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Jens Christian Jensenius

Mannose-binding lectin (MBL) substitution: recovery of opsonic function in vivo lags behind MBL serum levels

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Standard

Mannose-binding lectin (MBL) substitution: recovery of opsonic function in vivo lags behind MBL serum levels. / Brouwer, Nannette; Frakking, Florine N J; van de Wetering, Marianne D; van Houdt, Michel; Hart, Margreet; Budde, Ilona Kleine; Strengers, Paul F W; Laursen, Inga; Houen, Gunnar; Roos, Dirk; Jensenius, Jens C; Caron, Huib N; Dolman, Koert M; Kuijpers, Taco W.

In: Journal of Immunology, Vol. 183, No. 5, 2009, p. 3496-504.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Brouwer, N, Frakking, FNJ, van de Wetering, MD, van Houdt, M, Hart, M, Budde, IK, Strengers, PFW, Laursen, I, Houen, G, Roos, D, Jensenius, JC, Caron, HN, Dolman, KM & Kuijpers, TW 2009, 'Mannose-binding lectin (MBL) substitution: recovery of opsonic function in vivo lags behind MBL serum levels', Journal of Immunology, vol. 183, no. 5, pp. 3496-504. https://doi.org/10.4049/jimmunol.0900445

APA

Brouwer, N., Frakking, F. N. J., van de Wetering, M. D., van Houdt, M., Hart, M., Budde, I. K., Strengers, P. F. W., Laursen, I., Houen, G., Roos, D., Jensenius, J. C., Caron, H. N., Dolman, K. M., & Kuijpers, T. W. (2009). Mannose-binding lectin (MBL) substitution: recovery of opsonic function in vivo lags behind MBL serum levels. Journal of Immunology, 183(5), 3496-504. https://doi.org/10.4049/jimmunol.0900445

CBE

Brouwer N, Frakking FNJ, van de Wetering MD, van Houdt M, Hart M, Budde IK, Strengers PFW, Laursen I, Houen G, Roos D, Jensenius JC, Caron HN, Dolman KM, Kuijpers TW. 2009. Mannose-binding lectin (MBL) substitution: recovery of opsonic function in vivo lags behind MBL serum levels. Journal of Immunology. 183(5):3496-504. https://doi.org/10.4049/jimmunol.0900445

MLA

Vancouver

Brouwer N, Frakking FNJ, van de Wetering MD, van Houdt M, Hart M, Budde IK et al. Mannose-binding lectin (MBL) substitution: recovery of opsonic function in vivo lags behind MBL serum levels. Journal of Immunology. 2009;183(5):3496-504. https://doi.org/10.4049/jimmunol.0900445

Author

Brouwer, Nannette ; Frakking, Florine N J ; van de Wetering, Marianne D ; van Houdt, Michel ; Hart, Margreet ; Budde, Ilona Kleine ; Strengers, Paul F W ; Laursen, Inga ; Houen, Gunnar ; Roos, Dirk ; Jensenius, Jens C ; Caron, Huib N ; Dolman, Koert M ; Kuijpers, Taco W. / Mannose-binding lectin (MBL) substitution: recovery of opsonic function in vivo lags behind MBL serum levels. In: Journal of Immunology. 2009 ; Vol. 183, No. 5. pp. 3496-504.

Bibtex

@article{d93cecd00b1d11dfb95d000ea68e967b,
title = "Mannose-binding lectin (MBL) substitution: recovery of opsonic function in vivo lags behind MBL serum levels",
abstract = "Mannose-binding lectin (MBL) deficiency is often associated with an increased risk of infection or worse prognosis in immunocompromised patients. MBL substitution in these patients might diminish these risks. We therefore performed an open, uncontrolled safety and pharmacokinetic MBL-substitution study in 12 pediatric oncology patients with chemotherapy-induced neutropenia. Twice weekly MBL infusions with plasma-derived MBL yielded MBL trough levels >1.0 microg/ml. We tested whether MBL substitution in vivo increased MBL-dependent complement activation and opsonophagocytosis of zymosan in vitro. Upon MBL substitution, opsonophagocytosis by control neutrophils increased significantly (p < 0.001) but remained suboptimal, although repeated MBL infusions resulted in improvement over time. The MBL-dependent MBL-associated serine protease (MASP)-mediated complement C3 and C4 activation also showed a suboptimal increase. To explain these results, complement activation was studied in detail. We found that in the presence of normal MASP-2 blood levels, MASP-2 activity (p < 0.0001) was reduced as well as the alternative pathway of complement activation (p < 0.05). This MBL-substitution study demonstrates that plasma-derived MBL infusions increase MBL/MASP-mediated C3 and C4 activation and opsonophagocytosis, but that higher circulating levels of plasma-derived MBL are required to achieve MBL-mediated complement activation comparable to healthy controls. Other patient cohorts should be considered to demonstrate clinical efficacy in phase II/III MBL-substitution studies, because we found a suboptimal recovery of (in vitro) biological activity upon MBL substitution in our neutropenic pediatric oncology cohort.",
keywords = "Adolescent, Amino Acid Substitution, Child, Child, Preschool, Complement Activation, Female, Humans, Male, Mannose-Binding Lectin, Mannose-Binding Protein-Associated Serine Proteases, Neutropenia, Opsonin Proteins, Phagocytosis, Prospective Studies",
author = "Nannette Brouwer and Frakking, {Florine N J} and {van de Wetering}, {Marianne D} and {van Houdt}, Michel and Margreet Hart and Budde, {Ilona Kleine} and Strengers, {Paul F W} and Inga Laursen and Gunnar Houen and Dirk Roos and Jensenius, {Jens C} and Caron, {Huib N} and Dolman, {Koert M} and Kuijpers, {Taco W}",
year = "2009",
doi = "10.4049/jimmunol.0900445",
language = "English",
volume = "183",
pages = "3496--504",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "5",

