IgA is a major immunoglobulin in the gut and is important to maintain gut homeostasis. Secretory IgA (SIgA) is predominant in the mucosal immune system while it has various bioactivities in the gut including regulating microbiota composition and developing the immune system. In the past 40 years, a number of clinical and experimental evidence has suggested that the liver is affected by the SIgA system seriously. Due to the liver being the front-line organ that receives gut-derived products through the portal vein, disrupted intestinal homeostasis could affect the liver severely. Therefore, the SIgA function appears as a significant factor for the pathogenesis of liver diseases associated with the altered gut microbiome. Hence, Creative Biolabs established mature IgA research platforms and we are glad to share our experience about IgA in liver diseases with our partners over the world.
SIgA in the Gut
Naive B cells are gathered in gut lymphoid follicles, which can be activated by antigens and become IgA-producing plasma cells under the aids of T cells. As a main source of the gut IgA, mature B cells translocate to the lamina propria and produce predominantly dimeric IgA. IgA is transposed across gut epithelium by pIgR and regulates host-microbiota homeostasis in the gut. However, SIgA starts to be produced several months after birth and milk SIgA contributes to the composition of the first gut microbiome. Nowadays, clear mechanisms of how SIgA maintains gut homeostasis have not been revealed, while studies about IgA deficiency on the human gut microbiome attract more attention in the biotherapy industry.
IgA-microbiota in Liver Diseases
The resident microbiota plays an important role not only in intestinal but also in hepatic diseases, which was determined by SIgA in the gut. Indeed, IgA has been studied in the field of alcoholic liver disease (ALD) for a long time. Research data confirmed that higher systemic IgA levels and liver IgA deposits appeared in ALD patients. Moreover, SIgA levels in the gut of chronic liver diseases seem more important than systemic and liver IgA changes because SIgA regulates gut homeostasis. Besides ALD, nonalcoholic fatty liver diseases (NAFLD) and primary sclerosing cholangitis (PSC) also shows a strong relationship with IgA level.
Fig.1 Host-microbial interactions that contribute to liver disease. (Brandl, 2015)
IgA in Liver Diseases
Although SIgA in the intestinal lumen shows a huge influence on various liver diseases, it has been suggested that serum and lamina propria IgA occupied an important position in mucosal immunity binding FcαRI receptors. Such a mechanism has been found in patients with ALD and NAFLD that IgA promotes phagocytosis of the invading bacteria via binding to FcαRI on phagocytes, which prevent translocated bacteria from the gut to liver. Moreover, IgA also plays a role in the molecular transport and metabolism of the liver.
Fig.2 Potential ways to treat liver disease by modulation of the gut microbiota. (Wahlström, 2019)
Although the relationship between IgA and liver disease has been realized, how the gut microbiome contributes to the disease pathogenesis is still not clear. Therefore, Creative Biolabs pays more attention to the research of the liver-microbiome axis. If you are interested in the research of IgA and liver diseases, or want more details in the research of the therapeutic molecular field, please feel free to contact us.
References
- Brandl, K.; et al. Is intestinal inflammation linking dysbiosis to gut barrier dysfunction during liver disease? Expert review of gastroenterology & hepatology. 2015, 9(8), 1069-1076.
- Wahlström, A.; et al. Outside the liver box: The gut microbiota as pivotal modulator of liver diseases. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease. 2019, 1865(5), 912-919.
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