Myeloma Flashcards
What is antibodies produced by?
B cells
mostly plasma cells
Primary role of antibodies
To recognise and bind to pathogens
How do antibodies recognise and bind to pathogens?
They may directly impede a biological process or
Direct other compounds of the immune system by ‘tagging’ the antigen
What is the Fab region of the antibody?
Variable
Defines target binding
What is the Fc region of the antibody?
Constant
defines subclass
What is the shape of an antibody?
Y shaped
What are the 5 different types of the 2 heavy chains of antibodys?
IgG IgA IgM IgD IgE
Which isotope of antibodies is the most prevalent?
IgG
What does IgA do?
Mucous membrane immunity
What is IgM involved with?
Initial phase of Ab production
Exist as a pentamer with high molecular weight so viscous
2 light chains of antibodies
Kappa
Lambda
Serum immunoglobulin total level involves….
Measuring Ig subclasses by heavy chain/Fc section
Electrophoresis and immunofixation
Serum light chain levels / urine Bench Jones protein
What does electrophoresis do?
Assesses antibody diversity and identifies paraprotein
separates protein based on size and charge
Forms a characteristic pattern of bands of different widths and intensities based on protein present
- paraprotein or monoclonal band
What does a paraprotein appear as on electrophoresis?
A spike
If the same Ig is found in a region, what is this known as?
Paraprotein
What does immunofixation do?
Identifies which class of paraprotein is present i.e. IgG, IgM
What does serum light chain levels / urine bench jones protein look at?
Assess imbalance / excess of light chains in urine or serum
Features of paraprotein and what does it tell us?
Monoclonal immunoglobulin present in blood or urine (should all be different)
If present tells us that there is monoclonal proliferation of a B lymphocyte / plasma cell somewhere in the body
What should be done to identify a paraprotein?
Electrophoresis
What are IgM paraproteins found in?
Lymphoma
Maturing B lymphocytes make IgM antibody at the start of the immune response
What are IgG and IgA paraproteins found in?
Myeloma
Mature plasma cells generate these types of immunoglobulin after isotope switching
What is myeloma?
Neoplastic disorder of the plasma cells (abnormal plasma cells) in bone, resulting in excessive production of a single type of immunoglobulin (paraprotein)
Who is myeloma most commonly seen in?
Elderly
Black
Presentation of myeloma
CRAB - raised calcium - renal failure - anaemia (bone marrow failure) - lethargy - bone lesions Bone disease - lytic bone lesions - osteoporosis leading to pathological fractures - cord compression - bone pain Infections (lack of normal Ig) Amyloidosis
Effects of paraprotein in myeloma
Renal failure - cast nephropathy - immunoglobulin deposit in renal tubules blocking it (light chains clogging up the kidneys) Hyper viscosity - increased blood viscosity - impaired microcirculation - Hypoperfusion - bleeding - retinal, oral, nasal, cutaneous Hypogammaglobulinaemia - impaired production of normal IgG - tendency to infection Amyloidosis - AL amyloid if caused by light chain or paraprotein - nephrotic syndrome - cardiac failure (LVH) - carpal tunnel syndrome - autonomic neuropathy - cutaneous infiltration
What is amyloidosis?
A group of diseases characterised by the deposition of fibrillary protein
How do you get rid of paraprotein?
Chemotherapy
Pathology of myeloma
Excess plasma cells in bon marrow >10%
Paraproteins common
Types of paraprotein in myeloma
IgG myeloma = 55%
IgA myeloma = 21%
Light chain only = 22%
Other (IgD, non secretory)
Stage of myeloma is based on what?
Albumin and beta-2 macroglobulin
- if albumin goes down, paraprotein goes up
- beta 2 macroglobulin marker of how fast it is growing
Treatment of myeloma
"Watch and wait" until problems arise Chemotherapy Thalidomide Bisphosphonate therapy RT Steriods Surgery (pinning of long bones, decompression of spinal cord) Autologous stem cell transplants in younger patients
Why does IgM myeloma not exist?
IgM is made by the B lymphocytes not the plasma cells
What are IgM paraproteins associated with?
Low grade lymphomas
Clinical presentation of IgM paraproteins
Bone marrow failure - anaemia - thrombocytopenia Lymphadenopathy HSM B symptoms
Why are immunoglobulins usually made?
In response to an antigen
The making of immunoglobulins causes what to happen?
Clonal reproduction of plasma cells which release the same immunoglobulin to destroy the antigen
What is the most common immunoglobulin produced in myeloma?
IgG
Light chains of the immunoglobulins clogging up the kidneys can sometimes lead to what?
Amyloid sheet
Why is it vital to look at urine electrophoresis and serum?
Excess light chains have low molecular weight and they are often not detected by serum protein electrophoresis
What are the light chains found in urine called?
Bence Jones protein
Diagnosis for myeloma - must have 2 out of 3 for
Lytic bone lesions
Excess plasma cells in marrow
Serum paraprotein or urinary bence jones protein
What is monoclonal gammopathy of uncertain significance? (MGUS)
5% of people > 60 years old have a paraprotein
The vast majority are asymptomatic and will go onto develop myeloma
Overall survival of myeloma
7 years
Side effects of chemotherapy
Toxic to dividing cells - hair - GI - skin - blood - mucositis Nausea and vomiting Tumour lysis syndrome Bone marrow failure (neutropenic sepsis) Hyperuricaemia Specific drug side effects e.g. pulmonary fibrosis (busulphan) Secondary malignancy
What KEY blood results should be looked at in myeloma?
Total proteins
Albumin
CRABI numonic for remembering symptoms of myeloma
Hypercalcaemia Renal disease Anaemia Bone problems (overactivity of osteoclasts) Immunoglobulins
What features of a presentation would point towards a diagnosis of multiple myeloma?
Hypercalcaemia
Renal failure
High total protein
Investigations of multiple myeloma
Monoclonal proteins (IgA or IgG) in the serum
Urine Bench Jones Protein
Increased plasma cells in the bone marrow
Skeletal survey - for lytic bone lesions
X ray
- rain drop skull
What criteria is needed to diagnose multiple myeloma?
One major and one minor needed OR three minor who has signs of symptoms
Major criteria for multiple myeloma
Plasmacytoma (biopsy)
30% plasma cells in bone marrow
Elevated levels of M protein in blood or urine
Minor criteria for multiple myeloma
10 - 30% plasma cells in bone marrow
Minor elevations of M protein in blood or urine
Osteolytic lesions on imaging
Low levels of Abs (not produced by cancer cells) in the blood
Pathology of the hypercalcaemia present in myeloma
Primary factor
- increased osteoclastic bone resorption caused by local cytokines released by the myeloma cells
Much less common contributing factors
- impaired renal function
- increased renal tubular calcium reabsorption
- elevated PTH-rP levels
What can precipitate renal failure in patients with myeloma?
NSAIDs
What would multiple myeloma look like on blood film?
Rouleaux formation