}

RIS

TY - JOUR

T1 - Mannose-binding lectin (MBL) substitution: recovery of opsonic function in vivo lags behind MBL serum levels

AU - Brouwer, Nannette

AU - Frakking, Florine N J

AU - van de Wetering, Marianne D

AU - van Houdt, Michel

AU - Hart, Margreet

AU - Budde, Ilona Kleine

AU - Strengers, Paul F W

AU - Laursen, Inga

AU - Houen, Gunnar

AU - Roos, Dirk

AU - Jensenius, Jens C

AU - Caron, Huib N

AU - Dolman, Koert M

AU - Kuijpers, Taco W

PY - 2009

Y1 - 2009

N2 - Mannose-binding lectin (MBL) deficiency is often associated with an increased risk of infection or worse prognosis in immunocompromised patients. MBL substitution in these patients might diminish these risks. We therefore performed an open, uncontrolled safety and pharmacokinetic MBL-substitution study in 12 pediatric oncology patients with chemotherapy-induced neutropenia. Twice weekly MBL infusions with plasma-derived MBL yielded MBL trough levels >1.0 microg/ml. We tested whether MBL substitution in vivo increased MBL-dependent complement activation and opsonophagocytosis of zymosan in vitro. Upon MBL substitution, opsonophagocytosis by control neutrophils increased significantly (p < 0.001) but remained suboptimal, although repeated MBL infusions resulted in improvement over time. The MBL-dependent MBL-associated serine protease (MASP)-mediated complement C3 and C4 activation also showed a suboptimal increase. To explain these results, complement activation was studied in detail. We found that in the presence of normal MASP-2 blood levels, MASP-2 activity (p < 0.0001) was reduced as well as the alternative pathway of complement activation (p < 0.05). This MBL-substitution study demonstrates that plasma-derived MBL infusions increase MBL/MASP-mediated C3 and C4 activation and opsonophagocytosis, but that higher circulating levels of plasma-derived MBL are required to achieve MBL-mediated complement activation comparable to healthy controls. Other patient cohorts should be considered to demonstrate clinical efficacy in phase II/III MBL-substitution studies, because we found a suboptimal recovery of (in vitro) biological activity upon MBL substitution in our neutropenic pediatric oncology cohort.

AB - Mannose-binding lectin (MBL) deficiency is often associated with an increased risk of infection or worse prognosis in immunocompromised patients. MBL substitution in these patients might diminish these risks. We therefore performed an open, uncontrolled safety and pharmacokinetic MBL-substitution study in 12 pediatric oncology patients with chemotherapy-induced neutropenia. Twice weekly MBL infusions with plasma-derived MBL yielded MBL trough levels >1.0 microg/ml. We tested whether MBL substitution in vivo increased MBL-dependent complement activation and opsonophagocytosis of zymosan in vitro. Upon MBL substitution, opsonophagocytosis by control neutrophils increased significantly (p < 0.001) but remained suboptimal, although repeated MBL infusions resulted in improvement over time. The MBL-dependent MBL-associated serine protease (MASP)-mediated complement C3 and C4 activation also showed a suboptimal increase. To explain these results, complement activation was studied in detail. We found that in the presence of normal MASP-2 blood levels, MASP-2 activity (p < 0.0001) was reduced as well as the alternative pathway of complement activation (p < 0.05). This MBL-substitution study demonstrates that plasma-derived MBL infusions increase MBL/MASP-mediated C3 and C4 activation and opsonophagocytosis, but that higher circulating levels of plasma-derived MBL are required to achieve MBL-mediated complement activation comparable to healthy controls. Other patient cohorts should be considered to demonstrate clinical efficacy in phase II/III MBL-substitution studies, because we found a suboptimal recovery of (in vitro) biological activity upon MBL substitution in our neutropenic pediatric oncology cohort.

KW - Adolescent

KW - Amino Acid Substitution

KW - Child

KW - Child, Preschool

KW - Complement Activation

KW - Female

KW - Humans

KW - Male

KW - Mannose-Binding Lectin

KW - Mannose-Binding Protein-Associated Serine Proteases

KW - Neutropenia

KW - Opsonin Proteins

KW - Phagocytosis

KW - Prospective Studies

U2 - 10.4049/jimmunol.0900445

DO - 10.4049/jimmunol.0900445

M3 - Journal article

C2 - 19657091

VL - 183

SP - 3496

EP - 3504

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 5

ER -