Myeloma Flashcards
1
Q
What are the 5 types of heavy chains of antibodies?
A
- gamma- IgG
- most prevelant antibody subclass (75%)
- alpha- IgA
- mucous membrane immunity
- mu- IgM
- initial phase of antibody production
- is a pentamer (highest molecular weight)
- delta- IgD
- epsilon- IgE
- parasites immune response, hypersensitivity
2
Q
What are the 2 types of light chains of antibodies?
A
- kappa or lambda
- random selection for each cell
- each cell will only make 1 type of light chain with 1 specificity
* free light chains are also found in blood, low levels
3
Q
What do light chain tests assess?
A
- imbalance/excess of light chain in urine/serum
4
Q
What is the structure of immunoglobulin?
A
- Fab region
- variable
- defines target binding
- Fc region
- constant
- heavy chains
- defines subclass
5
Q
What is total immunoglobulin level?
A
- measures Ig subclasses by heavy chain/Fc section
- IgG: 6-15g/L
- IgA: 1-4.5g/L
- IgM: 0.5-2.0g/L
6
Q
What is a paraprotein?
A
- monoclonal immunoglobulinpresent in blood or urine
- presence indicated monoclonal proliferation of a B lymphocyte/plasma cell
7
Q
What is serum protein electropheresis?
A
- assesses antibody diversity, identifies paraprotein
- seperates proteins based on size + charge
- forms a characteristic pattern of bands of different widths + intensities, based on proteins present
8
Q
What is immunofixation?
A
- identifies what class of paraprotein is present
- i.e. IgG, IgM
9
Q
Which immunoglobulin subclasses are involved in lymphoma and myeloma?
A
- lymphoma- IgM paraproteins
- maturing B-lymphocytes amke IgM antibody at the start of the immune response
- myeloma- IgG, IgA paraproteins
- mature plasma cells generate these types of immunoglobulin after isotype switching
10
Q
What are features of myeloma?
A
- neoplastic disorder of plasma cells -> excessive production of a single type of paraprotein (immunoglobulin)
- peak in 7th decade
- black ethnicity
- plasma cells and/or paraprotein cause clinical manifestations
11
Q
What are the signs of myeloma?
A
- bone disease
- lytic bone lesions
- pathological bone fractures
- cord compression
- hypercalcaemia
- bone marrow failure
- anaemia
- infections
- CRAB
- hyperCalcaemia
- Renal failure
- Anaemia
- Bone disease
12
Q
What are the effects of the paraprotein in myeloma?
A
- renal failure- cast nephropathy
- immunoglobulin deposition + blcokage of renal tubes
- hyperviscosity
- inc. blood viscosity, impaired microcirculation, hypoperfusion
- bleeding- retinal, oral, nasal, cutaneous
- cardiac failure, pulmonary congestion, confusion, renal failure
- hypogammaglobulinaemia
- dec. production of normal immunoglobulin
- infections
- amyloidosis- AL amyloid (cause; paraprotein/light chains)
- deposition of fibrillar protein
- morphological appearances, physical structure similar
- biochemical/protein composition variable
- nephrotic syndrome, cardiac failure (LVH), carpal tunnel syndrome, autonomic neuropathy, cutaneous infiltration
13
Q
What is the diagnosis for myeloma?
A
- paraprotein common
- 3-4% over 75 yrs
- monoclonal gammopathy of uncertain significance (MGUS)
- IgG (55%), IgA (21%), light chain only (22%), other (IgD, non-secretory) (2%)
- excess plasma cells in bone marrow
- > 10% of total bone marrow cell population
- stage
- based on albumin + beta-2 microglobulin
14
Q
What is the treatment for myeloma?
A
- chemotherapy
- proteasome inhibitors (zcarfilzomib)
- IMiDs (lenolidomide)
- monoclonal antibodies
- biphosphonate therapy
- zoledronic acid
- radiotherapy
- steroids
- surgery
- pinning long bone, spinal cord decompression
- autologus stem cell transplant
15
Q
What are features of IgM paraproetins?
A
- associated with low grade lymphoma
- bone marrow failure
- anaemia, thrombocytopenia
- lymphadenopathy
- hepatosplenomegaly
- B symptoms
* IgM myeloma does not exist
* bone disease very rare
