The role of immunoglobulin D in autoimmunity

Immunoglobulins, or antibodies, are used by the immune system to recognise and neutralise pathogens such as bacteria and viruses. Over the years, we have come to characterise the five classes of antibodies (IgA, IgD, IgG, IgE and IgM) secreted by B cells and their function in health and disease. However, despite the evolutionary perpetuation of IgD antibodies, it remains unclear how they work.

Recent evidence shows that IgD orchestrates an ancestral surveillance system at the interface between immunity and inflammation. To shed light on the function of IgD antibodies, scientists on the EU-funded ACIGDSLE (Regulation and function of IgD in systemic lupus erythematosus) project investigated their role in autoimmunity and in SLE in particular.

As a first step, they characterised the regulation of IgD by B cells, and discovered a functional connection with vitamin D (VD3). VD3 was shown to negatively regulate IgD induction by interfering with the IgM to IgD class switching at the DNA level. This finding was supported by the observation that SLE patients have high levels of IgD antibodies and VD3 insufficiency.

Preclinical data in a mouse model showed that IgD enhances primary Th2 responses by interacting with basophils and perhaps other effector cells of the innate immune system. Furthermore, researchers saw that IgD interacts with the transmembrane protein CD44, a process that may become deregulated in autoimmune disorders.

Collectively, the results of the ACIGDSLE study indicate that IgD antibodies are high in autoimmunity and may exacerbate the inflammatory process. The functional association with VD3 suggests novel ways to attenuate inflammation in SLE.