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PREDICTIVE VALUE OF AUTOANTIBODIES AGAINST M2-MUSCARINIC ACETYLCHOLINE RECEPTOR FOR THE ONSET OF CARDIAC AMYLOIDOSIS IN MULTIPLE MYELOMA
Author(s):
Lihong Li
Lihong Li
Affiliations:
(Abstract release date: 05/19/16) EHA Library. Li L. 06/09/16; 135373; LB2262
Dr. Lihong Li
Dr. Lihong Li
Contributions
Abstract
Abstract: LB2262

Type: Eposter Presentation

Background
Multiple myeloma (MM) is a clonal late B-cell disorder in which malignant plasma cells (PCs) expand and accumulate in the bone marrow, leading to anemia, lytic or osteopenic bone disease and renal failure. Nowadays MM has accounted for the second most common hematological malignancy after non-Hodgkin lymphoma with its incidence of 1% in neoplastic diseases and 13% in hematological malignance1,2.According to the data3, approximately 10% of multiple myeloma tends to be complicated by cardiac amyloidosis, mainly AL amyloidosis, in which the amyloidosis protein is consisted of monoclonal immunoglobulin light chains produced excessively by plasma cell malignancy. Moreover, up to 50% of patients with AL amyloidosis would progressively develop restrictive heart failure4. Unfortunately the prognosis is still poor.    M2 muscarinic receptor is attached to the family of cardiac G-protein-coupled receptors. Previously the auto-antibodies against the second extracellular loop of M2-muscarinic acetylcholine receptor (anti-M2-R) have been verified to involve in the development of various heart diseases characterized by heart failure, such as idiopathic dilated cardiomyopathy, Chagas’s heart disease and peripartum cardiomyopathy5-7. Furthermore, the level of anti-M2-R is positively associated with the increased risk of onset of peripartum cardiomyopathy7. Consequently, our study aims to explore whether the level of anti-M2-R would rise in MM patients with or without cardiac amyloidosis and whether anti-M2-R would increase the risk of cardiac amyloidosis in MM patients.

Aims
1. Anti-M2-R might participate in the phathophysiologic mechanism of cardiac impairment complicated by MM;2. Anti-M2-R can be an earlier predictor to estimate the risk of cardiac amyloidosis in MM patients than NT-proBNP.

Methods
Totally 78 subjects were recruited, including23 MM with cardiac amyloidosis, 25 MM without amyloidosis (MM) and 30 normal control (NC). The frequency and titer of anti-M2-R were compared in the three groups. All MM were under detection of serum anti-M2-R by ELISA before chemotherapy. The risk of cardiac amyloidosis was estimated using the univariate and multivariate logistic regression. 

Results
The positive rates of anti-M2-R in the three groups are 69.6% (16/23) in MM with cardiac amyloidosis, 40.0% (10/25) in MM and 10.0% (3/30) in NC respectively (p=0.040,69.6% vs. 40% and p=0.003, 40.0% vs.10%).Moreover, multivariate logistic regression indicates that the presence of anti-M2-R is associated with an increased risk of complicated cardiac amyloidosis in MM patients (OR, 5.5; 95% CI, 1.4-21.4; p=0.013).

Conclusion
This study demonstrates that the elevated level of anti-M2-R is an earlier independent predictor for the risk of cardiac amyloidosis in MM patients.

Session topic: E-poster

Keyword(s): Myeloma
Abstract: LB2262

Type: Eposter Presentation

Background
Multiple myeloma (MM) is a clonal late B-cell disorder in which malignant plasma cells (PCs) expand and accumulate in the bone marrow, leading to anemia, lytic or osteopenic bone disease and renal failure. Nowadays MM has accounted for the second most common hematological malignancy after non-Hodgkin lymphoma with its incidence of 1% in neoplastic diseases and 13% in hematological malignance1,2.According to the data3, approximately 10% of multiple myeloma tends to be complicated by cardiac amyloidosis, mainly AL amyloidosis, in which the amyloidosis protein is consisted of monoclonal immunoglobulin light chains produced excessively by plasma cell malignancy. Moreover, up to 50% of patients with AL amyloidosis would progressively develop restrictive heart failure4. Unfortunately the prognosis is still poor.    M2 muscarinic receptor is attached to the family of cardiac G-protein-coupled receptors. Previously the auto-antibodies against the second extracellular loop of M2-muscarinic acetylcholine receptor (anti-M2-R) have been verified to involve in the development of various heart diseases characterized by heart failure, such as idiopathic dilated cardiomyopathy, Chagas’s heart disease and peripartum cardiomyopathy5-7. Furthermore, the level of anti-M2-R is positively associated with the increased risk of onset of peripartum cardiomyopathy7. Consequently, our study aims to explore whether the level of anti-M2-R would rise in MM patients with or without cardiac amyloidosis and whether anti-M2-R would increase the risk of cardiac amyloidosis in MM patients.

Aims
1. Anti-M2-R might participate in the phathophysiologic mechanism of cardiac impairment complicated by MM;2. Anti-M2-R can be an earlier predictor to estimate the risk of cardiac amyloidosis in MM patients than NT-proBNP.

Methods
Totally 78 subjects were recruited, including23 MM with cardiac amyloidosis, 25 MM without amyloidosis (MM) and 30 normal control (NC). The frequency and titer of anti-M2-R were compared in the three groups. All MM were under detection of serum anti-M2-R by ELISA before chemotherapy. The risk of cardiac amyloidosis was estimated using the univariate and multivariate logistic regression. 

Results
The positive rates of anti-M2-R in the three groups are 69.6% (16/23) in MM with cardiac amyloidosis, 40.0% (10/25) in MM and 10.0% (3/30) in NC respectively (p=0.040,69.6% vs. 40% and p=0.003, 40.0% vs.10%).Moreover, multivariate logistic regression indicates that the presence of anti-M2-R is associated with an increased risk of complicated cardiac amyloidosis in MM patients (OR, 5.5; 95% CI, 1.4-21.4; p=0.013).

Conclusion
This study demonstrates that the elevated level of anti-M2-R is an earlier independent predictor for the risk of cardiac amyloidosis in MM patients.

Session topic: E-poster

Keyword(s): Myeloma

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