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the symptoms of multiple myeloma
Shavon Williams was a 52 year old postal worker in February of 2004, when she began to experience excessive fatigue on her mail route. Prior to this she had been in good health. She is married and has two teenage sons and has always been an active soccer mom, driving her sons to practice and going to all their games. At the time of her annual checkup, she reported to her primary care physician that she was feeling very tired lately and couldn’t even sit through her son’s entire soccer games. No abnormalities were found upon physical examination but a blood test revealed she had mild anemia; her red blood cell count was 3.6 x 106 ul-1 (normal 4.2–5.0 x 106 ul-1). Her white blood cell count was 4000 ul-1 (normal 5000 ul-1). The sedimentation rate of her red blood cells (RBCs) was 34 mm h-1 (normal < 20 mm h-1). The sedimentation rate measures how far red blood cells will sediment in a narrow bore tube, in one hour. Sedimentation is caused by rouleaux formation in which RBCs stack on one another and it is accelerated when the blood plasma contains high levels of fibrinogen or IgG. Because of her high sedimentation rate, the physician decided to measure her serum immunoglobulin levels. Her IgG concentration was 3500 mg/dl (normal 600 – 1500 mg/dl), her IgA was 18 mg/dl (normal 150 -250 mg/dl) and her IgM was 60 mg/dl (normal 75- 150 mg/dl). Serum protein electrophoresis of Shavon’s serum revealed the presence of a monoclonal, IgG, kappa antibody (Figure 1). Urine analysis also revealed the presence of Bence-Jones proteins. No treatment was advised at this time.
Shavon’s physician measured her serum IgG levels at each of her annual visits and noticed that they were rising gradually. In January of 2005 her IgG concentration was 4400 mg/dl and in January of 2006 it was 5020 mg/dl. Her blood count at that time revealed that her anemia had worsened and her RBC count was now 3.1 x 106 ul-1. Her white blood cell count had also dropped and was now 3320 ul-1. In May of 2006, Shavon had a sudden onset of upper back pain and a soreness in her lower left arm, so she was referred to a radiologist. X-rays of her brain, spine, and extremeties revealed the presence of bone lesions (Figure 2). A follow up MRI of the spine revealed destruction of the second thoracic vertebral body with extrusion of a plasmacytoma (a tumor of plasma cells) from the affected vertebral body compressing the spinal cord. Shavon was treated for her back pain with the corticosteroid, decadron and irradiation to the spine. Her pain was alleviated but her serum IgG levels continued to rise and reached 6000 mg/dl and she required blood transfusions because of her worsening anemia. She was treated with methylphenylalanine mustard (melphalan) and prednisone.
In February of 2007, Shavon’s IgG levels were rising again so she was given additional chemotherapy treatment with vincristine, adriamycin, and decadron for 9 months. Her serum IgG dropped from 6800 mg/dl to 5200 mg/dl over the next 2 months but then rose again to 7900 mg/dl so she was treated with a course of cyclophosphamide, etoposide, and decadron. This reduced her serum IgG to 6200 mg/dl. In October of 2007 she developed high fever and chest pain. An X-ray revealed she had pneumonia. She was treated successfully with antibiotics. However, in June of 2008 she again developed, fever, chills and chest pain and was diagnosed with pneumonia. Streptococcus pyogenes was cultured from her sputum and blood. She was given antibiotics intravenously and recovered. She is currently doing well but requires occasional blood transfusions for her anemia and complains of bone pain. Her serum IgG has been stable at 6200 mg/dl for the past 6 months.
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Serum protein electrophoresis reveals the presence of a monoclonal antibody. Electophoresis of a normal serum (lane 1) is shown next to Shavon’s serum (lane 2). Heterogeneous immunoglobulins from normal serum stained as a smear whereas monoclonal antibody from Shavon’s serum was a tight band. Normal serum in lanes 3 and 5 and Shavon’s serum in lanes 4 and 6 were electrophoresed and immunoblotted with antibody to the g heavy chain (lanes 3 and 4) and antibody to k light chain (lanes 5 and 6). |
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QUESTIONS:
1. The serum IgG from Shavon was assumed to be monoclonal because it migrated as a tight band on serum protein electrophoresis (SPEP). What other evidence could prove monoclonality of this IgG (think of other types of assays you could do to detect monoclonality)?
ANSWER 1.
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Clonal analysis of a B-cell tumor. Southern blotting technique to demonstrate monoclonality. DNA from a healthy individual in lane one and a patient with a B cell myeloma in lane 2. In a sample from a healthy person (lane 1), Ig genes are in the germline configuration in non B cells, so a digest with a restriction enzyme yields a single germline DNA fragment when probed with an Ig heavy chain JH probe. Normal B cells make many rearrange-ments producing a spectrum of bands so faint that they are undetectable. However, in a patient with a B cell myeloma, in which a single cell has given rise to all the tumor cells in the sample, two extra bands are seen with the JH probe. |
2. What are Bence-Jones proteins and how are they detected?
ANSWER 2.
3. What was the cause of Shavon’s anemia and neutropenia (low white blood cell count)?
ANSWER 3.
4. As Shavon’s disease progressed she became more susceptile to pyogenic infections, and she developed pneumonia twice. What is the basis of her susceptibility to these infections?
ANSWER 4.
5.
A monoclonal immunoglobulin in the serum is called an M-component (‘M’ for myeloma. Is the presence of an M-component in serum diagnostic of multiple myeloma?ANSWER 5. .
6.
Very rarely an individual with multiple myeloma has two M-components in the blood. Although these two M-components use different constant region genes, their antigen binding regions are encoded by the same variable region gene. Can you hypothesize how this can happen?ANSWER 6.
