Functional autoantibodies against SSX-2 and NY-ESO-1 in multiple myeloma patients after allogeneic stem cell transplantation
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Functional autoantibodies against SSX-2 and NY-ESO-1 in multiple myeloma patients after allogeneic stem cell transplantation. / Luetkens, Tim; Kobold, Sebastian; Cao, Yanran; Ristic, Marina; Schilling, Georgia; Tams, Sinje; Bartels, Britta Marlen; Templin, Julia; Bartels, Katrin; Hildebrandt, York; Yousef, Sara; Marx, Andreas; Haag, Friedrich; Bokemeyer, Carsten; Kröger, Nicolaus; Atanackovic, Djordje.
In: CANCER IMMUNOL IMMUN, Vol. 63, No. 11, 01.11.2014, p. 1151-62.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Functional autoantibodies against SSX-2 and NY-ESO-1 in multiple myeloma patients after allogeneic stem cell transplantation
AU - Luetkens, Tim
AU - Kobold, Sebastian
AU - Cao, Yanran
AU - Ristic, Marina
AU - Schilling, Georgia
AU - Tams, Sinje
AU - Bartels, Britta Marlen
AU - Templin, Julia
AU - Bartels, Katrin
AU - Hildebrandt, York
AU - Yousef, Sara
AU - Marx, Andreas
AU - Haag, Friedrich
AU - Bokemeyer, Carsten
AU - Kröger, Nicolaus
AU - Atanackovic, Djordje
PY - 2014/11/1
Y1 - 2014/11/1
N2 - BACKGROUND: Multiple myeloma (MM) is the malignancy with the most frequent expression of the highly immunogenic cancer-testis antigens (CTA), and we have performed the first analysis of longitudinal expression, immunological properties, and fine specificity of CTA-specific antibody responses in MM.METHODS: Frequency and characteristics of antibody responses against cancer-testis antigens MAGE-A3, NY-ESO-1, PRAME, and SSX-2 were analyzed using peripheral blood (N = 1094) and bone marrow (N = 200) plasma samples from 194 MM patients.RESULTS: We found that antibody responses against CTA were surprisingly rare, only 2.6 and 3.1 % of patients evidenced NY-ESO-1- and SSX-2-specific antibodies, respectively. NY-ESO-1-specific responses were observed during disease progression, while anti-SSX-2 antibodies appeared after allogeneic stem cell transplantation and persisted during clinical remission. We found that NY-ESO-1- and SSX-2-specific antibodies were both capable of activating complement and increasing CTA uptake by antigen-presenting cells. SSX-2-specific antibodies were restricted to IgG3, NY-ESO-1 responses to IgG1 and IgG3. Remarkably, NY-ESO-1-positive sera recognized various non-contiguous regions, while SSX-2-specific responses were directed against a single 6mer epitope, SSX-2(85-90).CONCLUSIONS: We conclude that primary autoantibodies against intracellular MM-specific tumor antigens SSX-2 and NY-ESO-1 are rare but functional. While their contribution to disease control still remains unclear, our data demonstrate their theoretic ability to affect cellular anti-tumor immunity by formation and uptake of mono- and polyvalent immune complexes.
AB - BACKGROUND: Multiple myeloma (MM) is the malignancy with the most frequent expression of the highly immunogenic cancer-testis antigens (CTA), and we have performed the first analysis of longitudinal expression, immunological properties, and fine specificity of CTA-specific antibody responses in MM.METHODS: Frequency and characteristics of antibody responses against cancer-testis antigens MAGE-A3, NY-ESO-1, PRAME, and SSX-2 were analyzed using peripheral blood (N = 1094) and bone marrow (N = 200) plasma samples from 194 MM patients.RESULTS: We found that antibody responses against CTA were surprisingly rare, only 2.6 and 3.1 % of patients evidenced NY-ESO-1- and SSX-2-specific antibodies, respectively. NY-ESO-1-specific responses were observed during disease progression, while anti-SSX-2 antibodies appeared after allogeneic stem cell transplantation and persisted during clinical remission. We found that NY-ESO-1- and SSX-2-specific antibodies were both capable of activating complement and increasing CTA uptake by antigen-presenting cells. SSX-2-specific antibodies were restricted to IgG3, NY-ESO-1 responses to IgG1 and IgG3. Remarkably, NY-ESO-1-positive sera recognized various non-contiguous regions, while SSX-2-specific responses were directed against a single 6mer epitope, SSX-2(85-90).CONCLUSIONS: We conclude that primary autoantibodies against intracellular MM-specific tumor antigens SSX-2 and NY-ESO-1 are rare but functional. While their contribution to disease control still remains unclear, our data demonstrate their theoretic ability to affect cellular anti-tumor immunity by formation and uptake of mono- and polyvalent immune complexes.
U2 - 10.1007/s00262-014-1588-x
DO - 10.1007/s00262-014-1588-x
M3 - SCORING: Journal article
C2 - 25078248
VL - 63
SP - 1151
EP - 1162
JO - CANCER IMMUNOL IMMUN
JF - CANCER IMMUNOL IMMUN
SN - 0340-7004
IS - 11
ER -
