Summary
A standardized cell surface antibody assay was used to measure binding of circulating human immunoglobulins to rat or piglet splenocytes. In 100-fold diluted serum fractions, lymphocyte surface antibodies were detected in 30% of Type 1 (insulin-dependent) diabetic patients under 20 years of age but in none of 33 control subjects. Binding occurred with T and B lymphocytes, appeared unrelated to Fc receptors or protein glycosylation and was not attributable to insulin or albumin antibodies. At clinical onset of the disease, the lymphocyte surface antibodies belonged primarily to the IgM-class. Their presence was positively correlated to that of IgM-pituitary cell surface antibodies and their absorption by anterior pituitary cells occurred as well as by splenocytes. Lymphocyte surface antibodies remained present during the first years of insulin treatment. They were also detected in first degree relatives of lymphocyte surface antibody-positive patients. It is unlikely that IgM-lymphocyte surface antibodies mark the destructive process in the pancreatic B cell population. They may, instead, express a state of immune reactivity which precedes the formation of IgG-autoantibodies and therefore be associated with an event in the development of diseases such as Type 1 (insulin-dependent) diabetes.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
MacLaren NK, Huang S-W, Fogh J (1975) Antibody to cultured human insulinoma cells in insulin-dependent diabetes. Lancet I: 997–1000
Lernmark Å, Freedman ZR, Hofmann C, Rubenstein A, Steiner DF, Jackson RL, Winter RJ, Traisman HS (1978) Islet-cell-surface antibodies in juvenile diabetes mellitus. N Engl J Med 299: 375–380
Dobersen MJ, Scharff JE, Ginsberg-Fellner F, Notkins AL (1980) Cytotoxic autoantibodies to beta cells in the serum of patients with insulin-dependent diabetes mellitus. N Engl J Med 303: 1493–1498
Van De Winkel M, Smets G, Gepts W, Pipeleers D (1982) Islet cell surface antibodies from insulin-dependent diabetics bind specifically to pancreatic B cells. J Clin Invest 70: 41–49
Vercammen M, Gorus F, Foriers A, Segers O, Somers G, Van De Winkel M, Pipeleers D (1989) Cell surface antibodies in type 1 diabetic patients. I. Presence of immunoglobulins M which bind to rat pituitary cells. Diabetologia 32: 611–617
Dyrberg T, Nakhooda AF, Baekkeskov S, Lernmark Å, Poussier P, Marliss EB (1982) Islet cell surface antibodies and lymphocyte antibodies in the spontaneously diabetic BB Wistar rat. Diabetes 31: 278–281
Dyrberg T, Poussier P, Nakhooda F, Marliss EB, Lernmark Å (1984) Islet cell surface and lymphocyte antibodies often precede the spontaneous diabetes in the BB rat. Diabetologia 26: 159–165
Ozturk G, Terasaki PI (1979) Non-HLA lymphocyte cytotoxins in various diseases. Tissue Antigens 14: 52–58
Serjeantson S, Theophilus J, Zimmet P, Court J, Crossley JR, Elliott RB (1981) Lymphocytotoxic antibodies and histocompatibility antigens in juvenile-onset diabetes mellitus. Diabetes 30: 26–29
Charlesworth JA, Peake P, Campbell LV, Rumma J, Pussell BA, Howard N, Elder GJ (1986) Detection of lymphocytotoxic antibodies in relatives of patients with type I diabetes. Br Med J 292: 292–294
Vialettes B, Mercier P, De Micco Ph, Lassmann V, Vague Ph (1987) Cold reacting antilymphocyte antibodies in type I (insulin-dependent) diabetes. Diab Metab 13: 12–15
Terasaki PI, Mottironi VD, Barnett EV (1970) Cytotoxins in disease. Autocytotoxins in lupus. N Engl J Med 283: 724–728
Naito S, Mickey MR, Hirata A, Terasaki PI (1971) Autolymphocytotoxins following immunization by pregnancy, tranplantation and disease. Tissue Antigens 1: 219–228
DeHoratius RJ, Messner RP (1975) Lymphocytotoxic antibodies in family members of patients with systemic lupus erythematosus. J Clin Invest 55: 1254–1258
Park MS, Terasaki PI, Bernoco D (1977) Autoantibody against B lymphocytes. Lancet I: 465–467
Morimoto C, Rheinherz EL, Abe T, Homma M, Schlossman SF (1979) Characteristics of anti T cell antibodies in SLE: evidence for selective reactivity with normal suppressor cells defined by monoclonal antibodies. Clin Immunol Immunopathol 16: 474–484
Böyum A (1968) Isolation of mononuclear cells and granulocytes from human blood. Scand J Clin Lab Invest 21: 77–89
Oi VT, Glazer AN, Stryer L (1982) Fluorescent phycobiliprotein conjugates for analyses of cells and molecules. J Cell Biol 93: 981–986
Loken MR, Lanier LL (1984) Three-colour immunofluorescence analysis of Leu-antigens on human peripheral blood using two lasers on a fluorescence-activated cell sorting. Cytometry 5: 151–158
Pipeleers DG, Pipeleers-Marichal MA (1981) A method for the purification of single A, B and D cells and for the isolation of coupled cells from isolated rat islets. Diabetologia 20: 654–663
Simon M, Cuan J (1982) Hemoglobin A1c by isoelectric focusing. Clin Chem 28: 9–12
Piessens WF, Hoffman SL, Wadee AA, Piessens PW, Ratiwayanto S, Kurniawan L, Campbell JR, Marwoto HA, Laughlin LL (1985) Antibody-mediated killing of suppressor T lymphocytes as a possible cause of macroglobulinemia in the tropical splenomegaly syndrome. J Clin Invest 75: 1821–1827
Drell DW, Notkins AL (1987) Multiple immunological abnormalities in patients with Type 1 (insulin-dependent) diabetes mellitus. Diabetologia 30: 132–143
Huang SW, Lattos DB, Nelson DB, Reeb K, Hong R (1973) Antibody-associated lymphotoxin in acute infection. J Clin Invest 52: 1033–1040
Dighiero G, Lymberi P, Guilbert B, Ternynck T, Avrameas S (1986) Natural autoantibodies constitute a substantial part of normal circulating immunoglobulins. Ann NY Acad Sci 475: 135–145
Nakamura M, Burastero SE, Notkins AB, Casali P (1988) Human monoclonal rheumatoid factor-like antibodies from CD5 (Leu-1)+ cells are polyreactive. J Immunol 140: 4180–4186
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Segers, O., Gorus, F., Somers, G. et al. Cell surface antibodies in Type 1 (insulin-dependent) diabetic patients. Diabetologia 32, 618–623 (1989). https://doi.org/10.1007/BF00285337
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00285337