A., Homo-Delarche, F., Ginestet, D., Loo, H., Zarifan, E. & Bach, J. F. (1989). Aberrant T-cell immunity in untreated schizophrenic patients: deficient IL-2 production. American Journal of Psychiatry 146, 609616.Google Scholar
Whittingham, S., Mackay, I. R., Jones, I. H. & Davies, B. (1968). Absence of brain antibodies in patients with schizophrenia. British Medical Journal 1, 347348.Google Scholar