Myeloma and Plasma Cell Dyscrasias Flashcards
Are B cells part of the adaptive or innate immune system response?
Adaptive
What are the main functions of B cells?
Make antibodies
- can also act as antigen presenting cells
Describe the structure of the Antibodies produced by B cells?
2 heavy chains (denoted by greek letters, but indicate type of Ab => M,G,D,A,E)
2 light chains (kappa or lambda)
What type of antibody can form a dimer?
IgA
What type of antibody can form a pentamer?
IgM
Why do antibodies have variable regions?
To change their structure in order to bind different antigens
- VDJ proteins are rearranged in order to do this
Describe the Precursors of the B cell, starting with a haematopoietic stem cell
Stem cell lymphoid progenitor Pro B cell (can make IgM) Pre B cell (can make IgM and IgD) **then leave bone marrow and enter circulation** B cell can then mature to plasma cell
B cells have to undergo class switching before maturing to a plasma cell. TRUE/FALSE?
TRUE
- as plasma cell can only make one type of Ab
Where do B cells travel to after they leave the bone marrow and what is their role here?
- travel to follicle germinal centre in lymph node
- identify antigen and improve fit
- can return to marrow as plasma cell or circulate as memory B cell
Describe the appearance of a plasma cell on blood film
- “eccentric” clock face nucleus with H+E staining
- open chromatin nucleus
- plentiful blue cytoplasm (lots of protein)
- pale perinuclear area (golgi apparatus)
Describe the difference between a polyclonal and monoclonal expansion
Polyclonal = increase in number of cells, but all are different monoclonal = increase in cells but all are the same
What would cause a polyclonal rise in Ig (i.e. different types of Ab produced?
- infection
- autoimmune
- malignancy (reaction of the host to non-haem malignancy in their body)
- liver disease
What would cause a monoclonal rise in Ig?
clonal expansion of B cells (also called paraprotein)
identical Ab produced
marker of underlying clonal B cell disorder
How are Ig detected?
Serum electrophoresis
- detects abnormal protein bands (i.e. if there is too much of a specific protein)
How are the abnormal Ig in the blood classified and quantifed?
serum immunofixation
What is Bence Jones protein and where is it found?
- light chains are found in the patients urine
- can either be monomer light chain (kappa)
OR can be dimer light chain (lambda)
What are the potential causes of paraproteinaemia?
MGUS - Monoclonal Gammaopathy of Unknown Significance
Myeloma
Amyloidosis
Lymphoma
What is MGUS?
Monoclonal expansion of a B cell creating a high number of certain Ig
- considered a benign/pre-malignant stage of Myeloma
What are the two ways in which myeloma can affect the body?
Direct tumour effects:
- bone lesions and pain
- increased calcium
- marrow failure
Paraprotein effects
- renal failure
- immunosuppression
- hyperviscosity
- amyloid
Describe how myeloma bone lesions normally appear on X-ray?
lytic bone disease
=> punched out lesions are common in the skull
=> wedge fractures in the spine = common
What types of Ig are most commonly produced in myeloma?
IgG
IgA
Why does lytic bone disease occur in myeloma?
myeloma cells increase IL-6 from marrow stromal cells
=> these activate osteoclasts to breakdown bone and release Ca2+
What symptoms do patients often experience if they have hypercalcaemia?
- stones
- bones
- abdominal groans
- psychiatric moans
- thirst
- polyuria
- dehydration
- renal impairment
Why do patients with myeloma get cast nephropathy if the kidneys can usually filter light chains?
- proximal tubules usually reabsorb light chains
- if overwhelmed they pass into loop of henle and combine with Tamm-Horsfall Protein in thick ascending limb
- this compound then can block the nephron
How is cast nephropathy treated?
- switch off light chain production with steroids and chemotherapy
- this may be able to reverse the damage
What is the median age of myeloma diagnosis?
65 years
How is myeloma treated?
Combination chemotherapy
- steroids
- alkylating agent (e.g. cyclophosphamide)
- novel agents (e.g. thalidomide)
- stem cell transplants also used in fit patients
How can we monitor response to myeloma treatment?
Paraprotein level
Describe what happens in an Autologous Haematopoietic stem cell transplant (AUSCT)?
- pre treatment (releases stem cells from marrow)
- collect stem cells and freeze in lab
- administer chemo to wipe out immune system
- return thawed blood stem cells
- supportive tx for 4 weeks as immune system rebuilds
What monoclonal antibody treatment can be used in myeloma?
Daratumab
- targets CD38
What is prognosis like in myeloma?
5-10 years for younger patients
BUT relapse is inevitable
How are myeloma symptoms controlled?
- bone pain = opiate analgesia (NOT NSAIDs)
- local radiotherapy
- bisphosphonates
- vertebroplasty
How much paraprotein is found in the blood in an MGUS?
<30g/L
What percentage of plasma cells are found in the blood in MGUS?
<10%
MGUS causes no end organ damage. TRUE/FALSE?
TRUE
- normal Ca, renal function and Hb
What gender has a higher prevalence of MGUS?
Males
What is AL amyloidosis?
light chain mutation
causes accumulation of beta pleated sheets
these deposit in organs and cause damage
What organs can be damaged by amyloid deposits?
kidney heart liver neuropathy GI tract
What treatment is used in amyloidosis?
Chemotherapy => similar to myeloma
How is amyloidosis diagnosed/staged?
- organ biopsy
- congo red staining
- shows apple green birefringence under light
HOw can you check if amyloid has deposited in other organs?
- SAP scan (full body scan with iodine contrast)
- ECHO
- proteinuria
What is Waldenstrom’s Macroglobulinaemia?
IgM paraprotein disorder
- problem with maturation of B cell to plasma cell
What direct effects are caused by the tumour in Waldenstrom’s Macroglobulinaemia
- lymphadenopathy
- splenomegaly
- marrow failure
What effects are caused by the raised IgM paraprotein in Waldenstrom’s Macroglobulinaemia?
- hyperviscosity of blood
=> fatigue, visual disturbance, confusion, bleed, HF - neuropathy
How is Waldenstrom’s Macroglobulinaemia treated?
Chemo plasma exchange (to remove pararprotein from circulation)
