and is a major component of colostrum (the form of milk produced by the mammary
gland immediately after giving birth). IgA is the primary immunological barrier against
pathogenic invasion of the mucosal membranes. IgM is found in the intravascular space
and its role is to eliminate circulatingmicroorganisms and antigens. IgM accounts for
about 8% of plasma immunoglobulins and has a half-life of 5 days. IgM is the first
antibody to be synthesised after an antigenic challenge. IgD and IgE are minor immuno-
globulins whose roles are not clear sincea deficiency of either seems to be associatedCase study MYELOMA
A 72-year-old woman presented to her GP with a 3 week history of painful hips, chest and shoulders,
and with shortness of breath on exertion. She was constipated and had lost 12.5 kg over the last
6 months. She complained that she was very thirsty and had to get up to urinate during the night,
something that she had previously never had to do.
Initial laboratory investigations found her to be hypercalcaemic, dehydrated and anaemic. Her
biochemistry results showed marked renal impairment, with raised urea and creatinine. Her alkaline
phosphatase (AP) was within the reference range. Her serum protein concentration was raised, despite
having a low albumin. Serum protein electrophoresis showed a large monoclonal band in the gamma
globulin region. By comparison of area under the peak with total protein, the band was quantified as
61 g dm^3. The band was typed as IgAkby immunofixation, using antisera specific against individual
immunoglobulin subclasses to bind the monoclonal protein to the electrophoresis before staining. An early
morning urine sample was requested for Bence Jones protein analysis by electrophoresis. This detected
a large band of freeklight chains in the urine. Her immunoglobulins were quantified by turbidimetry,
a method that measures the refraction of light by antibody complexes. The results indicated that her other
immunoglobulins were suppressed, leaving her susceptible to infection. An isotope bone scan using
diphosphonates labelled with^99 Te demonstrated osteolytic lesions (bone loss) that are characteristic
of multiple myeloma.Comment The two most common causes of hypercalcaemia are primary hyperparathyroidism and malignancy.
The signs and symptoms in a person of this age are typical of multiple myeloma, especially in the context
of hypercalcaemia with a normal AP, which is raised in primary hyperparathyroidism. Hypercalcaemia
results from stimulation of osteoclasts (a type of bone cell) released by the myeloma cells and can cause
polyuria, polydipsia (need to drink excessive fluid) and dehydration. The impaired renal function in this
lady may be a result of hypercalcaemia and Bence Jones protein as both are nephrotoxic. As the
malignant plasma cells proliferate throughout the bone marrow, the bone marrow has a reduced
capacity to produce normal cells, causing anaemia and immunosuppression. The difference between the
concentration of serum total protein and albumin is attributed to the Bence Jones proteins. These
proteins contribute to this fraction and consequently myeloma patients can have a high total protein
concentration in the presence of normal or low albumin.
The patient was rehydrated with intravenous saline and started on a bisphosphonate to lower her
calcium. Her renal failure resolved over time, although some patients with advanced myeloma will require
haemodialysis. A bone marrow aspiration was performed, which showed>80% infiltration of plasma
cells, confirming the diagnosis of multiple myeloma. A serumb2-microglobulin was requested as a
prognostic indicator. Once she had stabilised, she was commenced on a course of dexamethasone, a
synthetic glucocorticoid that binds immunoglobulins and hence relieves some of the symptoms of the
malignancy. Her response to treatment was monitored by regular quantification of her monoclonal band.
657 16.3 Examples of biochemical aids to clinical diagnosis