The Role of a Receptor-Ligand Pathway in Autoimmune Diseases, Lupus

Malika Ammam, PhD avatar

by Malika Ammam, PhD |

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Lupus research

In a recent review paper published in Seminars in Arthritis and Rheumatism entitled “The CD27–CD70 pathway and pathogenesis of autoimmune disease“, researchers examined the role of the CD27 receptor and its ligand protein CD70 in functional changes of autoimmune diseases with particular focus on systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).

Autoimmune diseases emerge from an anomalous immune response of the body against our own substances/tissues. According to statistics, mainly women suffer from chronic, debilitating, and life-threatening autoimmune diseases. More than 80 illnesses are caused by autoimmunity, among these RA and SLE. While RA particularly affects the joints, SLE commonly involves a number of organs/tissues like skin, heartjointslungsblood vesselsliverkidneys, and nervous system. Symptoms of autoimmune disorders depend on the affected organ/tissues. For example, while patients with joint RA suffer from warm, swollen, and painful joints, additional symptoms like fever, malaisemuscle pains, and fatigue appear in patients with SLE. There is no known cure for both conditions but various medications are available to relieve the symptoms and limit disease progression. Life style changes, surgery and alternative medicines have also been considered.

The causes of autoimmune disorders are not fully understood but it is believed that genetics and environmental factors trigger the diseases. A normal immune system produces proteins named antibodies that have the role of protecting against pathogens such as viruses/bacteria. However, in autoimmune diseases, the presence of antibodies against a person’s own proteins inducing inflammation occurs.

In the recently published review paper, researchers tried to understand the role of the receptor CD27 and its ligand CD70 in the functional changes occurring during autoimmune diseases, particularly RA and SLE. They preformed an in depth literature search on PubMed using key words like CD27, CD70, autoimmune disease, systemic lupus erythematosus and rheumatoid arthritis. In the process, only publications in English related to human and animal studies were considered and these articles were further searched for relevant citations.

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The results suggest that in humans and animal models, receptor–ligand pair CD27–CD70 plays a key role in the regulation and activation of white cells named T and B lymphocytes. Particularly, the membrane receptor CD27 and its soluble form sCD27 are found to stimulate signalling in the activation and proliferation of T and B lymphocytes. Also, CD70 ligand is found to participate in the proliferations of CD4 T lymphocytes. As a consequence, they are present in high numbers in diseases like RA and SLE. On the other hand, preclinical studies have proposed that CD27–CD70 signalling could qualitatively differ with cell type/stage particularly for white cells B lymphocytes. Finally, obstruction the CD27–CD70 pathway has been shown to improve disease manifestation in animal models like murine collagen-induced arthritis and experimental colitis.

In conclusion, it is clear that the CD27–CD70 pathway plays key roles in functional changes underlying autoimmune diseases in both animal model and human patients. This suggests that targeting the components responsible of this pathway, by means of antibodies, may lead to novel therapies for autoimmune diseases.