To determine disease progression and severity, researchers often use biomarkers, a measurable substance that indicates disease state. According to Myasthenia Gravis News, a new study shows that acetylcholine receptor (AChR) antibodies, as well as blood protein C5a, mark disease severity in patients with myasthenia graves (MG). Check out the full findings in Therapeutic Advances in Neurological Disorders.
C5a and AChR Antibodies
Generally, MG results from the immune system mistakenly targeting AChR in areas where your nerves and muscles communicate. This results from the complement system being activated. According to the British Society of Immunology (BSI), the complement system is a series of over 20 proteins that exist within blood and tissue. Generally, they activate in response to some immune problems. So:
complement can be activated via three different pathways , which can each cause the activation of C3, cleaving it into a large fragment, C3b, that acts as an opsonin, and a small fragment C3a (anaphylatoxin) that promotes inflammation. Activated C3 can trigger the lytic pathway, which can damage the plasma membranes of cells and some bacteria. C5a, produced by this process, attracts macrophages and neutrophils and also activates mast cells.
For those who don’t know, opsonin means an antibody or other substance that either recycles dead cells or marks antigens to prompt immune response.
Researchers were unsure whether anti-AChr antibodies could highlight disease severity. To begin, they measured antibody levels in 60 patients with myasthenia gravis (MG). Of these patients, 65% were female and 35% were male. Patient ages ranged from 20 to 88 years old, with disease onset appearing anywhere from 3 to 82 years old. The median amount of time since diagnosis was 9 years. Approximately 14 patients had their thymus removed. Additionally, the study included 49 controls.
Next, researchers also measured C3, C4, and C5a proteins. Finally, patients took a neurological examination. Researchers discovered that patients with more anti-AChR antibodies had more severe cases of MG. Patients with higher anti-AChR antibodies also had lower C3 and higher C5 levels. However, patients with early-onset MG had lower C3 and C4 levels. Ultimately, researchers determined that there was no relationship between C3, C4, and MG severity. Finally, researchers found that patients taking mycophenolate mofetil had higher levels of C5a and anti-AChR antibodies.
Overall, researchers determined that analyzing AChR antibodies could highlight disease severity and progression. However, additional research is needed to determine the use of complement proteins as biomarkers.
Myasthenia Gravis (MG)
The aptly named myasthenia gravis (MG), which means “grave muscle weakness,” is a rare autoimmune neuromuscular disorder. In most cases, MG results from antibodies disrupting neurotransmitter activity. However, in extremely rare cases, MG results from CHRNE, COLQ, DOK7, CHAT, or RAPSN gene mutations. Patients with MG experience muscle weakness and fatigue in voluntarily controlled muscle groups. Typically, symptoms worsen with activity. Most patients with MG have normal life spans, although around 10% of patients develop severe respiratory complications. There are three main forms of MG: congenital, transient neonatal, and juvenile. The first begins in infancy and lasts throughout one’s life. Next, transient neonatal MG begins in infancy but ends within a few months of birth. Finally, juvenile MG occurs in adolescence and may occur in alternating periods of remission and symptoms.
- Drooping eyelids
- Difficulty speaking, swallowing, or chewing
- Muscle weakness in the arms, legs, and neck
- (Life-threatening) chest wall weakness
- Double vision
- Slurred speech
- Shortness of breath
Learn more about MG.