Lecture 6 - Monoclonal Gammopathies Flashcards
1
Q
Normal serum protein values
A
Total protein - 7.79 g/dl
Albumin - 4.62 g/dl Alpha-1 - 0.23 g/dl Alpha-2 - 0.74 g/dl Beta - 0.92 g/dl Gamma - 1.29 g/dl
2
Q
Plasma cell disease
A
- Plasma cells are derived from B lymphocytes
- Produce and secrete antibodies
- Range from 900,000 Da for IgM to 24,000 Da for free light chains
- Hence broad and diffuse gamma region
3
Q
Cancerous plasma cells and their antibodies
A
- When a plasma cells proliferates (cancerous) it will produce and secrete an antibody of specific type
- Monoclonal immunoglobulin (M protein)
- Many clones of the cell and so excess amount of the specific Ab
- Detection and measurement of the specific Ab is used to diagnose and monitor the disease
- Biomarker of disease
4
Q
Classification of plasma cell diseases
A
- Malignant–large tumour burden, must be controlled or eradicated
- Premalignant–no clinical symptoms, need only to be monitored, may lead to malignant disease
- Protein/low tumour burden–secreted monoclonal protein causes the disease
- some disease may eventually progress and become malignant
5
Q
Examples of plasma cell diseases
A
Malignant:
- Multiple myeloma
- Plasmacytoma
- Plasma cell leukaemia
Premalignant:
- MGUS
- Smouldering multiple myeloma
- Bence Jones proteinuria
Protein/low tumour:
- Waldenstrom’s macroglobulimaemia
6
Q
Immuno Fixation Electrophoresis (IFE)
A
- An Immuno-precipitation Assay
- Used to detect monoclonal immunoglobulin in serum
- To test for Monoclonal Gammopathies
- Electrophoresis of serum in agarose gel is followed by over laying with specific antisera (anti- G, M, A, Κ and λ)
- Antigen –antibody complex precipitates in gel
- Monoclonal Ig has heavy and light chain precipitation, surrounding gamma region is reduced
7
Q
Distribution of monoclonal proteins in MM patients and MGUS subjects (immunoglobulins)
A
• IgG
- 52% in MM
- 59% in MGUS
• IgA
- 21% in MM
- 12% in MGUS
• IgM
- 0.5% in MM
- 18% in MGUS
• IgD
- 2% in MM
- 0.5% in MGUS
8
Q
Distribution of monoclonal proteins in MM patients and MGUS subjects
(other)
A
• Biclonal
- 2% in MM
- 5% in MGUS
• Light chain only
- 20% in MM
- 6% in MGUS
• None detected
- 2.8% in MM
9
Q
What does MGUS stand for
A
Monoclonal Gammopathy of Undetermined Significance
10
Q
MGUS
A
- The prevalence of MGUS increases with age
- The median age at diagnosis is about 70 years, and less than 2% of patients with MGUS are younger than 40 years of age.
- The prevalence of MGUS is higher in men than in women (4.0% vs. 2.7% among persons 50 years of age or older
- IgG was the most common immunoglobulin affected (69% of cases), followed by IgM (17%) and IgA (11%)
11
Q
Dealing with MGUS
A
- History and physical examination
- Haemoglobin concentration
- Serum calcium and creatinine concentrations
- Protein studies
- Total serum protein concentration and serum electrophoresis
- Skeletal survey
12
Q
Multiple myeloma signs and symptoms
A
- Five year survival rate of about 49%
- Bone pain
- Anemia
- Fatigue
- Bone fractures
- Kidney failure
- Increased susceptibility to infections
13
Q
Multiple myeloma diagnosis
A
- Plasma electrophoresis
- Beta 3 micro-globulin levels
- Bone marrow biopsy
- Skeletal survey (x-ray, CT scan)
14
Q
Multiple myeloma treatment
A
- Autologous stem cell therapy
- Proteasome inhibitors (bortezomid, carfilzomid, ixazomid)
- Phthalimide derivatives (thalidomide, lenalidomide, pomalidomide)
- Abs (Daratumumab anti CD38, Elotuzumab anti SLAM7)
15
Q
Waldenström’s macroglobulinemia (WM)
A
- Rare IgM monoclonal gammopathy
- It is a B cell neoplasm not related to MM
- Slow, indolent nature
- Involvement of lymph nodes, hyperviscosity
- IFE, Bone marrow biopsy, Flow cytometry
