Altered expression of gangliosides in erythrocytes of paroxysmal nocturnal hemoglobinuria.

Nakakuma, Hideki; Kawaguchi, Tatsuya; Horikawa, Kiyoshi; Hidaka, Masaaki; Yonemura, Yuji; Kawakita, Makoto; Kagimoto, Tadashi; Iwamori, Masao; Nagai, Yoshitaka; Takatsuki, Kiyoshi

doi:10.1172/jci114591

Cited by 14 publications

(13 citation statements)

References 39 publications

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“…Nevertheless, the basic defect in this disorder may not lie in the assembly of the phosphatidylinositol linkage, because these proteins appear to be present on precursor bone marrow cells and are lost during maturation (315,368). In addition, proteins other than those bearing the phosphatidylinositol linkage are also absent from PNH cells (242). Last, the pattern of glycosphingolipids present in erythrocyte cell membranes is altered in PNH cells, the biggest difference being the loss of a sialosylparagloboside.…”

Section: Deficiencies Of Membrane Complement Proteinsmentioning

confidence: 99%

“…Last, the pattern of glycosphingolipids present in erythrocyte cell membranes is altered in PNH cells, the biggest difference being the loss of a sialosylparagloboside. Thus, both glycoproteins and glycolipids are affected in this disorder, which suggests that the basic defect involves altered metabolism of membrane glycoconjugates (242).…”

Section: Deficiencies Of Membrane Complement Proteinsmentioning

confidence: 99%

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Infectious diseases associated with complement deficiencies

1991

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The complement system consists of both plasma and membrane proteins. The former influence the inflammatory response, immune modulation, and host defense. The latter are complement receptors, which mediate the cellular effects of complement activation, and regulatory proteins, which protect host cells from complement-mediated injury. Complement activation occurs via either the classical or the alternative pathway, which converge at the level of C3 and share a sequence of terminal components. Four aspects of the complement cascade are critical to its function and regulation: (i) activation of the classical pathway, (ii) activation of the alternative pathway, (iii) C3 convertase formation and C3 deposition, and (iv) membrane attack complex assembly and insertion. In general, mechanisms evolved by pathogenic microbes to resist the effects of complement are targeted to these four steps. Because individual complement proteins subserve unique functional activities and are activated in a sequential manner, complement deficiency states are associated with predictable defects in complement-dependent functions. These deficiency states can be grouped by which of the above four mechanisms they disrupt. They are distinguished by unique epidemiologic, clinical, and microbiologic features and are most prevalent in patients with certain rheumatologic and infectious diseases. Ethnic background and the incidence of infection are important cofactors determining this prevalence. Although complement undoubtedly plays a role in host defense against many microbial pathogens, it appears most important in protection against encapsulated bacteria, especially Neisseria meningitidis but also Streptococcus pneumoniae, Haemophilus influenzae, and, to a lesser extent, Neisseria gonorrhoeae. The availability of effective polysaccharide vaccines and antibiotics provides an immunologic and chemotherapeutic rationale for preventing and treating infection in patients with these deficiencies.

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Section: Deficiencies Of Membrane Complement Proteinsmentioning

confidence: 99%

Section: Deficiencies Of Membrane Complement Proteinsmentioning

confidence: 99%

Infectious diseases associated with complement deficiencies

1991

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“…(b) Although Th+ platelets were not demonstrable in our patient, the role played by cryptantigens on platelets could be of interest in the development of thrombosis which partly shares the causes with episodic hemolysis in PNH (4). Further, the more rapid appearance of cryptantigens on PNH erythrocytes than on control cells in the treatment with sialidase may reflect the increased susceptibility of PNH cells to the enzyme due to structural changes in erythrocyte membrane (5,19,29) representing the hemolytic diathesis of PNH cells.…”

Section: Discussionmentioning

confidence: 99%

“…Taken together with the metabolic alteration of sugar chains of gangliosides (16,29) and glycosylphosphatidylinositol anchor (5), the appearance of cryptantigens suggests that the structural modification of membrane carbohydrates plays a critical role in the pathogenesis of PNH.…”

Section: Discussionmentioning

confidence: 99%

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

Nakakuma

Hidaka²,

Nagakura³

et al. 1995

J. Clin. Invest.

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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 coldlike 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. (J. Clin. Invest. 1995. 96:201-206.)

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“…The C3d deposition could also be affected by the altered expression of erythrocyte glycolipids. 9 In general, infection amplifies both intravascular hemolysis of PNH 10 and extravascular hemolysis of hereditary spherocytosis. Eculizumab may not completely eliminate the infection-associated precipitation of hemolysis in PNH patients having both types of hemolysis.…”

Section: To the Editormentioning

confidence: 99%