Myeloma Flashcards
What are the five types of heavy chain in immunoglobulins?
Gamma - IgG Alpha - IgA Mu - IgM Delta - IgD Epsilon - IgE
What are the immunoglobulin 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 blood at low measure; hard to measure
What is a paraprotein?
Monoclonal immunoglobulin present in blood or urine
If present, tells us that there is monoclonal proliferation of B lymphocyte/plasma cell somewhere in the body
What does IgM do?
Initial phase antibody production
Exists as a pentamer - highest molecular weight
What does IgA do?
Mucous membrane immunity
What does IgE do?
Parasite immune responses, hypersensivity (allergy)
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
What is a total immunoglobulin levels test?
Measurement of Ig subclasses by heavy chain/Fc section
What does electrophoresis assess?
Antibody diversity
Identifies paraprotein
What does immunofixation test?
Identifies what class of paraprotein is present i.e. IgG, IgM
When would IgM paraproteins be present?
Lymphoma
- maturing b lymphocytes make IgM at start of immune response
When would IgG, IgA paraproteins be present?
Myeloma
- mature plasma cells generate these after isotype switching
Describe myeloma
Neoplastic disorder of plasma cells
usually results in excessive production of a single immunoglobulin (paraprotein)
Peaks in 7th decade
Clinical manifestations may result from direct effect of plasma cells or effect of paraprotein
What are some features of myeloma?
CRAB; hyperCalcaemia, Renal failure, Anaemia, Bone disease
Bone disease
- lytic bone lesions
- pathological fractures
- cord compression
- hypercalcaemia
Bone marrow failure esp anaemia
Infections
What are some effects of paraprotein?
Renal failure - cast nephropathy
- immunoglobulin deposition and blockage of renal tubules
hyperviscosity
- bleeding; retinal, oral, nasal, cutaneous
- cardiac failure, pulmonary congestion, confusion, renal failure
hypogammaglobulinaemia
- impaired production of normal immunoglobulin
- tendency to infection
Amyloidosis
What is amyloidosis?
Group of diseases characterised by deposition fibrillar protein
Diagnosed by taking a biopsy
morphological appearances, physical structure similar
When caused by paraprotein or light chains; AL amyloid
Nephrotic syndrome Cardiac failure (LVH) Carpal tunnel syndrome Autonomic neuropathy Cutaneous infiltration
how is myeloma diagnosed?
Paraproteins are common
- 3-4% population > 75
- vast majority nothing wrong with them
- this is termed monoclonal gammopathy of uncertain significance
Diagnosed by finding excess plasma cells in bone marrow
Salt and pepper skull may be present on imaging
What is MGUS?
Monoclonal gammopathy of uncertain significance
Paraproteins present where nothing wrong with patient
Must comprise >10% of total bone marrow population
What is treatment for myeloma?
Chemotherapy
- proteasome inhibitors, IMiDs, monoclonal abs
Bisphosponate therapy
- Zoledronic acid
Radiotherapy
Steroids
Surgery
- pinning of long bones; decompression spinal cord
Autologous stem cell transplant
Describe IgM paraproteins
IgM myeloma does not exist
IgM paraproteins associated with low grade lymphomas
Clinical presentation
- bone marrow failure
- lymphadenopathy
- hepatosplenomegaly
- B symptoms
Bone disease rare
Type of paraprotein in myeloma
IgG: 55%
IgA: 21%
Light chain only: 2%
