Deviant proteome profile of equine granulocytes associates to latent activation status in organ specific autoimmune disease.

The research investigates the role of granulocytes, a type of innate immune cell, in equine recurrent uveitis (ERU), an autoimmune disease in horses. The study identified significant changes in the abundance of proteins in granulocytes from ERU cases suggesting a latent activation status in the disease.

Research Focus and Techniques

• The research primarily focuses on ERU, a type of autoimmune disease affecting horses. It occurs spontaneously and is characterized by episodes of relapse and remission.
• Though traditionally, T cells (a type of white blood cell) have been known to play a key role in ERU, this study explores the potential role of granulocytes, another type of white blood cell.
• The research used mass spectrometry, a technique used to identify and quantify proteins within a sample, to study the proteins present in granulocytes from ERU affected horses and healthy controls.

Findings Overview

• Out of 2362 proteins identified in the granulocyte cells, 96 proteins showed significant differences in abundance between ERU horses and healthy ones. This equates to about 4.1% of the total granulocyte proteome.
• A protein named calgranulin B, which has been associated with pathogenesis in other autoimmune diseases, showed the highest abundance in ERU horses (18-fold more).
• The researchers added a threshold for biological significance to better interpret the results, focusing on proteins that had an ERU/controls ratio greater than 2. This resulted in 36 proteins.
• These differentially abundant proteins primarily related to the RAF/MAP kinase signaling pathway, MHC-I antigen presentation, and neutrophil degranulation. All these processes are associated with activation of the immune cells, suggesting a latent activated phenotype in ERU animals.

Significance and Translational Potential

• The study provides new insights into the protein compositions of granulocytes in ERU cases, highlighting shifts in proteins that suggest a more activated state of these immune cells.
• The latent activation of granulocytes contributes to the understanding of the role these innate immune cells play in ERU.
• This research is of high relevance to veterinary medicine as it furthers the understanding of the importance of granulocytes in this T cell-driven disease.
• Lastly, the findings may have translational application for human autoimmune uveitis due to the strong similarities in disease occurrence, progression, and pathogenesis.