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SPS Associated Antibodies

SPS is a rare, progressive neurological disorder characterized by severe muscle spasms that can break bones, dislocate joints, and result in life-threatening breathing problems. The impact on a patient’s quality of life reaches far beyond the physical — challenging their mental, emotional, and social well-being.

GAD 65 Antibodies

GAD is the abbreviation for an enzyme called either glutamate decarboxylase or glutamic acid decarboxylase. The “65” is a measure of the size of GAD. As an enzyme, GAD speeds up specific chemical reactions. In the brain, GAD facilitates the formation of GABA, (gamma-aminobutyric acid) which is a neurotransmitter that helps to reduce nerve and muscle excitation. Antibodies to GAD would be expected to interfere with the function of GAD and therefore lower GABA and reduce the inhibitory signals to muscles, resulting in more muscle contractions. However, it is important to emphasize that while

GAD antibodies are usually present in SPS, the antibodies have not yet been shown to be the definitive cause of SPS. GAD 65 antibodies are currently only considered a “marker” of SPS. About 70 – 80% of people with SPS have GAD antibodies.

GAD antibodies may also be seen in other neuro autoimmune disorders and in many people who have type 1 diabetes. About 40% of people with GAD-antibody-positive SPS will also have type 1 diabetes.

The presence of GAD antibodies does not mean that someone has SPS or type 1 diabetes. In fact, a small portion of the general population have GAD antibodies and are completely healthy. GAD antibody levels do not correlate with the severity of symptoms.

Glycine receptor α1 (alpha 1) antibodies

About 10% of people with SPS have glycine receptor alpha-1 (GlyRα1) antibodies. The glycine receptor is found in the brain and spinal cord and produces inhibitory signals to the nerves in response to the neurotransmitter glycine. Glycine receptor antibodies reduce the number of functioning glycine receptors. Therefore, transmission of inhibitory signals is reduced allowing for excessive excitatory neurotransmitter signals, or otherwise stated, decreasing normal inhibition results in excessive stimulation. This may cause seizures, muscle stiffness and spasms.

Amphiphysin antibodies

Antibodies to amphiphysin are a much less frequent (about 5%) finding in SPS. Amphiphysin is found in the brain and in nerve terminals. The abnormal antibody to amphiphysin is usually triggered by cancer, therefore described as a “paraneoplastic” variant of SPS. Treatment of the cancer usually improves SPS symptoms.

Other Antibodies in Stiff Person Syndrome

Other rare antibodies which have been found in SPS include gephyrin (extremely rare), and dipeptidyl peptidase-like protein 6 (DPPX). There are some people diagnosed with SPS who have no detectable known antibodies. There may be other SPS antibodies which have not yet been discovered.

Disclaimer: The content of this Website is provided for informational and educational purposes only, and does not in any way intend to substitute for professional medical advice, diagnosis, or treatment. The content is not intended to be medical advice for any particular person or patient and should not be relied upon as medical advice. You should always seek the advice of a physician or other qualified healthcare provider for medical advice, including any questions you may have regarding diagnosis or treatment of any medical condition.

Contributors to this document include: Jim Weiss, MD; Vered Lewy-Weiss, MD; Tara Zier, DDS and SPS patient.

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