Myeloma and Paraproteins Flashcards
what is an antibody? and what is their function?
Antibody = Immunoglobulin
- Produced by B cells, mostly plasma cells
- Can be either soluble or membrane-bound (Most of them are bound to cells themselves and this is hard to measure but a significant portion is released into the blood and extracellular fluid and this is what we measure)
- 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
what is the structure of an immunoglobulin?
- Basic structure - Y –shaped
- 2 heavy chains (Heavy chains are the longer bits)
- 2 light chains
- Variable domains -FAB (fragment antigen binding domain)
- Everything else (constant)
- Fc portion – defined by the heavy chains (as its only made up form the heavy chain as the light chain is designed to influence the variable antigen binding bit)
what are the five different types of heavy chains?
(Leads to 5 subclasses of immunoglobulins)
Gamma – IgG
Alpha – IgA
Mu – IgM
Delta – IgD
Epsilon - IgE
Heavy chains:
what is IgM?
Initial phase of antibody production
Exists as a pentamer – highest molecular weight
5 IgM molecules stuck together all roaming around looking for infection
Heavy chains:
what is IgG?
Most prevalent antibody subclass (75% of total)
Heavy chains:
what is IgA?
Mucous membrane immunity (tends to be what you find in the gut)
Heavy chains:
what is IgE?
Parasite immune responses, hypersensitivity
IgE is less important in the developed world compared to the developing world
what are the types of light chains?
•(Can be) Kappa or lambda
- Random selection for each cell
- But, each cell will only make 1 type of light chain with 1 specificity
Should have around half and half
- Free light chains are also found in the blood at low levels – difficult to measure
Slightly more light chains are made compared to heavy chains
what is the Immunoglobulin structure?
Top bit is very diverse – ability to recognize any epitope on virus or bacterial infection
what is Immunoglobulin production done by?
plasma cells
Plasma cell on left
Plasma cell main job is productizing immunoglobulin factor 8
How can you tell which is wrong or not as lots of them and look similar at first glance
Should all be slightly different
All a bit different
how do you detect the immunoglobulin?
Identify the immunoglobulin by the Fc portion, the subclass, and can use an assay that detects IgG heavy chain, IgA heavy chain etc
Immunoglobulin total levels - what is the most common?
Can measure quantities of individual subtypes
IgG most common followed by IgA
See a population of antibodies all the same
So how do we pick out this abnormal population
what is shown here?
paraproteins
what is a paraprotein?
- A paraprotein – monoclonal immunoglobulin present in blood or urine
- If present, it tells us that there is monoclonal proliferation of a B lymphocyte / plasma cell somewhere in the body
A paraprotein is an abnormal protein that is produced by plasma cells in the bone marrow
(monoclonal immunoglobulin - means we have identical unique clonal population of IG somewhere)
what is 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
Most prevalent protein in the blood is albumin and acts as a buffer
Gamma region is where immunoglobulins are
Allows us to see if there is an abnormality in the immunoglobulin composition, can see if they are all different or al the same
Picutre on front of card = This is showing normal
In contrast this is showing a one unique band
Showing paraprotein – unique population of IGs and this is how it is identified
Electrophoresis is the key test and tells you if they are all the same or different, tells us if you have a paraprotein
where do myelomas occur and what IGs are involved?
B cells start to encounter antigens in the germinal centre
Cancerous transformation can happen at ay point
what are the features of a myeloma?
bone disease:
- lytic bone lesions
- pathological fractures
- (spinal) cord compression
- Hypercalcaemia (relased from damaged bone as a result of lytic bone disease)
bone marrow failure esp. anaemia (growth of the plasma cells in the bone marrow results in bone marrow failure, 2nd commonest manifestation of myeloma)
Infections (increased tendency to infections due to bone marrow failure resulting in low white cells but also through the effect of the paraprotein drowning out the production of normal immunoglobulins and this is called immunoparesis)
Pictures:
Thoracic soft tissue mass, cord compression
Extensive lytic bone disease in the skull
This tells us if there is a paraprotein
- May tell you something funny is going on e.g. if it is sky high off the charts as arnt many things that cause protein to double
- This can also let you know something is wrong
- just measures how sticky blood is and how fast it sinks and is a measure of how much protein in the blood so will go up in patients with paraprotein/elevated proteins but not specific enough for this case
2, means big globulin or thick blood, lymphoplasmic lymphoma where you have a IgM paraprotein. IgM have increased viscosity
Melanoma have nothing to do with the blood
Most people do require some monitoring
- If you have any of them you don’t have MGUS and probably myeloma in that situation
If you have more than 10% plasma cells then you have myeloma
Not 4. as you have excess plasma cells and you don’t have lymphoma and you have a IgG paraprotein rather than a IgM paraprotein
myeloma isn’t curable and doesn’t go away for most patients
No point in treating if it isn’t causing harm as no point in giving chemotherapy
Probably just mechanical back pain
We do give bisphosphonate to protect her bones and watch her closely
She doesn’t have anything to gain form treatment at this stage
Developed symptomatic myeloma, got end organ damage
Give more bisphosphonate
Fluids for renal function
Needs antimyeloma therapy
