myeloma and paraproteins Flashcards

1
Q

what are antibodies

where are they produced

A

immunoglobulins

produced by B cells (mostly plasma cells)

can be either soluble or membrane bound

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

1y role of antibodies and how they do this

A

recognise and bind pathogens

this may directly impede the biological process of direct other components of the immune system by ‘tagging’ the antigen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

immunoglobulin structure

A

Y shaped structure
2 heavy chains
2 light chains

variable domain - fragment antigen binding (FAB)
everything else is constant - Fc portion (defined by the heavy chains)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what does the Fc portion of the antibody define

A

defines the role/subclass of the antibody

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

what are the 5 types of heavy chains

A
gamma - IgG
alpha - IgA
Mu - IgM
delta - IgD
epsilon - IgE
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

IgM - role

A

initial phase of antibody production

exists as a pentamer (5 molecules circulate together) - highest molecular weight

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

how prevalent is IgG

A

most prevalent antibody subclass - 75% of total

followed by IgA then IgM

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

what is IgA for

A

mucous membrane immunity - tends to be in the gut

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

what is IgE for

A

parasite immune responses

hypersensitivity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

what are the 2 types of light chains

A

kappa of lambda

  • random selection for each cell
  • each cell will only make 1 type of light chain w/ 1 specificity

free light chains are also found in the blood at low levels - difficult to measure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

what is a paraprotein

A

monoclonal immunoglobulin present in blood or urine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

what do paraproteins indicate

A

if present, it tells us that there is monoclonal proliferation of a B lymphocyte/plasma cell somewhere in the body

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

how do we detect paraproteins

A

separates protein based on size and charge

forms a characteristic pattern of bands of different widths and intensities base on proteins present

tells us whether there are any abnormal levels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

what does total immunoglobulin levels tell us

A

measures Ig subclasses by heavy chain/Fc section

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

what does electrophoresis tell us

A

assesses antibody diversity, identifies paraprotein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

what does immunofixation tell us

A

identifies what class of paraprotein is present e.g. IgG, IgM

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

what does levels of light chains tell us

A

assesses imbalance/XS of light chains in urine/serum

you should have approximately equal levels of light chains

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

when does immunoglobulin gene rearrangement occur

A
19
Q

process of antibody production

A

initial IgM production

cells mature

IgA and IgG production

20
Q

what do IgM paraproteins indicate

A

lymphoma

maturing B lymphocytes make IgM antibody at the start of the immune response

21
Q

what do IgG and IgA paraproteins indicate

A

myeloma

mature plasma cells generate these types of immunoglobulin after isotype switching

22
Q

what is myeloma

A

neoplastic disorder of plasma cells, resulting in XS production of a single type of immunoglobulin (paraprotein)

23
Q

who gets myeloma

A

peaks in 7th decade

ethnicity - commoner in Black population than White

24
Q

why do clinical manifestations occur in myeloma

A

may result from direct effect of plasma cells, or effect of paraprotein

25
Q

why do clinical manifestations occur in myeloma

A

may result from direct effect of plasma cells, or effect of paraprotein

26
Q

clinical features of myeloma

A

bone disease:

  • lytic bone lesions
  • pathological fractions
  • cord compression
  • hypercalcaemia
  • bone marrow failure - esp anaemia
  • infections
  • CRAB - hyperCalcaemia, Renal failure, Anaemia, Bone disease
27
Q

effects of the paraprotein in myeloma

A

renal failure - cast nephropathy

hyperviscosity

hypogammaglobulinaemia

amyloidosis

28
Q

how do paraproteins lead to cast nephropathy

A

immunoglobulin deposition and blockage of renal tubules

29
Q

how do paraproteins cause hyperviscosity

clinical features

A

syndrome caused by increased viscosity in blood, impaired microcirculation and hypoperfusion

commonest clinical feature is bleeding - retinal, oral, nasal, cutaneous

can also cause cardiac failure, pulmonary congestion, confusion, renal failure

30
Q

how do paraproteins lead to hypogammaglobulinaemia

A

impaired production of normal immunoglobulin

tendency to infection

31
Q

what is amyloidosis

A

group of diseases characterised by deposition of fibrillar protein

morphological appearances, physical stucture are similar

when caused by a paraprotein or light chains - AL amyloid

32
Q

features of amyloidosis

A
nephrotic syndrome 
cardiac failure (LVH)
carpal tunnel syndrome 
autonomic neuropathy
cutaenous infiltration
33
Q

what is MGUS

A

paraproteins are common

  • 3-4% of pop >75y/o
  • vast majority have nothing wrong with them - monoclonal gammopathy of uncertain significance
34
Q

how is myeloma diagnosed

A

finding XS plasma cells in the bone marrow

must comprise >10% of total bone marrow cell population

35
Q

types of paraproteins seen in myeloma

A

IgG 55%
IgA 21%
light chain only 22%
other (IgD, non-secretory) 2%

36
Q

how is myeloma staged

A

based on albumin and beta-2 microglobulin

37
Q

treatment of myeloma

A
chemotherapy 
bisphosphonate therapy
radiotherapy - localised pain control 
steroids
surgery 
autologous stem cell transplant
38
Q

chemotherapy for myeloma

A

proteasome inhibitors - carfilzomib, bortezomib

IMiDs - lenalidomide, pomalidomide

monocloncal antibodies

39
Q

what bisphosphonate is used in myeloma and why is it used

A

zoledronic acid

used to strengthen bones in pts w/ osteoporosis

40
Q

surgery for myeloma

A

pinning of long bones

decompression of spinal cord

40
Q

surgery for myeloma

A

pinning of long bones

decompression of spinal cord

40
Q

surgery for myeloma

A

pinning of long bones

decompression of spinal cord

41
Q

does IgM myeloma exist

A

NO

IgM paraproteins are associated w/ various types of low grade lymphomas

42
Q

clinical presentation of low grade lymphomas

A

bone marrow failure - anaemia, thrombocytopaenia
lymphadenopathy
hepato splenomegaly
B symptoms

paraproteins related symptoms can occur
bone disease is very rare