Myeloma Flashcards
where are antibodies produced?
b cells - mostly plasma cells
what is the primary role of antibodies?
recognise and bind pathogens
describe and draw the basic structure of an antibody
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.
name the types of heavy chain found on antibodies
gamma alpha mu delta epsilon
what is the most prevalent antibody subclass?
IgG
what antibody is responsible for mucous membrane immunity?
IgA
what antibody is the initial phase of antibody production?
IgM
what antibody is responsible for parasite immune responses and hypersensitivity?
IgE
describe the light chains on antibodies
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.
what is a paraprotein?
A paraprotein is a monoclonal immunoglobulin present in blood or urine.
if present in blood or urine what does a paraprotein suggest?
there is a monoclonal proliferation of a B lymphocyte/plasma cell somewhere in the body
what is serum protein electrophoresis?
This separates protein based on size and charge. Forms a characteristic pattern of bands of different widths and intensities based on proteins present.
what is the function of the total immunoglobulin levels test?
measures Ig subclasses by heavy chains/Fc section
why perform electrophoresis?
assesses antibody diversity
identifies paraprotein
why perform immunofixation?
identifies what class of paraprotein is present (i.e. IgG, IgM)
why perform light chain analysis?
assesses imbalance/excess of light chains in urine/serum
IgM paraproteins =
lymphoma
o Maturing B-lymphocytes make IgM antibody at the start of the immune response
IgG, IgA paraproteins =
myeloma
o Mature plasma cells generate these types of immunoglobulin after isotype switching
what are myelomas?
neoplastic disorders of plasma cells, resulting in excessive production of a single type of immunoglobulin (paraprotein)
what decade has the peak incidence of myeloma?
7th
what ethnicity is most affected by myeloma?
black
features of myeloma
• Bone disease o Lytic bone lesions o Pathological fractures o Cord compression o Hypercalcaemia • Bone marrow failure esp. anaemia • Infections
list the effects of the paraprotein in myeloma
renal failure - cast nephropathy
hyperviscosity
hypogammaglobulinaemia
amyloidosis
how do paraproteins cause renal failure?
immunoglobulin deposition and blockage or renal tubules
how do paraproteins cause hyperviscosity?
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
how do paraproteins cause hypogammaglobinemia?
o Impaired production of normal immunoglobulin
o Tendency to infection
how do paraproteins cause amyloidosis?
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
describe the diagnosis of myeloma
• 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
treatment of myeloma
• 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
wht are IgM paraproteins associated with?
low grade lymphomas of various types
clinical presentation of IgM lymphoma
- Bone marrow failure (anaemia, thrombocytopenia)
- Lymphadenopathy
- Hepatosplenomegaly
- B-symptoms
