Plasma-derived mannose-binding lectin shows a direct interaction with C1-inhibitor

Mischa P. Keizer, Angela M. Kamp, Nannette Brouwer, Marianne D. van de Wetering, Diana Wouters, Taco W. Kuijpers

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

10 Citaten (Scopus)


MBL-deficiency has been associated with an increased frequency and severity of infection, in particular in children and under immunocompromized conditions. In an open uncontrolled safety and pharmacokinetic MBL-substitution study using plasma-derived MBL (pdMBL) in MBL-deficient pediatric oncology patients, we found that despite MBL trough levels above 1.0. μg/ml MBL functionality was not efficiently restored upon ex vivo testing.PdMBL showed C4-converting activity by itself, indicating the presence of MASPs. Upon incubation of pdMBL with MBL-deficient sera this C4-converting activity was significantly reduced. Depletion of the MASPs from pdMBL, paradoxically, restored the C4-converting activity. Subsequent depletion or inhibition of C1-inh, the major inhibitor of the lectin pathway, in the recipient serum restored the C4-converting activity as well. Complexes between MBL/MASPs and C1-inh (MMC-complexes) were detected after ex vivo substitution of MBL-deficient serum with pdMBL. These MMC-complexes could also be detected in the sera of the patients included in the MBL-substitution study shortly after pdMBL infusion.Altogether, we concluded that active MBL-MASP complexes in pdMBL directly interact with C1-inh in the recipient, leading to the formation of a multimolecular complex between C1-inh and MBL/MASPs, in contrast to the classical pathway where C1r and C1s are dissociated from C1q by C1-inh. Because of the presence of activated MASPs in the current pdMBL products efficient MBL-mediated host protection cannot be expected because of the neutralizing capacity by C1-inh.

Originele taal-2Engels
Pagina's (van-tot)187-193
Aantal pagina's7
TijdschriftMolecular Immunology
Nummer van het tijdschrift2
StatusGepubliceerd - apr. 2014
Extern gepubliceerdJa


Duik in de onderzoeksthema's van 'Plasma-derived mannose-binding lectin shows a direct interaction with C1-inhibitor'. Samen vormen ze een unieke vingerafdruk.

Citeer dit