Myeloma and Paraproteins Flashcards
1
Q
Describe the basic immunoglobulin structure?
A
- Y shaped
- 2 heavy chains
- 2 light chains
2
Q
What are the 2 regions of an immunoglobulin?
A
- Variable domains, also called Fab region
- Formed from heavy and light chain
- Defines target binding
- Fc portion
- Formed from only heavy chain
- Defines subclass of antibody
3
Q
What is the variable domain also called?
A
Fab region
4
Q
What is the variable domain formed from?
A
- Formed from heavy and light chain
5
Q
What does the variable domain define?
A
- Defines target binding
6
Q
What is the Fc portion formed from?
A
- Formed from only heavy chain
7
Q
What does the Fc portion define?
A
- Defines subclass of antibody
8
Q
What are the 5 types of heavy chains?
A
- Gamma IgG
- Most prevalent subclass (75%)
- Alpha IgA
- Mucous membrane immunity
- Mu IgM
- Initial phase of antibody production
- Exists as pentamer
- Delta IgD
- Epsilon IgE
- Parasite immune responses, hypersensitivity
9
Q
What is the most prevalent subclass of heavy chain?
A
- Gamma IgG
- Most prevalent subclass (75%)
10
Q
What is each of the 5 heavy chains for?
A
- Gamma IgG
- Most prevalent subclass (75%)
- Alpha IgA
- Mucous membrane immunity
- Mu IgM
- Initial phase of antibody production
- Exists as pentamer
- Delta IgD
- Epsilon IgE
- Parasite immune responses, hypersensitivity
11
Q
Which heavy chain exists as a pentamer?
A
- Mu IgM
- Initial phase of antibody production
- Exists as pentamer
12
Q
What are the 2 types of light chain?
A
- Kappa
- Lamba
13
Q
How is the light chain of a Ig selected?
A
Which light chain cell has is selected randomly, with each cell only making 1 type of light chain with 1 specificity
14
Q
What are the normal levels of:
- IgG
- IgA
- IgM
- IgD
- IgE
A
- IgG
- 6-15g/L
- IgA
- 1-4.5g/L
- IgM
- 0.5-2g/L
- IgD and IgE only present in small levels
15
Q
What is a paraprotein?
A
Paraprotein = monoclonal immunoglobulin present in blood or urine
16
Q
What does the presence of a paraprotein tell us?
A
If present, tells us there is monoclonal proliferation of a B lymphocyte/plasma cell somewhere in body
17
Q
What investigation detects paraproteins?
A
This can be detected by serum protein electrophoresis:
- Separates protein based on size and charge
- Forms characteristic pattern of bands of different widths and intensities based on what proteins present
- Gamma region is for immunoglobulins
18
Q
What is protein electrophoresis?
A
- Separates protein based on size and charge
- Forms characteristic pattern of bands of different widths and intensities based on what proteins present
- Gamma region is for immunoglobulins
19
Q
What region on protein electrophoresis is for immunoglobulins?
A
Gamma region
20
Q
What are investigation options to investigate paraproteins?
A
- Total immunoglobulin levels
- Measures Ig subclasses by heavy chain/Fc section
- Electrophoresis
- Assesses antibody diversity, identifies paraprotein
- Immunofixation
- Identifies what class of paraprotein is present (such as IgG or IgM)
- Light chains
- Assesses imbalance/excess of light chains in urine or serum
21
Q
What does total immunoglobulin levels tell us?
A
- Measures Ig subclasses by heavy chain/Fc section
22
Q
What does electrophoresis tell us?
A
- Assesses antibody diversity, identifies paraprotein
23
Q
What does immunofixation tell us?
A
- Identifies what class of paraprotein is present (such as IgG or IgM)
24
Q
What does light chains investigation tell us?
A
- Assesses imbalance/excess of light chains in urine or serum
25
What are: IgM, IgG and IgA paraproteins associated with?
* IgM paraproteins associated with lymphoma
* Maturing B cells make IgM antibody at start of immune response
* IgG, IgA paraproteins associated with myeloma
* Mature plasma cells generate these types of Ig after isotype switching
26
What is myeloma?
Neoplastic disorder of plasma cells, resulting in excessive production of single type of immunoglobulin (paraprotein)
27
Describe the epidemiology of myeloma?
| (age, ethnicity)
* Peaks in 7th decade
* Ethnicity – commoner in black people than white
28
Describe the clinical features of myeloma?
