@pattismith I just posted this somewhere else, so I'm
copy/pasting here for you. You may be interested.
I wanted to share what I’ve found/learned regarding the Complement system (part of the immune system), and treatment/peptides for Complement dysfunction I’ve found.
Most people do not know about the Complement system. But there’s a good chance that many here have symptoms due to either dysregulation, impairment, or inadvertent activation of complement components.
- Deficiencies of complement components are associated with increased susceptibility to infections
- Complement system dysfunction creates an imbalance of both host defense and inflammatory response leading to autoimmunity
- Uncontrolled complement activation can lead to inflammatory issues, autoimmune disorders, alterations of blood flow, and tissue destruction
The complement system is pretty complicated. There’s def a learning curve to being able to wrap your head around the general idea. And instead of going over all complement formation details, I’ll just say this – there are many components, proteins, and regulators involved in the complement system. One is C5, and therapeutic targeting on C5 I believe can benefit a lot of people here, especially w/ autoimmune issues, fatigue, and pain.
Complement component 5 (C5) is involved towards the end of the “cascade”. When C5 is cleaved, it creates C5a and C5b. From here, it can end up forming what’s called the Membrane Attack Complex (MAC) or Terminal Complement Complex (TCC), which is made up of C5b-9.
Inadvertent MAC (C5b-9) formation can result in autoimmune destruction, and is seen in numerous autoimmune diseases. I myself only started looking into this after learning about my Small Fiber Neuropathy with TS-HDS IgM antibodies, and how it’s associated w/ C5b-9 deposits in the capillaries at the sites of nerve damage. Then I learned that C5b-9 is found in skin biopsies of patients w/ Guttate Psoriasis, another thing I have. So, I started looking more into it and looking for inhibitors, and treatment for something like this.
Usually, you want to inhibit C5, because if you inhibit one of the earlier components, you might risk dysfunction throughout the rest of the cascade.
At first I just found the super-expensive Eculizumab, which is IVIG. But recently found multiple other C5 inhibitors that are subcutaneous. Here’s all the c5 inhibitors I’ve found.
- Eculizumab (Soliris)
- Ravulizumab (Ultomiris, ALXN1210)
- Zilucoplan (RA101495) – Subcutaneous - 0.3 mg/kg zilucoplan daily
- Tesidolumab (LFG316)
- Pozelimab (REGN3918) – Subcutaneous – 800 mg weekly
- Crovalimab (SKY59) – Subcutaneous (680 mg; 4 mL), administered once every 4 weeks, complete and sustained terminal complement pathway inhibition; improvements in fatigue, physical functioning, and global health status/QoL; sustained and effective suppression of complement activation
Here are some of the conditions I’ve found that a C5 inhibitor can help treat (I’m sure there’s more, this is just what I’ve found thus far).
- Small Fiber Neuropathy
- Paroxysmal nocturnal hemoglobinuria (PNH)
- Atypical haemolytic uraemic syndrome (aHUS)
- Myasthenia gravis
- Neuromyelitis optica spectrum disorder (NMOSD)
- Guillain–Barré syndrome (GBS) variants, particularly acute motor axonal neuropathy, acute motor and sensory axonal neuropathy and Miller–Fisher syndrome
- Lambert–Eaton myasthenic syndrome (LEMS)
- Dermatomyositis
- Diabetic Neuropathy
- Idiopathic membranous nephropathy (IMN)
- Thrombotic microangiopathy
- Necrotizing autoimmune myositis (NAM)
- COVID-19 and COVID-19 ARDS
- Psoriasis
National Jewish Health Advanced Diagnostic Laboratories is a good place to test for complement activation.
These are all good things to test for:
- Factor H – Levels, function
- Factor I – Levels, function
- Bb - Levels
- C4a – Levels
- C4d – Levels
- C5a – Levels (prob the link between complement activation and pain)
- SC5b-9 – Levels
- C1-INH – Levels, function
- C3 – Function
- C3a – Levels
- C3b - Levels
- iC3b - Levels
- Properdin – Levels
- Vitronectin/S-protein – Levels, function
- MBL – Levels
- CR1 - Levels
