Researchers identify genetic risk factors of SLO, study provides insights on human nail diseases

The immune-mediated disease SLO can lead to severe claw problems in dogs. Researchers have now identified genetic risk factors underlying this disease.

The obtained results that were recently reported in the scientific journal PLoS ONE can lead to increased knowledge about similar nail diseases that affect humans.

Researchers at the Swedish University of Agricultural Sciences (SLU), Norwegian School of veterinary Science (NVH), and Uppsala University (UU) have identified one of the genetic risk factors responsible for development of an autoimmune disease affecting the claws. The study is an example of a well-established collaboration between geneticists and veterinarians at the three universities.

A disease called Symmetrical Lupoid Onychodystrophy (SLO), which is an immune-mediated disease with suspected autoimmune etiology, causes the claw problems that were analyzed. This means that the body's own immune system reacts abnormally which leads to sloughing of claws from claw beds.

As the disease progresses all claws will become affected and this ultimately leads to destruction of the underlying claw tissue and deformation of the claws. The disease is painful and involves large degree of pain and suffering for affected dogs.

- SLO is a disease that affects many different dog breeds and in this study the researchers have focused on a few breeds with high incidence of the disease; Gordon Setter, Bearded Collie and Giant Schnauzer, says PhD student Maria Wilbe who is the first author of the report.

The identified genetic risk factors are genes in the major histocompatibility complex (MHC) class II region that encodes proteins that control the immune response. These genes have been shown to be important genetic risk factors for different autoimmune diseases in both dogs and humans.

When the immune system is activated, MHC proteins determine towards which molecules the attack should be directed. In autoimmunity, MHC proteins will erroneously recognize the body's self-molecules and trigger destruction of the body's own tissues and organs. Such disturbances can, in certain cases, result in development of autoimmune diseases like for example SLO.

- We have earlier shown that MHC class II is a genetic risk factor for some other autoimmune diseases in dogs, says Maria Wilbe. In the current study, we identify both a protective MHC class II type and another one that leads to increased risk for the claw disorder.

A major increased risk for SLO development was found in Gordon Setter dogs that had inherited the MHC class II risk type from both parents. In dogs that had inherited the two variants from either parents it was found that the effect of the protective type dominated and such dogs were healthy.

- The molecules in claw tissue that the affected dogs react against remain unknown, states Frode Lingaas, NVH, and Göran Andersson, SLU, who jointly have directed the genetic analyses.

The researchers are currently pursuing additional genetic research and are hopeful to fund continuous research to identify additional genetic risk factors for this claw disease.

- The finding that dogs with two copies of the MHC type that leads to increased risk, as well as the finding that the effect of the protective MHC class II type dominates, are two important findings that have increased our knowledge about how this claw disease develops. The research is yet another good example for how genetic studies, using the dog as a model for complex diseases, lead to increased knowledge.