Pathogenesis of immunoglobulin light chain (AL) amyloidosis and light and heavy chain deposition diseases
- S Vincent Rajkumar, MD
S Vincent Rajkumar, MD
- Edward W. and Betty Knight Scripps Professor of Medicine
- Mayo Clinic
- Section Editors
- Richard J Glassock, MD, MACP
Richard J Glassock, MD, MACP
- Editor-in-Chief — Nephrology
- Section Editor — Glomerular Diseases
- Emeritus Professor
- The David Geffen School of Medicine at UCLA
- Robert A Kyle, MD
Robert A Kyle, MD
- Section Editor — Plasma Cell Disorders
- Professor of Medicine
- Mayo Medical School
- Steve J Schwab, MD
Steve J Schwab, MD
- Editor-in-Chief — Nephrology
- Section Editor — Dialysis
- University of Tennessee Health Science Center
Immunoglobulin light chain (AL) amyloidosis (previously referred to as primary amyloidosis), light chain deposition disease (LCDD), and heavy chain deposition diseases (HCDD) are clonal plasma cell proliferative disorders characterized by tissue deposits of light chain or heavy chain fragments, leading to organ dysfunction. Heavy chain deposition disease and light chain deposition disease are collectively referred to as monoclonal immunoglobulin deposition disease. A minority of patients has or develops multiple myeloma or Waldenstrom macroglobulinemia. (See "The heavy chain diseases".)
The pathogenesis of these disorders will be reviewed here. An overview of the amyloid disorders, as well as the diagnosis, prognosis, and treatment of AL amyloidosis are discussed separately. (See "Overview of amyloidosis" and "Clinical presentation, laboratory manifestations, and diagnosis of immunoglobulin light chain (AL) amyloidosis (primary amyloidosis)" and "Prognosis and treatment of immunoglobulin light chain (AL) amyloidosis and light and heavy chain deposition diseases".)
GENERAL DISCUSSION AND DEFINITIONS
Amyloidosis — Amyloidosis is a generic term that refers to the extracellular tissue deposition of insoluble fibrils as a result of protein misfolding. These fibrils have an antiparallel beta-pleated sheet configuration (noted on x-ray diffraction), and can be identified on biopsy specimens both by their characteristic appearance on electron microscopy, and by their ability to bind Congo red (leading to green birefringence under polarized light) and thioflavine T (producing an intense yellow-green fluorescence). (See "Overview of amyloidosis" and "Genetic factors in the amyloid diseases".)
Several forms of amyloidosis with distinct clinical patterns are recognized based on the nature of the precursor protein; the term "primary" amyloidosis refers specifically to the form of amyloidosis in which the precursor proteins are monoclonal immunoglobulin light chains produced by an underlying clonal plasma cell proliferative disorder. However, the preferred terminology is AL amyloidosis, in which AL denotes that the amyloid protein is immunoglobulin light chain-derived. In approximately 10 percent of cases the disorder overlaps with overt multiple myeloma.
In all forms of amyloidosis, the precursor proteins involved undergo transformation (misfolding) to a beta-pleated fibrillar configuration. Many distinct low molecular weight proteins are recognized to form amyloid fibrils. Besides monoclonal immunoglobulin light chains that cause AL amyloidosis, the most common examples are:
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- GENERAL DISCUSSION AND DEFINITIONS
- Light chain deposition disease
- Heavy chain deposition disease
- Nature of the tissue deposits
- - AL amyloidosis
- - Light chain deposition disease
- Determinants of tissue deposits
- - AL amyloidosis and LCDD
- - Heavy chain deposition disease and heavy chain (AH) amyloidosis