Antigen-specificity of oligoclonal abnormal protein bands in multiple myeloma after allogeneic stem cell transplantation.
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Antigen-specificity of oligoclonal abnormal protein bands in multiple myeloma after allogeneic stem cell transplantation. / Rahlff, Janina; Trusch, Maria; Haag, Friedrich; Bacher, Ulrike; Horst, Andrea; Schlüter, Hartmut; Binder, Mascha.
In: CANCER IMMUNOL IMMUN, Vol. 61, No. 10, 10, 10.2012, p. 1639-1651.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Antigen-specificity of oligoclonal abnormal protein bands in multiple myeloma after allogeneic stem cell transplantation.
AU - Rahlff, Janina
AU - Trusch, Maria
AU - Haag, Friedrich
AU - Bacher, Ulrike
AU - Horst, Andrea
AU - Schlüter, Hartmut
AU - Binder, Mascha
PY - 2012/10
Y1 - 2012/10
N2 - Myeloma patients may develop oligoclonal immunoglobulins, so-called abnormal protein bands (APB), after stem cell transplantation. APB do not correspond to the patient's paraprotein and confer a good prognosis. We set out to investigate whether such APB represent a humoral anti-myeloma immune response by screening immunoglobulins of 15 myeloma patients after allogeneic stem cell transplantation and a control group of healthy donors for reactivity with myeloma protein extracts. While the immunoglobulins of healthy donors did not react with myeloma protein extracts, patient-derived immunoglobulins showed variable levels of interaction, depending on the presence of APB on immunofixation. Most commonly, we detected interactions with heat-shock proteins, followed by neutral alpha-glucosidase, alpha-enolase and vimentin, as well as proliferating cell nuclear antigen and MAGEA4. More than 80% of targets were upregulated in myeloma. Heat-shock protein 60 (HSP60) was subsequently evaluated as an exemplary antigen. We found that HSP60 was aberrantly displayed on the surface of primary myeloma cells. Indeed, patient-derived APB-containing immunoglobulins recognized surface HSP60 suggesting that this antigen becomes accessible to the immune system after aberrant membrane exposition. We conclude that immunoglobulin fractions with APB recognize recurrent myeloma antigens and that this humoral response may contribute to the more favorable prognosis in patients with APB.
AB - Myeloma patients may develop oligoclonal immunoglobulins, so-called abnormal protein bands (APB), after stem cell transplantation. APB do not correspond to the patient's paraprotein and confer a good prognosis. We set out to investigate whether such APB represent a humoral anti-myeloma immune response by screening immunoglobulins of 15 myeloma patients after allogeneic stem cell transplantation and a control group of healthy donors for reactivity with myeloma protein extracts. While the immunoglobulins of healthy donors did not react with myeloma protein extracts, patient-derived immunoglobulins showed variable levels of interaction, depending on the presence of APB on immunofixation. Most commonly, we detected interactions with heat-shock proteins, followed by neutral alpha-glucosidase, alpha-enolase and vimentin, as well as proliferating cell nuclear antigen and MAGEA4. More than 80% of targets were upregulated in myeloma. Heat-shock protein 60 (HSP60) was subsequently evaluated as an exemplary antigen. We found that HSP60 was aberrantly displayed on the surface of primary myeloma cells. Indeed, patient-derived APB-containing immunoglobulins recognized surface HSP60 suggesting that this antigen becomes accessible to the immune system after aberrant membrane exposition. We conclude that immunoglobulin fractions with APB recognize recurrent myeloma antigens and that this humoral response may contribute to the more favorable prognosis in patients with APB.
KW - Humans
KW - Up-Regulation
KW - Stem Cell Transplantation
KW - Multiple Myeloma/immunology
KW - Antigens, Neoplasm/blood/immunology
KW - Bone Marrow Cells/immunology
KW - Chaperonin 60/blood/immunology
KW - Immunoglobulins/blood/immunology
KW - Mitochondrial Proteins/blood/immunology
KW - Neoplasm Proteins/blood/immunology
KW - Phosphopyruvate Hydratase/blood/immunology
KW - Proliferating Cell Nuclear Antigen/blood/immunology
KW - Vimentin/blood/immunology
KW - alpha-Glucosidases/blood/immunology
KW - Humans
KW - Up-Regulation
KW - Stem Cell Transplantation
KW - Multiple Myeloma/immunology
KW - Antigens, Neoplasm/blood/immunology
KW - Bone Marrow Cells/immunology
KW - Chaperonin 60/blood/immunology
KW - Immunoglobulins/blood/immunology
KW - Mitochondrial Proteins/blood/immunology
KW - Neoplasm Proteins/blood/immunology
KW - Phosphopyruvate Hydratase/blood/immunology
KW - Proliferating Cell Nuclear Antigen/blood/immunology
KW - Vimentin/blood/immunology
KW - alpha-Glucosidases/blood/immunology
U2 - 10.1007/s00262-012-1220-x
DO - 10.1007/s00262-012-1220-x
M3 - SCORING: Journal article
C2 - 22350072
VL - 61
SP - 1639
EP - 1651
JO - CANCER IMMUNOL IMMUN
JF - CANCER IMMUNOL IMMUN
SN - 0340-7004
IS - 10
M1 - 10
ER -
