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STOP-JIA

Biomarkers

By: Brian Feldman | March 12, 2016 | What Caught Our Eye

What’s old is new, right? We used to have the patient history – now we have “patient reported outcome measures“. We used to have the physical exam, and other signs (like, say, lab tests or Xrays) – now we have “biomarkers“. It’s kind of cool how we can spin all that old fashioned stuff into… well… new-fashioned stuff.

But, spin or no spin, for the last while, biomarkers and biomarker research has been really hot.

So, when a group of eye docs and pedi rheum docs – from Germany and Switzerland – published a paper looking at S100 proteins (think, chemicals that our macrophages and innate immune cells let loose in response to tissue damage – damage-associated molecular pattern molecules (DAMPs) as a measure of eye inflammation in uveitis, we took notice1.

Our colleagues in Muenster (and their collaborators, of course) have shown that these proteins – especially, (technical alert) S100A8, S100A9 and S100A12 (or calgranulin A, B and C) – are really useful in a bunch of ways.

For instance, the S100A12 can help tell which kids have sJIA rather than systemic infection with a pretty decent Likelihood Ratio of 11 (that is, when the cutoff level is 1400 ng/ml, the sensitivity is 66% and the specificity is 94%). This would be super helpful for some of the patients we see on ward consults.

Also, if a JIA patient’s S100A8/A9 level is ≥ 690 ng/mL, or S100A12 is ≥ 175 ng/mL, then they are twice (or more) as likely to have a flare when stopping treatment. This could be pretty helpful in the clinic.

And, S100A8/A9 is a (very slightly) better measure of disease activity than CRP and ESR in patients with sJIA. (This one may not be so useful, all things considered.)

Since uveitis in our JIA patients so often doesn’t cause pain or redness, it can be difficult to monitor – and even the slit lamp exam is only a gross measure of activity. So, it would be cool to have a lab test (sorry, “biomarker”) that was a good indicator of uveitis activity.

The authors of this study got their patients from the ophthalmology clinic in Muenster. There were 79 children with JIA who had uveitis, 24 with idiopathic uveitis, and 24 “controls” who were either healthy, or who had cataract (or other) surgery that didn’t have anything to do with uveitis.

They found a few important things:
1) Kids with JIA uveitis, and those with idiopathic uveitis, had no real difference in these protein levels in their blood (serum);
2) JIA patients, whether joints were active or not, and whether uveitis was active or not, had higher levels than non-uveitis controls (some comparisons were statistically significant, and some not);
3) Kids with active uveitis had higher levels than those with inactive uveitis (but this was only statistically significant for those kids in the JIA group, and when looking at S100A8/A9 proteins);
4) In the same JIA patients, levels were (mostly) higher at those times when uveitis was active compared to when it was inactive (statistically significant for the S100A8/A9 levels)
and
5) The S100A8/A9 protein is detectable in most uveitis patients (even while inactive) from inside the eye (gross!), but hardly ever present in patients without uveitis. (We’re not sure this is a diagnostic test that we’d like to do routinely in our clinic.)

So, how useful is this particular lab test (sorry, “biomarker”) for our uveitis patients? Well, based on this study, we’d have to say not ready for prime time. The patient numbers were small, the patients were highly selected from an ophthalmology practice, the control patients were mostly adults, and many of the results were not statistically significant.

However, this is a really cool avenue of research, and we’d like to see it pursued further. It would be very cool, indeed, to have a lab test that tells us which patients have uveitis, and helps us tailor treatment in those that do.