Abstract
We have found complement-dependent cytotoxic antibodies in the serum of 8 of 24 patients with insulin-dependent diabetes mellitus using a 51Cr cytotoxicity assay with monolayers of cloned rat islet cells (clones RINm 5F and RINm 14B). In contrast, complement-dependent cytotoxicity with 51Cr release greater than 24% was found with sera from 34 controls or from 5 patients with polyglandular failure without diabetes, and was present in only 1 serum our of 12 from patients with insulin-independent diabetes mellitus. The prevalence of antibodies appears to decrease with duration of insulin-dependent diabetes, and in one patient studied, cytotoxic antibodies were present at the time of diagnosis of diabetes. Cytotoxicity is independent of insulin synthesis, as evidenced by the linear correlation of cytotoxicity of sera for the insulin-producing clone RINm 5F and the somatostatin-producing clone RINm 14B. The present study identifies nonspecies-specific cytotoxic antibodies in the serum of patients with diabetes mellitus, and the assay used should facilitate studies of humoral immunity in the pathogenesis of diabetes mellitus.
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- 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. 1980 Mar 29;1(8170):668–672. [PubMed] [Google Scholar]
- Bottazzo G. F., Florin-Christensen A., Doniach D. Islet-cell antibodies in diabetes mellitus with autoimmune polyendocrine deficiencies. Lancet. 1974 Nov 30;2(7892):1279–1283. doi: 10.1016/s0140-6736(74)90140-8. [DOI] [PubMed] [Google Scholar]
- Dobersen M. J., Bell A. M., Jenson A. B., Notkins A. L., Ginsberg-Fellner F. Detection of antibodies to islet cells and insulin with paraffin-embedded pancreas as antigen. Lancet. 1979 Nov 17;2(8151):1078–1078. doi: 10.1016/s0140-6736(79)92477-2. [DOI] [PubMed] [Google Scholar]
- Eisenbarth G. S., Haynes B. F., Schroer J. A., Fauci A. S. Production of monoclonal antibodies reacting with peripheral blood mononuclear cell surface differentiation antigens. J Immunol. 1980 Mar;124(3):1237–1244. [PubMed] [Google Scholar]
- Eisenbarth G. S., Wilson P. W., Ward F., Buckley C., Lebovita H. The polyglandular failure syndrome: disease inheritance, HLA type, and immune function. Ann Intern Med. 1979 Oct;91(4):528–533. doi: 10.7326/0003-4819-91-4-528. [DOI] [PubMed] [Google Scholar]
- Gazdar A. F., Chick W. L., Oie H. K., Sims H. L., King D. L., Weir G. C., Lauris V. Continuous, clonal, insulin- and somatostatin-secreting cell lines established from a transplantable rat islet cell tumor. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3519–3523. doi: 10.1073/pnas.77.6.3519. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lernmark A., Freedman Z. R., Hofmann C., Rubenstein A. H., Steiner D. F., Jackson R. L., Winter R. J., Traisman H. S. Islet-cell-surface antibodies in juvenile diabetes mellitus. N Engl J Med. 1978 Aug 24;299(8):375–380. doi: 10.1056/NEJM197808242990802. [DOI] [PubMed] [Google Scholar]
- Maclaren N. K., Huang S. W., Fogh J. Antibody to cultured human insulinoma cells in insulin-dependent diabetes. Lancet. 1975 May 3;1(7914):997–1000. doi: 10.1016/s0140-6736(75)91945-5. [DOI] [PubMed] [Google Scholar]
- Reinherz E. L., Kung P. C., Goldstein G., Schlossman S. F. Separation of functional subsets of human T cells by a monoclonal antibody. Proc Natl Acad Sci U S A. 1979 Aug;76(8):4061–4065. doi: 10.1073/pnas.76.8.4061. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rittenhouse H. G., Oxender D. L., Pek S., Ar D. Complement-mediated cytotoxic effects on pancreatic islets with sera from diabetic patients. Diabetes. 1980 Apr;29(4):317–322. doi: 10.2337/diab.29.4.317. [DOI] [PubMed] [Google Scholar]