Activation of complement system in adult T-cell leukemia (ATL) occurs mainly through lectin pathway: a serum proteomic approach using mass spectrometry.
Adult T-cell leukemia (ATL) is a fatal malignancy caused by infection with human T lymphotropic virus type-1 (HTLV-1). To search for a new biomarker of ATL, we analyzed sera from ATL patients using ProteinChip arrays. The spectral comparison of ATL patients with HTLV-1 carriers and healthy volunteers showed that the intensities of five peaks (1779, 1866, 2022, 4467, and 8930 m/z) were significantly increased in ATL, while those of four peaks (4067, 4151, 8130, and 8597 m/z) were decreased. From these differentially expressed peaks, we chose peaks of 1779, 1866, and 2022 m/z as biomarker candidates of ATL. MS/MS ion search using tandem mass spectrometry and immunoprecipitation assay using anti-C3 antibody showed that factors derived from these candidate peaks were identified as C3f, which is a component of the complement system and a fragment of complement C3. These results indicate that the complement system was activated in ATL. Further analysis of markers specific to the activation pathways (classical, alternative, and lectin pathways) in the complement system showed that the serum concentration of the marker of the lectin pathway was significantly higher in ATL patients. These results suggest that activation of the complement system in ATL occurs mainly through the lectin pathway.
Ishida
Yo-ichi
Y
Miyazaki Prefectural Industrial Support Foundation, Miyazaki, Japan. ishida@mi-create.jp
Yamashita
Kiyoshi
K
Sasaki
Hidenori
H
Takajou
Ichirou
I
Kubuki
Yoko
Y
Morishita
Kazuhiro
K
Tsubouchi
Hirohito
H
Okayama
Akihiko
A
D000328:Adult; D016022:Case-Control Studies; D003167:Complement Activation; D020869:Gene Expression Profiling; D006801:Humans; D047468:Immunoprecipitation; D037102:Lectins / Q000378:metabolism*; D015458:Leukemia, T-Cell / Q000097:blood / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000097:blood / Q000235:genetics; D040901:Proteomics; D053719:Tandem Mass Spectrometry / Q000379:methods*
D037102:Lectins; D009363:Neoplasm Proteins