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I’m a highly-organized-very-structured-risk-taking-adventure-loving-scientist-slash-traveller; this sounds intensely better when I speed-say it in my native language of Portuguese. My work is highly structured and organized – it needs to be as I’m researching an autoimmune disease where very little is known. At the other end of the spectrum, I love to travel – and to travel by the seat of my pants though India and Guatemala – with a “let’s get there and see” approach.

This fine balance is also reflected in our biological systems, and when it’s upset, bad things can happen.

Much is unknown about Systemic Lupus Erythematosis

Our immune system should be able to tell the difference between self and non-self when deciding to launch an attack, and it should be able to temper or stop the attack when necessary. This recognition goes awry in patients with Systemic Lupus Erythematosis (SLE). SLE has a high prevalence in young females, and it may take years for an accurate diagnosis. Its cause is unknown, it’s not linked to particular gene, multiple environmental triggers may play a role and there is no cure. Renal disease affects about 30% of SLE patients and remains the most dangerous, life-threatening complication. Kidney failure results when autoantibodies (antibodies that recognize a person’s own cells as foreign) form immune complexes that deposit in the kidney inducing inflammation and blocking the kidney’s filtration capability.  

Immune checkpoints

Inhibitory receptors on the cell’s surface and play an important role in modulating the amplitude and duration of an inflammatory response. For example, when our body is “invaded” by sunlight, viruses or chemicals, our immune system activates a temporal frontal assault and then recedes back into standby position with the aid of inhibitory signals. We’re interested in a particular inhibitory receptor, CD200R and its ligand CD200.

Under normal conditions in mice, CD200R limits inflammation. In SLE, a continuous immune response develops, completely disorganizing the immune system. Interestingly, we see that CD200R is expressed, but no longer functional (it’s not suppressing the system like it should). So, where does it go wrong?

We’re at the tip of the iceberg in this complex disorder, and our questions have the possibility to change the course of this disease and future outlook for patients with SLE.

Drawing a molecular map of SLE

Because so little is known about the molecular pathways of SLE, and because CD200-CD200R is expressed almost everywhere in the body on myeloid and T-cells, we’re looking at a huge matrix of pathways and possibilities. We’re imposing a systematic approach into what’s essentially a black box, which allows me to merge my organizational tendencies with the spontaneity of following multiple new directions at the same time.

Using tissues from healthy and SLE patients, we’re trying to outline the network of CD200-CD200R and its role in SLE: does the receptor recruit helpers and other partners and what are their roles; is its structure altered such that it confers dysregulation; and why can’t SLE patients access a backup pathway to restore the balance of their immune system?

Finding a specific molecular target that can restore the CD200 pathway and being able to make it clinically relevant would be of great importance to both cancer and autoimmune patients. We’re at the tip of the iceberg in this complex disorder, and our questions have the possibility to change the course of this disease and future outlook for patients with SLE.

Ines Pascoal Martins Ramos
PhD Candidate
Promotor: Professor Linde Meyaard
Department of Immunology
UMC Utrecht