8. Myeloma and Paraproteins

Question 1

What are the Features of Antibody’s?

Answer 1

1. Antibody = Immunoglobulin
2. They are Produced by B-Cells - Mostly Plasma Cells
3. They can be Soluble / Membrane Bound

Question 2

What is the Function of Antibody’s?

Answer 2

Recognise and Bind Pathogens - by “Tagging” the Antigen, this may:
1. Directly Impede the Biological Process
Direct other Components of the Immune System

Question 3

What is the Basic Structure of an Antibody / Immunolobulin?

Answer 3

1. “Y” Shaped
2. 2 x Heavy Chains - Constant
3. 3 x Light Chains - Variable Domains

Question 4

What are the 5 Subclasses of Heavy Chains for an Antibody / Immunoglobulin?
What are there Features?

Answer 4

1. Mu - IgM - Initial Phase of Antibody Production
2. Gamma - IgG - Most Prevalent Antibody Subclass
3. Alpha - IgA - Mucous Membrane Immunity
4. Epsilon - IgE - Parasite Immune Response / Hypersensitivity
5. Delta -IgD

Question 5

What are the 2 Subclasses of Light Chains for an Antibody / Immunoglobulin?

Answer 5

1. Kappa
2. Lambda
   Note - This is a Random Selection for Each Cell

Question 6

What is a Paraprotein?

Answer 6

Monoclonal Immunoglobulin present in Blood / Urine

Question 7

What does the Presence of Paraprotein tells us?

Answer 7

There is Monoclonal Proliferation of a B-Lymphocyte / Plasma Cell somewhere in the Body

Question 8

What does a Total Immunoglobulin Level Test measure?

Answer 8

Immunoglobulin Subclasses by Heavy Chain / Fc Section

Question 9

What does a Serum Protein Electropheresis Test measure?

Answer 9

Assesses Antibody Diversity, identifies Paraprotein by:

1. Separates Protein Based on the Size / Charge
2. Forms a Characterisyic Pattern of Bands of Different Widths and Intensities based on Proteins Present

Question 10

What does an Immunofixation Test measure?

Answer 10

Identifies what Class of Paraprotein is Present - i.e. IgG / IgM …

Question 11

What does a Light Chain Test measure?

Answer 11

Assesses Imbalance / Excess Light Chains in Urine / Serum

Note - Kappa and Lambda should be about Equal

Question 12

What do IgM Paraproteins Indicate?

Answer 12

Lymphoma - Maturing B-Lymphocytes make IgM antibody at the start of the Immune Response

Question 13

What do IgG / IgA Paraproteins Indicate?

Answer 13

Myeloma - Mature Plasma Cells generate these types of Immunoglobulins after Isotope Switching

Question 14

What is a Myeloma?

Answer 14

Neoplastic Disorder of Plasma Cells, Resulting in Excessive Production of a Single Type of Immunoglobulin (Paraprotein)

Question 15

What are the Clinical Features of Myeloma?

Answer 15

1. Bone Disease:
2. a) Lytic Bone Lesions
3. b) Pathological Fractures
4. c) Cord Compression
5. d) Hypercalcaemia
6. Bone Marrow Failure - Anaemia / Thrombocytopenia
7. Infections

Question 16

What Effects can the Paraprotein in Myeloma cause?

Answer 16

1. Renal Failure - Cast Nephropathy
2. Hyperviscocity - Microcirculation Bleeding
3. Hypogammaglobulinaemia
4. Amyloidosis - AL Amyloid

Question 17

How is Myeloma Diagnosed?

Answer 17

1. Finding Excess Plasma Cells in the Bone Marrow - > 10% of Total Bone Marrow Cell Population
2. Type of Paraprotein - IgG = 55% / IgA = 21% / Light Chain Only = 22% / Other = 2%
3. Stage - Based on Albumin / Beta-2 Microglobulin

Question 18

What is the Treatment of Myeloma?

Answer 18

1. Chemotherapy - Proteasome Inhibitors / IMiDs / Monoclonal Antibodies
2. Bisphosphonate Therapy - Zoledronic Acid
3. Radiotherapy
4. Steroids
5. Surgery - Pinning of Long Bones / Spinal Cord Decompression
6. Autologous Stem Cell Transplant

Question 19

What are IgM Paraproteins associated with?

Answer 19

Low-Grade Lymphomas - NEVER MYELOMA

Question 20

What is the Clinical Presentation of an IgM Paraprotein Associated Low-Grade Lymphoma?

Answer 20

1. Bone Marrow Failure - Anaemia / Thrombocytopenia
2. Lymphadenopathy
3. Hepatosplenomegaly
4. B Symptoms