Myeloma and paraproteins Flashcards
What are the different types of heavy chain immunoglobulins?
- 5 types of heavy chain
□ Gamma – IgG
® Most prevalent antibody subclass (75% of total)
□ Alpha – IgA
® Mucous membrane immunity
□ Mu – IgM
® Initial phase of antibody production
® Exists as a pentamer – highest molecular weight
□ Delta – IgD
□ Epsilon – IgE (typically mucosal)
® Parasite immune responses, hypersensitivity
What are the different types of light chain immunoglobulins?
- Kappa or lambda
□ Random selection for each cell
□ But, each cell will only make 1 type of light chain with 1 specificity
□ Free light chains are also found in the blood at low levels – difficult to measure
What are immunoglobulins made by?
Plasma cells
What is a paraprotein?
○ A paraprotein – monoclonal immunoglobulin present in blood or urine
○ If present, it tells us that there is monoclonal proliferation of a B lymphocyte/ plasma cell somewhere in the body
What is serum protein electrophresis?
○ Separates protein based on size and charge
○ Forms a characteristic pattern of bands of different widths and intensities based on proteins present
What are the different tests for myeloma and paraproteins?
○ Total immunoglobulin levels
- Measures Ig subclasses by heavy chain/ Fc section
○ Electrophoresis
- Assesses antibody diversity, identifies paraprotein
○ Immunofixation
- Identifies what class of paraprotein is present (i.e. IgG, IgM)
○ Light chains
- Assesses imbalance/ excess of light chains in urine / serum
What isa myeloma?
○ Neoplastic disorder of plasma cells, resulting (usually) in excessive production of a single type of immunoglobulin (paraprotein)
○ Peaks in 7th decade
○ Ethnicity – commoner in black population than white
○ Clinical manifestations may result from direct effect of plasma cells, or effect of paraprotein
What are the features of myeloma?
- bone disease □ lytic bone lesions □ pathological fractures □ cord compression □ hypercalcaemia - bone marrow failure esp. anaemia - infections
What are the effects of paraproteins in myeloma?
- Renal failure: cast nephropathy
□ Immunoglobulin deposition and blockage of renal tubules - Hyperviscosity
□ 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 - Hypogammaglobulinemia
□ Impaired production of normal Immunoglobulin
□ Tendency to infection - Amyloidosis
What is Amyloidosis?
□ Group of diseases characterised by deposition of fibrillar protein
□ Morphological appearances, physical structure are similar
□ Biochemical or protein composition can vary
□ When caused by a paraprotein or light chains – AL amyloid
How is myeloma diagnosed?
- Paraproteins are common
□ 3-4% of population over age of 75
□ The vast majority have nothing wrong with them
□ 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
How is myeloma treated?
- Chemotherapy □ Proteasome inhibitors, IMiDs, monoclonal antibodies - Bisphosphonate therapy □ Zoledronic acid - Radiotherapy - Steroids - Surgery □ Pinning of long bones; decompression of spinal cord - Autologous stem cell transplant
What is IgM myeloma?
○ IgM myeloma does not exist!
○ IgM paraproteins are associated with low-grade lymphomas (various types)
What might someone with IgM paraproteins present with?
- Bone marrow failure (anaemia, thrombocytopenia)
- Lymphadenopathy
- Hepatosplenomegaly
- B symptoms
- Paraprotein-related symptoms can occur
- Bone disease is very rare
What does it mean if there are IgM paraproteins?
- lymphoma
> Maturing B-lymphocytes make IgM antibody at the start of the immune response
