NMR-Based Serum Metabolomics Revealed Distinctive Metabolic Patterns in Reactive Arthritis Compared with Rheumatoid Arthritis

Abstract

Reactive arthritis (ReA) is a member of seronegative spondyloarthropathy (SSA), which involves an acute/subacute onset of asymmetrical lower limb joint inflammation weeks after a genitourinary/gastrointestinal infection. The diagnosis is clinical because it is difficult to culture the microbes from synovial fluid. Arthritis patients with a similar clinical picture but lapsed history of an immediate preceding infection that do not fulfill the diagnostic criteria of other members of SSA, such as ankylosing spondylitis, psoriatic arthritis, and arthritis associated with inflammatory bowel disease, are labeled as peripheral undifferentiated spondyloarthropathy (uSpA). Both ReA and uSpA patients show a strong association with class I major histocompatibility complex allele, HLA-B27, and a clear association with an infectious trigger; however, the disease mechanism is far from clear. Because the clinical picture is largely dominated by rheumatoid-arthritis (RA)-like features including elevated levels of inflammatory markers (such as ESR, CRP, etc.), these overlapping symptoms often confound the clinical diagnosis and represent a clinical dilemma, making treatment choice more generalized. Therefore, there is a compelling need to identify biomarkers that can support the diagnosis of ReA/uSpA. In the present study, we performed NMR-based serum metabolomics analysis and demonstrated that ReA/uSpA patients are clearly distinguishable from controls and further that these patients can also be distinguished from the RA patients based on the metabolic profiles, with high sensitivity and specificity. The discriminatory metabolites were further subjected to area under receiver operating characteristic curve analysis, which led to the identification of four metabolic entities (i.e., valine, leucine, arginine/lysine, and phenylalanine) that could differentiate ReA/uSpA from RA.

Metabolomic analysis of biochemical changes in the tissue and urine of proteoglycan-induced spondylitis in mice after treatment with moxibustion

“… 25 Valine and L-alanine, known as branched chain amino acids (BCAAs), have been implicated to stimulate the production of pro-inflammatory cytokines in rheumatic diseases. 26 The dysregulation of glycine, serine and threonine metabolism was frequently associated with the process of HLA-B27 protein misfolding 27 , the decrease of anti-inflammatory properties and the reducing of immunoglobulin production. 28 However, moxibustion appeared to restore the metabolites and phenotypic indicators correlated with Amino Acid metabolism.…”

NMR‐based clinical metabolomics revealed distinctive serum metabolic profiles in patients with spondyloarthritis

“…[ 45 ] Previously, high levels have been described in inflammatory bowel disease, rheumatoid arthritis, lupus, and Takayasu's arteritis. [ 27–29,46,47 ] This may suggest that the inflammatory burden is higher in peripheral SpA as compared with axial SpA. Further, the levels of glutamine have been found to be decreased in peripheral SpA along with the increased levels of glutamate.…”

Cold storage reveals distinct metabolic perturbations in processing and non-processing cultivars of potato (Solanum tuberosum L.)

“…Pareto-scaling was chosen over the unit variance scaling approach as it gives more importance to abundant metabolites thereby avoiding noise from low signal-to-noise peaks into the analysis. Pareto-scaling has typically been the method of choice in NMR-based metabolomics studies [71][72][73] . Correlation between the first two principal components was drawn as the scores plot for all the samples and clusters of normal distribution were marked using ellipses showing 95% confidence limits for each group in PCA analysis.…”