Antibodies: Our Body's Disease Fighters
New findings reveal how antibodies can improve disease predictions and treatments.
Onyekachi Nwogu, Kirandeep K. Gill, Carolina Moore, John W. Kroner, Wan-Chi Chang, Jeffrey Burkle, Mariana L. Stevens, Asel Baatyrbek kyzy, Emily R. Miraldi, Jocelyn M. Biagini, Ashley L. Devonshire, Leah Kottyan, Justin T. Schwartz, Amal H. Assa’ad, Lisa J. Martin, Sandra Andorf, Gurjit K. Khurana Hershey, Krishna M. Roskin
― 6 min read
Table of Contents
- The Quest for Convergent Antibodies
- The New Way: Structural Convergence
- Comparing VJ3 and SCAGs Approaches
- The Role of Antibody Isotypes
- Results of the Study
- Discovery of Predictive Antibody Features
- Cloning and Grouping Antibody Sequences
- Understanding Food Sensitization
- In Summary: What Have We Learned?
- Original Source
Antibodies are like the body's little soldiers, ready to fight off any germs that invade. They are made by special cells called B cells when they encounter something that doesn’t belong, like viruses or bacteria. Each time our body meets an invader, it remembers it, which helps it respond faster in the future. This memory makes us better at fighting off the same invader if it shows up again.
In recent years, scientists have developed new technologies that allow them to take a close look at these antibodies. They can now sequence the genes responsible for making antibodies, giving insight into how our immune system works. This is important for understanding diseases and finding ways to help people who are sick.
The Quest for Convergent Antibodies
One interesting area of study is how different people's bodies can produce similar antibodies when exposed to the same germs. This is called convergent antibodies. Think of it like a team of superheroes: different people might have different powers, but they can all fight against the same villain. Scientists want to see how these convergent antibodies can help in diagnosing diseases, like HIV or allergies.
To find these antibodies, researchers have been looking at specific parts of the antibody genes, particularly the heavy chain variable regions. These areas can show similarities between antibodies that seem different at first glance. By identifying these similarities, scientists can create tools to help with disease prediction.
The New Way: Structural Convergence
While looking at the genes is important, it turns out that two antibodies can look very similar in shape even if their sequences are not alike. This is like having two different people who can dance the same way but have different styles of music. To address this, researchers came up with a new definition called "structurally convergent antibody groups" or SCAGs for short.
SCAGs look at the shape of the binding sites of antibodies to group them together, even if the sequences are different. This gives a better understanding of how antibodies work and how they can be used in medical prediction models.
Comparing VJ3 and SCAGs Approaches
To figure out which method worked best, scientists compared the traditional approach using the variable region of the antibody, called VJ3, with the new SCAGs approach. They tested both in predicting two medical conditions: HIV and food allergies.
In their experiments, they found that using SCAGs helped improve predictions, especially for understanding food sensitization. This means that looking at the shape of antibodies provides valuable information that helps doctors make better diagnoses.
The Role of Antibody Isotypes
Antibodies come in different flavors, called isotypes. These isotypes can act differently in our bodies, just like different types of chocolate: some are sweet, some are dark, and some have nuts. Knowing the isotype can help scientists understand the antibody's function better.
The researchers included this isotype information in their models to see if it would improve their predictions even further. What they found was that adding the isotype information indeed enhanced the accuracy of their models for predicting both HIV and food sensitization status.
Results of the Study
When the researchers used their methods to predict HIV infection, they found that the traditional VJ3 features performed very well. However, the SCAGs features were not as strong for HIV but did perform well for food sensitization. This means that SCAGs proved to be particularly useful for understanding how well people respond to certain foods rather than viruses.
Interestingly, when SCAGs and VJ3 were combined with isotype information, they saw a marked improvement in predictions. They noted that the models prioritizing certain isotypes, especially IgG, were more successful in predicting HIV infection than those focusing mostly on naïve isotypes.
Discovery of Predictive Antibody Features
The researchers also looked into which specific features of these antibodies were driving the predictions. They focused on a smaller set of antibody features that were particularly good at predicting HIV infection and food sensitization. For HIV, many features were linked to naive isotypes like IgD and IgM. For food sensitization, however, it was the IgE isotype that stood out.
