| Autor: |
Zaleska, Joanna, Skorka, Katarzyna, Zajac, Malgorzata, Karczmarczyk, Agnieszka, Karp, Marta, Tomczak, Waldemar, Hus, Marek, Wlasiuk, Paulina, Giannopoulos, Krzysztof |
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| Zdroj: |
British Journal of Haematology; Aug2016, Vol. 174 Issue 4, p582-590, 9p, 1 Diagram, 2 Charts, 2 Graphs |
| Abstrakt: |
Mounting evidence suggests that autoreactivity and inflammatory processes are involved in the pathogenesis of chronic lymphocytic leukaemia ( CLL). Cytoskeletal proteins, including non-muscle myosin heavy chain IIA ( MYHIIA), vimentin ( VIM) and cofilin-1 ( CFL1), exposed on the surface of apoptotic cells have been identified as autoantigens that are recognized by the specific B-cell receptors of the CLL cells. In 212 CLL patients analysed with quantitative reverse transcriptase-polymerase chain reaction we found CFL1 overexpression and low expression of MYH9 in comparison with healthy volunteers. We detected specific cytotoxic immune responses for peptides derived from MYHIIA in 66·7%, VIM in 87·5% and CFL1 in 62·5% CLL patients in an Enzyme-Linked ImmunoSpot assay. Low frequencies of autoreactive peptide-specific T cells were detected against MYHIIA, VIM and CFL1 in CLL patients ex vivo; most of the detected cells had an effector-memory phenotype. Our findings support the existence of cytotoxic immune responses against three autoantigens that have been identified as targets of CLL clonotypic B-cell receptors. The presence of autoreactive CD8+ T cells against MYHIIA, VIM and CFL1 in CLL patients indicates the involvement of antigen-specific autoreactive T cells in the pathogenesis of CLL. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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