As part of our CSP Charitable Trust-AKC/CHF funded study, Dr. Avery is looking for blood samples from dogs with FSF (Familial Shar-Pei Fever) at the time they are spiking a fever.  Please have your veterinarian obtain 6-10 ml of EDTA whole blood (lavender top tube) and the serum from 3-5 ml blood (red top or serum separator tube) and contact Dr. Avery at (970) 491-1170 to arrange overnight shipment of the samples to: Dr. Anne Avery, Dept. of MIP, 1619 Campus Delivery, Fort Collins, CO 80523-1619 by overnight express.  You will need to provide a signed consent form, the dog’s AKC number and complete a questionnaire which can be faxed or e-mailed to you.  Shipping costs via UPS will be covered by the research grant (an account number will be provided for billing) but there is no funding available to reimburse you for veterinary expenses.  Please help.  She also still needs samples from ANY dog with a history of FSF episodes.  Your cooperation will benefit your dog and the entire breed.    

Preliminary results have shown that a statistically significant greater number of Shar-Pei with FSF or Shar-Pei with close relatives with FSF/A have elevated background levels of IL-6.  Shar-Pei without evidence of FSF and no close relatives with FSF/A did not have statistically significantly elevated background levels of IL-6.  This was shown in my study with Cornell and confirmed by Dr. Avery's recent testing.  So far, it looks like SAA and CRP levels are “all over the place” and do not correlate with health or disease but analysis is on-going. Also, no Shar-Pei (with or without FSF) that Dr. Avery examined had elevated levels of TNF-alpha.  Serum IL-10 and HA (hyaluronan or mucin) levels are next.  We do not know yet if serum HA levels correlate with their auto-inflammatory disease.  All we can do at this time is speculate which is why that research is a priority.  I am also working to get Dr. Avery's study to include checking levels of IL-1-beta as soon as possible because this has been implicated in some of the human periodic fever disorders.  Since IL-6 is one of the main chemical signals to turn on the acute phase reactant proteins (the precursors of amyloid A), chronic elevation of IL-6 in FSF patients is not a surprising finding.  My study with immunologists at Cornell in the early '90s suggested that there may be problem with down-regulation of IL-6 so we are going to take another look at that (a blocked receptor for an IL-6 inhibitor?)

The studies are as yet incomplete.  S-P had dramatically elevated levels of IL-6 and SAA during fever events.  We are looking for samples from more dogs during events (see above).  These elevations are not unexpected because these are the messengers of inflammation but we want to compare their response to normal controls to see if they are exaggerated. 

The problem with IL-6 as a test is that not every dog with FSF had elevated background levels - there may be a lot of false negatives so I don't know how useful it might prove as a diagnostic test. One of the other cytokines yet to be examined may prove to be more predictive.  A specific genetic mutation that is shared by all Shar-Pei with FSF would be ideal – the elusive holy grail of tests.  Linkage studies for this will be starting as soon as we can get all the information possible on the dogs in the pedigrees being examined by Dr. Puppo at the NIH. (Very soon).

My heartfelt thanks to Alice Fix, Barbara LaVere, Pat Zimmel-Roach, Dr. Jeff Vidt and all the members of the Centennial Club in the Colorado area (too numerous to list but without which Dr. Avery’s project would not be moving forward!) for their help and to the many CSPCA members who have so kindly taken the time to provide information for the pedigree analysis component of the DNA study at the NIH.  Dr. Avery told me today how enormously impressed she is by the lengths to which Shar-Pei breeders have been willing to go to help with this project.  Shar-Pei people are as special as their dogs!

Dr. Linda Tintle
Wurtsboro Veterinary Clinic
163 Sullivan Street, PO Box 910
Wurtsboro, New York 12790
wvc@warwick.net
www.wvc.vetsuite.com

April 14, 2006