Jornal de Proteômica e Bioinformática
Acesso livre
ISSN: 0974-276X
ISSN: 0974-276X
Michael Kruse Meyer, Marlene Andersen, Tue Bjerg Bennike, Svend Birkelund, Grethe Neumann Andersen and Allan Stensballe
Objective: The availability of biological disease-modifying anti-rheumatic drugs (bDMARDs) has increased during the last decade, and while focus has been on treating clinical symptoms, the associated changes in the immune system remains poorly understood. Several key immunological regulators, including Interleukin (IL)-6 are intimately associated with rheumatoid arthritis disease progression. In this proof-of-concept case study we assess the immunological changes in multiple important immune cell populations to treatment with the commonly applied bDMARD tocilizumab, a humanized monoclonal antibody against the IL-6 receptor.
Methods: Peripheral blood was obtained from one rheumatoid arthritis patient with poor response to conventional DMARD, before biological treatment and 4 months after. Peripheral blood mononuclear cells were extracted and separated into CD14+, CD4+, CD8+, CD19+, and CD56+ immune cells. Each cell-type was prepared through a discovery proteomics pipeline, and analyzed on a Q Exactive Plus mass spectrometer by gel-free shotgun proteomics.
Results: The patient responded well to tocilizumab monotherapy, and reached clinical remission without any observed side effects. A combined total of 4,343 proteins were identified at <1% false discovery rate, hereof 3,242 proteins qualified for label free quantification. We systematically evaluated the metabolic, inflammatory and signaling pathways of each immune cell type as a result of the IL-6R inhibition. The CD14+ cells were the most responsive to therapy, and proteins involved in the JAK/STAT and MAPK signaling pathways were less abundant.
Conclusion: Our data support that effective treatment of rheumatoid arthritis with tocilizumab causes decrease in the JAK/STAT and MAPK signaling pathways, increases glucose metabolism, and reduces stress responses.