Metabolic profiling reveals new serum signatures to discriminate lupus nephritis from systemic lupus erythematosus

Abstract

BackgroundLupus nephritis (LN) occurs in 50% of patients with systemic lupus erythematosus (SLE), causing considerable morbidity and even mortality. Previous studies had shown the potential of metabolic profiling in the diagnosis of SLE or LN. However, few metabonomics studies have attempted to distinguish SLE from LN based on metabolic changes. The current study was designed to find new candidate serum signatures that could differentiate LN from SLE patients using a non-targeted metabonomics method based on ultra high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS).MethodMetabolic profiling of sera obtained from 21 healthy controls, 52 SLE patients and 43 LN patients. We used SPSS 25.0 for statistical analysis. Principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) and metabolic pathway analysis were used to analyze the metabolic data.ResultsUpon comparison of SLE and LN groups, 28 differential metabolites were detected, the majority of which were lipids and amino acids. Glycerolphospholipid metabolism, pentose and glucuronate interconversions and porphyrin and chlorophyll metabolism were obviously enriched in LN patients versus those with SLE. Among the 28 characteristic metabolites, five key serum metabolites including SM d34:2, DG (18:3(9Z,12Z,15Z)/20:5(5Z,8Z,11Z,14Z,17Z)/0:0), nervonic acid, Cer-NS d27:4, and PC (18:3(6Z,9Z,12Z)/18:3(6Z,9Z,12Z) performed higher diagnostic performance in discriminating LN from SLE (all AUC > 0.75). Moreover, combined analysis of neuritic acid, C1q, and CysC (AUC = 0.916) produced the best combined diagnosis.ConclusionThis study identified five serum metabolites that are potential indicators for the differential diagnosis of SLE and LN. Glycerolphospholipid metabolism may play an important role in the development of SLE to LN. The metabolites we screened can provide more references for the diagnosis of LN and more support for the pathophysiological study of SLE progressed to LN.

Identification of driver genes in lupus nephritis based on comprehensive bioinformatics and machine learning

“…This increase is characterized by elevated release of cytokines and chemokines, as well as increased infiltration of immune cells, predominantly myeloid cells. Additionally, we observed structural and metabolic damage in the glomerulus of patients with LN, observations consistent with previous studies and further validating our study’s convincing evidence ( 36 – 39 ).…”

Longitudinal gut microbiome analyses and blooms of pathogenic strains during lupus disease flares

“…All of these LN RG strains contain an anti-oxidant peroxiredoxin gene (PanPhlAn identifier xg001425), postulated to provide a competitive advantage in a host affected by oxidative stress from increased generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS), which affects both host cells and gut commensals 14 15. Highly relevant, a recent metabolomics report found that increased serum ROS and RNS levels distinguish LN patients from non-renal SLE and healthy CTL 16. Further, both the S107-48 and S47-18 RG strains from LN donors contain orthologues of a putative RG PTS sugar transporter and for alpha-L-fucosidase (xg000037 and xg000038), which have been implicated in catabolism of host mucin that is a component of the intestinal barrier, although alone these factors are not currently considered sufficient to cause intestinal injury 17 18.…”

“… 14 15 Highly relevant, a recent metabolomics report found that increased serum ROS and RNS levels distinguish LN patients from non-renal SLE and healthy CTL. 16 Further, both the S107-48 and S47-18 RG strains from LN donors contain orthologues of a putative RG PTS sugar transporter and for alpha-L-fucosidase (xg000037 and xg000038), which have been implicated in catabolism of host mucin that is a component of the intestinal barrier, although alone these factors are not currently considered sufficient to cause intestinal injury. 17 18 Yet we found that the type strains, RG1 and RG2 also share 24 of the 34 above-mentioned IBD-associated genes ( figure 4 and online supplemental table S5 ).…”

Metabolite Alterations in Autoimmune Diseases: A Systematic Review of Metabolomics Studies

“…In 11 studies, aromatic amino acids (tyrosine, tryptophan, and phenylalanine) were altered [ 44 , 45 , 49 , 51 , 53 , 57 , 79 , 80 , 105 , 110 , 111 ], four of which were found to be associated with SLE and PBC. Ten studies reported an alteration in branched amino acids (leucine, isoleucine and valine) [ 44 , 45 , 49 , 52 , 53 , 59 , 79 , 98 , 105 , 110 ], of which four studies found an association with SLE [ 49 , 52 , 53 , 59 ]. Alterations in fatty acids were observed in eight studies [ 44 , 50 , 53 , 57 , 61 , 104 , 106 , 108 ].…”