I called my neurologist last week hoping for some form of relief from all this pain and fatigue I am in … I am still bedridden. I can only stay out of bed for tops a half hour at a time then back to bed I go. I need to get out of bed to assist my son with daily activities (he has cerebral palsy) so staying in bed is not an option. My oldest son does help me a lot with my youngest so that is a great relief.

I know I have not written a post for a while, I am still down and out. Right now my neurologist wants to wait until the LP is done to see why my protein is so high. I do have some proteins that are high and/or borderline but a few years ago I had other proteins that were all over the place high/normal/low so she is very curious and is motivated in seeing what is causing it hence why she wants to wait for the results of the LP.

My neurologist does not want to prescribe anything for me until she gets the results from the LP but I am still waiting for the hospital to call to schedule it. I see my neurologist again around July 20th.

My neurologist said she was going to test my CSF for EBV, MS and others things that may be causing the high protein. Years ago when I saw a hemotologist and all my proteins were out of whack he said it was due to inflammation and did not refer me to another doctor or for further testing.

The protein currently high is my alpha-1-globulins and my alpha-2-globulins and beta globulins are at the high end of normal (1 number higher I’d be high). These proteins means the Protein Electrophoresis is abnormal primarily due to the alpha-1-globulins. My sed rate (ERS) is also high. My carbon dioxide level is low. Calculated Osmolality is also low. (In 2012 I had many protein levels high/low which is why my doc wants to look further into a cause)

So your guess is as good as mine.

Here is a document I found on globulins as a reference:

Just in case the link is not working here is the info:

GLOBULINS

Basic science

Globulins are a group of proteins within the blood. They are produced by the liver and the immune system. Albumin makes up more than half of the total protein within the blood, and globulins make up the remainder. Globulins have multiple different functions; the group includes immunoglobulins, enzymes, carrier proteins and
complement.

There are four groups of globulins. Serum protein electrophoresis is the test used to distinguish one from another and establish levels of each within the bloodstream.

Alpha 1 globulins

  • Mainly alpha-1 antitrypsin.

Alpha 2 globulins
– Alpha 2 macroglobulin.
– Haptoglobin.

