Myeloma and Paraproteins

Question 1

What cells produce antibodies?

Answer 1

Plasma cells (IgM produced by B lymphocytes)

Question 2

What are the two forms in which Ig can exist?

Answer 2

Membrane bound

Soluble

Question 3

What is the role of antibodies?

Answer 3

Recognise and bind to pathogens to be tagged for destruction

Question 4

What is the basic structure of Ig?

Answer 4

Y shaped
2 heavy chains and 2 light chains
Variable and constant domains
Fc and Fab region

Question 5

What is the constant fraction of Ig useful for?

Answer 5

It is a flag for the immune system

Question 6

What are the five heavy chain types of Ig?

Answer 6

IgM, IgG, IgA, IgE, IgD

Question 7

What is IgM?

Answer 7

Initial phase antibody

Exists as pentamer

Question 8

What is IgG?

Answer 8

Most prevalent antibody subclass
Long lived immunity

Question 9

What is IgA implicated in?

Answer 9

Mucosal membrane immunity

Question 10

What is IgE involved in?

Answer 10

Parasite immune responses

Also implicated in hypersensitivity reactions

Question 11

What are the two types of light chains?

Answer 11

Kappa or lambda

NB one cell will only make 1 type of light chain

Question 12

Can free light chains be found in the blood?

Answer 12

Only at low levels

Question 13

What does the Fab region determine?

Answer 13

It is variable and defines target binding

Question 14

What does the Fc region determine?

Answer 14

Constant and defines subclass

Question 15

What cells make Ig?

Answer 15

Plasma cells

Question 16

What is normal IgG level?

Answer 16

6-15g/L

Question 17

What is normal IgA level?

Answer 17

1-4.5g/L

Question 18

What is a normal IgM level?

Answer 18

0.5-2g/l

Question 19

What is a paraprotein?

Answer 19

A monoclonal Ig present in the blood or urine

Question 20

What does a paraprotein tell us?

Answer 20

There is a monoclonal proliferation of a B lymphocyte/plasma cell elsewhere in the body

Question 21

What tests can you do to assess Ig levels?

Answer 21

Total Ig levels
Electrophoresis
Immunofixation
Light chains (assessing imbalance/xs in urine/serum)

Question 22

What is electrophoresis?

Answer 22

Separation of proteins based on size and charge using an electric current
Spikes may be indicative of a paraprotein

Question 23

What is immunofixation used for?

Answer 23

Finding out what class of paraprotein is present (IgG, IgM)

Question 24

What kinds of cells do lymphomas tend to arise from and why?

Answer 24

B cells due to germinal centre reaction

Question 25

What occurs in the germinal centre reaction?

Answer 25

Each of the cells start with a germline configuration B lymphocyte chops up DNA to see what variable domains can be made If it encounters an antigen it binds it and undergoes somatic hypermutation whereby the Ab mutates further to form a v. specific mutation

Question 26

What is an IgM paraprotein indicative of?

Answer 26

Lymphoma (as maturing B lymphocytes make IgM)

Question 27

What is an IgA/IgG paraprotein indicative of?

Answer 27

Myeloma | mature plasma cells generate these types of Ab after isotope switching

Question 28

What is myeloma?

Answer 28

Neoplastic disorder of plasma cells, usually resulting in excessive production of a single paraprotein

Question 29

What age is myeloma most common in?

Answer 29

70s

Question 30

What are the clinical features of myeloma?

Answer 30

``` Lytic bone lesions Pathological fractures Cord compression Hypercalcaemia Bone marrow failure (anaemia, bleeding, infections) Renal failure Hyperviscosity Hypogammaglobulinaemia Amyloidosis ```

Question 31

Why do you get lytic bone disease in myeloma?

Answer 31

Osteoclast activation by cytokines

Question 32

Why do you get bone marrow failure in myeloma?

Answer 32

Bone marrow becomes overrun with plasma cells | Infections as no normal Ab left in later stages

Question 33

Why do you get renal failure in myeloma?

Answer 33

Cast nephropathy | Ig deposition and blockage of renal tubules

Question 34

Why do you get hypogammaglobulinaemia in myeloma?

Answer 34

Impaired normal production of Ig

Question 35

What is amyloidosis?

Answer 35

Deposition of fibrillar proteins (formed by abnormal folding of proteins to form crystalloid structure)

Question 36

What kind of amyloidosis is caused by light chain/paraprotein deposition?

Answer 36

AL amyloidosis

Question 37

What kind of amyloidosis is caused by excess protein from an uncontrolled inflammatory reaction?

Answer 37

AA amyloidosis

Question 38

What conditions are associated with AA amyloidosis?

Answer 38

``` Nephrotic syndrome Cardiac failure Carpal tunnel Autonomic neuropathy (dizziness, diarrhoea) Cutaneous infiltration ```

Question 39

What can result from hyperviscosity?

Answer 39

Increased viscosity of blood --> impaired microcirculation and hypoperfusion Commonly get bleeding as capillaries burst Can also --> cardiac failure, pulmonary congestion, confusion, renal failure

Question 40

true or false: | Finding paraproteins in serum = myeloma?

Answer 40

No, 3-4% of population over 75 have these with no clinical consequences = monoclonal gammopathy of uncertain significance

Question 41

How do you diagnose myeloma?

Answer 41

By finding excess plasma proteins in the bone marrow (>10% of bone marrow)

Question 42

What is the most common type of paraprotein?

Answer 42

IgG

Question 43

How do you stage myeloma?

Answer 43

Albumin and beta-2 microglobulin

Question 44

How do you treat myeloma?

Answer 44

Chemo - proteasome inhibitors, IMiDs (thalidomide), monoclonal antibodies Bisphosphonates (zoledronic acid) Steroids Surgery (pinning of long bones, cord decompression) Autologous stem cell transplant

Question 45

What are IgM paraproteins associated with?

Answer 45

Low grade lymphoma

Question 46

What is the presentation of low grade lymphoma?

Answer 46

``` Bone marrow failure Lymphadenopathy Hepatosplenomegaly B symtpoms Protein related symptoms Bone disease RARE ```