Understanding Paraprotein
in Myeloma
Understanding the medical language IMMUNOGLOBULIN
surrounding myeloma can be difficult, it
doesn’t help that the medical profession uses figure 1
complex words and often has a number of
words to describe the same thing. Many of
you will have heard the words paraprotein, Antigen
m protein, antibodies, immunoglobulins and
light chains when speaking with the treating Heavy chains
team or doing your own research.
This fact sheet aims to help you understand
these complex concepts as it is important to
understand how myeloma is categorised, how
response to treatment is assessed and how
myeloma is monitored over time.
Antigen
Light chain binding
Myeloma and the plasma cell site
Plasma cells are made in the bone marrow and form part
of the immune system. Their usual function is to make
antibodies to fight infections against invading bacteria or
viruses. These antibodies then attach to the bacteria or virus
by finding a surface protein or ‘antigen’ to bind to. This then
signals other immune cells to remove the invading bacteria
or virus and overcome/eliminate the infection. Antibodies
are also referred to as immunoglobulins.
Myeloma is a cancer of the plasma cells. When plasma cells
become cancerous, they make abnormal antibodies in large
quantities that serve no useful function. These abnormal
antibodies can be found and measured in the blood and
are referred to as paraprotein or m protein. Most people Each immunoglobulin has their own role to play in the
with myeloma will have a paraprotein in their blood, but immune system as outlined in the table below.
some do not. Those without paraprotein will most likely
have light chain myeloma or non-secretory myeloma. Immunoglobulin Usual Function
Understanding immunoglobulins (antibodies) Type
There are many different proteins in the body and
the blood, the most common being albumin and Most common immunoglobulin.
immunoglobulins. Immunoglobulins are molecules made Attaches itself to germs and
IgG
up of 2 heavy chains and 2 light chains (see figure 1). mobilises the immune system to
kill the germ.
There are five types of heavy chains; IgG, IgA, IgM, IgD and
IgE and two types of light chains; Kappa and Lambda.
Each immunoglobulin is made up of 1 type of heavy chain Accumulates in mucous
and 1 type of light chain. Each diagnosis of myeloma is IgA membranes and responds first
labelled according to the type of immunoglobulin that to infection of these tissues
has become abnormal eg IgG Kappa. Sometimes only
light chains become abnormal and break away from the First response to sight of
IgM
heavy chain and reproduce on their own. We then label the infection in the blood
myeloma according to the type of light chain eg. Lambda
light chain myeloma. Occurs in low levels in the blood.
IgD
Some people may over produce two different Thought to help IgM
immunoglobulins eg. IgG Kappa and IgA Lambda. These
are then measured as two different paraproteins and is IgE Responsible for allergic reactions
referred to as bi-clonal myeloma.
Published December 2020 – page 1
Paraprotein measurements are done regularly at intervals
Usual Function of Light Chains (eg monthly or three monthly) to see how well the treatment
(Kappa and Lambda) is working and to check that the myeloma is remaining
stable during periods between treatments.
• Light chains help to make the antibody specific
In those that overproduce light chains, the same approach
for a specific antigen or infection. Eg measles
will be taken to monitor the myeloma’s activity. Unlike
• In myeloma the light chains can detach from the paraprotein, everyone will have some light chains in their
heavy chains and be more abundant than normal blood. It is only when they increase above normal levels that
(light chain myeloma) monitoring is required.
• Also called Bence Jones proteins because they were The doctor will also be assessing other levels in the blood
discovered in the urine by a doctor called Henry and any other symptoms that might be present as the
Bence Jones in 1845 paraprotein is only one feature of the disease.
• Light chain proteins can pass through the kidneys Assessing response to treatment
but can also get stuck, causing kidney damage The doctor will use the International Myeloma Working
Group’s Response Criteria to assess the response to
treatment, that is, how well is the treatment working against
It is important to note that the presence of paraprotein in the myeloma. This is done by comparing the blood and/or
the blood is not always caused by myeloma. Monoclonal urine level of paraprotein or light chains before treatment
Gammopathy of Uncertain Significance (MGUS) produces to certain timepoints during treatment, typically once each
small amounts of paraprotein without causing any cycle of treatment has been completed.
problems. Not all people with MGUS go on to develop
myeloma however we know that all people with myeloma If no paraprotein is detected after treatment or light chains
once had MGUS but it may not have been detected at the return to normal levels, it is considered a complete response
time. In fact, there is only a 1% chance per year of MGUS (CR). If the paraprotein has fallen and is still detectable and
progressing to myeloma and many people with MGUS stable after treatment it is considered a partial response (PR).
never develop myeloma. Monoclonal Gammopathy of Renal A stable low level of paraprotein maintained over time is
Significance (MGRS) is a disease that can cause significant often described as plateau phase. The term ‘plateau’ phase is
damage to the kidneys. A rise in IgM immunoglobulin used because a graph of the paraprotein results appears flat
can cause a rare form of lymphoma called Waldenström like a plateau.
macroglobulanaemia. Light chain amyloidosis is a condition For those with non-secretory myeloma it may be necessary
where the light chains change their shape and get stuck in to measure response to treatment with bone marrow
tissues such as the nerves, heart and kidneys. Amyloidosis biopsies or scans.
can occur on its own or with myeloma as well.
It is possible for myeloma to become active again without
Monitoring myeloma with the producing a paraprotein. This is why it’s so important to
paraprotein and light chains report any new symptom such as pain to the doctor for
For those that produce a paraprotein, it is often the easiest investigation.
way to keep track of the myeloma’s activity. When myeloma
is active, we will see a rise in paraprotein and when
myeloma is responding to treatment, we will see a decrease
in paraprotein. It is important to note that a small rise in
paraprotein will not always mean that more treatment is
needed straight away. It is normal for the paraprotein to
fluctuate slightly and the doctor will be monitoring the
trend closely. The paraprotein result can also differ slightly
if processed in different laboratories. Keeping tests with
the same pathology service is recommended for accurate
comparisons.
For more information about myeloma and treatments, please see our book, Myeloma a Comprehensive Guide
and our range of other resources. They can be found at www.myeloma.org.au or contact head office
e: support@myeloma.org.au t : 03 9428 7444 (AEDT) for hard copies
Published December 2020 – page 2
