Low Levels of Factor H Family Proteins During Meningococcal Disease Indicate Systemic Processes Rather Than Specific Depletion by Neisseria meningitidis .

Autor:	van Beek AE; Sanquin Research, Department of Immunopathology, and Landsteiner Laboratory, Amsterdam University Medical Centre, Amsterdam Infection and Immunity Institute, Amsterdam, Netherlands.; Department of Pediatric Immunology, Rheumatology, and Infectious Diseases, Emma Children's Hospital, Amsterdam University Medical Centre, Amsterdam, Netherlands., Pouw RB; Sanquin Research, Department of Immunopathology, and Landsteiner Laboratory, Amsterdam University Medical Centre, Amsterdam Infection and Immunity Institute, Amsterdam, Netherlands.; Department of Pediatric Immunology, Rheumatology, and Infectious Diseases, Emma Children's Hospital, Amsterdam University Medical Centre, Amsterdam, Netherlands., Wright VJ; Section for Paediatric Infectious Disease, Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, United Kingdom., Sallah N; Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom., Inwald D; Section for Paediatric Infectious Disease, Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, United Kingdom., Hoggart C; Section for Paediatric Infectious Disease, Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, United Kingdom., Brouwer MC; Sanquin Research, Department of Immunopathology, and Landsteiner Laboratory, Amsterdam University Medical Centre, Amsterdam Infection and Immunity Institute, Amsterdam, Netherlands., Galassini R; Section for Paediatric Infectious Disease, Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, United Kingdom., Thomas J; Micropathology Ltd., University of Warwick, Warwick, United Kingdom., Calvo-Bado L; Micropathology Ltd., University of Warwick, Warwick, United Kingdom., Fink CG; Micropathology Ltd., University of Warwick, Warwick, United Kingdom., Jongerius I; Sanquin Research, Department of Immunopathology, and Landsteiner Laboratory, Amsterdam University Medical Centre, Amsterdam Infection and Immunity Institute, Amsterdam, Netherlands.; Department of Pediatric Immunology, Rheumatology, and Infectious Diseases, Emma Children's Hospital, Amsterdam University Medical Centre, Amsterdam, Netherlands., Hibberd M; Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom., Wouters D; Sanquin Research, Department of Immunopathology, and Landsteiner Laboratory, Amsterdam University Medical Centre, Amsterdam Infection and Immunity Institute, Amsterdam, Netherlands., Levin M; Section for Paediatric Infectious Disease, Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, United Kingdom., Kuijpers TW; Department of Pediatric Immunology, Rheumatology, and Infectious Diseases, Emma Children's Hospital, Amsterdam University Medical Centre, Amsterdam, Netherlands.; Sanquin Research, Department of Blood Cell Research, and Landsteiner Laboratory, Amsterdam University Medical Centre, Amsterdam, Netherlands.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2022 May 26; Vol. 13, pp. 876776. Date of Electronic Publication: 2022 May 26 (Print Publication: 2022).
DOI:	10.3389/fimmu.2022.876776
Abstrakt:	Neisseria meningitidis , the causative agent of meningococcal disease (MD), evades complement-mediated clearance upon infection by 'hijacking' the human complement regulator factor H (FH). The FH protein family also comprises the homologous FH-related (FHR) proteins, hypothesized to act as antagonists of FH, and FHR-3 has recently been implicated to play a major role in MD susceptibility. Here, we show that the circulating levels of all FH family proteins, not only FH and FHR-3, are equally decreased during the acute illness. We did neither observe specific consumption of FH or FHR-3 by N. meningitidis , nor of any of the other FH family proteins, suggesting that the globally reduced levels are due to systemic processes including dilution by fluid administration upon admission and vascular leakage. MD severity associated predominantly with a loss of FH rather than FHRs. Additionally, low FH levels associated with renal failure, suggesting insufficient protection of host tissue by the active protection by the FH protein family, which is reminiscent of reduced FH activity in hemolytic uremic syndrome. Retaining higher levels of FH may thus limit tissue injury during MD. Competing Interests: RP, MB, DW and TK are co-inventors of patents describing the potentiation of FH with monoclonal antibodies and therapeutic uses thereof. JT, LCB and CF are employed by Micropathology Ltd. All other authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 van Beek, Pouw, Wright, Sallah, Inwald, Hoggart, Brouwer, Galassini, Thomas, Calvo-Bado, Fink, Jongerius, Hibberd, Wouters, Levin and Kuijpers.)
Databáze:	MEDLINE
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