Beta globulins
Transferrin.
Complement components C3, C4, C5.
Gamma globulins
Mostly immunoglobulins (antibodies):
IgG: majority of the immunoglobulin component. Many antibodies to bacteria and viruses are IgG.
IgE: involved in allergic response. Triggers histamine release. Also protects against parasites.
IgM: largest antibodies and first type produced in response to infection.
IgD: exists in very small quantities in blood. Function not very well understood.
IgA: found in mucous membranes, blood, saliva and tears. Protect body surfaces which are exposed
to foreign substances.
Tests and their clinical significance
Globulin level
Total protein is routinely done as part of the LFTs. Subtracting albumin from serum protein leaves the total globulin
level.
Decreased total globulin level:
Malnutrition (due to decreased synthesis).
Congenital immune deficiency (due to decreased synthesis).
Nephrotic syndrome (due to protein loss through the kidneys).
Increased albumin level causing decreased globulin fraction – eg, acute dehydration.
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Increased total globulin level:
Acute infection.
Chronic inflammatory disease – eg, rheumatoid arthritis, systemic lupus erythematosus
(SLE).
Multiple myeloma.
Waldenström’s macroglobulinaemia.
Hyperimmunisation.
Low albumin level causing increased globulin fraction – cirrhosis, nephrotic syndrome.
Globulin ratio may also be used, which is the ratio of albumin to globulin, and is usually between 1.7-2.2, ie there
is normally around twice as much albumin as globulin.
Serum protein electrophoresis (SPEP)
Electrophoresis divides serum proteins in order to determine if any group of protein is present in abnormal levels.
Serum is exposed to an electrical current which causes the different proteins to migrate in bands. It thus divides
globulins into the alpha-1, alpha-2, beta and gamma fractions. It is more sensitive than the quantitative
immunoglobulin tests (below).
Alpha-1 abnormalities are usually due to alpha-1 antitrypsin changes.
Decreased levels in congenital alpha-1-antitrypsin deficiency.
Increases are found in acute inflammatory disorders (it is an acute phase reactant).
Alpha-2 abnormalities mainly involve alpha-2 macroglobulin and haptoglobin.
Alpha-2 macroglobulin rises in nephrotic syndrome.
Haptoglobin levels increase in stress, infection, inflammation and tissue necrosis. Levels decrease
with haemolytic reactions.
The beta fraction consists mostly of transferrin. This is elevated in severe iron deficiency.
Where the gamma fraction is increased, it can then be further established whether this is a narrow spike-like
increase of a single immunoglobulin (a monoclonal rise) or a broader-based increase (polyclonal rise.)
Monoclonal rises are then further evaluated with immunoelectrophoresis or immunofixation electrophoresis (see
below.) Monoclonal spikes are more likely to have a malignant cause, with multiple myeloma being the most
common of these. However, the most common cause of a monoclonal rise is monoclonal gammopathy of
uncertain significance (MGUS) which is usually a benign condition. Abnormal immunoglobulins produced in
excess monoclonally are also known as paraproteins.
To establish a diagnosis of myeloma or Waldenström’s macroglobulinaemia, urine electrophoresis is also carried
out to look for monoclonal immunoglobulin bands within urine. The finding of Bence Jones’ protein is suggestive
of myeloma or Waldenström’s macroglobulinaemia.
SPEP can be further used to monitor response to treatment in myeloma.
Immunoelectrophoresis or immunofixation electrophoresis
Immunoelectrophoresis or immunofixation electrophoresis is usually performed when SPEP has found the
presence of increased gammaglobulin levels in order to further establish the nature of the abnormality. It identifies
the type of gammaglobulin. This is commonly used in the diagnosis of myeloma.
Quantitative immunoglobulin levels
These test the levels of the three major immunoglobulin groups (IgG, IgMand IgA).
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Causes of low immunoglobulin levels (hypogammaglobulinaemia)
Congenital immunodeficiency syndromes.
Conditions causing excess loss of immunoglobulins:
Sepsis
Nephrotic syndrome
Burns
Protein-losing enteropathy
Conditions causing less production of immunoglobulins:
Malnutrition
Alcoholism
Drugs – phenytoin, carbamazepine, immunosuppressants
Haematological malignancies – multiple myeloma, chronic lymphocytic leukaemia (CLL),
lymphoma
Rheumatoid arthritis
SLE
Viral causes – cytomegalovirus (CMV), human immunodeficiency virus (HIV), Epstein-Barr
virus (EBV), rubella
Causes of raised immunoglobulin levels
Electrophoresis will establish if these are polyclonal or monoclonal rises. The most common rise in
immunoglobulin levels is polyclonal, and due to immune system activity caused by infection or autoimmune
diseases.
Polyclonal rises in immunoglobulin levels:
Infections
