Altered Cell Protein Expression in Lupus May Be a Step Toward Potential Treatment

Scientists recently discovered the altered expression of one protein in the body that may change the way physicians treat and diagnose lupus in the future.

Lupus is an autoimmune disease, in which the body starts attacking its own major tissues and organs. It is a disease that does not have any fixed pattern, with symptoms varying greatly among patients. In some, it may be a disease of the joints, while in others it may involve multiple organs at a time. It is mostly a disease of young women and is known to affect the quality of someone's existence and lifespan.

So, why is this disease so difficult to treat and diagnose? The answer to this question perhaps lies in the fact that we still do not know much about how our natural immune responses work and what stimulates or inhibits our immunity in a particular threat situation. Though in recent times, with the improvement in technology, a lot has been discovered in this direction. Any improvement in the working-knowledge of immunity would help us to tackle the autoimmune diseases in a more efficient manner.

At present, there are many diagnostic and treatment methods used in lupus. However, none of them are 100% specific to lupus itself. Thus, we use drugs that suppress the immune system, and in most cases, this is done non-selectively, causing patients to exhibit several side effects. Similarly, for diagnosis, we use tests that indicate inflammation and autoimmunity. ESR, antinuclear antibodies test, imaging are some of the commonly used methods by physicians, however, they are still not very specific for lupus. So, the search for more precise diagnostic and therapeutic approaches continues. Researchers are also trying to find out all about the factors, receptors, messengers, and switches that help to regulate immunity. Understanding the expression of the newer protein is one more step forward in that direction.

Discovery of altered expression of new type of cell protein

In a recent investigation, Anna-Marie Fairhurst and her research team noticed the increased presence of a specific kind of protein on the surface of the cell wall of immune cells of those known to be suffering from lupus. This is a finding that has a potential to change the way we diagnose or treat lupus in the future.

Discovery of this protein is not a new thing, but its increased expression on specific immune cells in lupus was not known until now.  It is a protein or rather group of proteins that are found on the cell walls, and are together called Siglecs. These proteins are thought to regulate the way our body's cells and immune system interact with each other and are also considered to play a critical role in the regulation of various immune functions. It is thought that most of these proteins are a part of a distinct signaling pathway, which when excited would lead to the inhibition of the immune system’s interaction with our body's cells. However, some of the sub-proteins from the group Siglecs are known to have a stimulating effect. It means that the combination of these proteins on the cell wall plays an important role in either inhibiting or stimulating particular immune responses and thus regulating the immune system.

Fairhurst and her team from Institute of Molecular and Cell Biology and Singapore Immunology Network, recently discovered that in lupus one of the Siglecs called “Siglec-14” was present on the surface of more immune cells than expected. Siglec-14 is different from other proteins of the group in a way that it stimulates cellular interaction, while most Siglecs are known to rather inhibit other responses. This means that Siglec-14 may have something to do with overactivity of the immune system in lupus. Overactivity of Siglec-14 may be playing some role in triggering our immune responses in a fashion where they start to attack our body's cells. At present, researchers do not understand the role of Siglecs in autoimmunity and inflammatory processes completely, but it seems entirely possible that these proteins may have some central role.

There is a reason to think that an increased expression of Siglec-14 may be playing a role in the disease development or flares. In some of the earlier studies done on the patients suffering from the chronic obstructive pulmonary disease, it was found that those with gene mutation causing loss of Siglec-14 expression were less prone to the exacerbations of the disease. However, Fairhurst’s study did not show any relation between lupus activity and gene variations.

This research is vital in a way that it is the first of its kind that demonstrated the higher presence of Siglec proteins on the surface of some of the immune cells. If not revolutionary, this discovery is undoubtedly one more step forward in the right direction. In the future, as we start to learn more about Siglecs and their role in immune control, it is quite possible that we may be able to use them to predict lupus development and flares. The drugs targeting Siglec may help to control not only lupus but also many other autoimmune diseases. Thus, it could very well be a small but significant step in the right direction to counter the upsurge of autoimmunity related ailments in recent times.

References

1. Lupus Diagnosis. nhs.uk. https://www.nhs.uk, www.nhs.uk, www.nhs.uk/conditions/lupus/diagnosis/. Accessed December 17, 2017.
2. Thornhill SI, Mak A, Lee B, et al. Monocyte Siglec-14 expression is upregulated in patients with systemic lupus erythematosus and correlates with lupus disease activity. Rheumatology. 2017;56(6):1025-1030. doi:10.1093/rheumatology/kew498.
3. Ali SR, Fong JJ, Carlin AF, et al. Siglec-5 and Siglec-14 are polymorphic paired receptors that modulate neutrophil and amnion signaling responses to group B Streptococcus. J Exp Med. 2014;211(6):1231. doi:10.1084/jem.20131853.
4. Crocker PR, Varki A. Siglecs in the immune system. Immunology. 2001;103(2):137-145. doi:10.1046/j.0019-2805.2001.01241.x.