Antibodies as Markers of Disease

[Guest guest]

Hi Everyone,

This is a pretty interesting article about how antibodies may be used to

diagnose Mixed Connective Tissue Disorders and rheumatological diseases,

and maybe even help to predict their course. The article was found at:

http://www.hsc.missouri.edu/~arthritis/u1rna.html

Unfortunately, it isn't dated, so some of you have probably seen this

before now. Still, it's written in easily understandable terminology, so

it may be good for us to take a look at, to get a better understanding

of some of the research that's taking place.

Take care,

Georgina

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Anti U1–RNA Antibody:

New lab test helps diagnose disease

Rheumatic diseases can be difficult to diagnose. It’s also hard to

predict when they will become more or less active. A new lab

test assists in the diagnosis and treatment of mixed connective tissue

disease (MCTD), one of the multi–systemic rheumatic

diseases. The test looks for an antibody called anti–U1 RNA. Researchers

at the University of Missouri–Columbia have found that the level of this

antibody in a patient’s blood corresponds to the severity of her

disease. It’s only the second antibody known to show this kind of

relationship. The other one, anti–DNA, is a marker for lupus.

Antibodies are proteins produced by the blood. Antibodies usually fight

off foreign proteins, called antigens, that exist on

viruses and bacteria. In autoimmune diseases like MCTD, lupus, and some

forms of arthritis, the antibodies react with the

body’s own tissues. While studying anti–U1 RNA antibody, doctors at the

University of Missouri observed a woman in her 30s with MCTD. Her

disease was in remission; she was working and feeling fine. The doctors

thought she could be used as a control, a standard of comparison, in

their search for the antibody in patients with active MCTD. Much to the

researchers’ surprise, the woman’s anti–U1 RNA antibody count was very

high.

“There must be something wrong with our test,” one of the researchers,

Dr. Gordon Sharp, recalls thinking. The next week, however, the woman

experienced chest pain and muscle weakness, a relapse of her MCTD. The

increase in her anti–U1 RNA antibody level had been a warning sign. Her

medication was subsequently increased and her disease went into

remission again.

Now Sharp and his colleagues are monitoring the levels of anti–U1 RNA

antibodies in all their patients with MCTD. An

increase in the antibody level signals them to re–evaluate the patient

and consider adjusting the dosage of the medication,

usually a corticosteroid, to prevent flare–ups of the disease.

Discovering the antibody

The anti–U1 RNA antibody was discovered in 1983 by Deutscher, PhD,

a biochemist, and her colleagues at Duke

University. They took the sera from two patients with connective tissue

disease and found that their antibodies attached to a

type of ribonucleic acid (RNA), the cell material that helps decode

genetic instructions held in DNA. Most antibodies bind

proteins, so they knew they had something unusual. They later identified

the type of RNA as U1–RNA, named for its

abundance of a compound called uracil.

When Deutscher joined the Biochemistry Department at the University of

Missouri–Columbia, she found physicians with a

strong interest in connective tissue diseases and access to their large

population of patients. She has collaborated with Dr.

Hoffman, an immunogeneticist and Dr. Sharp, the rheumatologist

who heads the MARRTC.

The ANA lab

The anti–U1 RNA antibody is the most recent addition to the autoantibody

profile offered by the ANA (Antinuclear Antibody)

laboratory at the University of Missouri. The lab analyzes over 6,000

blood samples a year from patients with various

autoimmune diseases. “The antigen is our tool,” said lab supervisor

Grace Wang.

The lab tests for anti–U1 RNA by adding a radioactively–labelled antigen

to a patient’s serum sample. The antibody in the

serum combines with the antigen, making it precipitate, or fall out of

the solution. The amount of radioactivity in the precipitate

then tells how much anti–U1 RNA antibody is present.

The University of Missouri ANA lab, begun about 20 years ago, is one of

the oldest labs of its type and may be the only clinical

pathology lab in the United States offering the new anti–U1 RNA antibody

test.