Recently, our group did some work in which we looked for markers of AIH (autoimmune hepatitis) and we found 2 proteins which upregulated expression in different approach. So we expect that the 2 proteins will be of value in our next study.
However, after receiving the reviewer comments, I have no idea how to answer the comment. Can anyone offer advice on this?
The comment: "The approach is unique in that it looks for markers downstream of autoantibody binding, whereas all other proteomic studies cited by authors for autoimmune hepatitis look for targets of autoantibodies. However, specificity of these two potential biomarkers is not addressed. The authors should have access to numerous patients with other forms of hepatitis based on previously published work from their institution."
It's difficult to answer without knowing which proteins you are talking about. But the reviewer ask you to verify that theses two proteins are specific of AIH and are not found elevated also in other forms of Hepatitis (Viral, cyrosis...) so that they can be used as biomarker of AIH.
They are asking to provide sensitivity and specificity of the markers you have identified by your 'unique' approaches. The last sentence tells you to process the samples of patients with other forms of hepatitus with your approach and then address the specificity and sensitivity question. Talk to your statistician on how to address this
I agree with precedents answers. I think you have to test samples of patients with other form of hepatitis, processing with your news biomarkers. Serums samples with viral hepatitis, alcoholic hepatitis or other etiology could be taken from another patient and test. With all the results, you could be able to find sensitivity/specificity/NPValue and PPV ! Statistical test are easy to do for that...
It is an usual ask for biomarker to know how it could be use in clinical practice !
I will be happy to learn more about your biomarkers and the results of this test...
I agree with all precedent answers. Furthermore you also must add references concerning protein changes used as biomarkers different from autoantibodies.
I agree with the above comments. For example, are these markers also potentially present in other forms of chronic liver disease, autoimmune or otherwise, e.g., primary biliary cirrhosis (PBC), viral hepatitides (hepatitis C), alcoholic liver disease, etc.
To clarify the specificity of your findings, you need to look for the expression of the two new potential biomarkers in related liver dieases like primary biliary cirrhosis and other control groups preferaably patients suffering from viral hepatitis (B and C). In the best case, you will not determine their expression in these control group.
Best regards,
Dirk
I agree with the above researchers. In your manuscript, you’ve probably compared the expression of your two putative marker proteins in healthy controls and autoimmune hepatitis. The reviewers are asking whether the putative markers of AIH actually indicate inflammation of the liver or whether they are specific for AIH. To test this hypothesis, the reviewers are asking the authors to test additional groups of patients who have other liver diseases. For example, patients with primary biliary cirrhosis, viral hepatitis, and / or alcoholic liver disease would be suitable groups of patients with liver diseases. Regardless of the outcomes, the two proteins that you’ve mentioned appear significant. Your conclusions will depend on the expression results: you state which diseases are associated with the elevated expression of the two proteins. You also need to calculate the specificity (basically, how many patients have the marker vs how many have AIH) and sensitivity (basically, how many patients have AIH but not express the elevated marker proteins). Standard statistical formulas are available for specificity and sensitivity.
For determination of specificity and sensitivity, I looked it up on the Internet but I don't remember now the formulas. But it is basically taking into consideration the number of false positives and negatives. So you can goggle the formulas.
To address the queries from the reviewers you need to estimate the two putative proteins in other forms of hepatitis (non AIH) and demonstrate conclusively that these two proteins are not elevated in non AIH hepatitis. You can use a ROC curve analysis to demonstrate the utility of these two putative biomarkers for a diagnosis of AIH both singly and in combination.
- Badges
- Science topic
- Similar topics
- Biological Science
- Immunology