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Clinical MedicineIn-Press PreviewInfectious diseaseMicrobiology Open Access | 10.1172/JCI176466
1Division of Infectious Disease and International Medicine, Department of In, University of South Florida, Morsani College of Medicine, Tampa, United States of America
2Center for Genomics and Systems Biology, Department of Biology, New York University, New York, United States of America
3Blantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi
4Clinical Programme, Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi
5Department of Osteopathic Medical Specialties, Michigan State University, East Lansing, United States of America
6Department of Medicine, The University of Melbourne, Victoria, Australia
7Academy of Medical Sciences, Malawi University of Science and Technology, Thyolo, Malawi
8Department of Pathology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, United States of America
9Department of Osteopathic Medicial Specialties, Michigan State University, East Lansing, United States of America
10Division of Infectious Disease and International Medicine, Department of In, University of South Florida Morsani College of Medicine, Tampa, United States of America
Find articles by Vera, I. in: JCI | PubMed | Google Scholar
1Division of Infectious Disease and International Medicine, Department of In, University of South Florida, Morsani College of Medicine, Tampa, United States of America
2Center for Genomics and Systems Biology, Department of Biology, New York University, New York, United States of America
3Blantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi
4Clinical Programme, Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi
5Department of Osteopathic Medical Specialties, Michigan State University, East Lansing, United States of America
6Department of Medicine, The University of Melbourne, Victoria, Australia
7Academy of Medical Sciences, Malawi University of Science and Technology, Thyolo, Malawi
8Department of Pathology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, United States of America
9Department of Osteopathic Medicial Specialties, Michigan State University, East Lansing, United States of America
10Division of Infectious Disease and International Medicine, Department of In, University of South Florida Morsani College of Medicine, Tampa, United States of America
Find articles by Kessler, A. in: JCI | PubMed | Google Scholar
1Division of Infectious Disease and International Medicine, Department of In, University of South Florida, Morsani College of Medicine, Tampa, United States of America
2Center for Genomics and Systems Biology, Department of Biology, New York University, New York, United States of America
3Blantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi
4Clinical Programme, Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi
5Department of Osteopathic Medical Specialties, Michigan State University, East Lansing, United States of America
6Department of Medicine, The University of Melbourne, Victoria, Australia
7Academy of Medical Sciences, Malawi University of Science and Technology, Thyolo, Malawi
8Department of Pathology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, United States of America
9Department of Osteopathic Medicial Specialties, Michigan State University, East Lansing, United States of America
10Division of Infectious Disease and International Medicine, Department of In, University of South Florida Morsani College of Medicine, Tampa, United States of America
Find articles by Harawa, V. in: JCI | PubMed | Google Scholar
1Division of Infectious Disease and International Medicine, Department of In, University of South Florida, Morsani College of Medicine, Tampa, United States of America
2Center for Genomics and Systems Biology, Department of Biology, New York University, New York, United States of America
3Blantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi
4Clinical Programme, Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi
5Department of Osteopathic Medical Specialties, Michigan State University, East Lansing, United States of America
6Department of Medicine, The University of Melbourne, Victoria, Australia
7Academy of Medical Sciences, Malawi University of Science and Technology, Thyolo, Malawi
8Department of Pathology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, United States of America
9Department of Osteopathic Medicial Specialties, Michigan State University, East Lansing, United States of America
10Division of Infectious Disease and International Medicine, Department of In, University of South Florida Morsani College of Medicine, Tampa, United States of America
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1Division of Infectious Disease and International Medicine, Department of In, University of South Florida, Morsani College of Medicine, Tampa, United States of America
2Center for Genomics and Systems Biology, Department of Biology, New York University, New York, United States of America
3Blantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi
4Clinical Programme, Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi
5Department of Osteopathic Medical Specialties, Michigan State University, East Lansing, United States of America
6Department of Medicine, The University of Melbourne, Victoria, Australia
7Academy of Medical Sciences, Malawi University of Science and Technology, Thyolo, Malawi
8Department of Pathology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, United States of America
9Department of Osteopathic Medicial Specialties, Michigan State University, East Lansing, United States of America
10Division of Infectious Disease and International Medicine, Department of In, University of South Florida Morsani College of Medicine, Tampa, United States of America
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1Division of Infectious Disease and International Medicine, Department of In, University of South Florida, Morsani College of Medicine, Tampa, United States of America
2Center for Genomics and Systems Biology, Department of Biology, New York University, New York, United States of America
3Blantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi
4Clinical Programme, Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi
5Department of Osteopathic Medical Specialties, Michigan State University, East Lansing, United States of America
6Department of Medicine, The University of Melbourne, Victoria, Australia
7Academy of Medical Sciences, Malawi University of Science and Technology, Thyolo, Malawi
8Department of Pathology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, United States of America
9Department of Osteopathic Medicial Specialties, Michigan State University, East Lansing, United States of America
10Division of Infectious Disease and International Medicine, Department of In, University of South Florida Morsani College of Medicine, Tampa, United States of America
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1Division of Infectious Disease and International Medicine, Department of In, University of South Florida, Morsani College of Medicine, Tampa, United States of America
2Center for Genomics and Systems Biology, Department of Biology, New York University, New York, United States of America
3Blantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi
4Clinical Programme, Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi
5Department of Osteopathic Medical Specialties, Michigan State University, East Lansing, United States of America
6Department of Medicine, The University of Melbourne, Victoria, Australia
7Academy of Medical Sciences, Malawi University of Science and Technology, Thyolo, Malawi
8Department of Pathology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, United States of America
9Department of Osteopathic Medicial Specialties, Michigan State University, East Lansing, United States of America
10Division of Infectious Disease and International Medicine, Department of In, University of South Florida Morsani College of Medicine, Tampa, United States of America
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1Division of Infectious Disease and International Medicine, Department of In, University of South Florida, Morsani College of Medicine, Tampa, United States of America
2Center for Genomics and Systems Biology, Department of Biology, New York University, New York, United States of America
3Blantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi
4Clinical Programme, Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi
5Department of Osteopathic Medical Specialties, Michigan State University, East Lansing, United States of America
6Department of Medicine, The University of Melbourne, Victoria, Australia
7Academy of Medical Sciences, Malawi University of Science and Technology, Thyolo, Malawi
8Department of Pathology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, United States of America
9Department of Osteopathic Medicial Specialties, Michigan State University, East Lansing, United States of America
10Division of Infectious Disease and International Medicine, Department of In, University of South Florida Morsani College of Medicine, Tampa, United States of America
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1Division of Infectious Disease and International Medicine, Department of In, University of South Florida, Morsani College of Medicine, Tampa, United States of America
2Center for Genomics and Systems Biology, Department of Biology, New York University, New York, United States of America
3Blantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi
4Clinical Programme, Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi
5Department of Osteopathic Medical Specialties, Michigan State University, East Lansing, United States of America
6Department of Medicine, The University of Melbourne, Victoria, Australia
7Academy of Medical Sciences, Malawi University of Science and Technology, Thyolo, Malawi
8Department of Pathology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, United States of America
9Department of Osteopathic Medicial Specialties, Michigan State University, East Lansing, United States of America
10Division of Infectious Disease and International Medicine, Department of In, University of South Florida Morsani College of Medicine, Tampa, United States of America
