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. 1995 Jul;96(1):201–206. doi: 10.1172/JCI118021

Expression of cryptantigen Th on paroxysmal nocturnal hemoglobinuria erythrocytes in association with a hemolytic exacerbation.

H Nakakuma 1, M Hidaka 1, S Nagakura 1, Y Nishimura 1, N Iwamoto 1, K Horikawa 1, T Kawaguchi 1, T Kagimoto 1, K Takatsuki 1
PMCID: PMC185189  PMID: 7542278

Abstract

Paroxysmal nocturnal hemoglobinuria (PNH) erythrocytes lack complement regulatory membrane proteins and are susceptible to complement. Although the critical role of complement in intravascular hemolysis in PNH is accepted, the precise mechanism of complement activation in vivo is unknown. Accordingly, in a PNH patient who was suffering from a hemolytic precipitation soon after a common cold-like upper respiratory infection, we analyzed the erythrocytes with lectins and by flow cytometry to detect membrane alteration that lead to complement activation. The lectin reactivity of erythrocytes showed the expression of cryptantigen Th. The patient serum at the time of the hemolysis induced the expression of Th on erythrocytes from PNH patients and from healthy volunteers in vitro, whereas neither the patient serum after recovery from the hemolysis nor blood type-matched control serum from healthy donor showed this activity. Moreover, autologous serum selectively hemolyzed Th+ PNH erythrocytes, but not Th- PNH erythrocytes, or Th+ control erythrocytes. Hemolysis was not observed either in complement-inactivated serum or in blood type-matched cord blood serum, which lacks natural antibodies to cryptantigens. These findings indicate that the immunoreaction of infection-induced Th with natural antibody on PNH erythrocytes is a trigger of the complement activation, leading to intravascular hemolysis.

