of multiple myeloma cases; however, 1-5% of patients
do not show any detectable monoclonal protein in serum
or urine. These disorders are known as nonsecretory
myeloma. They fall into two classes: (a) producers of
a paraprotein that remains in the cytosol of the malig-
nant plasma cells due to secretory defects or (b) non-
producers of a paraprotein. Nonsecretory myelomas are
characterized by immunoperoxidase staining methods
using antibodies directed against light chain-specific
Monoclonal immunoglobulins in serum without signif-
icant clinical illness have also been found, and the inci-
dence increases with age. As many as 3% of patients older
than 70 show the presence of monoclonal immunoglobu-
lin (benign monoclonal proteinemia, also known as mon-
oclonal gammopathy of undermined significance). These
individuals require periodic serum and urine studies. In
some rare instances, monoclonal gammopathies of unde-
termined significance are associated with neuropathies and
the monoclonal immunoglobulin possesses an antinerve
activity. A lymphoproliferative disorder characterized by
monoclonal lymphocytes that produce monoclonal IgM is
known as
Waldenstrom’s macroglobulinemia.
In this dis-
order, the elevated serum viscosity is palliated by plasma-
pheresis and cytotoxic treatment (e.g., chlorambucil and
nucleoside analogs, respectively) due to the presence of
large quantities of IgM and the tumor burden.
It should be noted that pseudomonoclonal bands appear-
ing in the
region may be misidentified as authentic
monoclonal gammopathy. Pseudomonoclonal bands oc-
cur in those serum specimens due to hemolysis or to the
presence of fibrinogen due to inappropriate blood coagu-
lation techniques. Serum immunofixation studies should
clarify these problems.
Secondary paraproteinemias may be seen in associ-
ation with hematopoietic cancers (e.g., lymphomas and
leukemias), other neoplasms (e.g., colon carcinoma),
long-standing chronic urinary or biliary tract infection,
rheumatoid factor related to IgM monoclonal protein, and
Changes in Serum Proteins during Acute
Phase of Disorders of Tissue Injury
The alterations in serum proteins (acute phase response)
that occur within a few hours to a few days after tissue
injury due to infection, trauma, burns, surgery, or infarc-
tion and inflammatory condition are divided into two cat-
egories. The first category includes those proteins that are
increased by at least 25% (positive acute phase proteins),
and the second category includes proteins that are de-
creased by at least 25% (negative acute phase proteins).
During acute stress, macrophages and monocytes are acti-
vated and produce several intercellular signaling polypep-
tides, known as cytokines (Chapter 35). Some examples
of the released cytokines are interleukin-
, interleukin-
/?, tumor necrosis factor a, interferon-}/, and transform-
ing growth factor
One of the functions of these cy-
tokines is to alter the synthesis of acute phase proteins
in hepatocytes by regulating expression of acute phase
protein genes by both transcriptional and posttranscrip-
tional mechanisms. Glucocorticoids stimulate the action
of cytokines by promoting the production of some acute
phase proteins. The postulated function of the acute phase
response is to protect the body from the injurious pro-
cesses. One action is activation of the complement system
to fight infection or antagonize the activity of proteolytic
enzymes. Other actions initiate or sustain inflammation,
whereas others reflect antiinflammatory and antioxidant
Examples of positive and negative acute phase proteins
are given in Table VI-1. C-reactive protein and serum amy-
loid A are elevated in serum by as much as 1000-fold from
their basal values. Serum amyloid A is an apolipoprotein; it
is synthesized in hepatocytes in response to inflammatory
stimuli and associated with HDL. The function of serum
amyloid A is not clear and it is not commonly measured
as an acute phase reactant. However, serum C-reactive
protein (so named because it reacts with pneumococcal
C-polysaccharide) is measured. It binds with phospho-
choline of pathogens, phospholipid constituents of dam-
aged blood cells, and phagocytic cells, and it activates the
complement system. All of the functions of C-reactive pro-
tein modulate inflammatory conditions of the body. These
Examples of Positive and Negative Acute Phase Proteins
1. Several members of complement system (e.g., C3, C4)
2. Proteins of the coagulation and fibrinolytic systems
(e.g., fibrinogen, plasminogen)
3. Antiproteases (e.g.,
a {
4. Transport proteins (e.g., haptoglobin, ceruloplasmin,
5. Inflammatory response modulators and others (e.g.,
phospholipase A2, C-reactive protein, amyloid A,
fibronectin, ferritin)
Thyroxine-binding globulin
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