IgA antibodies constitute the second most abundant class of antibodies in the systemic circulation and the major Ig class at the mucosal surfaces. Most of the known IgA mediated functions require an interaction with the IgA receptors, some of which have been identified in humans. Transferrin receptor is a kind of mesangial IgA receptor and strongly related to IgA nephropathy, while the overexpression of this receptor for IgA in patients with IgA nephropathy has been observed. Recently, the research of transferrin receptors is more popular due to its possibility to act as a novel therapeutic target or biomarker to diagnose or treat IgA nephropathy. As a world-leading biotechnologies company, Creative Biolabs has kept in touch with the development of IgA receptors and accumulated related experience. It is our pleasure to introduce our studies about GPCRs to our partners all over the world.
Fig.1 Hypothetical model of FcαRI shedding to form circulating IgA complexes. (Monteiro, 2002)
Introduction of Transferrin Receptor
The transferrin receptor is a membrane glycoprotein whose only clearly defined function is to mediate cellular uptake of iron from a plasma glycoprotein, transferrin. Although transferrin receptors do not directly interact with iron, they mediate iron acquisition by most cells in the organism and are part and parcel of a complex system that has evolved to control iron uptake and storage. However, the bioactivities described above are unrelated to the IgA-transferrin receptor interaction, while the mechanism of how this interaction contributes to the immune response is still not clear, except that high expression of transferrin receptors in the mesangium of patients with IgA nephropathy could participate in the selective deposition of IgA complexes.
IgA Nephropathy and Transferrin Receptor
IgA nephropathy (IgAN) is the most common glomerulonephritis and a major cause of renal failure worldwide. This mesangial proliferative glomerulonephritis is defined by the mesangial deposition of IgA. Recurrence of IgA deposits in IgAN patients after transplantation of a normal kidney indicates that circulating, rather than local kidney, abnormalities are crucial in the development of IgAN, while the fact that the level of serum IgA is enhanced about threefold in approximately half of the IgAN patients also showed the influence of circulating. Although the pathogenesis of IgAN is still poorly understood, the discovery of the transferrin receptors as IgA receptors provides a novel approach to treat this disease.
Fig.2 Detection of transferrin receptors in mesangial cell areas in renal biopsy material from a patient with IgAN. (Moura, 2001)
A hypothetical model to explain the mechanism of IgAN suggested that polymeric IgA aggregates the FcαRI on monocytes to form polyIgA-FcαRI complexes, and be deposited in the kidney by binding to the transferrin receptors expressed by mesangial cells of IgAN patients. Such a model also explains the result that poly-IgA binds to transferrin receptors better than does mono-IgA. Moreover, transferrin receptor expression was undetectable by immunohistochemistry in normal glomeruli, hence the level of transferrin receptor has been developed as a biomarker in the diagnosis of IgAN.
There is no completely effective treatment aimed at IgAN due to the lack of realizing pathogenesis. However, the research of IgA-transferrin receptor interaction offers a potential target in IgAN treatment. If you are interested in IgAN research or other fields in therapeutic antibody development, please feel free to contact us.
References
- Monteiro, R. C.; et al. Pathogenic significance of IgA receptor interactions in IgA nephropathy. Trends in molecular medicine. 2002, 8(10), 464-468.
- Moura, I. C.; et al. Identification of the transferrin receptor as a novel immunoglobulin (Ig) A1 receptor and its enhanced expression on mesangial cells in IgA nephropathy. The Journal of experimental medicine. 2001, 194(4), 417-426.
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