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. 1988 Jun;85(11):4015–4019. doi: 10.1073/pnas.85.11.4015

Anti-endothelial cell antibodies: detection and characterization in sera from patients with autoimmune hypoparathyroidism.

A Fattorossi 1, G D Aurbach 1, K Sakaguchi 1, A Cama 1, S J Marx 1, E A Streeten 1, L A Fitzpatrick 1, M L Brandi 1
PMCID: PMC280351  PMID: 3287382

Abstract

In a previous report, we described antibodies in autoimmune hypoparathyroidism (AHP) that are cytotoxic for cultured bovine parathyroid cells. In the present study, we show that sera from six AHP patients, but not from 26 patients with other autoimmune diseases or from 7 healthy subjects, react with bovine endothelial cells in culture (by flow cytometry and fluorescence microscopy) and in tissue sections (by immunohistology). We found uniformly that the immunoglobulin class reacting is IgM. Adsorption experiments showed that the antigenic determinants reacting with AHP sera were similar on bovine cultured endothelial cell membranes and in tissue sections of bovine parathyroid glands. The AHP sera also reacted with endothelial cells cultured from bovine adrenal medulla and pulmonary artery. Immunoblot analysis showed antibody binding to two major bands of 200 and 130 kDa solubilized from the membrane fraction of bovine parathyroid endothelial cells. Only one AHP serum consistently recognized endothelium-related structures on frozen sections of three different human parathyroid adenomas; two other sera reacted with one adenoma each; and three did not react with human adenomas. This indicates that human material is less suitable than bovine in detecting endothelium-related immune phenomena in AHP sera. The anti-endothelium IgM antibodies appear to be disease-specific but are not organ- or species-specific. The identification of endothelial cells as the target for antibodies in AHP raises the possibility that the endothelium subserves an important local function for endocrine epithelium.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Banerjee D. K., Ornberg R. L., Youdim M. B., Heldman E., Pollard H. B. Endothelial cells from bovine adrenal medulla develop capillary-like growth patterns in culture. Proc Natl Acad Sci U S A. 1985 Jul;82(14):4702–4706. doi: 10.1073/pnas.82.14.4702. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Betterle C., Caretto A., Zeviani M., Pedini B., Salviati C. Demonstration and characterization of anti-human mitochondria autoantibodies in idiopathic hypoparathyroidism and in other conditions. Clin Exp Immunol. 1985 Nov;62(2):353–360. [PMC free article] [PubMed] [Google Scholar]
  3. Blizzard R. M., Chee D., Davis W. The incidence of parathyroid and other antibodies in the sera of patients with idiopathic hypoparathyroidism. Clin Exp Immunol. 1966 Apr;1(2):119–128. [PMC free article] [PubMed] [Google Scholar]
  4. Bottazzo G. F., Todd I., Mirakian R., Belfiore A., Pujol-Borrell R. Organ-specific autoimmunity: a 1986 overview. Immunol Rev. 1986 Dec;94:137–169. doi: 10.1111/j.1600-065X.1986.tb01168.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brandi M. L., Aurbach G. D., Fattorossi A., Quarto R., Marx S. J., Fitzpatrick L. A. Antibodies cytotoxic to bovine parathyroid cells in autoimmune hypoparathyroidism. Proc Natl Acad Sci U S A. 1986 Nov;83(21):8366–8369. doi: 10.1073/pnas.83.21.8366. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Brandi M. L., Fitzpatrick L. A., Coon H. G., Aurbach G. D. Bovine parathyroid cells: cultures maintained for more than 140 population doublings. Proc Natl Acad Sci U S A. 1986 Mar;83(6):1709–1713. doi: 10.1073/pnas.83.6.1709. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Burckhardt P. Idiopathic hypoparathyroidism and autoimmunity. Horm Res. 1982;16(5):304–307. doi: 10.1159/000179518. [DOI] [PubMed] [Google Scholar]
  8. Cines D. B., Lyss A. P., Reeber M., Bina M., DeHoratius R. J. Presence of complement-fixing anti-endothelial cell antibodies in systemic lupus erythematosus. J Clin Invest. 1984 Mar;73(3):611–625. doi: 10.1172/JCI111251. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Fattorossi A., Dolei A., Pizzolo J. G., Cafolla A., Mandelli F., Dianzani F. Recombinant interferon alpha-2 modulates hairy cell phenotype "in vitro". J Biol Regul Homeost Agents. 1987 Apr-Jun;1(2):87–92. [PubMed] [Google Scholar]
