Cold agglutinin disease (CAD) is a rare disease in which the immune system mistakenly attacks red blood cells at cold temperatures.

How does the immune system work?

The immune system is divided into two categories: adaptive and innate.

The adaptive immune system “learns” to attack new threats and is made of immune cells that produce antibodies and “remember” previous infections.

The innate immune system is non-adaptive, but can greatly enhance the effects of antibody attacks against threats. It also handles new threats that the immune system has not “seen” before until the adaptive portion of the immune system learns to respond to them.

One part of the innate immune system is the complement system, also called the complement cascade.

What is the complement system?

The complement system is made of a series of proteins activated when the immune system is responding to a threat. One complement protein becomes active and activates the next protein in the chain, and so on. These downstream complement proteins bind to antibodies that are bound to threats — which can be an infected cell or a bacterium, etc. — and interact with the immune system components that can deal with the threat.

When complement proteins are bound to antibodies that have recognized a target, the complex dramatically increases the immune response to the threat — more so than would occur when an antibody alone binds to the target.

What happens in CAD?

In CAD, the adaptive portion of the immune system mistakenly produces antibodies called cold agglutinins. These antibodies bind to the body’s own normal red blood cells in cold temperatures. which can trigger or activate the complement cascade, causing the red blood cells to be attacked by immune system cells. This leads to the destruction of the red blood cells. The effects of the complement system are cumulative, so the longer the complement cascade is active, the worse the downstream consequences — or the disease symptoms — are.

Treatments that target and block some portions of the complement cascade have been shown to reduce some of the symptoms of CAD, though more extensive studies need to be performed.

 

Last updated: Jan. 23, 2020

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Cold Agglutinin Disease News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.

Emily holds a Ph.D. in Biochemistry from the University of Iowa and is currently a postdoctoral scholar at the University of Wisconsin-Madison. She graduated with a Masters in Chemistry from the Georgia Institute of Technology and holds a Bachelors in Biology and Chemistry from the University of Central Arkansas. Emily is passionate about science communication, and, in her free time, writes and illustrates children’s stories.
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Özge has a MSc. in Molecular Genetics from the University of Leicester and a PhD in Developmental Biology from Queen Mary University of London. She worked as a Post-doctoral Research Associate at the University of Leicester for six years in the field of Behavioural Neurology before moving into science communication. She worked as the Research Communication Officer at a London based charity for almost two years.
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Emily holds a Ph.D. in Biochemistry from the University of Iowa and is currently a postdoctoral scholar at the University of Wisconsin-Madison. She graduated with a Masters in Chemistry from the Georgia Institute of Technology and holds a Bachelors in Biology and Chemistry from the University of Central Arkansas. Emily is passionate about science communication, and, in her free time, writes and illustrates children’s stories.
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