Myeloma and paraprotein Flashcards
Myeloma pathogenesis
Plasma cells move back into the bone marrow commonly
What is a paraprotein?
A paraprotein is an abnormal protein that is produced by plasma cells in the bone marrow.
They are made from monoclonal proliferation and all subsequent antibodies derived this way trace back to a unique parent cell (b-cell/plasma cell) somewhere in the body.
So basically myeloma is characterised by paraproteins which are populations of abnormal antibodies (paraproteins - produced by plasma cells) that have udnergone monoclonal proliferation so that there are lots of identical copies in the body.
Which cells produce immunoglobulins?
B-cells, mostly plasma cells specifically
The majority of immunoglobulin is bound to the B-cell surface but a significant proportion is released into the ECF of the blood and this is what can be measured.
What is the primary role of immunoglobulins?
Primary role is to recognise and bind pathogens to fight infection
They may directly impede the biological process or direct other components of the immune system by “tagging” the antigen
Describe the structure of an antibody/immunoglobulin
Basic Y-shaped structure
- 2 heavy chains - Fc region - constant (the same in each antibody) - determines subclass
- 2 light chains - Fab region - variable (this bit changes) this part determines antigen binding and varies massively
What are the 5 types of heavy chain (these determine the 5 subclasses of immunoglobulins)?
- Gamma – IgG - most prevalent antibody subclass (75% of total)
- Alpha – IgA - mucous membrane immunity so commonly found in the gut
- Mu – IgM - initial phase of antibody production, exists as a pentamer (highest weight)
- Delta – IgD - present in smaller quantities
- Epsilon - IgE - present in smaller quantities - parasite immune responses - determines allergic hypersensitivity/atopic responses
Light chains can be 1 of 2 things?
Kappa or lambda
This is randomly selected by the B cell but should be about 50/50 in total
So if you have a sample full of immunoglobulins that all look relatively the same, how can you tell if there’s something wrong/abnormal going on?
- You can identify the subclass by the Fc portion and measure the quantity of each subtype = total immunoglobulin levels test
- Now have lots of different antibodies – different sizes and shape - you can use lab tests to determine between them
- You can also have populations of antibody that are identical in their Fc and Fab region => paraprotein
Which lab test can be used to assess antibody diveristy and identify paraproteins?
Serum protein electropheresis - separates protein based on their size and charge
Forms a characteristic pattern of bands of different widths and intensities based on proteins present. See image - unique population of immunoglobulins is present in large quanitity and has been identified
Which test can be used to identify what class of paraprotein is present? i.e IgG or IgM
Immunofixation
If you have a massive imbalance or excess of one antibody over another somwhere in the body what can you test?
Light chain test to see if there is imbalance/excess of light chains in the urin or serum - however this test isn’t really done anymore
IgM paraproteins are commonly seen in which disease?
Lymphoma
- Maturing B-cells make IgM antibodies at the start of the immune response
IgG and IgA paraproteins are seen in which disease?
Myeloma
- Mature plasma cells generate these types of immunoglobulin after isotype switching
What is Myeloma?
- A neoplastic disorder of plasma cells
- Usually results in excessive production of a single type of immunoglobulin (paraprotein)
- Peaks in 70s
- Clinical manifestations may result from direct effect of plasma cells, or effect of paraprotein
Clinical features of Myeloma
-
Bone disease - widespread due to clonal proliferation in bone marrow.
- Lytic bone disease
- Pathological fractures
- Cord compression
- Back pain
- Hypercalcaemia - release of Ca2+ as a result of damaged bone due to lytic bone disease
- Bone marrow failure - growth of plasma cells into bone marrow esp. anaemia
- Infection due to bone marrow failure (lower WCC) or through effect of paraprotein drowning out normal immunoglobulins
