Biological functions
• transport
– albumin
– transferin
– ceruloplasmin
– haptoglobin
• oncotic pressure regulation
• coagulation
• immunity
Hypoproteinemia
• with hypoalbuminemia
– impairment of liver function
– protein loss
– changes in ECF
• without hypoalbuminemia
– severe immunoglobulin deficiency
Hyperproteinemia
• hypergammaglobulinemia
– polyclonal
 chronic inflammation
 chronic liver disease
 autoimmune diseases
– monoclonal
• multiple myeloma
• Waldenstrom`s macroglobulinemia
• heavy-chains disease
• dehydration
Methods of separation
• SPE - serum protein electrophoresis
• IEP – immunoelectrophoresis
• IFE – immunofixation electophoresis
Immunoelecctrophoresis (IEP)
Immunofixation (IFE)
Albumin (migrates to the anode)
-1 globulins
• -1 protease inhibitor (a-1 antitrypsin)
• *-1 glycoprotein (* orosomucoid)
•  fetoprotein (if present)
• high density lipoprotein (HDL)
-2 globulins
• -2 macroglobulin
• antithrombin III
• ceruloplasmin
• haptoglobin (this is usually the predominant component)
Beta globulins
• beta and pre-beta lipoproteins (LDL and VLDL)
• C3
• C-reactive protein
• hemoglobin (free)
• plasminogen
• transferrin (*"principal component of the beta1 subdivision")
Gamma globulins
• Immunoglobulins
Acute phase response (APR)
• positive APR
• negative APR
beta - gamma (IgA) junction
Multiple myeloma
• B cell proliferation
• monoclonal protein, Bence-Jones
proteinuria
• anemia, leukopenia, low platelet count
• hypercalcemia
• „myeloma kidney”
• increased viscosity
•  TP, ESR
• SPE, IEP, quantitating serum Ig
Heavy chain disease
• lymphocytic cell proliferation
• only heavy chain production
Benign monoclonal gammopathy
• "monoclonal gammapathy of uncertain
significance"
• "MGUS”
• paraprotein < 2.0 gm/dL, Bence-Jones
protein (rarely present) < 60 mg/L
Benign monoclonal gammopathy
Case 1
• A 66-year-old man presented with sharp,
constant, low back pain, dating from a fall from
a ladder 6 weeks earlier. On direct questioning,
he did admit to vague malaise for over 6
months. On examination, he was in
considerable pain but otherwise seemed fairly
fit.
• He was mildly anaemic but had no
lymphadenopathy and no fever. There were no
signs of bruising, no finger clubbing, no
hepatosplenomegaly and no abdominal masses
Case 1
• On investigation, his haemoglobin was low
(102g/l) due to fewer red cells but his
white-cell count was normal (6.2 x 109/l).
He had a normal differential white-cell
count and a normal platelet count but his
ESR was 98mm/h.
• Total serum proteins were raised at 98g/l
(NR 65-75g/l)
Case 1
• His serum albumin, creatinine and urea were
normal.
• He had a raised serum calcium level
(3.2mmol/l) but a normal alkaline
phosphatase.
• Serum protein electrophoresis revealed a
monoclonal band in the gamma region, with
considerable immunosuppression of the rest
of this region.
• The band was typed by
immunoelectrophoresis and shown to be IgG
of kappa type.
• Quantitation of serum immunoglobulins showed
a raised IgG of 67g/l (NR 7.2-19.0g/l), a low IgA
of 0.3g/l (NR 0.8-5.0g/l), and a low IgM of
0.2g/l (NR 0.5-2.0g/l).
• Electrophoretic examination of concentrated
urine showed a monoclonal band in the beta
region. On immunoelectrophoresis, this band
was composed of free kappa light chains.
• X-rays of his back showed a small, punched-out
lesion in the second lumbar vertebra
Case
• Bone marrow examination showed an
increased number of atypical plasma
cells; these constituted 45% of the
nucleated cells found on the film. This
man showed the features required for a
diagnosis of multiple myeloma
Case
• A 49-year-old woman presented with a 6month history of vague aches and pains in
her chest. On examination, she was
overweight but had no abnormal physical
signs.
Case 2
• Her haemoglobin was 136g/l with a
white-cell count of 6.7 x 109/l and a
normal differential.
• Her ESR was 34mm/h.
• Tests of thyroid function were normal.
Case 2
• However, protein electrophoresis showed a small
paraprotein band in the gamma region; this band was
an IgG of lambda type.
• Her serum IgG was raised at 20.1g/l (NR 7.2-19.0g/l),
• with an IgA of 1.9g/l (NR 0.8-5.0g/l) and an IgM of
3.0g/l (NR 0.5-3.0g/l).
• electrophoresis of concentrated urine showed no
proteinuria. The paraprotein measured 10g/l by
densitometry.
• A bone marrow examination showed only 12% plasma
cells.
Case 2
• the absence of
– osteolytic lesions,
– monoclonal free light chains in the urine
• normal serum IgA and IgM levels,
• these findings supported a diagnosis of benign
monoclonal gammopathy, also known as a
monoclonal gammopathy of unknown
significance (MGUS)
• This woman has been followed at 6-monthly intervals
for 3 years with no change in the paraprotein level,
and the urine remains free of monoclonal light chains.
She will continue to be seen at yearly intervals.