In-Depth Serum Proteomics by DIA-MS with In Silico Spectral Libraries Reveals Dynamics during the Active Phase of Systemic Juvenile Idiopathic Arthritis

Abstract

In serum proteomics using mass spectrometry, the number of detectable proteins is reduced due to high-abundance proteins, such as albumin. However, recently developed data-independent acquisition mass spectrometry (DIA-MS) proteomics technology has made it possible to remarkably improve the number of proteins in a serum analysis by removing high-abundance proteins. Using this technology, we analyzed sera from patients with systemic juvenile idiopathic arthritis (sJIA), a rare pediatric disease. As a result, we identified 2727 proteins with a wide dynamic range derived from various tissue leakages. We also selected 591 proteins that differed significantly in their active phases. These proteins were involved in many inflammatory processes, and we also identified immunoproteasomes, which were not previously found in serum, suggesting that they may be involved in the pathogenesis of sJIA. A detailed high-depth DIA-MS proteomic analysis of serum may be useful for understanding the pathogenesis of sJIA and may provide clues for the development of new biomarkers.

Profiling Proteasome Activities in Peripheral Blood – A Novel Biomarker Approach

“…In accordance with these data, a recent study has also suggested profiling the activity of PBMC's immunoproteasome as a sensitive biomarker for the disease activity of Systemic juvenile idiopathic arthritis (sJIA), enabling the detailed evaluation of response to treatment. This study also demonstrated that proteasome subunits expression, as measured by mass-spectrometry analysis, immediately increased upon inflammatory activation in sJIA [78].…”

Ultra-deep proteomics by Thin-diaPASEF with a 60-cm long column system

“…Throughput is important in large cohort studies and in major diseases with large numbers of patients, but for diseases with low morbidity, it is difficult to collect many samples; therefore, a deep analysis is considered more suitable than throughput. We often study rare and intractable diseases in children (23)(24)(25)(26), and it is not possible to actually collect a large number of specimens; therefore, a deeper analysis is required. Depending on the purpose and target disease, the combination of the LEL method and the ultra-deep proteome analysis system will be a useful method for biomarker discovery.…”

Evaluation of the Suitability of Dried Saliva Spots for In-Depth Proteome Analyses for Clinical Applications

“…Advances in mass spectrometry (MS) and proteome analysis technologies have revealed that body fluids not only contain locally expressed proteins but also many disease-related proteins secreted and shed from distant pathological tissues. , The collection of body fluids is less costly and less invasive to subjects. Considering these advantages, body fluid proteome analysis has attracted attention as a useful approach for clinical and pharmacological studies. − …”