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

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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

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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)

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4
Q

what does the Fc portion of the antibody define

A

defines the role/subclass of the antibody

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5
Q

what are the 5 types of heavy chains

A
gamma - IgG
alpha - IgA
Mu - IgM
delta - IgD
epsilon - IgE
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6
Q

IgM - role

A

initial phase of antibody production

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

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7
Q

how prevalent is IgG

A

most prevalent antibody subclass - 75% of total

followed by IgA then IgM

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8
Q

what is IgA for

A

mucous membrane immunity - tends to be in the gut

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9
Q

what is IgE for

A

parasite immune responses

hypersensitivity

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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

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11
Q

what is a paraprotein

A

monoclonal immunoglobulin present in blood or urine

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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

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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

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14
Q

what does total immunoglobulin levels tell us

A

measures Ig subclasses by heavy chain/Fc section

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15
Q

what does electrophoresis tell us

A

assesses antibody diversity, identifies paraprotein

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16
Q

what does immunofixation tell us

A

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

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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

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18
Q

when does immunoglobulin gene rearrangement occur

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
why do clinical manifestations occur in myeloma
may result from direct effect of plasma cells, or effect of paraprotein
26
clinical features of myeloma
bone disease: - lytic bone lesions - pathological fractions - cord compression - hypercalcaemia - bone marrow failure - esp anaemia - infections - CRAB - hyperCalcaemia, Renal failure, Anaemia, Bone disease
27
effects of the paraprotein in myeloma
renal failure - cast nephropathy hyperviscosity hypogammaglobulinaemia amyloidosis
28
how do paraproteins lead to cast nephropathy
immunoglobulin deposition and blockage of renal tubules
29
how do paraproteins cause hyperviscosity clinical features
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
how do paraproteins lead to hypogammaglobulinaemia
impaired production of normal immunoglobulin tendency to infection
31
what is amyloidosis
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
features of amyloidosis
``` nephrotic syndrome cardiac failure (LVH) carpal tunnel syndrome autonomic neuropathy cutaenous infiltration ```
33
what is MGUS
paraproteins are common - 3-4% of pop >75y/o - vast majority have nothing wrong with them - monoclonal gammopathy of uncertain significance
34
how is myeloma diagnosed
finding XS plasma cells in the bone marrow must comprise >10% of total bone marrow cell population
35
types of paraproteins seen in myeloma
IgG 55% IgA 21% light chain only 22% other (IgD, non-secretory) 2%
36
how is myeloma staged
based on albumin and beta-2 microglobulin
37
treatment of myeloma
``` chemotherapy bisphosphonate therapy radiotherapy - localised pain control steroids surgery autologous stem cell transplant ```
38
chemotherapy for myeloma
proteasome inhibitors - carfilzomib, bortezomib IMiDs - lenalidomide, pomalidomide monocloncal antibodies
39
what bisphosphonate is used in myeloma and why is it used
zoledronic acid used to strengthen bones in pts w/ osteoporosis
40
surgery for myeloma
pinning of long bones decompression of spinal cord
40
surgery for myeloma
pinning of long bones decompression of spinal cord
40
surgery for myeloma
pinning of long bones decompression of spinal cord
41
does IgM myeloma exist
NO IgM paraproteins are associated w/ various types of low grade lymphomas
42
clinical presentation of low grade lymphomas
bone marrow failure - anaemia, thrombocytopaenia lymphadenopathy hepato splenomegaly B symptoms paraproteins related symptoms can occur bone disease is very rare