Myeloma

Question 1

What are immunoglobulins?

Answer 1

Antibodies

Question 2

What are Ig produced by?

Answer 2

B cells, mostly plasma cells (terminal cells of B cell maturation)

Question 3

What is the primary role of Ig?

Answer 3

• Recognise and bind to pathogens
• This may directly impede the biological process or direct other components of the immune system by ‘tagging’ the antigen

Question 4

What is the basic structure of Ig?

Answer 4

• Soluble or membrane bound
• Y shaped
• 2 heavy chains
• 2 light chains
• Variable domains

Question 5

What is the Fc portion of Ig defined by?

Answer 5

Heavy chains

Question 6

What are the 5 types of heavy chain?

Answer 6

• IgG: Gamma
• IgA: Alpha
• IgM: Mu
• IgD: Delta
• IgE: Epsilon

Question 7

What is a feature of IgG?

Answer 7

Most prevalent antibody subclass

Question 8

What type of immunity is IgA involved in?

Answer 8

Mucous membrane immunity

Question 9

What are the features of IgM?

Answer 9

• Initial phase of antibody production
• Exists as a pentamer - highest molecular weight
• Viscous

Question 10

What is IgE involved in?

Answer 10

• Parasite immune response
• Hypersensitivity

Question 11

What are the 2 types of light chains?

Answer 11

Kappa or lamda

Question 12

How are kappa and lamda selected?

Answer 12

• Random selection for each cell
• Each cell will only make 1 type of light chain with 1 specificity

Question 13

Where can free light chains be found?

Answer 13

In the blood at low levels but they are difficult to measure

Question 14

What does the FC region define?

Answer 14

Constant region that defines subclass

Question 15

What does the Fab region define?

Answer 15

Variable region that defines target binding

Question 16

What is a paraprotein?

Answer 16

A monoclonal immunoglobulin present in blood or urine

Question 17

What do paraproteins tell us?

Answer 17

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

Question 18

What does serum protein electrophoresis do?

Answer 18

• Separates protein based on size and charge
• Forms a characteristic pattern of bands of different widths and intensities based on proteins present

Question 19

What do total immunoglobulin levels tell us?

Answer 19

Measures Ig subclasses by heavy chain/Fc section

Question 20

What does electrophoresis tells us?

Answer 20

Assesses antibody diversity and identifies paraprotein

Question 21

What does immunofixation do?

Answer 21

Identifies what class of paraprotein is present

Question 22

What do light chain levels tell us?

Answer 22

Assesses imbalance/excess of light chains in urine or serum such as Bence-Jones protein

Question 23

What do IgM paraproteins suggest and why?

Answer 23

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

Question 24

What do IgG and IgA paraproteins suggest and why?

Answer 24

• Myeloma
• Mature plasma cells generate these types of Ig after isotope switching

Question 25

What is myeloma?

Answer 25

Neoplastic disorder of plasma cells, resulting (usually) in excessive production of a single type of Ig (paraprotein)

Question 26

When does myeloma incidence peak?

Answer 26

7th decade (commoner in black populations)

Question 27

What may cause the clinical manifestations of myeloma?

Answer 27

Direct effect of plasma cells or effect or paraprotein

Question 28

What are the clinical features of myeloma?

Answer 28

* Bone disease * Lytic bone lesions * Pathological fractures * Cord compression * Hypercalcaemia * Bone marrow failure especially anaemia * Infections

Question 29

What effects can paraproteins have?

Answer 29

* Renal failure (cast nephropathy) * Hyper viscosity * Hypogammaglobulinaemia * Amyloidosis

Question 30

Why can renal failure occur on myeloma?

Answer 30

Immunoglobulin deposition and blockage of renal tubules

Question 31

How does hyper viscosity associated with myeloma present?

Answer 31

* Syndrome caused by increased viscosity in blood, impaired microciculartion and hypoperfusion * Commonest clinical feature is bleeding - retinal, oral, nasal, cutaneous * Can also cause cardiac failure, pulmonary congestion, confusion, renal failure

Question 32

Why does hypogammaglobulinaemia occur in myeloma?

Answer 32

Impaired production of normal IG leads to a tendency to infection

Question 33

What is amyloidosis?

Answer 33

* A group of disorders characterised by deposition of firbillar protein (abnormal configuration of proteins)

Question 34

What is amyloidosis caused by paraprotein of light chains known as?

Answer 34

AL amyloid

Question 35

How does AL amyloid present/?

Answer 35

* Nephrotic syndrome * Cardiac failure (LVH) * Carpal tunnel syndrome * Autonomic neuropathy * Cutaneous infiltration

Question 36

How is myeloma diagnosed?

Answer 36

* Finding excess plasma cells in the bone marrow * Must comprise \>10% of total bone marrow cell population

Question 37

What is monoclonal gammopathy of uncertain significance (MGUS)?

Answer 37

Paraproteins that are present in 3-4% of the over 75 population that are not pathological

Question 38

What types of paraprotein are implicated in myeloma?

Answer 38

* IgG: 55% * IgA: 21% * Light chain only 22% * Other: 2%

Question 39

How is myeloma treated?

Answer 39

* Chemo: proteasome inhibitors. thalidomide, monoclonal antibodies * Bisphosphonate therapy: zoledronic acid * Radiotherapy * Steroids * Surgery: pinning of long bones, decompression of spinal cord * Autologous stem cell transplant

Question 40

What are IgM paraproteins associated with?

Answer 40

Low-grade lymphomas

Question 41

What is the clinical presentation of IgM paraproteins?

Answer 41

* Bone marrow failure (anaemia, thrombocytopenia) * Lymphadenopathy * Hepatosplenomegaly * B symptoms * Paraprotein-related symptoms can occur * Bone disease is very rare

Question 42

Staging of myeloma

Answer 42

Based on albumin & beta-2 microglobulin