Myeloma and Paraproteins Flashcards
IgG Heavy Gain
Gamma
IgA Heavy Chain
Alpha
IgM heavy chain
Mu
IgD heavy chain
delta
IgE heavy chain
Epsilon
IgM
Intitial phase of antibody production. Exists as a pentamer (highest molecular weight). Total levels 0.5-2g/l.
IgG
Most prevalent (75%). Typical total levels 6-25g/l.
IgA
Mucous membrane immunity
Typical total levels 1-4.5g/l
IgE
Parasite immune responses, hypersensitivity
Light Chain
Can be Kappa of Lambda Random selection for each cell
But, each cell will only make 1 type of light chain with 1 specificity
Fc Region
Covers the antibody sub-class and remains constant
Paraprotein
Monoclonal immunoglobulin present in the blood or urine. If present, it tells us that there is a monoclonal proliferation of a B lymphocyte/plasma cells somewhere in the body.
Serum Protein Electropheresis
Separates protein based on size and charge. Forms a characteristic pattern of bands of different widths and intensities based on proteins present.
Total Immunoglobulin Levels
Measures Ig subclasses by heavy chain/ Fc section
Immunofixation
Identifies what class of paraprotien is present (IgG or IgM)
Light Chains
Assesses imbalance/ excess of light chains in the urine or the serum
IgM paraproteins
Lymphoma
Maturing B-lymphocytes make IgM antibody at the start of the immune response
IgG, IgA paraproteins
Myeloma
Mature Plasma Cells generate these types of immunoglobulin after isotope switching
Myeloma
A neoplastic disorder of plasma cells, resulting in excessive production of single type of immunoglobulin (paraprotein)
Age Myeloma Peaks
7th decase
Clinical manifestations of myeloma
Bone disease (lytic bone lesions, pathological fractures, chord compression, hypercalcaemia).
Bone marrow failure (anaemia)
Infections
Effects of High Paraprotein
Renal Failure
- cast nephropathy due to immunoglobulin deposition and bloackage of renal tubules
Hyperviscosity
Hypogammaglobinaemia
Amyloidosis
Hyperviscosity due to paraprotein
Syndrome caused by increased viscosity in blood, impaired microciculartion and hypoperfusion
Commonest clinical feature is bleeding – retinal, oral, nasal, cutaneous, confusion
Can also cause cardiac failure, pulmonary congestion, confusion, renal failure
Hypogammaglobinaemia
Impaired production of normal Immunoglobulin
Tendency to infection
Amyloidosis
Group of diseases caused by deposition of fibrillar protein. When it is caused by paraprotein or light chains it is AL amyloid.
Results in nephrotic syndrome, cardiac failure, carpal tunnel, autonomic neuropathy, cutaneous infiltration
Percentage of the population with paraprotein
3-4% over age 75. This is termed monoclonal gammopathy of uncertain significance.
How is myeloma diagnosed
Excess plasma cells in the bone marrow (>10% of total bone marrow in the cell population)
Stage of Myeloma
Based on albumin and beta-2 micro globulin
Treatment of myeloma
Chemotherapy (Proteasome inhibitors, IMiDs, monoclonal antibodies)
Bisphosphonate therapy - Zoledronic acid
Radiotherapy
Steroids
Surgery - pinning of long bones, decompression of the spinal chord
Autologous stem cell transplant
IgM paraproteins are associated with what conditions
Low grade lymphomas
Clinical presentation of low grade lymphoma
Bone marrow failure
Lymphadenopathy
Hepatosplenomegaly
B symptoms
