Abstract
Islet cell surface antibodies (ICSA) were investigated by an ELISA method using a commercial kit in 146 subjects with and without islet cell antibodies (ICA): 28 with insulin-dependent diabetes mellitus (IDDM), 24 with noninsulin-dependent diabetes mellitus (NIDDM), 22 first-degree relatives (FDR) of IDDM patients, 31 organ-specific autoimmune patients (OSAP), 21 nonautoimmune hospitalized patients (NAP), and 20 ICA-negative normal controls. Furthermore, insulin autoantibodies (IAA) were evaluated in 87 of these subjects. ICSA were found in 11% of IDDM patients and in 14% of their FDR, in 4% of NIDDM patients, in 10% of OSAP, in 10% of NAP, and in 5% of normal controls. After absorption with rat liver powder, ICSA were detected in 7% of IDDM patients, in 5% of their FDR, in 4% of NIDDM, in 6% of OSAP, in 5% of NAP and in none of normal controls. ICSA were also detected in 4% of IAA-positive compared to 3% of IAA-negative sera. Neither correlation was found between ICSA and ICA in each group of subjects, nor between ICSA and IAA, suggesting that these autoantibodies recognize different pancreatic targets. Moreover, no significant difference was observed for ICSA prevalence in the various groups of patients studied when compared with normal controls. The prevalence of ICSA assessed by this ELISA method has been compared to that reported by other workers, who employed different techniques. We also discuss here the pathogenetic role and the clinical relevance of the most common markers of pancreatic autoimmunity. We conclude that the role of ICSA as possible indicators of β cell damage still remains to be evaluated in humans, and that the standardization of such antibodies is an essential prerequisite for understanding their actual prevalence and planning useful prospective investigations.
Similar content being viewed by others
References
Eisenbarth G.S. type I diabetes mellitus. A chronic autoimmune disease. N. Engl. J. Med. 314: 1360, 1986.
Drell D.W., Notkins A.L. Multiple immunological abnormalities in patients with Type I (insulin-dependent) diabetes mellitus. Diabetologia 30: 132, 1987.
MacLaren N.K., Huang S.W., Fog. G.H.J. Antibody to cultured human insulinoma cells in insulin-dependent diabetes. Lancet 1: 997, 1975.
Lernmark A., Freedman Z.R., Hofmann C., Rubenstein H., Steiner D.F., Jackson R.L., Winter R.G., Traisman H.S. Islet cell surface antibodies in juvenile diabetes mellitus. N. Engl. J. Med. 299: 375, 1978.
Pujol-Borrell R., Khoury E.L., Bottazzo G.F. Islet cell surface antibodies in Type I (insulin-dependent) diabetes mellitus: use of human fetal pancreas cultures as substrates. Diabetologia 22: 89, 1982.
Ginsberg-Fellner F., Witt M.E., Franklin B.H., Yagihashi S., Toguchi Y., Dobersen M.J., Rubinstein P., Notkins A.L. Trial of markers for identifying children at high risk of developing insulin-dependent diabetes mellitus. JAMA 254: 1469, 1985.
Toguchi Y., Ginsberg-Fellner F., Rubinstein P. Cytotoxic islet cell surface antibodies (ICSA) in patients with Type I diabetes and their first-degree relatives. Diabetes 34: 855, 1985.
Van de Winkel M., Smets G., Gepts W., Pipeleers D. Islet cell surface antibodies from insulin-dependent diabetics bind specifically to pancreatic B cells. J. Clin. Invest. 70: 41, 1982.
Dobersen M.J., Scharff J.E., Ginsberg-Fellner F., Notkins A.L. Cytotoxic autoantibodies to beta cells in the serum of patients with insulin-dependent diabetes mellitus. N. Engl. J. Med. 303: 1493, 1980.
Lernmark A., Hagglof B., Freedman Z., Irvine J., Ludvigsson J., Holmgren G. A prospective analysis of antibodies reacting with pancreatic islet cells in insulin-dependent diabetic children. Diabetologia 20: 471, 1981.
