Physicians recognize systemic lupus erythematosus (SLE) as an autoimmune disease with diverse clinical manifestations and acknowledge a need for tools to diagnose and monitor disease activity. Anders A. Bengtsson, MD, PhD, chair of the Department of Rheumatology, University Hospital Lund, Sweden, and colleagues found changes in tryptophan levels may serve that purpose. The results of their metabolomics paper comparing SLE patients with primary Sjögren’s syndrome and systemic sclerosis (SSc) were published July 21, 2016, in PLoS ONE.1
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The investigators analyzed serum from 30 patients with SLE. The researchers acknowledge that some patients were receiving immunomodulatory treatment and analgesic drugs that may have changed the metabolic profiles by introducing new metabolites.
“Utilizing a set of 73 uniquely identified metabolites, we found a markedly different metabolic profile in SLE patients as compared with healthy individuals with five metabolites significantly up-regulated and 15 down-regulated in SLE compared with controls according to P values,” write the authors in their discussion. “These results of the ROC [receiver operating characteristic] curve analysis of cross-validated predictive scores proved excellent accuracy of the applied OPLS-DA [orthogonal projections to latent structures discriminant analysis] modeling of metabolic profiles for the discrimination between studied diseases and controls. Furthermore, the individual models of SLE and healthy individuals showed acceptable classification strength with regard to other diagnoses, with specificity above 67% for all analyses (SLE, primary Sjögren’s syndrome and SSc).”
The researchers found increased oxidative activity in SLE patients. Specifically, the patients had increased xanthine oxidase activity and increased turnover in the urea cycle as indicated by decreased levels of arginine and ornithine. However, the most discriminatory metabolite for SLE patients was tryptophan. The lower levels of tyrosine and tryptophan in SLE patients relative to controls suggested that increased activity of aromatic amino acid decarboxylase may exist in these patients. The investigators also found caffeine, as well as other parts of caffeine metabolism, such as theobromine and quinic acid, were down-regulated in SLE patients. The authors were unsure if this difference reflected decreased caffeine consumption or more efficient caffeine metabolism.
The results suggest metabolomics may have the ability to measure disease severity in SLE, as well as partly distinguish the patients with less severe disease from those with the more severe lupus nephritis. Because the pattern of lowered levels of amino acids seen in SLE patients was not as pronounced in patients with SSc, it appears metabolomics may be able to distinguish SLE patients from those with similar immunological diseases, such as SSc and primary Sjögren’s syndrome.
The data also demonstrate that SLE patients have prevalent oxidative stress, as well as abnormal tryptophan metabolism through activity of aromatic amino acid decarboxylase or the kynurenine pathway. Taken together, the results suggest a path toward the development of a much needed diagnostic tool for SLE patients.
Lara C. Pullen, PhD, is a medical writer based in the Chicago area.
- Bengtsson AA, Trygg J, Wuttge DM, et al. Metabolic profiling of systemic lupus erythematosus and comparison with primary Sjögren’s syndrome and systemic sclerosis. PLoS One. 2016 Jul 21;11(7):e0159384. eCollection 2016