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Red blood cells (RBCs) infected with Plasmodium falciparum are protected from complement-mediated lysis by surface membrane glycosylphosphatidylinositol (GPI)-anchored proteins, which include decay accelerating factor (DAF or CD55) and CD59. To determine if P. falciparum avoids or replicates less efficiently in GPI protein-deficient cells at a higher risk for complement-mediated lysis, we compared P. falciparum infectivity among control RBCs with those from subjects with paroxysmal nocturnal hemoglobinuria (PNH), a condition in which RBCs express variable levels of DAF (negative and positive) and CD59 (negative [-], intermediate [I], and high [H]). Co-cultures of 19 matched samples of control and PNH RBCs were infected with P. falciparum to directly compare parasitic invasion. Each PNH RBC sample was then assessed for P. falciparum infectivity across the spectrum of GPI protein deficiency. Identification methods included biotin-streptavidin for RBC populations, fluorescein isothiocyanate-labeled antibodies to DAF and CD59, hydroethidine for parasite DNA, and flow cytometry. The mean ± SD parasitemias in co-cultured PNH and control RBCs were 24.7 ± 6.9% versus 21.0 ± 5.9% (P 30.12). For individual PNH samples, parasitemias were significantly higher in DAF (-) cells versus DAF (+) cells (25.0 ± 8.9% versus 19.1 ± 8.7%; P < 0.001) and in CD59 (-) cells versus I/H cells (22.5 ± 6.4% versus 17.6 ± 4.2%; P < 0.0003). Across the CD59 spectrum, mean parasitemias were highest in CD59 (-) cells (24.5 ± 6.4%), followed by CD59-H cells (19.5 ± 5.4%), and CD59-I cells (16.4 ± 4.8%). Expression of DAF in 12 (63%) of 19 infected PNH samples was reduced. Thus, P. falciparum does not selectively avoid RBCs with fewer GPI proteins and parasite replication in PNH cells is at least as robust as in normal RBCs.
Received August 22, 2002. Accepted for publication June 26, 2003.
Acknowledgments: We thank Prapatsorn Ngaowichit and Egarit Noulsri for administrative support.
Financial support: This work was supported in part by the Malaria Program of the United States Army Medical Research and Materiel Command (Fort Detrick, Frederick, MD) and Becton Dickinson Biosciences.
Disclaimer: The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense.
Authors’ addresses: Kovit Pattanapanyasat, Center of Excellence for Flow Cytometry, Office for Research and Development, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand. Douglas S. Walsh and Kosol Yongvanitchit, Department of Immunology and Medicine, United States Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand. Nattawan Piyawatthanasakul and Wanchai Wanachiwanawin, Division of Hematology, Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand. H. Kyle Webster, Becton Dickinson Biosciences, 2350 Qume Drive, San Jose, CA 95131-1807.
Reprint requests: Kovit Pattanapanyasat, Office for Research and Development, Faculty of Medicine, Siriraj Hospital, Bangkok 10700, Thailand, Telephone: 66-2-419-8946 extension 6644, Fax: 66-2-411-0155, E-mail: grkpy{at}mahidol.ac.th.
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