Central and peripheral nervous system

Stiff-person syndrome

Stiff person syndrome (SPS) is a disease that is characterized by progressive muscle stiffness typically in the trunk and extremities along with both spontaneous and triggered muscle spasms. Quite interestingly, around 80% of the patients with stiff person syndrome develop antibodies against glutamic acid decarboxylase (anti-GAD antibodies). Moreover, about 5 percent of the cases are in actual paraneoplastic syndromes associated with antibodies amphiphysin.

Diseases with demyelination

Demyelinating diseases are characterized by destruction of the myelin sheath of nerve fibers which results in impairment of nerve signal transmission along nerve fibers and across synapses. The disease mostly affects regions in the brain and spinal cord and gives rise to both sensory and motor symptoms.

Neuromyelitis optica spectrum disorder (NMOSD): These particularly affect the optic nerve and involve antibodies directed against a water channel protein in the central nervous system called aquaporin-4 (AQP-4). Other important antibodies include those against myelin oligodendrocyte glycoprotein (MOG). Their presence is also indicative of the disease as around 20 percent of the cases are negative for anti-AQP4 but positive for anti-MOG. Also, detection of these antibodies helps in early disease diagnosis of NMOSD and separating it from multiple sclerosis, which is by far the most important differential.

Autoimmune neuropathies

Peripheral nervous system and its cells are equally vulnerable to autoagression and immune mediated damage to both neurons and glial cells. The result is a variety of motor and sensory manifestations as well as dystonias. In peripheral nervous system, the potential targets for these antibodies are the glycoproteins and glycolipids in the cell membranes of neurons and glial cells. Their presence is highly indicative of a disease process. More so, specific antibodies can also predict specific forms of peripheral neuropathies. For example, antibodies against gangliosides are diagnostic markers for Guillain Barré syndrome and its various types. Similarly, IgM antibodies against myelin associated glycoprotein (MAG) are indicative of demyelinating polyneuropathy with monoclonal IgM gammopathy.

Myasthenia syndrome

Myasthenia syndrome or myasthenia gravis is an autoimmune disease characterized by the development of antibodies against the post-synaptic acetylcholine receptors at neuromuscular junctions. Destruction of these receptors reduces signal transduction across the junction resulting in muscle weakness. Antibodies against nicotinic acetylcholine receptors (AChR) are detected in at least 85 to 90% of the patients with generalized myasthenia gravis. Additionally, some protein antigens of striated muscles also serve as targets for antibodies for example titin. Such type of associations are related to underlying neoplasms (most commonly thymomas which are seen in fifteen percent of all myasthenia cases). Presence of an associated tumor dictates a highly aggressive disease course. Nevertheless, early diagnostic assays and detection of specific antibodies followed by early therapeutic interventions have shown good results and an overall good disease prognosis.