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Title: The influence of inhibition of C3aR-C3a complement axis on hematopoietic stem cell mobilization in mice and correlation between C3 and C4 complement components and clinical follow-up after stem cell transplantation

Abstract:

The complement system consists of proteins and biological reactions playing a role in innate and aquired immunity against infections. The basic role of the complement system is to be a ‘guard against invading pathogens’. Recently accumulated evidence suggests recently that the complement might have an important role in diverse biological processes such as organ regeneration, reproduction, cartilage-bone development as well as immunosuppression and hematopoiesis. Based on latest knowledge of the role of the complement system in the regulation of hematopoiesis following aims of the experiments were formulated: a) does the use of C3a/C3aR axis inhibitor (C3aR antagonist) improve hematopietic stem cell mobilization in mice model? b) is there any correlation between C3 and C4 concentrations in hematopoietic stem cell transplant recipients and follow-up after transplantation? The experiments were performed in two stages: 1) the quality of stem cell mobilization with G-CSF and C3a/C3aR inhibitor in different combinations (5 groups: control, G-CSF for 3 days, G-CSF for 5 days, G-CSF for 5 days+C3aR antagonist 10 µg/ml PB and G-CSF for 5 days+C3aR antagonist 100 µg/ml PB) was investigated in mice model, 2) retrospective analysis in children after first hematopoietic stem cell transplantation was provided concerning: • correlation between C3/C4 concentrations before HSCT, on day +10 and +30 after transplantation and engraftment (n=10),• correlation between C3 and C4 concentrations and clinical follow-up after transplantation including posttransplant complications (n=73).Following conclusions were supported by the results:1. The optimal hematopoietic stem cell mobilization was observed after 5 days G-CSF administration (leukocytosis, amount of c-kit+/Thy-1+ cells in mice).2. The use of C3a antagonist was related to the increase of stem cell amount after 5 days mobilization with G-CSF and was independent on the antagonist’s dose.3. No simple correlation between C3/C4 concentrations in the first 30 days after transplantation and engraftment was found.4. Statistical relevance (p=0,0403) of higher incidence of quiescent cGvHD in maximal 2 organs in children with abnormal C3/C4 concentrations during 3-year-follow-up after transplantation was shown. ; 5. There was no statistical relevance of: patient’s sex and age, clinical diagnosis, type of donor, source of stem cells, type of conditioning therapy, in vivo/ex vivo lymphocyte depletion, GvHD prophylaxis, aGvHD incidence and staging, cGvHD occurrence, sepsis, virus reactivation (CMV, EBV, ADV), mycosis, VOD or survival rate in a group of children with abnormal C3/C4 concentrations after transplantation.These findings imply minor clinical importance of complement disorders in the post-transplant follow-up in children. Nevertheless the increased incidence of quiescent chronic GvHD in a group of patients with disturbed C3 and/or C4 concentrations highlight the necessity of their monitoring in patients after hematopoietic stem cell transplantation.

Place of publishing:

Kraków

Level of degree:

2 - studia doktoranckie

Degree discipline:

transplantologia ; immunologia

Degree grantor:

Uniwersytet Jagielloński. Collegium Medicum. Wydział Lekarski.

Promoter:

Anna Pituch-Noworolska

Date issued:

2011

Format:

application/pdf

Identifier:

oai:dl.cm-uj.krakow.pl:3403

Call number:

ZB-115546

ControlNumberVIRTUA:

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Language:

pol

Access rights:

tylko w bibliotece

Location of original object:

Biblioteka Medyczna Uniwersytetu Jagiellońskiego- Collegium Medicum

Object collections:

Last modified:

Feb 5, 2020

In our library since:

Mar 5, 2013

Number of object content hits:

5

Number of object content views in PDF format

5

All available object's versions:

http://dl.cm-uj.krakow.pl:8080/publication/3403

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Edition name Date
ZB-115546 Feb 5, 2020

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