Abstract
The capsular polysaccharide of Hemophilus influenzae type b, polyribosyl ribitol phosphate (PRP), is released from growing organisms during human infection and can be found in body fluids. It binds to untreated erythrocytes. Many patients with invasive infections with this organism develop significant hemolysis, but the mechanism has been unclear. We have found that PRP binds to human erythrocytes in vivo. PRP-coated erythrocytes have a shortened circulation time in mice, but do not lyse spontaneously or fix complement. PRP-coated erythrocytes exposed to antiserum to H. influenzae type b are undamaged in the absence of complement, but are rapidly and effectively lysed in the presence of an intact complement system both in vitro and in vivo in mice. PRP-coated red cells are taken up by liver and spleen. Antiserum to PRP increases hepatic uptake of PRP-coated red cells more than splenic, and appears to induce intravascular, complement-mediated hemolysis, as well as extravascular hemolysis. Patients with invasive infection develop hemolysis when circulating PRP and antibody to PRP are present simultaneously. PRP can sometimes be detected on patient erythrocytes when free PRP is present in serum, but this is an inconsistent finding. The hemolytic anemia that occurs during human infection with H. influenzae type b may be due to absorption of PRP to red cells and immune destruction of sensitized erythrocytes. The process requires an intact complement system; both complement-mediated cell lysis and extravascular hemolysis contribute to red cell destruction.
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- Abdalla S., Weatherall D. J. The direct antiglobulin test in P. falciparum malaria. Br J Haematol. 1982 Jul;51(3):415–425. doi: 10.1111/j.1365-2141.1982.tb02797.x. [DOI] [PubMed] [Google Scholar]
- Abdalla S., Weatherall D. J., Wickramasinghe S. N., Hughes M. The anaemia of P. falciparum malaria. Br J Haematol. 1980 Oct;46(2):171–183. doi: 10.1111/j.1365-2141.1980.tb05956.x. [DOI] [PubMed] [Google Scholar]
- Amole B. O., Clarkson A. B., Jr, Shear H. L. Pathogenesis of anemia in Trypanosoma brucei-infected mice. Infect Immun. 1982 Jun;36(3):1060–1068. doi: 10.1128/iai.36.3.1060-1068.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Anderson P., Insel R. A. A polysaccharide-protein complex from Haemophilus influenzae type b. I. Activity in weanling rabbits and human T lymphocytes. J Infect Dis. 1981 Dec;144(6):509–520. doi: 10.1093/infdis/144.6.509. [DOI] [PubMed] [Google Scholar]
- Anderson P., Johnston R. B., Jr, Smith D. H. Human serum activities against Hemophilus influenzae, type b. J Clin Invest. 1972 Jan;51(1):31–38. doi: 10.1172/JCI106793. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Anderson P., Peter G., Johnston R. B., Jr, Wetterlow L. H., Smith D. H. Immunization of humans with polyribophosphate, the capsular antigen of Hemophilus influenzae, type b. J Clin Invest. 1972 Jan;51(1):39–44. doi: 10.1172/JCI106794. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Anderson P., Pitt J., Smith D. H. Synthesis and release of polyribophosphate by Haemophilus influenzae type b in vitro. Infect Immun. 1976 Feb;13(2):581–589. doi: 10.1128/iai.13.2.581-589.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Anderson P., Smith D. H. Isolation of the capsular polysaccharide from culture supernatant of Haemophilus influenzae type b. Infect Immun. 1977 Feb;15(2):472–477. doi: 10.1128/iai.15.2.472-477.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Atkinson J. P., Frank M. M. Studies on the in vivo effects of antibody. Interaction of IgM antibody and complement in the immune clearance and destruction of erythrocytes in man. J Clin Invest. 1974 Aug;54(2):339–348. doi: 10.1172/JCI107769. [DOI] [PMC free article] [PubMed] [Google Scholar]
- BOYDEN S. V. Fixation of bacterial products by erythrocytes in vivo and by Leucocytes. Nature. 1953 Feb 28;171(4348):402–403. doi: 10.1038/171402a0. [DOI] [PubMed] [Google Scholar]