Bonifacio E., Lernmark A., Dawkins R.L. Serum exchange and use of dilutions have improved precision of measurement of islet cell antibodies. J. Immunol. Methods 106: 83, 1988.
Betterle C., Zanette F., Tiengo A., Trevisan A. Five year follow-up study of non-diabetics with islet cell antibodies. Lancet 1: 984, 1982.
Tan K., De Silva M., Moyle S., Pepperell L., Marks V. Validation of a rapid ELISA for the detection of islet cell surface antibodies. Diabetes 37(Suppl. 1): 204A, 1988 (Abstract).
Zanchetta R., Russo V., Presotto F., Magrin L., Pedini B., Betterle C. Detection of insulin autoantibodies using an ELISA technique in first-degree relatives of IDDM patients and in autoimmune patients. Diabetes Res. 6: 189, 1987.
Palmer J.P., Wilkin T.J., Kurtz A.B., Bonifacio E. The Third International Workshop on the Standardization of Insulin Autoantibody Measurement. Diabetologia 33: 60, 1990.
Dotta F., Colman P.G., Lombardi D., Scharp D.W., Andreani D., Pontieri G.M., Di Mario U., Lenti L., Eisenbarth G.S., Nayak R.C. Ganglioside expression in human pancreatic islets. Diabetes 38: 1478, 1989.
Kanatsuna T., Baekkeskov S., Lernmark A., Ludvigsson J. Immunoglobulin from insulin-dependent diabetic children inhibits glucose induced insulin release. Diabetes 32: 520, 1983.
Svenningsen A., Dyrberg T., Gerling I., Lernmark A., Mackay P., Rabinovitch A. Inhibition of insulin release after passive transfer of immunoglobulin from insulin-dependent diabetic children to mice. J. Clin. Endocrinol. Metab. 57: 1301, 1983.
Bottazzo G.F., Dean B.M., Gorsuch A.N., Cudworth A.G., Doniach D. Complement-fixing islet cell antibodies in Type I diabetes: possible monitors of active beta cell damage. Lancet 1: 668, 1982.
Betterle C., Presotto F., Pedini B., Moro L., Slack R.S., Zanette F., Zanchetta R. Islet cell and insulin autoantibodies in organ-specific autoimmune patients. Their behaviour and predictive value in the development of Type I (insulin-dependent) diabetes mellitus. A ten year follow-up study. Diabetologia 30: 292, 1987.
Tarn A.C., Dean B.M., Schwartz G., Thomas J.M., Ingram D., Bottazzo G.F., Gale E.A.M. Predicting insulin-dependent diabetes. Lancet 1: 845, 1988.
Dean B.M., Becker F., McNally J.M., Tarn A.C., Schwartz G., Gale E.A.M., Bottazzo G.F. Insulin autoantibodies in the prediabetic period: correlation with islet cell antibodies and development of diabetes. Diabetologia 29: 339, 1986.
Srikanta S., Ricker A.T., McCulloch D.K., Soeldner J.S., Eisenbarth G.S., Palmer J.P. Autoimmunity to insulin, beta cell dysfunction, and development of insulin-dependent diabetes mellitus Diabetes 35: 139, 1986.
Betterle C., Magrin L., Presotto F., Zanchetta R., Fenzi G., Chiovato L., Tonini G. Insulin autoantibodies as markers of potential diabetes mellitus. Lancet 2: 223, 1989.
Ziegler A.G., Ziegler R., Vardi P., Jackson R.A., Soeldner J.S., Eisenbarth G.S. Life-table analysis of progression to diabetes of anti-insulin autoantibody-positive relatives of individuals with Type I diabetes. Diabetes 38: 1320, 1989.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Betterle, C., Presotto, F., Magrin, L. et al. Islet cell surface antibodies by an ELISA method in diabetic and nondiabetic patients. J Endocrinol Invest 14, 293–297 (1991). https://doi.org/10.1007/BF03346816
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF03346816