Myeloma and Paraproteins Flashcards
What is an immunoglobulin?
Antibody produced by B cells, mostly plasma cells
Can be soluble or membrane bound
Recognises and binds to pathogens
This may directly impede on the biological process or other components of the immune system
Describe the basic structure of a immunoglobulin
Y-shaped with 2 heavy chains and 2 light chains
Variable domains and Fc portion - defined by the heavy chain
What are the 5 types of heavy chains?
IgG, IgA, IgM, IgD and IgE
What is the role of IgM?
Initial phase of antibody production
Exists as a pentamer - highest molecular weight
What is IgA for?
Mucous membrane immunity
What is IgE for?
Parasite immune responses and hypersensitivity
What are the types of light chains?
Kappa or Lambda
Random selection for each cell - each cell will only make one type of light chain
Free light chains are also found in the blood at low levels
What is the Fc region and Fab region?
Fab - variable which defines target binding
Fc - constant which defines the subclass
What is a paraprotein?
Monoclonal immunoglobulin present in the blood or urine
If present - tells there is monoclonal proliferation of B lymphocyte/ plasma cell somewhere in the body
Describe serum protein electrophoresis
Separates protein on size and shape
Forms characteristic bands of different widths and intensities differ based on proteins present
Gamma region contains the immunoglobulins
What are the summary of tests for immunoglobulins?
Total immunoglobulin levels - measures Ig subclass by heavy chain/ Fc region
Electrophoresis - identifies paraprotein
Immunofixation - identifies which class of paraprotein is present
Light chains - assesses imbalance - excess in serum or urine
Describe IgM paraproteins
Lymphoma
Maturing B-lymphocyte make IgM antibody at the start of the immune response
Describe IgG and IgA paraproteins
Myeloma
Mature plasma cells generate these types of immunoglobulins after isotype switching
Describe myeloma
Neoplastic disorder of plasma cells resulting in excessive production of single type of immunoglobulin (paraprotein)
Peaks in 7th decade and commoner in black population
What are the feature of myeloma?
Bone disease - lytic bone lesions, pathological fractures, spinal cord compression and hypercalcaemia
Bone marrow failure - anaemia
Infections
CRAB - hypercalcaemia, renal failure, anaemia and bone disease
What are the effects of the paraprotein in myeloma?
Renal failure - cast nephropathy
Hyper-viscosity - causes bleeding, cardiac failure, pulmonary congestion, confusion and renal failure
Hypogammaglobulinemia - impaired production of normal immunoglobulin so tendency to infection
Amyloidosis
Describe amyloidosis
Group of disease characterised by deposition of fibrillar protein
Morphological appearances and physical structure are similar
AL amyloid when caused by a paraprotein or light chains
What can be seen as a result of AL amyloid?
Nephrotic syndrome, cardiac failure, carpal tunnel syndrome, autonomic neuropathy and cutaneous infiltration
How is myeloma diagnosed?
Paraproteins are common - can increase with age and some people have MGUS
Diagnosed by finding excess plasma cells in the bone marrow
Must comprise > 10% of total bone marrow cell population
What types of paraproteins are seen in myeloma?
Mainly IgG then IgA + light chain only
What is the stage of myeloma based on?
Albumin and beta-2 microglobulin
How is myeloma treated?
Chemo (proteasome inhibitors and IMiDs), bisphosphonate therapy (Zoledronic acid), radiotherapy, steroids, surgery and autologous stem cell transplant
Describe IgM paraproteins
IgM myeloma does not exist
Associated with low-grade lymphomas
What is the clinical presentation of lymphoma?
Bone marrow failure, lymphadenopathy, hepatosplenomegaly and B symptoms - sweats and weight loss
Can have paraprotein related symptoms
Bone disease is very rare