- BOYDEN S. V. The adsorption of proteins on erythrocytes treated with tannic acid and subsequent hemagglutination by antiprotein sera. J Exp Med. 1951 Feb;93(2):107–120. doi: 10.1084/jem.93.2.107. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Böyum A. Isolation of mononuclear cells and granulocytes from human blood. Isolation of monuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g. Scand J Clin Lab Invest Suppl. 1968;97:77–89. [PubMed] [Google Scholar]
- CHI-YEN CHU D., HOYT R. E. Reactions of T Vi and Ballerup Vi haptenes with antisera against Vi-coated erythrocytes. J Hyg (Lond) 1954 Mar;52(1):100–104. doi: 10.1017/s0022172400027297. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Corrall C. J., Winkelstein J. A., Moxon E. R. Participation of complement in host defense against encapsulated Haemophilus influenzae types a, c, and d. Infect Immun. 1982 Mar;35(3):759–763. doi: 10.1128/iai.35.3.759-763.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Davis C. A., Shurin S. B., Pate K., Congeni B. L. Neutrophil function in a patient with meningococcal meningitis and C7 deficiency. Am J Dis Child. 1983 Apr;137(4):404–406. doi: 10.1001/archpedi.1983.02140300082026. [DOI] [PubMed] [Google Scholar]
- Facer C. A., Bray R. S., Brown J. Direct Coombs antiglobulin reactions in Gambian children with Plasmodium falciparum malaria. I. Incidence and class specificity. Clin Exp Immunol. 1979 Jan;35(1):119–127. [PMC free article] [PubMed] [Google Scholar]
- Facer C. A. Direct Coombs antiglobulin reactions in Gambian children with Plasmodium falciparum malaria. II. Specificity of erythrocyte-bound IgG. Clin Exp Immunol. 1980 Feb;39(2):279–288. [PMC free article] [PubMed] [Google Scholar]
- GUEST G. M., BROWN E. W. Erythrocytes and hemoglobin of the blood in infancy and childhood. III. Factors in variability, statistical studies. AMA J Dis Child. 1957 May;93(5):486–509. doi: 10.1001/archpedi.1957.02060040488002. [DOI] [PubMed] [Google Scholar]
- Haneberg B., Matre R., Winsnes R., Dalen A., Vogt H., Finne P. H. Acute hemolytic anemia related to diphtheria-pertussis-tetanus vaccination. Acta Paediatr Scand. 1978 May;67(3):345–350. doi: 10.1111/j.1651-2227.1978.tb16332.x. [DOI] [PubMed] [Google Scholar]
- Kaplan K. M., Oski F. A. Anemia with Haemophilus influenzae meningitis. Pediatrics. 1980 Jun;65(6):1101–1104. [PubMed] [Google Scholar]
- MARGOLIS J. Haemolytic anaemia in haemophilus influenzae meningitis treated with specific rabbit serum. Med J Aust. 1955 Jun 18;42(1 25):912–920. [PubMed] [Google Scholar]
- Mendes N. F., Tolnai M. E., Silveira N. P., Gilbertsen R. B., Metzgar R. S. Technical aspects of the rosette tests used to detect human complement receptor (B) and sheep erythrocyte-binding (T) lymphocytes. J Immunol. 1973 Sep;111(3):860–867. [PubMed] [Google Scholar]
- NETER E. Bacterial hemagglutination and hemolysis. Bacteriol Rev. 1956 Sep;20(3):166–188. doi: 10.1128/br.20.3.166-188.1956. [DOI] [PMC free article] [PubMed] [Google Scholar]
- NETER E., WESTPHAL O., LUDERITZ O., GORZYNSKI E. A., EICHENBERGER E. Studies of enterobacterial lipopolysaccharides; effects of heat and chemicals on erythrocyte-modifying, antigenic, toxic and pyrogenic properties. J Immunol. 1956 May;76(5):377–385. [PubMed] [Google Scholar]
- NIH conference. Pathophysiology of immune hemolytic anemia. Ann Intern Med. 1977 Aug;87(2):210–222. doi: 10.7326/0003-4819-87-2-210. [DOI] [PubMed] [Google Scholar]
- Newman R. B., Stevens R. W., Gaafar H. A. Latex agglutination test for the diagnosis of Haemophilus influenzae meningitis. J Lab Clin Med. 1970 Jul;76(1):107–113. [PubMed] [Google Scholar]
- O'Brien R. T., Santos J. I., Glasgow L., Landaw S. A. Pathophysiologic basis for anemia associated with Haemophilus influenzae meningitis: preliminary observations. J Pediatr. 1981 Jun;98(6):928–931. doi: 10.1016/s0022-3476(81)80591-4. [DOI] [PubMed] [Google Scholar]
- O'Reilly R. J., Anderson P., Ingram D. L., Peter G., Smith D. H. Circulating polyribophosphate in Hemophilus influenzae, type b meningitis. Correlation with clinical course and antibody response. J Clin Invest. 1975 Oct;56(4):1012–1022. doi: 10.1172/JCI108148. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Peltola H., Käyhty H., Virtanen M., Mäkelä P. H. Prevention of Hemophilus influenzae type b bacteremic infections with the capsular polysaccharide vaccine. N Engl J Med. 1984 Jun 14;310(24):1561–1566. doi: 10.1056/NEJM198406143102404. [DOI] [PubMed] [Google Scholar]
