Anti-glomerular basement membrane (anti-GBM) disease is a kidney autoimmune disease where the immune system attacks the kidney's glomerular basement membrane and damages the kidneys. Usually diagnosed by blood anti-GBM antibodies and kidney biopsy of kidney disease. Not only that, epitope diffusion and mimicry also play a role in anti-GBM disease. Epitope transmission (autoimmunity to novel self-epitopes that increase the disease) and epitope emulation (replication of key residues with microbial peptides that trigger autoimmunity). Early treatment, glucocorticoids, cytotoxic medications and plasma exchange are some. The disease is defined by the accumulation and circulating antibodies to basement membrane antigens. The immune system misunderstands the basement membrane in healthy tissue and anti-GBM disease is induced. This results in a reaction of antibodies, which attack the basement membrane and inflame and kill the tissues.
Related Products
Autoimmunity and Epitope Spreading
Autoimmunity can spread to epitopes on an antigen (intramolecular epitope spread) or to epitopes on other endogenous antigens (intermolecular epitope spread). Epitope distribution is an established process, one that is involved in every kind of autoimmune disease from systemic lupus to diabetes54 and anti-GBM disease. The team noted that one T-cell epitope on rat 3(IV)NC1 produced disease in animal experiments and antibodies against a range of B-cell epitopes on native GBM. Their findings show the first signs of epitope dispersal in anti-GBM pathology. The antibodies of patients with varying degrees of renal injury identified different chains. At the same time, autoantibodies present in patients with higher degrees of kidney injury identified more chains, which suggests intermolecular epitope transfer in patients with anti-GBM disease.
Fig. 1 Spread of epitopes in anti-GBM disease (Kuang, H., et al. 2023).
Autoimmunity and Epitope Mimicry
Molecular mimicry is when an antigen in the host and bacteria react in an immune fashion when their amino acids or structures are similar. We already know that anti autoimmunity immunity is based on the negative selection of autoreactive T cells in the thymus and the tolerance-induced periphery. Antecedent infection in anti-GBM disease has been reported up to 80%. 66 According to these results, infection might account for one cause of disease through molecular mimicry. Noteworthy, aside from molecular mimicry, there are other mechanisms possibly involved in autoimmune disease etiology: bystander and superantigen activation. We still need more studies to clarify these pathways and how they might influence therapeutic approaches to anti-GBM disease.
Immunotherapy
Standard treatment for anti-GBM disease today involves immunosuppressive therapy and exchange of plasma to flush circulating pathogenic antibodies. Searching for novel immunotherapeutics that might be responsive early on in autoimmunity seems promising. Exploring how HLA-mediated autoimmunity works might allow for more specific immunotherapies in patients with anti-GBM disease. Medicinal effects come through regulation of T cell differentiation towards anti-inflammatory markers, such as the reduction of T helper 17 (TH 17 ) cells and the increase of regulatory T cells about TH 17 cells, and by suppressing the activity of pathogenic antibodies. At the tip of the 3 monomers is an LCL (Loop-slot-loop) bioactive pocket with cryptic epitopes related to the anti-GBM disease. The 345 hexameric variants can change the conformation of the LCL site along with other endogenous and exogenous stimuli to expose self-epitopes to anti-GBM autoantibodies. All of this is to imply that these LCLs could be used as therapeutic sites for anti-GBM disease.
Anti-glomerular Basement Membrane Disease
Anti-glomerular basement membrane disease (anti-GBM disease) is a very rare organ-specific autoimmune disease. Kidney biopsy and serum antibody testing diagnose anti-GBM disease. It is the first thing that triggers the autoimmune response, and it is antigenic epitope exposure. The two commonly known immunodominant conformational epitopes E A and E B are identified as 17-31 and 127-141 of 3(IV)NC1, respectively. The mapping of T-cell and B-cell epitopes is essential for the immune response in anti-GBM disease. This in turn makes it more feasible to design useful immunotherapies.
References
- Kuang, H., et al. Autoimmunity in Anti–Glomerular Basement Membrane Disease: A Review of Mechanisms and Prospects for Immunotherapy. American Journal of Kidney Diseases. 2023, 81(1): 90-99.
- Ponticelli, C., et al.. Anti-glomerular basement membrane vasculitis. Autoimmunity Reviews. 2023, 22(1): 103212.
.
