Scientists unlock cause of cat allergies

"Scientists discover cure for cat allergies," is the premature claim in The Daily Telegraph. 

Most cat allergies are caused by an abnormal immune response to what is known as dander – the microscopic particles of dead skin shed by cats and other animals with fur or feathers. 

But it is unclear what biological processes are involved when a person has an allergic reaction to cat dander. The research hitting the headlines set out to clarify precisely how these allergic reactions come about by examining the effect of a common protein found in cat dander on a key molecular pathway in cells.

The researchers identified not only the pathway involved in starting the immune response, but the other molecules and proteins that turn innocuous cat dander into something that can cause a person to wheeze, sniffle and sneeze. They discovered that a protein found in cat dander binds to a molecule called LPS. LPS in turn is recognised by a receptor called TLR4, which triggers the start of an allergic reaction.

Clinical trials appear to be underway for drugs designed to block the binding of LPS and TLR4, which could help prevent – but not cure – cat allergies. While this is promising research, any talk of a cure is premature.

Where did the story come from?

The study was carried out by researchers from the University of Cambridge, the Karolinska Institute in Sweden and the University of Massachusetts in the US, and was funded by the Wellcome Trust and the Medical Research Council.

It was published in the peer-reviewed Journal of Immunology.

The research was generally covered appropriately by the media, with the Mail Online and BBC News providing a good summary of the research. 

But it seems that some headline writers were unable to resist the temptation of "sexing up" the implications of the research. The Mail and Telegraph headlines claiming that cat allergies have been "cured" are both premature and inaccurate. They skip over the fact that these so-called cures are yet to be tested in people with severe allergies to determine their effectiveness. Even if an effective drug did come out of this line of enquiry, it would arguably not represent a cure, but treatment on demand.

What kind of research was this?

This was a laboratory and animal study that examined the cellular mechanisms that underlie cat dander allergies.

The researchers examined the effect of the protein LPS on TLR4 signalling in cells, measuring signalling when cat dander protein was introduced to cell structures so they could learn more about immune responses to these allergens.

What did the research involve?

The researchers examined the effect of LPS on TLR4 signalling in cells (a marker of immune system activity). They then added the cat dander protein (Fel d 1) to the cell cultures and compared the level of signalling. 

Researchers investigated the precise mechanism by which this protein interacts with the LPS molecule to activate TLR4 signalling, which causes an immune response.

They also investigated whether other known animal allergens work in a similar manner. They specifically looked at a dog dander protein called Can f 6.

What were the basic results?

The researchers discovered that the cat dander protein Fel d 1 does not directly activate the immune system. Instead it must bind to the bacterial surface molecule LPS. LPS in turn is recognised by TLR4, which kicks off a signalling cascade, ultimately leading to a (sometimes severe) immune response. The researchers found this only occurs in the presence of an additional protein called MD2, which binds LPS to TLR4.

When Fel d 1 was introduced to cells with no MD2 on their surface, there was a small increase in TLR4 signalling, even at very high concentrations. But when MD2 was present, there was a 16-fold increase in TLR4 signalling. Another surface protein called CD14 was similarly required for the reaction to occur.

Essentially, cat dander (Fel d 1) binds to a bacterial molecule called LPS, which is known to cause acute immune responses. In this way, Fel d 1 presents more LPS to a cell, where it binds with the protein MD2. Once LPS and MD2 are bound together, TLR4 is then activated and starts to signal the cell to produce an immune response.

Put simply, cat dander on its own is not enough to get you sneezing and sniffling – there must be at least two additional molecules and proteins involved before you have to reach for the tissues.

The researchers also found that the dog dander protein Can f 6 activates the immune system in a similar manner, by enhancing TLR4 cell signalling in the presence of the bacterial surface molecule LPS.

How did the researchers interpret the results?

By identifying the mechanism by which cat dander causes the immune system to react, researchers suggest that treatments could be developed to prevent the reaction from occurring in the first place.

Conclusion

This research identified the series of events that must occur at a molecular level for cat dander to activate the immune system.

The researchers suggest that the two animal proteins they studied are responsible for 80% of cat allergies and 35% of dog allergies.

They propose that drugs that could bind to TLR4, blocking the ability of cat dander and LPS to bind, may prevent an immune response from occurring in the first place. 

A drug that blocks certain biological processes from taking place is known as an antagonist. This potential for drugs to prevent a reaction from occurring could offer an alternative to current treatment options, such as antihistamines.

It is important to remember that this was a laboratory study using mainly cell cultures. Further research is needed in humans before we can declare cat allergies cured.

While most media coverage suggests that such drugs could be available within five years, this is not discussed in the research paper itself and is likely derived from a press release. That said, such a time frame is not unfeasible. There are currently phase III clinical trials underway for drugs called TLR4 antagonists, which are designed to prevent LPS binding to TLR4 and initiating an immune response.

These trials are being conducted for indications other than cat allergies – one trial is among patients in intensive care units with severe sepsis. Additional trials would be required to assess the effectiveness of these potential drugs in people with cat dander allergies.

It is unlikely there will be changes to the way allergies are treated on the basis of this research in the absence of further research. Current treatments for allergic responses involve the either use of antihistamines, steroids or, in more severe cases, immunotherapy (where small amounts of the allergen are gradually given to the person by injection). 

Read more about the treatment of allergies.