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. 1980 Sep;66(3):517–522. doi: 10.1172/JCI109883

Erythropoietic protoporphyria. Photoactivation of the complement system.

I Gigli, A A Schothorst, N A Soter, M A Pathak
PMCID: PMC371680  PMID: 7400327

Abstract

The complement system was analysed in 14 asymptomatic patients with erythropoietic protoporphyria. In the majority of the sera studied the levels of complement components C1, C4, C2, and C3 were within the normal range. Upon ultraviolet light (330--460 nm) irradiation of the serum samples in vitro, a marked decrease in total hemolytic activity accompanied by reduction of C1, C4, C2, and C3 levels was observed. The loss of total hemolytic activity can be directly correlated with the levels of protoporphyrin (PP) and similar changes can be obtained in normal serum upon addition of PP followedf by ultraviolet light irradiation. It is postulated that after irradiation the excited PP develops the capacity to activate the complement sequence with the production of cleavage products, which may contribute to the skin changes observed in these patients upon sun exposure.

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Selected References

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  1. Aeschbach R., Amadò R., Neukom H. Formation of dityrosine cross-links in proteins by oxidation of tyrosine residues. Biochim Biophys Acta. 1976 Aug 9;439(2):292–301. doi: 10.1016/0005-2795(76)90064-7. [DOI] [PubMed] [Google Scholar]
  2. Allison A. C., Magnus I. A., Young M. R. Role of lysosomes and of cell membranes in photosensitization. Nature. 1966 Feb 26;209(5026):874–878. doi: 10.1038/209874a0. [DOI] [PubMed] [Google Scholar]
  3. Baart de la Faille-Kuyp, Cormane R. H. The occurrence of certain serum factors in the dermal-epidermal junction and vessel walls of the skin in lupus erythematosus and other (skin) diseases. Acta Derm Venereol. 1968;48(6):578–588. [PubMed] [Google Scholar]
  4. Bonkowsky H. L., Bloomer J. R., Ebert P. S., Mahoney M. J. Heme synthetase deficiency in human protoporphyria. Demonstration of the defect in liver and cultured skin fibroblasts. J Clin Invest. 1975 Nov;56(5):1139–1148. doi: 10.1172/JCI108189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Borsos T., Rapp H. J. Immune hemolysis: a simplified method for the preparation of EAC'4 with guinea pig or with human complement. J Immunol. 1967 Aug;99(2):263–268. [PubMed] [Google Scholar]
  6. Cripps D. J., MacEachern W. N. Hepatic and erythropoietic protoporphyria. Delta-aminolevulinic acid synthetase, fluorescence, and microfluorospectrophotometric study. Arch Pathol. 1971 Jun;91(6):497–505. [PubMed] [Google Scholar]
  7. DeLeo V. A., Poh-Fitzpatrick M., Mathews-Roth M., Harber L. C. Erythropoietic protoporphyria. 10 years experience. Am J Med. 1976 Jan;60(1):8–22. doi: 10.1016/0002-9343(76)90528-3. [DOI] [PubMed] [Google Scholar]
  8. Dubbelman T. M., de Bruijne A. W., van Steveninck J. Photodynamic effects of protoporphyrin on red blood cell deformability. Biochem Biophys Res Commun. 1977 Aug 8;77(3):811–817. doi: 10.1016/s0006-291x(77)80050-8. [DOI] [PubMed] [Google Scholar]
  9. Dubbelman T. M., de Goeij A. F., van Steveninck J. Photodynamic effects of protoporphyrin on human erythrocytes. Nature of the cross-linking of membrane proteins. Biochim Biophys Acta. 1978 Aug 4;511(2):141–151. doi: 10.1016/0005-2736(78)90309-7. [DOI] [PubMed] [Google Scholar]
  10. Epstein J. H., Tuffanelli D. L., Epstein W. L. Cutaneous changes in the porphyrias. A microscopic study. Arch Dermatol. 1973 May;107(5):689–698. [PubMed] [Google Scholar]