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1Division of Infectious Disease and International Medicine, Department of In, University of South Florida, Morsani College of Medicine, Tampa, United States of America
2Center for Genomics and Systems Biology, Department of Biology, New York University, New York, United States of America
3Blantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi
4Clinical Programme, Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi
5Department of Osteopathic Medical Specialties, Michigan State University, East Lansing, United States of America
6Department of Medicine, The University of Melbourne, Victoria, Australia
7Academy of Medical Sciences, Malawi University of Science and Technology, Thyolo, Malawi
8Department of Pathology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, United States of America
9Department of Osteopathic Medicial Specialties, Michigan State University, East Lansing, United States of America
10Division of Infectious Disease and International Medicine, Department of In, University of South Florida Morsani College of Medicine, Tampa, United States of America
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1Division of Infectious Disease and International Medicine, Department of In, University of South Florida, Morsani College of Medicine, Tampa, United States of America
2Center for Genomics and Systems Biology, Department of Biology, New York University, New York, United States of America
3Blantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi
4Clinical Programme, Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi
5Department of Osteopathic Medical Specialties, Michigan State University, East Lansing, United States of America
6Department of Medicine, The University of Melbourne, Victoria, Australia
7Academy of Medical Sciences, Malawi University of Science and Technology, Thyolo, Malawi
8Department of Pathology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, United States of America
9Department of Osteopathic Medicial Specialties, Michigan State University, East Lansing, United States of America
10Division of Infectious Disease and International Medicine, Department of In, University of South Florida Morsani College of Medicine, Tampa, United States of America
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1Division of Infectious Disease and International Medicine, Department of In, University of South Florida, Morsani College of Medicine, Tampa, United States of America
2Center for Genomics and Systems Biology, Department of Biology, New York University, New York, United States of America
3Blantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi
4Clinical Programme, Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi
5Department of Osteopathic Medical Specialties, Michigan State University, East Lansing, United States of America
6Department of Medicine, The University of Melbourne, Victoria, Australia
7Academy of Medical Sciences, Malawi University of Science and Technology, Thyolo, Malawi
8Department of Pathology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, United States of America
9Department of Osteopathic Medicial Specialties, Michigan State University, East Lansing, United States of America
10Division of Infectious Disease and International Medicine, Department of In, University of South Florida Morsani College of Medicine, Tampa, United States of America
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Published April 23, 2024 - More info
BACKGROUND. Features of consumptive coagulopathy and thromboinflammation are prominent in cerebral malaria (CM). We hypothesized that thrombogenic autoantibodies contribute to a procoagulant state in CM.
METHODS. Plasma from children with uncomplicated malaria (UM, n = 124) and CM (n = 136) was analyzed by ELISA for a panel of 8 autoantibodies including anti-Platelet Factor 4/polyanion (anti-PF4/P), anti-Phospholipid, anti-Phosphatidylserine, anti-Myeloperoxidase, anti-Proteinase 3, anti-dsDNA, anti-Beta-2-Glycoprotein I (β2GPI), and anti-Cardiolipin. Non-malaria coma (NMC, n = 49) and healthy controls (HC, n = 56) were assayed for comparison. Associations with clinical and immune biomarkers were determined using univariate and logistic regression analyses.
RESULTS. Median anti-PF4/P and anti-PS IgG levels were elevated with malaria infection relative to HC (P < 0.001) and NMC (PF4/P: P < 0.001). Anti-PF4/P IgG levels were elevated in CM (median = 0.27, IQR: 0.19–0.41) compared to UM (median = 0.19, IQR: 0.14–0.22, P ≤ 0.0001). Anti-PS IgG levels did not differ between UM and CM (P = 0.39). When CM cases were stratified by malaria retinopathy (Ret) status, levels of anti-PF4/P IgG correlated negatively with peripheral platelet count in Ret+ CM cases (Rs = 0.201, P = 0.04) and associated positively with mortality (OR = 15.2, 95% CI: 1.02–275, P = 0.048). Plasma from CM patients induced a greater platelet activation capacity in an ex-vivo assay relative to plasma from UM patients (P = 0.02). Platelet activation was associated with anti-PF4/P IgG levels (Rs = 0.293, P = 0.035).
CONCLUSIONS. Thrombosis mediated by elevated anti-PF4/P autoantibodies may be one mechanism contributing to the clinical complications of CM.