Myeloma and Paraproteins Flashcards
what is meant by the term paraprotein?
A paraprotein is a monoclonal immunoglobulin present in blood or urine.
If present, it tells us that there is monoclonal proliferation of a B lymphocyte/plasma cell somewhere in the body.
What is myeloma?
- neoplastic disorder of plasma cells, resulting (usually) in excessive production of a single type of immunoglobulin (paraprotein).
- peaks in 70s, more common in black population
- clinical manifestations may result from direct effect of plasma cells, or effect of paraprotein
Myeloma Clinical features
- bone disease: lytic bone lesions, pathological fractures, cord compression, hypercalcaemia.
- bone marrow failure esp. anaemia
- infections
CRAB: hyperCalcaemia, Renal failure, Anaemia, Bone disease
SLim:
- sixty percent plasma cells on marrow
- light chain imbalance > 100
- MRI lesion > 1 in bone marrow
What are the clinical effects of the paraprotein itself?
- Renal failure - cast nephropathy: immunoglobulin deposition and blockage of renal tubes
- Hyperviscosity: syndrome caused by increased viscosity in blood, impaired microcirculation and hypoperfusion. Most common clinical feature is bleeding - retinal, oral, nasal etc. Can also cause cardiac failure, pulmonary congestion, confusion, renal failure
- Hypogammaglobulinaemia: impaired production of normal immunoglobulin > tendency to infection.
- Amyloidosis
Describe monoclonal gammopathy of uncertain significance (MGUS).
Monoclonal gammopathy of undetermined significance (MGUS) involves the production of a specific paraprotein without other features of myeloma or cancer. Monoclonal refers to identical copies or clones originating from a single cell. MGUS is often an incidental finding in an otherwise healthy person. It has a small risk of progression to myeloma (about 1% per year).
- incidence is higher than myeloma
myeloma diagnosis
- Diagnosed by finding excess plasma cells in the bone marrow - Must comprise > 10% of total bone marow cell population.
- lab tests do determine which type of paraprotein is presen e.g. serum protein electrophoresis or if there is light chains present e.g. serum-free light-chain assay
- staging is based on albumin & beta-2 microglobulin
Myeloma treatment
- Chemotherapy: Bortezomib & carfilzomib (proteasome inhibitor), lenalidomide, pomalidomide, monoclonal antibodies
- Bisphosphonate therap: zoledronic acid
- Radiotherapy
- Steroids
- Surgery: pinning of long bones, decompression of spinal cord
- autologous stem cell transplant
describe the structure of immunoglobulins
- basic structure - Y-shaped
- 2 heavy chains
- 2 light chains
- variable domains > Fab region defines target binding
- everything else (constant) > Fc region defines subclass
- Fc portion - defined by heavy chains
what are the 5 types of heavy chains that can compose the Fc portion of an immunoglobulin?
- Gamma - IgG, most prevalent antibody subclass (75% of total)
- Alpha - IgA, mucuous membrane immunity
- Mu - IgM, initial phase of antibody production, exists as pentamer > highest molecular weight
- Delta - IgD
- Epsilon - IgE, parasite immune responses, hypersensitivity
describe light chains of immunoglobulin
- either kappa or lambda
- random selection for each cell
- but, each cell will only make 1 type of light chain with 1 specificity
- free light chains are also found in the blood at low levels, difficult to measure
what does serum protein electrophoresis do?
- separates protein based on size and charge
- forms a characteristic pattern of bands of different widths and intensities based on proteins present.
- used to assess antibody diversity, identifies paraprotein
what do total immunoglobulin levels measure?
Measures Ig subclasses by heavy chain//Fc section.
what does immunofixation do?
Identifies what class of paraprotein is present i.e. IgG, IgM
what do we measure in a serum-free light chain assay?
assess imbalance/excess of light chains in urine/serum
IgM paraproteins are associated with which malignancy?
lymphoma
- maturing B-lymphocytes make IgM antibody at the start of the immune response
IgG and IgA paraproteins could indicate which malignancy?
myeloma
- mature plasma cells generate these types of immunoglobuline after isotype switching
When requesting lab tests for possible multiple myeloma, which is the single most useful test?
serum total electrophoresis