  11. Everett M. A., Yeargers E., Sayre R. M., Olson R. L. Penetration of epidermis by ultraviolet rays. Photochem Photobiol. 1966 Jul;5(7):533–542. doi: 10.1111/j.1751-1097.1966.tb09843.x. [DOI] [PubMed] [Google Scholar]
  12. Goldstein B. D., Harber L. C. Erythropoietic protoporphyria: lipid peroxidation and red cell membrane damage associated with photohemolysis. J Clin Invest. 1972 Apr;51(4):892–902. doi: 10.1172/JCI106884. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. HARBER L. C., FLEISCHER A. S., BAER R. L. ERYTHROPOIETIC PROTOPORPHYRIA AND PHOTOHEMOLYSIS. JAMA. 1964 Jul 20;189:191–194. doi: 10.1001/jama.1964.03070030013004. [DOI] [PubMed] [Google Scholar]
  14. KENT J. F., FIFE E. H., Jr Precise standardization of reagents for complement fixation. Am J Trop Med Hyg. 1963 Jan;12:103–116. doi: 10.4269/ajtmh.1963.12.103. [DOI] [PubMed] [Google Scholar]
  15. MAGNUS I. A., JARRETT A., PRANKERD T. A., RIMINGTON C. Erythropoietic protoporphyria. A new porphyria syndrome with solar urticaria due to protoporphyrinaemia. Lancet. 1961 Aug 26;2(7200):448–451. doi: 10.1016/s0140-6736(61)92427-8. [DOI] [PubMed] [Google Scholar]
  16. Nelson R. A., Jr, Jensen J., Gigli I., Tamura N. Methods for the separation, purification and measurement of nine components of hemolytic complement in guinea-pig serum. Immunochemistry. 1966 Mar;3(2):111–135. doi: 10.1016/0019-2791(66)90292-8. [DOI] [PubMed] [Google Scholar]
  17. Peterka E. S., Fusaro R. M., Goltz R. W. Erythropoietic protoporphyria. II. Histological and histochemical studies of cutaneous lesions. Arch Dermatol. 1965 Oct;92(4):357–361. doi: 10.1001/archderm.92.4.357. [DOI] [PubMed] [Google Scholar]
  18. Reed W. B., Wuepper K. D., Epstein J. H., Redeker A., Simonson R. J., McKusick V. A. Erythropoietic protoporphyria. A clinical and genetic study. JAMA. 1970 Nov 9;214(6):1060–1066. doi: 10.1001/jama.214.6.1060. [DOI] [PubMed] [Google Scholar]
  19. Ruddy S., Austen K. F. A stoichiometric assay for the fourth component of complement in whole human serum using EAC'la-gp and functionally pure human second component. J Immunol. 1967 Dec;99(6):1162–1172. [PubMed] [Google Scholar]
  20. Ruddy S., Everson L. K., Schur P. H., Austen K. F. Hemolytic assay of the ninth complement complement component: elevation and depletion in rheumatic diseases. J Exp Med. 1971 Sep 1;134(3 Pt 2):259s–275s. [PubMed] [Google Scholar]
  21. Ryan E. A. Histochemistry of the skin in erythropoietic protoporphyria. Br J Dermatol. 1966 Oct;78(10):501–518. doi: 10.1111/j.1365-2133.1966.tb12138.x. [DOI] [PubMed] [Google Scholar]
  22. Ryan E. A., Madill G. T. Electron microscopy of the skin in erythropoietic protoporphyria. Br J Dermatol. 1968 Sep;80(9):561–570. doi: 10.1111/j.1365-2133.1968.tb12354.x. [DOI] [PubMed] [Google Scholar]
  23. SCHEIDEGGER J. J. Une micro-méthode de l'immuno-electrophorèse. Int Arch Allergy Appl Immunol. 1955;7(2):103–110. [PubMed] [Google Scholar]
  24. Sasai Y. Erythropoietic protoporphyria. Histochemical study of hyaline material. Acta Derm Venereol. 1973;53(3):179–184. [PubMed] [Google Scholar]
  25. Schothorst A. A., van Steveninck J., Went L. N., Suurmond D. Photodynamic damage of the erythrocyte membrane caused by protoporphyrin in protoporphyria and in normal red blood cells. Clin Chim Acta. 1972 Jun;39(1):161–170. doi: 10.1016/0009-8981(72)90312-9. [DOI] [PubMed] [Google Scholar]
  26. Seery V. L., Muller-Eberhard U. Binding of porphyrins to rabbit hemopexin and albumin. J Biol Chem. 1973 Jun 10;248(11):3796–3800. [PubMed] [Google Scholar]
  27. Soter N. A., Austen K. F., Gigli I. Inhibition by epsilon-aminocaproic acid of the activation of the first component of the complement system. J Immunol. 1975 Mar;114(3):928–932. [PubMed] [Google Scholar]

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