Blau Syndrome (BS) is a very rare autosomal dominant inherited autoinflammatory disorder. Ophthalmic involvement is a severe, degenerative and often insufficiently controlled issue of BS. Currently, there are no predictive markers of disease at ocular level to target for treatments. Thus, we aim to investigate in depth the molecular aspects involved in ocular inflammation in BS.
To investigate the tear proteome of a BS patient with advanced eye degeneration, three healthy family members and three healthy controls, tear fluids collected via Schirmer’s strips were the starting materials. LC-MS/MS analysis was conducted with a LTQ-OrbitrapXL mass spectrometer. Data were searched against the Uniprot Database and filtered to consider only high confidence proteins. T test assessed the differential expressed proteins amongst samples.
Overall, 291 proteins (145 differential expressed between BS and healthy subjects, 40 BS-associated, 1 control-associated) were identified and considered clinically interesting with a fold change >5. BS-associated overexpressed proteins included immunoglobulins and proteins related to the innate immunity and the proteolysis. Among the proteins mainly expressed in BS, alpha2-macroglobulin (increased 27 times) and SERPINA1 (increased 9 times) may have a role in sustained ocular inflammation. Of particular interest the finding of the under-expression of Phospholipase A2 in BS patient. This protein has a crucial role in inflammatory response and signal trasduction.
Our study provides a first insight into the ocular proteomic of BS. The newly described BS-associated proteins might become tools for eye degeneration risk assessment in BS patients.