Serological proteome analysis (SERPA) as a tool for the identification of tumor antigens capable of eliciting immune responses in chronic lymphocytic leukemia (CLL)
Valentina
Griggio1, 2*,
Giorgia
Mandili2,
Candida
Vitale1, 2,
Michela
Capello2,
Francesco
Novelli2,
Mario
Boccadoro1,
Massimo
Massaia1, 2 and
Marta
Coscia1, 2
-
1
A.O. Città della Salute e della Scienza di Torino, Section of Hematology, Italy
-
2
University of Torino, Department of Molecular Biotechnology and Health Sciences, Italy
In this study, serological proteome analysis (SERPA) was applied for the first time to identify tumor-associated antigens (Ag) capable of eliciting humoral immune responses in 35 untreated patients (pts) with chronic lymphocytic leukemia (CLL).
Proteins from CLL cells were separated to obtain proteomic maps which were blotted with autologous sera to reveal antibody (Ab)-based reactivity. To verify the CLL-specificity of recognition, 7 pts maps were also probed with sera of 7 healthy donors (HD). Ag spots were identified by Mass Spectrometry (MS). Effector responses were evaluated by IFNγ-ELISPOT upon stimulation of T cells from 6 pts and 4 HD with autologous ENOA-pulsed and control dendritic cells (DC).
Twenty-nine out of 35 CLL sera were immunoreactive and produced 145 Ag spots. By contrast, HD sera were significantly less reactive with 3 spots (p=.007). MS identified 50 different proteins recurrently recognized by autoAb. Sera from 54% of pts exhibited reactivity toward α-Enolase (ENOA). Whereas none of the HD sera was ENOA-reactive. ENOA-pulsed DC stimulated autologous T cells to secrete IFNγ in 4 out of 6 pts. This response was ENOA-specific because it was not induced by unpulsed DC and CLL-specific because IFNγ release was not induced in controls. ENOA Ab-reactivity correlates with parameters of progressive disease, higher lymphocytosis and lower platelet counts.
In conclusion ENOA is a shared Ag eliciting humoral and cellular immune responses in most CLL pts. Our results suggest that the immunoreactivity against self-Ag detected in pts with progressive disease may be the expression of a dysfunctional immune system.
Keywords:
chronic lymphocytic leukemia,
serological proteome analysis,
alpha enolase,
Tumor antigens,
humoral response
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Immune-mediated disease pathogenesis
Citation:
Griggio
V,
Mandili
G,
Vitale
C,
Capello
M,
Novelli
F,
Boccadoro
M,
Massaia
M and
Coscia
M
(2013). Serological proteome analysis (SERPA) as a tool for the identification of tumor antigens capable of eliciting immune responses in chronic lymphocytic leukemia (CLL).
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00935
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Received:
25 Jun 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Valentina Griggio, A.O. Città della Salute e della Scienza di Torino, Section of Hematology, Torino, Italy, valentina.griggio@unito.it