This presents an interesting puzzle: How can the same isotype, like IgE, be associated with both sensitization and non-sensitization in food allergies? It turns out that this particular form of IgE might actually be protecting against certain food allergies rather than causing them. This is a bit like having a friendly dog that barks at strangers to keep them away, even though all dogs bark.
Cloning and Grouping Antibody Sequences
Looking at the genetic sequences that make up these antibodies is like assembling a jigsaw puzzle. By grouping similar characters together, scientists can see which antibodies belong to the same family. This helps them understand how these families react to infections.
They found that there was a lot of variety in the sequences of antibodies that were grouped using the new SCAGs approach, meaning there was a wide range of antibodies working together in response to the same germs.
Understanding Food Sensitization
Food allergies are becoming a major concern, and this study helps us understand how antibodies interact with food allergens. Interestingly, the research showed that certain IgE features were associated with protection against food sensitization. This means that some antibodies might actually help instead of harm when it comes to food allergies.
But wait, there’s more! The researchers also found that some IgG features were linked to food sensitization, suggesting that perhaps these IgG antibodies can hold a memory of sensitization that could switch to producing allergic responses in certain cases.
In Summary: What Have We Learned?
This exciting study helps to highlight how important antibodies are in understanding our health. By using new approaches to look at the structure of antibodies and combining that with the knowledge of their isotypes, scientists can predict disease states more accurately.
Imagine a future where a simple blood test could tell you if you might develop a food allergy or if you are at risk for HIV. That would be pretty cool, right?
While we are not quite there yet, this research provides a solid foundation. It opens the door for further exploration into how we can use antibodies not just as tools for diagnosis, but potentially as guides for treatments too.
So the next time someone says "antibodies," you can nod knowingly and think of them as the superheroes inside us, ready to spring into action. And who knows, maybe one day they will save us from food allergies or diseases like HIV!
Original Source
Title: Use of Antibody Structural Information in Disease Prediction Models Reveals Antigen Specific B Cell Receptor Sequences in Bulk Repertoire Data
Abstract: Convergent antibodies are highly similar antibodies elicited in multiple individuals in response to the same antigen. Convergent antibodies provide insight into shared immunological responses and show great promise as diagnostic biomarkers. They have typically been identified using methods that consider the amino acid sequence of the third complementarity-determining region (CDR3) of immunoglobulin heavy chain (IgH). In this study, we extend the definition of convergent antibodies to use structural information about the three IgH CDR regions (CDR1-3). We benchmark the performance of both definitions of convergence by their ability to predict disease status from bulk IgH sequencing data for two different diseases (HIV infection and food sensitization). We show that using predicted structural information outperforms prior approaches for the prediction of food sensitization status and performs on par for HIV infection status. Additionally, the structurally convergent antibody groups driving HIV prediction are from known HIV binders. Thus, the use of structural information allows for the identification of antigen specific antibody groups from bulk IgH sequencing data.
Authors: Onyekachi Nwogu, Kirandeep K. Gill, Carolina Moore, John W. Kroner, Wan-Chi Chang, Jeffrey Burkle, Mariana L. Stevens, Asel Baatyrbek kyzy, Emily R. Miraldi, Jocelyn M. Biagini, Ashley L. Devonshire, Leah Kottyan, Justin T. Schwartz, Amal H. Assa’ad, Lisa J. Martin, Sandra Andorf, Gurjit K. Khurana Hershey, Krishna M. Roskin
Last Update: 2024-12-15 00:00:00
Language: English
Source URL: https://www.biorxiv.org/content/10.1101/2024.12.10.627792
Source PDF: https://www.biorxiv.org/content/10.1101/2024.12.10.627792.full.pdf
Licence: https://creativecommons.org/licenses/by/4.0/
Changes: This summary was created with assistance from AI and may have inaccuracies. For accurate information, please refer to the original source documents linked here.
Thank you to biorxiv for use of its open access interoperability.