  10. Fattorossi A., Moretti S., Palermo A., Santucci M., Bondi R., Giannotti B. Cell surface marker studies in a patient with cutaneous multilobated T-cell lymphoma. Br J Dermatol. 1985 Nov;113(5):587–596. doi: 10.1111/j.1365-2133.1985.tb02383.x. [DOI] [PubMed] [Google Scholar]
  11. Forsberg E. J., Feuerstein G., Shohami E., Pollard H. B. Adenosine triphosphate stimulates inositol phospholipid metabolism and prostacyclin formation in adrenal medullary endothelial cells by means of P2-purinergic receptors. Proc Natl Acad Sci U S A. 1987 Aug;84(16):5630–5634. doi: 10.1073/pnas.84.16.5630. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hashemi S., Smith C. D., Izaguirre C. A. Anti-endothelial cell antibodies: detection and characterization using a cellular enzyme-linked immunosorbent assay. J Lab Clin Med. 1987 Apr;109(4):434–440. [PubMed] [Google Scholar]
  13. Haspel M. V., Onodera T., Prabhakar B. S., Horita M., Suzuki H., Notkins A. L. Virus-induced autoimmunity: monoclonal antibodies that react with endocrine tissues. Science. 1983 Apr 15;220(4594):304–306. doi: 10.1126/science.6301002. [DOI] [PubMed] [Google Scholar]
  14. Hoyer L. W., De los Santos R. P., Hoyer J. R. Antihemophilic factor antigen. Localization in endothelial cells by immunofluorescent microscopy. J Clin Invest. 1973 Nov;52(11):2737–2744. doi: 10.1172/JCI107469. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Irvine W. J., Scarth L. Antibody to the oxyphil cells of the human parathyroid in idiopathic hypoparathyroidism. Clin Exp Immunol. 1969 May;4(5):505–510. [PMC free article] [PubMed] [Google Scholar]
  16. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  17. Lindqvist K. J., Osterland C. K. Human antibodies to vascular endothelium. Clin Exp Immunol. 1971 Dec;9(6):753–760. [PMC free article] [PubMed] [Google Scholar]
  18. Lupulescu A., Potorac E., Pop A., Heitmanek C., Merculiev E., Chisiu N., Oprisan R., Neacsu C. Experimental investigations on immunology of the parathyroid gland. Immunology. 1968 Apr;14(4):475–482. [PMC free article] [PubMed] [Google Scholar]
  19. Neufeld M., Maclaren N. K., Blizzard R. M. Two types of autoimmune Addison's disease associated with different polyglandular autoimmune (PGA) syndromes. Medicine (Baltimore) 1981 Sep;60(5):355–362. doi: 10.1097/00005792-198109000-00003. [DOI] [PubMed] [Google Scholar]
  20. Neufeld M., Maclaren N., Blizzard R. Autoimmune polyglandular syndromes. Pediatr Ann. 1980 Apr;9(4):154–162. [PubMed] [Google Scholar]
  21. Penning C. A., Cunningham J., French M. A., Harrison G., Rowell N. R., Hughes P. Antibody-dependent cellular cytotoxicity of human vascular endothelium in systemic sclerosis. Clin Exp Immunol. 1984 Sep;57(3):548–556. [PMC free article] [PubMed] [Google Scholar]
  22. Posillico J. T., Wortsman J., Srikanta S., Eisenbarth G. S., Mallette L. E., Brown E. M. Parathyroid cell surface autoantibodies that inhibit parathyroid hormone secretion from dispersed human parathyroid cells. J Bone Miner Res. 1986 Oct;1(5):475–483. doi: 10.1002/jbmr.5650010512. [DOI] [PubMed] [Google Scholar]
  23. Rossi P., Chini L., Fattorossi A., Gidlund M., Galli E., Laan K., Jondal M., Wigzell H. 1,25-Dihydroxyvitamin D3 and phorbol esters (TPA) may induce select in vitro differentiation pathways in the HL60 promyelocytic cell line. Clin Immunol Immunopathol. 1987 Sep;44(3):308–316. doi: 10.1016/0090-1229(87)90074-2. [DOI] [PubMed] [Google Scholar]
  24. Sakaguchi K., Santora A., Zimering M., Curcio F., Aurbach G. D., Brandi M. L. Functional epithelial cell line cloned from rat parathyroid glands. Proc Natl Acad Sci U S A. 1987 May;84(10):3269–3273. doi: 10.1073/pnas.84.10.3269. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Tan E. M., Pearson C. M. Rheumatic disease sera reactive with capillaries in the mouse kidney. Arthritis Rheum. 1972 Jan-Feb;15(1):23–28. doi: 10.1002/art.1780150104. [DOI] [PubMed] [Google Scholar]
  26. Thom D., Powell A. J., Lloyd C. W., Rees D. A. Rapid isolation of plasma membranes in high yield from cultured fibroblasts. Biochem J. 1977 Nov 15;168(2):187–194. doi: 10.1042/bj1680187. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]

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