Study finds that 30 percent of human anti-glycan antibodies fail to activate the complement system!

Medical News: Scientists Uncover Surprising Findings About Human Antibodies
A groundbreaking study by researchers from the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, the Russian Academy of Sciences, the National Medical Research Center for Obstetrics, Gynecology, and Perinatology, the Zelinsky Institute of Organic Chemistry, the Clinical Center of Sechenov First Moscow State Medical University, and the University of Bern in Switzerland has revealed a surprising discovery about human antibodies. While many antibodies in the body actively fight infections by triggering the immune system, nearly 30% of anti-glycan antibodies fail to activate a key immune response known as the complement system.


Study finds that 30 percent of human anti-glycan antibodies fail to activate the complement system!

This Medical News report explains how scientists used advanced laboratory techniques to investigate these antibodies and what their findings could mean for medicine.
 
What Are Anti-Glycan Antibodies and Why Are They Important
Antibodies are proteins that help the body fight infections by recognizing harmful bacteria, viruses, and even cancer cells. A special group of these antibodies, known as anti-glycan antibodies, target sugar molecules (glycans) found on the surfaces of microbes and abnormal cells. Once they recognize a threat, they typically trigger a powerful immune response called the complement system, which helps destroy harmful invaders.
 
However, this new study found that not all anti-glycan antibodies are capable of activating the complement system. The reason why this happens remains unclear, but researchers believe it could have important implications for understanding immune function and disease.
 
How the Study Was Conducted
To investigate this phenomenon, scientists used a printed glycan array (PGA), a sophisticated tool that allows researchers to test how different antibodies in human blood interact with hundreds of sugar molecules at once. The study included samples from healthy individuals, focusing on two key types of antibodies: IgG and IgM.
 
Researchers measured whether these antibodies could deposit C3, a key protein in the complement system. They found that while many antibodies successfully triggered the complement response, about 30% of them did not - despite binding strongly to their target glycans.
 
Key Findings and Surprising Results
-IgM antibodies were more likely to activate the complement system, while many IgG antibodies did not.
 
-Antibodies that did not activate the complement system still strongly bound to their targets, raising questions about their function.
 
-Some bacterial polysaccharides (sugar molecules found on bacteria) were recognized by antibodies but failed to trigger an immune response.
 
-A group of antibodies bound to certain sugars but did not lead to C3 deposition, meaning they did no t activate the complement system at all.
 
-Some glycans triggered the complement system even without any detectable antibodies, suggesting alternative immune pathways might be involved.
 
Testing for Immune Activation in a Real-World Model
To confirm their findings, scientists conducted additional experiments using a special technique involving kodecytes - red blood cells modified with specific glycans. By exposing these modified cells to purified antibodies and human blood serum, they observed whether the immune system destroyed the cells.
 
The results matched their PGA findings:
-Antibodies that activated the complement system led to red blood cell destruction.
 
-Antibodies that failed to trigger complement activation did not cause cell destruction, even when binding strongly to glycans.
 
This provided strong evidence that some human anti-glycan antibodies naturally lack the ability to activate a full immune response.

What Do These Findings Mean for Medicine and Immunology
This discovery challenges long-standing assumptions about how antibodies work in the human body. Scientists previously believed that most antibodies targeting foreign or abnormal structures would trigger the immune system. However, this study shows that some antibodies may serve other unknown roles beyond immune activation.
 
Possible Explanations for Non-Activating Antibodies
The reason why some anti-glycan antibodies do not activate the complement system is still not fully understood, but researchers propose several possible explanations:
 
-Structural Differences in Antibody Function - Not all antibodies are designed to trigger the complement system. Certain IgG subclasses, such as IgG4, are known to have weaker complement-activating properties. Additionally, differences in glycosylation patterns (the way sugar molecules attach to antibodies) can influence their ability to engage immune components like C1q, a key protein that initiates complement activation.
 
-Protective Role Against Unwanted Immune Activation - Some antibodies might serve a regulatory role by binding to glycans without triggering inflammation. This could be important in preventing unnecessary immune responses against harmless or self-derived glycans, reducing the risk of autoimmune diseases or excessive tissue damage.
 
-Interaction with Other Immune Pathways - Instead of activating the complement system, these antibodies might participate in alternative immune mechanisms. For instance, they could interact with Fc receptors on immune cells, influencing immune regulation through mechanisms such as antibody-dependent cellular phagocytosis (ADCP) or modulating B cell activity.
 
-Evolutionary Adaptation to Prevent Self-Destruction - Many glycans are present on human cells as well as pathogens. If all anti-glycan antibodies triggered a strong complement response, there could be unintended damage to normal tissues, leading to autoimmune complications. The presence of non-activating antibodies may be an evolutionary safeguard to maintain immune tolerance while still allowing immune surveillance.
 
-Potential Role in Pathogen Evasion and Immune Modulation - Some bacteria and viruses have evolved to exploit immune responses by inducing the production of antibodies that bind but do not activate complement, thereby allowing the pathogen to evade immune destruction. This is seen in some chronic infections where non-activating antibodies might actually benefit the pathogen by dampening a full immune attack.
 
Further research is needed to confirm these hypotheses and determine whether non-activating anti-glycan antibodies play a protective role, a regulatory function, or are simply a byproduct of immune system complexity.
 
Conclusion
The study provides valuable new insights into the complexity of the human immune system. While most anti-glycan antibodies help activate immune responses, a significant portion does not. This discovery raises important questions about their function and could lead to new medical advancements in immunology, autoimmune diseases, and even cancer research.
 
The study findings were published in the peer-reviewed journal: Antibodies.
https://www.mdpi.com/2073-4468/13/4/105
 
For the latest on Immunology, keep on logging to Thailand Medical News.
 
Read Also:
https://www.thailandmedical.news/news/more-than-50-percent-of-individuals-exposed-to-covid-19-will-develop-antiphospholipid-autoantibodies
 
https://www.thailandmedical.news/news/emergence-of-antisperm-antibodies-causing-infertility-issues-in-men-who-had-covid-19-infections-or-vaccines
 
https://www.thailandmedical.news/news/study-shows-that-individuals-who-have-recovered-from-covid-19-are-more-likely-to-develop-antinuclear-antibodies