- Quinn P. H., Crosson F. J., Jr, Winkelstein J. A., Moxon E. R. Activation of the alternative complement pathway by Haemophilus influenzae type B. Infect Immun. 1977 Apr;16(1):400–402. doi: 10.1128/iai.16.1.400-402.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Robbins J. B., Parke J. C., Jr, Schneerson R., Whisnant J. K. Quantitative measurement of "natural" and immunization-induced Haemophilus influenzae type b capsular polysaccharide antibodies. Pediatr Res. 1973 Mar;7(3):103–110. doi: 10.1203/00006450-197303000-00001. [DOI] [PubMed] [Google Scholar]
- SCHIAVONE D. J., RUBBO S. D. Anaemia associated with Haemophilus influenzae meningitis. Lancet. 1953 Oct 3;265(6788):696–698. doi: 10.1016/s0140-6736(53)90421-8. [DOI] [PubMed] [Google Scholar]
- SHUMWAY C. N., POLLOCK D. THE EFFECT OF A PNEUMOCOCCAL PRODUCT UPON RABBIT ERYTHROCYTES IN VITRO AND IN VIVO. J Lab Clin Med. 1965 Mar;65:432–439. [PubMed] [Google Scholar]
- Schreiber A. D., Frank M. M. Role of antibody and complement in the immune clearance and destruction of erythrocytes. I. In vivo effects of IgG and IgM complement-fixing sites. J Clin Invest. 1972 Mar;51(3):575–582. doi: 10.1172/JCI106846. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sills R. H., Caserta M. T., Landaw S. A. Decreased erythrocyte deformability in the anemia of bacterial meningitis. J Pediatr. 1982 Sep;101(3):395–398. doi: 10.1016/s0022-3476(82)80066-8. [DOI] [PubMed] [Google Scholar]
- Smith D. H., Peter G., Ingram D. L., Harding A. L., Anderson P. Responses of children immunized with the capsular polysaccharide of Hemophilus influenzae, type b. Pediatrics. 1973 Nov;52(5):637–644. [PubMed] [Google Scholar]
- Stossel T. P., Mason R. J., Hartwig J., Vaughan M. Quantitative studies of phagocytosis by polymorphonuclear leukocytes: use of emulsions to measure the initial rate of phagocytosis. J Clin Invest. 1972 Mar;51(3):615–624. doi: 10.1172/JCI106851. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sutton A., Schneerson R., Kendall-Morris S., Robbins J. B. Differential complement resistance mediates virulence of Haemophilus influenzae type b. Infect Immun. 1982 Jan;35(1):95–104. doi: 10.1128/iai.35.1.95-104.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tarr P. I., Hosea S. W., Brown E. J., Schneerson R., Sutton A., Frank M. M. The requirement of specific anticapsular IgG for killing of Haemophilus influenzae by the alternative pathway of complement activation. J Immunol. 1982 Apr;128(4):1772–1775. [PubMed] [Google Scholar]
- Warren J. R., Harris A. S., Wallas C. H. Transformation of human erythrocyte shape by endotoxic lipopolysaccharide. Infect Immun. 1983 Jan;39(1):431–434. doi: 10.1128/iai.39.1.431-434.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weller P. F., Smith A. L., Anderson P., Smith D. H. The role of encapsulation and host age in the clearance of Haemophilus influenzae bacteremia. J Infect Dis. 1977 Jan;135(1):34–41. doi: 10.1093/infdis/135.1.34. [DOI] [PubMed] [Google Scholar]
- Woodruff A. W., Ansdell V. E., Pettitt L. E. Cause of anaemia in malaria. Lancet. 1979 May 19;1(8125):1055–1057. doi: 10.1016/s0140-6736(79)92952-0. [DOI] [PubMed] [Google Scholar]
- Woodruff A. W., Topley E., Knight R., Downie C. G. The anaemia of kala-azar. Br J Haematol. 1972 Mar;22(3):319–329. doi: 10.1111/j.1365-2141.1972.tb05678.x. [DOI] [PubMed] [Google Scholar]
- Woodruff A. W., Ziegler J. L., Hathaway A., Gwata T. Anaemia in African trypanosomiasis and 'big spleen disease' in Uganda. Trans R Soc Trop Med Hyg. 1973;67(3):329–337. doi: 10.1016/0035-9203(73)90109-0. [DOI] [PubMed] [Google Scholar]
- YOUNG V. M., GILLEM H. C., AKEROYD J. H. Sensitization of infant red cells by bacterial polysaccharides of Escherichia coli during enteritis. J Pediatr. 1962 Feb;60:172–176. doi: 10.1016/s0022-3476(62)80032-8. [DOI] [PubMed] [Google Scholar]