Recently, our group did some work which looked for markers of AIH (autoimmune hepatitis) and we found 2 proteins which upregulated expression in different ways. So we expect that the 2 proteins will be of value in our next study. While all other studies look for targets of autoantibodies, the specificity of these two potential biomarkers is not addressed. How can we understand the differences between the autoantibody and the protein's upregulation of expression, which is not detected by the autoantibody?
Upregulation of proteins do not manifest AIH. Please let me know those proteins and autoantibodies. Target autoantibodies may or may not be biomarkers of the disease. B cell epitope (s) is a key determinant of the disease, however, epitope (s) spreading may mask the original diagnosis. Liver pathology is one of the most important factor for making the diagnosis.
The best way to explore the contribution of any protein to autoimmunity as an inducer/ contributor is to look at its knockout. However, if the KO is unavailable, you can explore the known functions of these proteins and find out if directly or indirectly these proteins help in lymphocyte infiltration/ homing, B/T cell development and functions.
A pro-inflammatory environment can up-regulate several genes which may contribute to a further increase in the disease condition.
the question is not clear. In autoimmune diseases, many proteins will be up-regulated, also, many down-regulated. However, some are important, some are less important, because the compensation in vivo. If you want to give you a reason to follow these proteins, you should demonstrate the importance at first using KO mice or antibody neutralization or receptor blocking.
I agree with the the statements and suggestions made by the three colleagues answered before, in particular with the suggestion of Lifei Hou.
Without the knowledge to which functional class of proteins the two proteins of interest do belong it is not quite easy to give a constructive suggestion. Nevertheless, in general it could be a good idea to block the proteins each anlone or both together in vivo by administration of neutralizing antibodies. I guess working with the respective knockouts will make much more efforts at this stage of exploration, even if the required knockout mice would be available in other labs, the AIH model has to be adapted in the knockout strain at first which could take a lot of time. In contrast, antibodies can be generated in relatively short time span if they would actually not be available in your or other labs.
I agree with the above suggestions. I'd also check if the upregulation of these 2 proteins is present in human sera or human plasma of AIH patients who had been recently diagnosed versus patients with other inflammatory liver diseases such as viral hepatitis. If they are upregulated in early AIH patients but not in patients with other inflammatory hepatitis, then they may be very important markers and may play key roles in development of AIH. If the upregulation occurs later in AIH progression, these two upregulated proteins may still be important, suggesting that a shift in disease progression has occurred. Conversely, if these proteins are upregulated in both AIH and patients with other inflammatory liver disease, their role in AIH may be less specific to AIH but insights on resolution of inflammatory liver conditions may be elucidated. Understanding the regulatory mechanisms of these proteins may provide significant insights into inflammatory liver disease, and possibly AIH. Good luck with your research.
As I expressed my concerns earlier that up regulation/downregulation of certain proteins is not important to contribute to the AIH development and progression. We have to consider that whether those proteins are associated with the activation of T/B cells or inflammation. I agree with Kathy that you should look for signaling mechanisms of those proteins in relation to multiple immune tolerance check points. We have published two books on AIH and AILD. Some of your concerns may be outlined there. Thanks.
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