Myeloma Flashcards
What are immunoglobulins?
Antibodies
What are Ig produced by?
B cells, mostly plasma cells (terminal cells of B cell maturation)
What is the primary role of Ig?
- Recognise and bind to pathogens
- This may directly impede the biological process or direct other components of the immune system by ‘tagging’ the antigen
What is the basic structure of Ig?
- Soluble or membrane bound
- Y shaped
- 2 heavy chains
- 2 light chains
- Variable domains
What is the Fc portion of Ig defined by?
Heavy chains
What are the 5 types of heavy chain?
- IgG: Gamma
- IgA: Alpha
- IgM: Mu
- IgD: Delta
- IgE: Epsilon
What is a feature of IgG?
Most prevalent antibody subclass
What type of immunity is IgA involved in?
Mucous membrane immunity
What are the features of IgM?
- Initial phase of antibody production
- Exists as a pentamer - highest molecular weight
- Viscous
What is IgE involved in?
- Parasite immune response
- Hypersensitivity
What are the 2 types of light chains?
Kappa or lamda
How are kappa and lamda selected?
- Random selection for each cell
- Each cell will only make 1 type of light chain with 1 specificity
Where can free light chains be found?
In the blood at low levels but they are difficult to measure
What does the FC region define?
Constant region that defines subclass
What does the Fab region define?
Variable region that defines target binding
What is a paraprotein?
A monoclonal immunoglobulin present in blood or urine
What do paraproteins tell us?
If present, it tells us that there is monoclonal proliferation of a B lymphocyte / plasma cell somewhere in the body
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 do total immunoglobulin levels tell us?
Measures Ig subclasses by heavy chain/Fc section
What does electrophoresis tells us?
Assesses antibody diversity and identifies paraprotein
What does immunofixation do?
Identifies what class of paraprotein is present
What do light chain levels tell us?
Assesses imbalance/excess of light chains in urine or serum such as Bence-Jones protein
What do IgM paraproteins suggest and why?
- Lyphoma
- Maturing B-lymphocytes make IgM antibody at the start of the immune response
What do IgG and IgA paraproteins suggest and why?
- Myeloma
- Mature plasma cells generate these types of Ig after isotope switching
What is myeloma?
Neoplastic disorder of plasma cells, resulting (usually) in excessive production of a single type of Ig (paraprotein)
When does myeloma incidence peak?
7th decade (commoner in black populations)
What may cause the clinical manifestations of myeloma?
Direct effect of plasma cells or effect or paraprotein
What are the clinical features of myeloma?
- Bone disease
- Lytic bone lesions
- Pathological fractures
- Cord compression
- Hypercalcaemia
- Bone marrow failure especially anaemia
- Infections
What effects can paraproteins have?
- Renal failure (cast nephropathy)
- Hyper viscosity
- Hypogammaglobulinaemia
- Amyloidosis
Why can renal failure occur on myeloma?
Immunoglobulin deposition and blockage of renal tubules
How does hyper viscosity associated with myeloma present?
- Syndrome caused by increased viscosity in blood, impaired microciculartion and hypoperfusion
- Commonest clinical feature is bleeding - retinal, oral, nasal, cutaneous
- Can also cause cardiac failure, pulmonary congestion, confusion, renal failure
Why does hypogammaglobulinaemia occur in myeloma?
Impaired production of normal IG leads to a tendency to infection
What is amyloidosis?
- A group of disorders characterised by deposition of firbillar protein (abnormal configuration of proteins)
What is amyloidosis caused by paraprotein of light chains known as?
AL amyloid
How does AL amyloid present/?
- Nephrotic syndrome
- Cardiac failure (LVH)
- Carpal tunnel syndrome
- Autonomic neuropathy
- Cutaneous infiltration
How is myeloma diagnosed?
- Finding excess plasma cells in the bone marrow
- Must comprise >10% of total bone marrow cell population
What is monoclonal gammopathy of uncertain significance (MGUS)?
Paraproteins that are present in 3-4% of the over 75 population that are not pathological
What types of paraprotein are implicated in myeloma?
- IgG: 55%
- IgA: 21%
- Light chain only 22%
- Other: 2%
How is myeloma treated?
- Chemo: proteasome inhibitors. thalidomide, monoclonal antibodies
- Bisphosphonate therapy: zoledronic acid
- Radiotherapy
- Steroids
- Surgery: pinning of long bones, decompression of spinal cord
- Autologous stem cell transplant
What are IgM paraproteins associated with?
Low-grade lymphomas
What is the clinical presentation of IgM paraproteins?
- Bone marrow failure (anaemia, thrombocytopenia)
- Lymphadenopathy
- Hepatosplenomegaly
- B symptoms
- Paraprotein-related symptoms can occur
- Bone disease is very rare
Staging of myeloma
Based on albumin & beta-2 microglobulin
