Myeloma

Question 1

where are antibodies produced?

Answer 1

b cells - mostly plasma cells

Question 2

what is the primary role of antibodies?

Answer 2

recognise and bind pathogens

Question 3

describe and draw the basic structure of an antibody

Answer 3

The basic structure is a Y shape with 2 heavy and 2 light chains. Each antibody has variable antigen binding domains by everything else is constant. Fc portion is defined by the heavy chains.

Question 4

name the types of heavy chain found on antibodies

Answer 4

gamma
alpha
mu
delta
epsilon

Question 5

what is the most prevalent antibody subclass?

Answer 5

IgG

Question 6

what antibody is responsible for mucous membrane immunity?

Answer 6

IgA

Question 7

what antibody is the initial phase of antibody production?

Answer 7

IgM

Question 8

what antibody is responsible for parasite immune responses and hypersensitivity?

Answer 8

IgE

Question 9

describe the light chains on antibodies

Answer 9

The light chains are either kappa or lambda with a random selection for each cell. But, each cell will make only 1 type of light chain with 1 specificity. Free light chains are also found in the blood at low levels – difficult to measure.

Question 10

what is a paraprotein?

Answer 10

A paraprotein is a monoclonal immunoglobulin present in blood or urine.

Question 11

if present in blood or urine what does a paraprotein suggest?

Answer 11

there is a monoclonal proliferation of a B lymphocyte/plasma cell somewhere in the body

Question 12

what is serum protein electrophoresis?

Answer 12

This separates protein based on size and charge. Forms a characteristic pattern of bands of different widths and intensities based on proteins present.

Question 13

what is the function of the total immunoglobulin levels test?

Answer 13

measures Ig subclasses by heavy chains/Fc section

Question 14

why perform electrophoresis?

Answer 14

assesses antibody diversity

identifies paraprotein

Question 15

why perform immunofixation?

Answer 15

identifies what class of paraprotein is present (i.e. IgG, IgM)

Question 16

why perform light chain analysis?

Answer 16

assesses imbalance/excess of light chains in urine/serum

Question 17

IgM paraproteins =

Answer 17

lymphoma

o Maturing B-lymphocytes make IgM antibody at the start of the immune response

Question 18

IgG, IgA paraproteins =

Answer 18

myeloma

o Mature plasma cells generate these types of immunoglobulin after isotype switching

Question 19

what are myelomas?

Answer 19

neoplastic disorders of plasma cells, resulting in excessive production of a single type of immunoglobulin (paraprotein)

Question 20

what decade has the peak incidence of myeloma?

Answer 20

7th

Question 21

what ethnicity is most affected by myeloma?

Answer 21

black

Question 22

features of myeloma

Answer 22

•	Bone disease
o	Lytic bone lesions
o	Pathological fractures
o	Cord compression
o	Hypercalcaemia
•	Bone marrow failure esp. anaemia
•	Infections

Question 23

list the effects of the paraprotein in myeloma

Answer 23

renal failure - cast nephropathy
hyperviscosity
hypogammaglobulinaemia
amyloidosis

Question 24

how do paraproteins cause renal failure?

Answer 24

immunoglobulin deposition and blockage or renal tubules

Question 25

how do paraproteins cause hyperviscosity?

Answer 25

o Syndrome caused by increased viscosity in blood, impaired microcirculation and hypoperfusion o Commonest clinical features is bleeding – retinal, oral, nasal, cutaneous o Can also cause cardiac failure, pulmonary congestion, confusion, renal failure

Question 26

how do paraproteins cause hypogammaglobinemia?

Answer 26

o Impaired production of normal immunoglobulin | o Tendency to infection

Question 27

how do paraproteins cause amyloidosis?

Answer 27

o Group of diseases characterised by deposition of fibrillar protein o Morphological appearances, physical structure is similar o Biochemical or protein composition can vary o When caused by a paraprotein or light chains – AL amyloid o Nephrotic syndrome o Cardiac failure (LVH) o Carpal tunnel syndrome o Autonomic neuropathy o Cutaneous infiltration

Question 28

describe the diagnosis of myeloma

Answer 28

• Paraproteins are common o 3-4% of population over age of 75 o The vast majority have nothing wrong with them o This is termed monoclonal gammopathy of uncertain significance (MGUS) • Myeloma is diagnosed by finding excess plasma cells in the bone marrow • Must comprise > 10% of total bone marrow cell population • Type of paraprotein o IgG 55% o IgA 21% o Light chain only 22% o Other (IgD, non-secretory) 2% • Stage o Based on albumin and beta-2 microglobulin

Question 29

treatment of myeloma

Answer 29

``` • Chemotherapy o Proteasome inhibitors, IMiDs, monoclonal antibodies (in trials) • Bisphosphonate therapy o Zoledronic acid • Radiotherapy • Steroids • Surgery o Pinning of long bones; decompression of spinal cord • Autologous stem cell transplant ```

Question 30

wht are IgM paraproteins associated with?

Answer 30

low grade lymphomas of various types

Question 31

clinical presentation of IgM lymphoma

Answer 31

* Bone marrow failure (anaemia, thrombocytopenia) * Lymphadenopathy * Hepatosplenomegaly * B-symptoms