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C reactive protein update

GLP gif

Apicomplexans (Sarcocystis and Toxoplasma) are common infections in horses but these infections generally don’t cause clinical signs.  When infection doesn’t elicit clinical signs it is called a sub-clinical infection. However, even these non-progressive infections stimulate inflammatory cytokines. Cytokines are tightly regulated by the host to control infections, cytokine release results in both positive and negative effects. An imbalance or dysregulation of cytokines can play a part in tissue  damage and can be associated with protozoal infections. Pathogenic protozoa initially cause gut infections and in some cases they encyst in muscle tissue. Other parasites can encyst in horse tissues, small strongyle and tape worm larvae are examples.

C-reactive protein (CRP) is a non-specific marker for inflammation.  CRP is not specific (to one cytokine or infection) because it regulates several cytokines that are stimulated by infection.

A 2005 multi-center study found statistically significant gene signatures in horses with acute S. neurona sarcocystosis (EPM).  The cytokine signature was not found in chronically infected EPM horses.  Chronic infections were defined as horses that were clinically abnormal one month after infection by parasites. The disease-gene profiles were related to induced inflammatory cytokines and their regulatory molecules. Cytokine profiles in neural tissues in horses with EPM and herpes virus infection showed inflammatory cytokines were present in diseased, but not clinically normal horses. Again, these cytokine profiles were not specific to the organism but were present in inflammatory disease.

Some cytokines cause host tissue damage.  Host tissues are damaged by unregulated or dysregulated cytokines. The regulatory molecule CRP is useful to detect sub-clinical inflammation in horses that may have dysregulated pathways that cause tissue damage. As cytokine damage progresses the animals will show clinical signs.

We have some anecdotal information using CRP to detect inflammatory disease. An anecdote is an interesting story often proposed to support or demonstrate a point. Because anecdotes are singular events, they hold no scientific weight.  The person offering the anecdote is convinced of the outcome and not much will sway them from their opinion. Our anecdotal evidence leads us to think that 10% of horses tested for CRP will show up as a ‘0’ on the test result and these horses will continue to be ‘0’ on future testing.  We based our anecdotal opinion on 1000 tests that returned a 0-test result from over one hundred horses. The results were comprised of data that was compared to data from 15,000 horses. It seems like enough data.  We often hear clinicians confidently report anecdotal stories from several cases they have treated. Is our hypothesis true?

We ran a study using good laboratory practices (GLP) to test our hypothesis: the test will not be valid on 10% of horses. (We surmised that there is a genetic disposition in 10% of horses that preclude them from testing positive.)  Studies performed according to GLP are assigned the top rank of 1 (reliable without restriction) and are preferred by agencies. These GLP studies require many hundreds of man-hours for planning, performing, monitoring, recording, archiving and reporting. The studies have a lot of quality assurance (QA) built in.  And then there is QA on the QA. These studies are not inexpensive, they run into the mid-six figures by the time the final report is issued.

Based on GLP study results we can tell you our hypothesis is false!  Horses with a CRP of 0 will not always be tested as 0.  Further, horses with an elevated CRP can return to a CRP of 0 with proper treatment. The most likely cause of the elevated CRP is inflammation associated with encysted intestinal parasites. It may be important, but not proven, that treating the parasites and the dysregulated inflammatory cytokine responses are necessary.

We suggest, based on our GLP study results, that an elevated CRP should be taken seriously and treated by using an objective approach. The CRP serum concentration does remain elevated a bit longer than the days the literature suggests. The acute phase protein rises within days and our data indicated that 14 days is a reasonable time to expect a response (a decrease in CRP) after appropriate therapy. If you got a CRP result as ‘0’ it is not an indication that CRP testing has no value.