IgG subclass elevation and LPS

[tonysci]

I am trying to explain the following IgG subclass distribution:

 

IgG1: low normal

IgG2: ELEVATED

IgG3: low normal

IgG4: normal

 

I understand that IgG2 is targetted primarily towards LPS antigen, which is the product of gram-negative bacteria.

 

What I do not know is whether there is any other explanation (such as Th1/Th2 imbalance) that could account for the this distribution.

 

Is the pattern a reliable indicator of gram-negative bacterial infection? Lacking any distinguishing symptoms, is there any way to ID the species behind it?

[Immunologist]

Here is a reference agout IgGs...

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Search&db=books&doptcmdl=GenBookHL&term=IgG2+AND+imm%5Bbook%5D+AND+125553%5Buid%5D&rid=imm.figgrp.1215

 

I would like to underline that IgG2 are produced primarly against polysaccharides, not only lipopolysaccharides (LPS). Therefore other molecules might be involved.

 

As for the question of Th1/Th2, it would easily be sorted by a measurment of the IgEs (they are elevated in a Th2 response). But an indication is already there: IgG4 are not increased, therefore it does not seem to be suggesting a Th2 response (IgG4 and IgE are elevated in a Th2 response).

 

What is the background or context of this result? Human I guess (IgG4 are not in mice), but why was the person tested?

[tonysci]

Thank you for the reply. I thought I had stumped everyone!

 

The test was done as part of a workup for idiopathic fatigue. Subclass elevation was not what we expected to find. Deficiencies have been found in some studies of CFS.

 

The next logical step would be to identify what is driving the elevation. The only clinical test I know of for endotoxin is the LAL, which is supposedly unreliable.

 

I'm not sure where that leaves us. It's not realistic to test for all polysaccharide producing infections. We need to narrow it down somehow, but I don't know of any way to do this that is clinically feasible.

[Immunologist]

I think I would personnaly repeat the serum Ig testing, just in case your subject was exposed to something irrelevant the week before the sampling...

 

As IgG2 are a more rare form, an acute elevation in their amount is more likely to be noted than an increase in IgG1 for example. So it could be only some irrelevant (to your idiopathic fatigue context) observation. Can you correlate this observation with leucocyte counts in the blood? If an increased amount of neutrophils is found, search no more: infection with something.

 

In a case where there is nothing like that, could it be that increased [igG2] is only a consequence of something deeper, like overexpression of hormones leading to increased IL-6 or else? Having measured anything else in this serum?

 

Philippe

[tonysci]

CBC and diff all look quite normal. Neutrophil count around 4000 and sed rate = 1. Retest of subclasses, tests for hormone levels (cortisol, testosterone, thyroid panel) are aready underway. Thanks for the help thus far...

[tonysci]

OK, I'm back again with more labs:

 

IgG2 again elevated (slightly)

DHEA-S: elevated (slightly)

Testosterone, SHBG, AM Cortisol, TSH, free thyroxine & free T3, HGA1c all within reference.

[Igor Suman]

The test was done as part of a workup for idiopathic fatigue. Subclass elevation was not what we expected to find. Deficiencies have been found in some studies of CFS. ....

We need to narrow it down somehow' date=' but I don't know of any way to do this that is clinically feasible.[/quote']

 

How about testing for SLE ?, (SLE would produce chronic fatigue and elevated IgG).