Antibody-mediated resolution of light chain-associated amyloid deposits

R. Hrncic, Jonathan Wall, D. A. Wolfenbarger, C. L. Murphy, M. Schell, D. T. Weiss, Alan Solomon

Research output: Contribution to journalArticle

139 Citations (Scopus)

Abstract

Primary light-chain-associated (AL) amyloidosis is characterized by the deposition in tissue of monoclonal light chains as fibrils. With rare exception, this process is seemingly irreversible and results in progressive organ dysfunction and eventually death. To determine whether immune factors can effect amyloid removal, we developed an experimental model in which mice were injected with amyloid proteins extracted from the spleens or livers of patients with AL amyloidosis. Notably, the resultant amyloidomas were rapidly resolved, as compared to controls, when animals received injections, of an anti-light-chain monoclonal antibody having specificity for an amyloid-related epitope. The reactivity of this monoclonal antibody was not dependent on the V(L) or C(L) isotype of the fibril, but rather seemed to be directed toward a β-pleated sheet conformational epitope expressed by AL and other amyloid proteins. The amyloidolytic response was associated with a pronounced infiltration of the amyloidoma with neutrophils and putatively involved opsonization of fibrils by the antibody, leading to cellular activation and release of proteolytic factors. The demonstration that AL amyloid resolution can be induced by passive administration of an amyloid-reactive antibody has potential clinical benefit in the treatment of patients with primary amyloidosis and other acquired or inherited amyloid-associated disorders.

Original languageEnglish (US)
Pages (from-to)1239-1246
Number of pages8
JournalAmerican Journal of Pathology
Volume157
Issue number4
DOIs
StatePublished - Jan 1 2000

Fingerprint

Amyloid Plaques
Amyloid
Light
Antibodies
Amyloidosis
Epitopes
Monoclonal Antibodies
Amyloidogenic Proteins
Antibody Specificity
Immunologic Factors
Neutrophils
Theoretical Models
Spleen
Injections
Liver

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

Antibody-mediated resolution of light chain-associated amyloid deposits. / Hrncic, R.; Wall, Jonathan; Wolfenbarger, D. A.; Murphy, C. L.; Schell, M.; Weiss, D. T.; Solomon, Alan.

In: American Journal of Pathology, Vol. 157, No. 4, 01.01.2000, p. 1239-1246.

Research output: Contribution to journalArticle

Hrncic, R. ; Wall, Jonathan ; Wolfenbarger, D. A. ; Murphy, C. L. ; Schell, M. ; Weiss, D. T. ; Solomon, Alan. / Antibody-mediated resolution of light chain-associated amyloid deposits. In: American Journal of Pathology. 2000 ; Vol. 157, No. 4. pp. 1239-1246.
@article{fa714376ff81401e93dfcbc0737d8d59,
title = "Antibody-mediated resolution of light chain-associated amyloid deposits",
abstract = "Primary light-chain-associated (AL) amyloidosis is characterized by the deposition in tissue of monoclonal light chains as fibrils. With rare exception, this process is seemingly irreversible and results in progressive organ dysfunction and eventually death. To determine whether immune factors can effect amyloid removal, we developed an experimental model in which mice were injected with amyloid proteins extracted from the spleens or livers of patients with AL amyloidosis. Notably, the resultant amyloidomas were rapidly resolved, as compared to controls, when animals received injections, of an anti-light-chain monoclonal antibody having specificity for an amyloid-related epitope. The reactivity of this monoclonal antibody was not dependent on the V(L) or C(L) isotype of the fibril, but rather seemed to be directed toward a β-pleated sheet conformational epitope expressed by AL and other amyloid proteins. The amyloidolytic response was associated with a pronounced infiltration of the amyloidoma with neutrophils and putatively involved opsonization of fibrils by the antibody, leading to cellular activation and release of proteolytic factors. The demonstration that AL amyloid resolution can be induced by passive administration of an amyloid-reactive antibody has potential clinical benefit in the treatment of patients with primary amyloidosis and other acquired or inherited amyloid-associated disorders.",
author = "R. Hrncic and Jonathan Wall and Wolfenbarger, {D. A.} and Murphy, {C. L.} and M. Schell and Weiss, {D. T.} and Alan Solomon",
year = "2000",
month = "1",
day = "1",
doi = "10.1016/S0002-9440(10)64639-1",
language = "English (US)",
volume = "157",
pages = "1239--1246",
journal = "American Journal of Pathology",
issn = "0002-9440",
publisher = "Elsevier Inc.",
number = "4",

}

TY - JOUR

T1 - Antibody-mediated resolution of light chain-associated amyloid deposits

AU - Hrncic, R.

AU - Wall, Jonathan

AU - Wolfenbarger, D. A.

AU - Murphy, C. L.

AU - Schell, M.

AU - Weiss, D. T.

AU - Solomon, Alan

PY - 2000/1/1

Y1 - 2000/1/1

N2 - Primary light-chain-associated (AL) amyloidosis is characterized by the deposition in tissue of monoclonal light chains as fibrils. With rare exception, this process is seemingly irreversible and results in progressive organ dysfunction and eventually death. To determine whether immune factors can effect amyloid removal, we developed an experimental model in which mice were injected with amyloid proteins extracted from the spleens or livers of patients with AL amyloidosis. Notably, the resultant amyloidomas were rapidly resolved, as compared to controls, when animals received injections, of an anti-light-chain monoclonal antibody having specificity for an amyloid-related epitope. The reactivity of this monoclonal antibody was not dependent on the V(L) or C(L) isotype of the fibril, but rather seemed to be directed toward a β-pleated sheet conformational epitope expressed by AL and other amyloid proteins. The amyloidolytic response was associated with a pronounced infiltration of the amyloidoma with neutrophils and putatively involved opsonization of fibrils by the antibody, leading to cellular activation and release of proteolytic factors. The demonstration that AL amyloid resolution can be induced by passive administration of an amyloid-reactive antibody has potential clinical benefit in the treatment of patients with primary amyloidosis and other acquired or inherited amyloid-associated disorders.

AB - Primary light-chain-associated (AL) amyloidosis is characterized by the deposition in tissue of monoclonal light chains as fibrils. With rare exception, this process is seemingly irreversible and results in progressive organ dysfunction and eventually death. To determine whether immune factors can effect amyloid removal, we developed an experimental model in which mice were injected with amyloid proteins extracted from the spleens or livers of patients with AL amyloidosis. Notably, the resultant amyloidomas were rapidly resolved, as compared to controls, when animals received injections, of an anti-light-chain monoclonal antibody having specificity for an amyloid-related epitope. The reactivity of this monoclonal antibody was not dependent on the V(L) or C(L) isotype of the fibril, but rather seemed to be directed toward a β-pleated sheet conformational epitope expressed by AL and other amyloid proteins. The amyloidolytic response was associated with a pronounced infiltration of the amyloidoma with neutrophils and putatively involved opsonization of fibrils by the antibody, leading to cellular activation and release of proteolytic factors. The demonstration that AL amyloid resolution can be induced by passive administration of an amyloid-reactive antibody has potential clinical benefit in the treatment of patients with primary amyloidosis and other acquired or inherited amyloid-associated disorders.

UR - http://www.scopus.com/inward/record.url?scp=0033810109&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033810109&partnerID=8YFLogxK

U2 - 10.1016/S0002-9440(10)64639-1

DO - 10.1016/S0002-9440(10)64639-1

M3 - Article

VL - 157

SP - 1239

EP - 1246

JO - American Journal of Pathology

JF - American Journal of Pathology

SN - 0002-9440

IS - 4

ER -