* Bone disease
* Lytic bone lesions
* Pathological fractures
* Cord compression
* Hypercalcaemia
* Bone marrow failure
* Especially anaemia
* Infections
* For presentation remember CARB
* Hypercalcaemia, renal failure, anaemia, bone disease
29
What are symptoms/signs of bone disease?
* Lytic bone lesions
* Pathological fractures
* Cord compression
* Hypercalcaemia
30
What pneumonic should be remembered for the presentation of myeloma?
* For presentation remember CARB
* Hypercalcaemia, renal failure, anaemia, bone disease
31
Describe the clinical features of myeloma due to the paraproteins?
* Renal failure
* Immunoglobulin deposition and blockage or renal tubules
* Hyperviscocity
* Syndromes caused by increased viscosity in blood, impaired microcirculation and hypoperfusion
* Commonest feature is bleeding – retinal, oral, nasal, cutaneous
* Can also cause cardiac failure
* Hypogammaglobulinaemia
* Impaired production of normal immunoglobulin
* Tendency to infection
* Amyloidosis
* Group of diseases characterised by deposition of fibrillary protein
* Called AL amyloid when caused by paraprotein or light chains
* Symptoms (depends on where amyloid forms) – nephrotic syndrome, cardiac failure (LVH), carpal tunnel syndrome, autonomic neuropathy, cutaneous infiltration
32
What is amyloidosis?
* Group of diseases characterised by deposition of fibrillary protein
* Called AL amyloid when caused by paraprotein or light chains
33
Describe clinical features of amyloidosis?
* Symptoms (depends on where amyloid forms) – nephrotic syndrome, cardiac failure (LVH), carpal tunnel syndrome, autonomic neuropathy, cutaneous infiltration
34
What is amyloidosis called when caused by paraproteins or light chains?
* Called AL amyloid when caused by paraprotein or light chains
35
What is hypogammaglobulinaemia?
* Impaired production of normal immunoglobulin
36
What is a complication of hypogammaglobulinaemia?
* Tendency to infection
37
Do paraproteins always indicate pathology?
Some of population (3-4% of over 75s) have paraproteins, there is nothing wrong with them and is termed monoclonal gammopathy of uncertain significance (MGUS)
38
What does MGUS stand for?
Monoclonal gammapathy of uncertain significance
39
How is myeloma diagnosed?
* Diagnosed by finding excess plasma cells in the bone marrow
* Must comprise \>10% of total bone marrow cell population
40
What % of total bone marrow cell population must be plasma cells to be myeloma?
* Diagnosed by finding excess plasma cells in the bone marrow
* Must comprise \>10% of total bone marrow cell population
41
What are the most common kinds of paraproteins responsible for myeloma?
* IgG 55%
* IgA 21%
* Light chain only 22%
* Often not detected with electrophoresis as looks for heavy and light chains
* Other (IgD, non-secretory) 2%
42
What is staging of myeloma based on?
* Based on albumin and beta-2 microglobulin
43
Describe the treatment for myeloma?
* Chemotherapy
* Proteasome inhibitors
* Drugs – Carfilzomib, Bortezomib
* IMiDs
* Drugs – Lenalidomide, Pomalidomide
* Monoclonal antibodies
* Bisphosphonate therapy
* Drug – Zoledronic acid
* Effect – prevents bone breakdown
* Radiotherapy
* For localised symptom control
* Steroids
* Surgery
* Pinning of long bones
* Decompression of spinal cord
* Autologous stem cell transplant
44
What chemotherapy drugs are used for myeloma?
* Proteasome inhibitors
* Drugs – Carfilzomib, Bortezomib
* IMiDs
* Drugs – Lenalidomide, Pomalidomide
* Monoclonal antibodies
45
For biphosphonate therapy:
- drug
- effect
* Drug – Zoledronic acid
* Effect – prevents bone breakdown
46
What is IgM myeloma?
Remember IgM myeloma does not exist
47
What are IgM paraproteins associated with?
Associated with low-grade lymphomas
48
Describe the presentation of IgM paraproteins?
* Bone marrow failure
* Anaemia, thrombocytopenia
* Lymphadenopathy
* Hepatosplenomegaly
* B symptoms
* Paraprotein related symptoms can occur
* Bone disease very rare