Autoimmune connective tissue diseases – rheumatoid arthritis, SLE, scleroderma
Chronic active autoimmune hepatitis (IgG)
Primary biliary cirrhosis (IgM)
Chronic liver disease
Monoclonal rises in one class of immunoglobulin level:
Multiple myeloma (IgG or IgAusually)
MGUS. The most common cause of monoclonal rise, and usually a benign condition
CLL
Non-Hodgkin’s lymphoma
Waldenström’s macroglobulinaemia (IgM)
Primary systemic amyloidosis
Allergen-specific IgE tests
Blood tests can be done which measure the amount of IgE antibodies which have been produced in response to
specific allergens. These are usually done by the radioallergosorbent testing (RAST) or enzyme-linked
immunosorbent assay (ELISA) techniques. Blood allergy tests are more expensive and less sensitive than skin
prick testing, but can be useful in certain situations – for example, when there is a risk of anaphylaxis, or severe
skin rashes, or when the patient needs to continue taking antihistamines. Hundreds of different allergens can be
tested for in this way.
Common tests done in general practice
Common reasons GPs might order immunoglobulin tests or SPEP might include:
Excluding myeloma when other blood tests such as FBC or ESR are abnormal.
Serology tests for allergies.
Checking for immunodeficiency in patients with recurrent infections.
Checking responses to immunisations, such as hepatitis B or rubella.
Checking for immunity to infections, such as chickenpox in pregnant women.
Screening for coeliac disease.
Looking for autoimmune diseases.
Establishing the cause of abnormal protein levels found on LFTs. (Most often a raised globulin fraction
will be a polyclonal rise due to infection or inflammation.)
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Investigating the cause of a raised globulin level
Araised globulin level may be a relatively common coincidental finding. The work-up to establish the cause
involves history, examination and further investigations to determine which of the conditions listed above may be
causing the abnormality. This work-up would include:
History
Bone pain (myeloma).
Night sweats (lymphoproliferative disorders).
Weight loss (cancers).
Breathlessness, fatigue (anaemia).
Unexplained bleeding (lymphoproliferative disorders).
Symptoms of carpal tunnel syndrome (amyloidosis).
Fever (infections).
Joint pains (connective tissue diseases).
Patients with MGUS are asymptomatic by definition.
Examination
Temperature (infections, sepsis).
Arthropathy (connective tissue disorders).
Lymphadenopathy, hepatosplenomegaly (lymphoproliferative disorders).
Anaemia (lymphoproliferative disorders).
Signs of heart failure (amyloidosis).
Macroglossia (amyloidosis).
Signs of carpal tunnel syndrome (amyloidosis).
Investigations
FBC (anaemia, lymphocytosis, lymphopenia, thrombocytopenia).
ESR (raised in myeloma, sepsis, cancers).
Renal function (impaired renal function).
Calcium (hypercalcaemia in myeloma).
LFTs (hepatic diseases).
Serum protein electrophoresis (monoclonal vs polyclonal rise) and immunofixation electrophoresis
(defining immunoglobulin class in monoclonal rises).
Urine electrophoresis (Bence Jones’ protein).
X-rays if areas of bone pain.
Further investigations dependent on results of above, and where relevant performed in secondary
care.
Therapeutic uses of globulins
Some of the therapeutic uses of immunoglobulins:
Haemolytic disease of the newborn. IV immunoglobulin is given to the mother in pregnancy to prevent
antibody production.
Immunodeficiency diseases.
Guillain-Barré syndrome. IV immunoglobulin counteracts antibodies and slows progression.
Snake and spider bites – used with antivenom to help the immune system respond.
Kawasaki disease. IV immunoglobulin helps prevent coronary aneurysms.
Immune thrombocytopenic purpura (ITP).
Immediate short-term protection against hepatitis A, measles, polio, rubella.
Specific immunoglobulin preparations for hepatitis B, rabies, and varicella-zoster give short-term
immediate protection to a person exposed.
(See also the separate article Immunoglobulins – Normal and Specific.)
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Further reading & references
Loh RK, Vale S, McLean-TookeA;Quantitative serum immunoglobulin tests.Aust Fam Physician. 2013Apr;42(4):195-8.
Bird JM; Investigating an incidental finding of a paraprotein. BMJ. 2012 May4;344:e3033. doi: 10.1136/bmj.e3033.
Immunoglobulin; PublicHealth England
Busher JT; SerumAlbumin andGlobulin
Serum globulin electrophoresis; MedlinePlus
Monoclonal gammopathyof undetermined significance (MGUS); Melbourne Haematology
Immunoelectrophoresis – blood; MedlinePlus
Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical
conditions. EMIS has used all reasonable care in compiling the information but makes no warranty as to its
accuracy. Consult a doctor or other healthcare professional for diagnosis and treatment of medical conditions.
For details see our conditions.
OriginalAuthor:
Dr MaryHarding
Current Version:
Dr MaryHarding
Peer Reviewer:
Dr HayleyWillacy