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Selected References

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  1. Bird G. W. Lansteiner Award. Some aspects of serological specificity. Transfusion. 1990 Jun;30(5):390–400. doi: 10.1046/j.1537-2995.1990.30590296369.x. [DOI] [PubMed] [Google Scholar]
  2. Bird G. W., Wingham J., Beck M. L., Pierce S. R., Oates G. D., Pollock A. Th, a "new" form of erythrocyte polyagglutination. Lancet. 1978 Jun 3;1(8075):1215–1216. doi: 10.1016/s0140-6736(78)91013-9. [DOI] [PubMed] [Google Scholar]
  3. Buskila D., Levene C., Biran H., Levene N. A. Exposure of cryptantigens on erythrocytes in patients with breast cancer. Cancer. 1988 Jun 15;61(12):2455–2459. doi: 10.1002/1097-0142(19880615)61:12<2455::aid-cncr2820611212>3.0.co;2-g. [DOI] [PubMed] [Google Scholar]
  4. Feld L. G., Springate J. E., Darragh R., Fildes R. D. Pneumococcal pneumonia and hemolytic uremic syndrome. Pediatr Infect Dis J. 1987 Jul;6(7):693–695. doi: 10.1097/00006454-198707000-00019. [DOI] [PubMed] [Google Scholar]
  5. Herman J. H., Shirey R. S., Smith B., Kickler T. S., Ness P. M. Th activation in congenital hypoplastic anemia. Transfusion. 1987 May-Jun;27(3):253–256. doi: 10.1046/j.1537-2995.1987.27387235633.x. [DOI] [PubMed] [Google Scholar]
  6. Herman J. H., Whiteheart W., Shirey R. S., Johnson R. J., Kickler T. S., Ness P. M. Red cell Th activation: biochemical studies. Br J Haematol. 1987 Feb;65(2):205–209. doi: 10.1111/j.1365-2141.1987.tb02266.x. [DOI] [PubMed] [Google Scholar]
  7. Hidaka M., Nagakura S., Horikawa K., Kawaguchi T., Iwamoto N., Kagimoto T., Takatsuki K., Nakakuma H. Impaired glycosylation of glycosylphosphatidylinositol-anchor synthesis in paroxysmal nocturnal hemoglobinuria leucocytes. Biochem Biophys Res Commun. 1993 Mar 15;191(2):571–579. doi: 10.1006/bbrc.1993.1256. [DOI] [PubMed] [Google Scholar]
  8. Horikawa K., Nakakuma H., Nagakura S., Kawakita M., Kagimoto T., Iwamori M., Nagai Y., Abe T., Takatsuki K. Hemolysis of human erythrocytes is a new bioactivity of gangliosides. J Exp Med. 1991 Dec 1;174(6):1385–1391. doi: 10.1084/jem.174.6.1385. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hysell J. K., Hysell J. W., Nichols M. E., Leonardi R. G., Marsh W. L. In vivo and in vitro activation of T-antigen receptors on leukocytes and platelets. Vox Sang. 1976;31(1 Suppl):9–15. [PubMed] [Google Scholar]
  10. Janvier D., Guignier F., Reviron M., Benbunan M. Concomitant exposure of Tn and Th cryptantigens on the red cells of a patient with myelodysplasia. Vox Sang. 1991;61(2):142–143. doi: 10.1111/j.1423-0410.1991.tb00263.x. [DOI] [PubMed] [Google Scholar]
  11. Judd W. J. Review: polyagglutination. Immunohematology. 1992;8(3):58–69. [PubMed] [Google Scholar]
  12. Levene C., Levene N. A., Buskila D., Manny N. Red cell polyagglutination. Transfus Med Rev. 1988 Sep;2(3):176–185. [PubMed] [Google Scholar]
  13. Levene N. A., Levene C., Gekker K., Sigler E., Merhav H., Berrebi A. Th polyagglutination with fatal outcome in a patient with massive intravascular hemolysis and perforated tumor of colon. Am J Hematol. 1990 Oct;35(2):127–128. doi: 10.1002/ajh.2830350213. [DOI] [PubMed] [Google Scholar]
  14. Miyata T., Yamada N., Iida Y., Nishimura J., Takeda J., Kitani T., Kinoshita T. Abnormalities of PIG-A transcripts in granulocytes from patients with paroxysmal nocturnal hemoglobinuria. N Engl J Med. 1994 Jan 27;330(4):249–255. doi: 10.1056/NEJM199401273300404. [DOI] [PubMed] [Google Scholar]
  15. Nagakura S., Kawaguchi T., Horikawa K., Hidaka M., Iwamoto N., Takatsuki K., Nakakuma H., Kagimoto T. A deficiency in CDw52 (CAMPATH-1 antigen) of paroxysmal nocturnal hemoglobinuria lymphocytes. Blood. 1993 Dec 15;82(12):3790–3792. [PubMed] [Google Scholar]
  16. Nakakuma H., Kawaguchi T., Horikawa K., Hidaka M., Yonemura Y., Kawakita M., Kagimoto T., Iwamori M., Nagai Y., Takatsuki K. Altered expression of gangliosides in erythrocytes of paroxysmal nocturnal hemoglobinuria. J Clin Invest. 1990 May;85(5):1456–1461. doi: 10.1172/JCI114591. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Novak R. W. The pathobiology of red cell cryptantigen exposure. Pediatr Pathol. 1990;10(6):867–875. doi: 10.3109/15513819009064722. [DOI] [PubMed] [Google Scholar]
  18. Okubo Y., Seno T., Yamaguchi H. A persistent type of erythrocyte polyagglutinability Th. Transfusion. 1984 May-Jun;24(3):277–278. doi: 10.1046/j.1537-2995.1984.24384225043.x. [DOI] [PubMed] [Google Scholar]
  19. Parker C. J., Soldato C. M., Rosse W. F. Abnormality of glycophorin-alpha on paroxysmal nocturnal hemoglobinuria erythrocytes. J Clin Invest. 1984 Apr;73(4):1130–1143. doi: 10.1172/JCI111299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Rosse W. F. Evolution of clinical understanding: paroxysmal nocturnal hemoglobinuria as a paradigm. Am J Hematol. 1993 Jan;42(1):122–126. doi: 10.1002/ajh.2830420124. [DOI] [PubMed] [Google Scholar]
  21. Rosse W. F. The glycolipid anchor of membrane surface proteins. Semin Hematol. 1993 Jul;30(3):219–231. [PubMed] [Google Scholar]
  22. Rotoli B., Luzzatto L. Paroxysmal nocturnal hemoglobinuria. Semin Hematol. 1989 Jul;26(3):201–207. [PubMed] [Google Scholar]
  23. Sondag-Thull D., Levene N. A., Levene C., Manny N., Liew Y. W., Bird G. W., Schechter Y., François-Gérard C., Huet M., Blanchard D. Characterization of a neuraminidase from Corynebacterium aquaticum responsible for Th polyagglutination. Vox Sang. 1989;57(3):193–198. doi: 10.1111/j.1423-0410.1989.tb00822.x. [DOI] [PubMed] [Google Scholar]
  24. Thurnher M., Fehr J., Berger E. G. Differences in the regulation of specific glycosylation in the pathogenesis of paroxysmal nocturnal hemoglobinuria and the Tn-syndrome. Exp Hematol. 1994 Mar;22(3):267–271. [PubMed] [Google Scholar]
  25. Yamashina M., Ueda E., Kinoshita T., Takami T., Ojima A., Ono H., Tanaka H., Kondo N., Orii T., Okada N. Inherited complete deficiency of 20-kilodalton homologous restriction factor (CD59) as a cause of paroxysmal nocturnal hemoglobinuria. N Engl J Med. 1990 Oct 25;323(17):1184–1189. doi: 10.1056/NEJM199010253231707. [DOI] [PubMed] [Google Scholar]

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