Treated for possible lyme

[msf]

Ah, thanks for pointing that out...re: TB, I was trying to think of a chronic bacterial infection that isn't controversial. As for local infection, is the lung unique in this case, or would you expect any local infection to show similarly low levels of CRP?

 

[Jonathan Edwards]

RE: Yersinia IgG and IgA, IgA has been shown to correlate with Reactive Arthritis (which can be triggered by Yersinia). Some people (KDM included) think this is because the patient is still infected, since IgA doesn't last in the body very long (apparently). Since this is negative in your case, I believe KDM suspects that another infection (an active one) is to blame for your symptoms (or at least some of them).

IgA itself does not last more than a few weeks but as far as we know once you start making IgA from plasma cells to an infection those plasma cells will live for years. The most direct evidence probably comes from using rituximab, which probably blocks all new plasma cell formation for periods of 6 months to five years. When that is done the total IgA levels hardly fall at all, even after several years. That is presumably the stock of plasma cells built up against previous infections carrying on without new recruitment for several years. So to my mind a continued IgA level would not mean recent infection. IgM tends to be different in that IgM plasma cells probably last about 6 months only - IgM levels often fall after rituximab, especially if repeated.

 

[msf]

I just thought about the first paper again, and I don't really get it...doesn't sensitivity in this case mean how often it is found in patients with bacterial infection? If not, I apologise.

 

[msf]

re: IgA, I was just repeating what I've read, and in the study I posted before with the IF of Yersinia antigens, both the IgA and IgG levels decreased with antibiotic treatment (in a matter of months).

 

[msf]

They then increased again, starting 3 months after the end of antibiotic treatment...sorry to quote the same study all the time, but there haven't been many studies of Yersinia-triggered ReA, or of Yersinia in general.

 

[msf]

This one, in C. trachomatis, also makes the link between IgA and active infection, where active infection was established using an EIA assay to detect the antigens. I know (by now) that you will say that the presence of the antigen does not necessarily mean presence of the organism, but it does suggest that IgA and antigen levels are related.

http://www.scirp.org/journal/PaperInformation.aspx?PaperID=24387

 

[Jonathan Edwards]

I just thought about the first paper again, and I don't really get it...doesn't sensitivity in this case mean how often it is found in patients with bacterial infection? If not, I apologise.

I found this paper hard to follow since it purports to be about sensitivity and specificity in distinguishing infective from non-infective inflammation. I could not find a cut off level and maybe it was different for each study in the meta-analysis. If the idea was to distinguish you would probably need a cut off of about 20, so that non-infective processes fell below this. But it would all depend on what groups of patients were recruited. In acute gout (non-infective) CRP can rise to 100 very easily. The main point of the paper is to show that the other test, which I have not heard of elsewhere, is more discriminatory. I guess the difference did not impress people because the other test has not become standard.

 

[msf]

I just realised that the last point does not necessarily go against what you were saying, so please don't feel obliged to respond.

 

[Jonathan Edwards]

Ah, thanks for pointing that out...re: TB, I was trying to think of a chronic bacterial infection that isn't controversial. As for local infection, is the lung unique in this case, or would you expect any local infection to show similarly low levels of CRP?

I don't have any detailed information on this to quote. However, one of the things that seems to make CRP shoot up, for reasons I do not understand, is if inflammation is in a confined space and so gives rise to pressure. So acute inflammation in a small joint or in a tooth root abscess can put the CRP way up - and it also tends to make you feel absolutely dreadful when a larger area of inflammation without pressure might not. Maybe it is something to do with endothelial activation. What may be different about tubercle bacilli in the lung is that they may hang around in alveolar macrophages that actually sit outside the body in the tiny air spaces. And even within lung pressure is unlikely to build up because lung is so stretchy. Another factor is that it is very likely that a majority of people with a primary TB infection in early life still have a few bacteria in the lung for good. That is why a good proportion get sick with TB again if we give them TNF inhibitors. But without that the 'chronic infection' is more or less completely without inflammation or impact on health.

 

[dga5000]

@msf Thanks for the explanation of IgG and IgF. Makes complete sense.

 

[msf]

Yeah, I couldn't make much sense of it either...I think 'inflammation' might be a red herring in this case. I can't think of any way in which it would work other than the way I suggested, but I agree that the paper isn't clear enough to allow any conclusions to be made.

 

[msf]

Yeah, I was thinking along those lines but I wasn't sure where the TB lived in the lung.

 

[Jonathan Edwards]

re: IgA, I was just repeating what I've read, and in the study I posted before with the IF of Yersinia antigens, both the IgA and IgG levels decreased with antibiotic treatment (in a matter of months).

Yes, that's a good point and it is a bit more complicated. During acute infection you probably make short lived plasma cells as well as long lived ones. That means that you have really high antibody levels at the start to clear the infection (even if it is actually dead by the time the plasma cells get produced) but that the level drops to about half that maximum over 3-6 months. That would mean that you do not fill up your bone marrow with too many long lived plasma cells from every infection. So IgA antibody levels will fall after the acute infection if it is treated. However, there will still be good protective levels for years and I doubt you can reliably distinguish those levels between different people since the value you get with any particular assay is very variable from person to person and probably from test to test since different labs will use preparations with different mixtures of proteins from the bacterium.

So I guess the bottom line with these tests is that a doubling of level tends to indicate recent infection. A halving of level tends to indicate an infection a few months back, but a single reading of a highish level may not tell you very much because of the huge variation in the way people respond.

 

[msf]

I was interested in your speculation about it possibly being due to endothelial activation, Prof. Edwards. One of the things that bothers me about my case is trying to figure out (or have some idea of) what my very low VEGF level might mean.

 

[JaimeS]

Bump, because ditto, @msf. My VEGF is very, very low. I have issues that may or may not be related to this; and low VEGF strikes me as something that could explain a great deal of our symptoms.