Myeloma and Paraproteins Flashcards
Features of antibodies
An antibody is an immunoglobulin
Produced by B cells, mostly plasma cells
Can be either soluble or membrane-bound
Primary role is to recognise and bind pathogens
This may directly impede the biological process or direct other components of the immune system by “tagging” the antigen
Basic structure of an antibody/immunoglobulin
Y shaped
2 heavy chains and 2 light chains
2 variable domains but everything else constant
What is the Fc portion of an antibody defined by?
Heavy chains
Types of heavy chain
Gamma - IgG
most prevalent antibody subclass, 75% of total
Alpha - IgA
mucous membrane immunity
Mu - IgM
initial phase of antibody production, exists as pentamer - highest molecular weight
Delta - IgD
Epsilon - IgE
parasite immune responses, hypersensitivity
Types and features of light chains
Kappa or lambda
Random selection for each cell
Each cell will only make 1 type of light chain with 1 specificity
Free light chains also found in the blood flow at low levels - difficult to measure
Function of the Fab and Fc regions of immunoglobulins
Fab region - variable, defines target binding
Fc region - constant, defines subclass
Total levels of IgG, IgA and IgM, normally
IgG - 6-15g/L
IgA - 1-4.5g/L
IgM - 0.5-2g/L
What is a paraprotein?
Monoclonal immunoglobulin present in blood or urine
If a paraprotein is present, what does this tell us?
That there is monoclonal proliferation of a B lymphocyte/plasma cell somewhere in the body
What does serum protein electrophoresis do?
Separates proteins based on size and charge and forms a characteristic pattern of bands of different widths and intensities based on proteins present
Assesses antibody diversity and identifies paraprotein
What does total immunoglobulin levels measurement do?
Measures Ig subclasses by heavy chain/Fc section
What does immunofixation do?
Identifies what class of paraprotein is present
What does measurement of light chains do?
Assesses imbalance/excess of light chains in urine/serum
What disease are IgM associated with?
Lymphoma
Maturing B lymphocytes make IgM antibody at the start of the immune response
What disease are IgG and IgA paraproteins associated with?
Myeloma
Mature plasma cells generate these types of immunoglobulin after isotope switching
What paraproteins are associated with myeloma?
IgG
IgA
What is myeloma?
Neoplastic disorder of plasma cells resulting (usually) in excessive production of a single type of immunoglobulin (paraprotein)
Incidence of myeloma
Peaks in 7th decade
Ethnicity - commoner in black population than in white
What are clinical manifestations of myeloma a result of?
Direct effect of plasma cells or effect of paraprotein
Clinical features of myeloma
Bone disease
- lytic bone lesions
- pathological fractures
- cord compression
- hypercalcaemia
Bone marrow failure, especially anaemia (thrombocytopenia and neutropenia)
Infections
Effect of paraprotein on kidneys
Causes renal failure - cast nephropathy
Immunoglobulin deposition and blockage of renal tubules
Effect of paraprotein on blood viscosity
Hyperviscosity - syndrome caused by increased viscosity in blood, impaired microcirculation and hypoperfusion
Commonest clinical feature is bleeding - retinal, oral, nasal or cutaneous
Can also cause cardiac failure, pulmonary congestion, confusion and renal failure
Effect of paraprotein on immunoglobulin
Hypogammaglobulinaemia
Impaired production of normal immunoglobulin
Tendency for infection
Features of amyloidosis
Group of diseases characterised by deposition of fibrillary protein
Morphological appearances and physical structure are similar but biochemical or protein composition can vary
When caused by a paraprotein or light chains = AL amyloid
- nephrotic syndrome
- cardiac failure
- carpal tunnel syndrome
- autonomic neuropathy
- cutaneous infiltration
