Study Probes Multi-Omics Interactions at Play in SLE Pathogenesis

The study highlights differences between patients with systemic lupus erythematosus (SLE) and healthy controls, potentially shedding light on the disease’s underlying mechanisms.

A new “multi-omics” analysis of patients with systemic lupus erythematosus (SLE) offers new insights into the proteomic, metabolomic, and lipidomic profiles of patients with varying levels of disease activity.

The study, published in Frontiers in Immunology, is believed to be the first study of its kind.

Corresponding author Jun Tai, of China’s Children’s Hospital Affiliated Capital Institute of Pediatrics, and colleagues noted that SLE is a complex disease with heterogenous manifestations. While individual elements of SLE have been studied, the investigators said the molecular hallmarks of the disease are poorly understood.

“Systemic tissue damage may arise from a series of complex factors, and as a consequence, may alter the proteins and metabolites involved in SLE activity,” Tai and colleagues said. “These proteomic and metabolic disorders indirectly reflect the status of the patients and may be associated with multiple severe complications.”

Thus, the authors said, it is necessary to understand whether proteins and metabolites in the circulation systems of patients with SLE might play a role in the disease’s pathogenesis and activity levels. That task has been made easier, they said, by recent advances in multi-omics research.

The investigators recruited 10 healthy controls and 40 patients with SLE and collected serum samples from each. The patients were broken into 3 subgroups based on their SLE Disease Activity Index (SLEDAI) scores. Ten patients were deemed to have inactive disease (IA), another 10 had low activity disease (LA), and the remaining 20 were considered to have high activity levels (HA) because they had SLEDAI scores of 10 or above.

After conducting proteomic, metabolomic, and lipidomic analyses, Tai and colleagues said the data suggest the molecular changes present in the patients, compared with controls, indicate that both the immune system’s complement system and the body’s inflammatory response were activated in patients with SLE, and both had an impact on disease activity.

“In this study, many complement components were significantly changed in [patients with SLE], with the trend becoming more pronounced as disease activity increased,” they wrote.

In addition, the investigators found that activation of the immunoglobulin mediated immune response was identifiable in patients with low activity levels, but not in patients with high levels of activity.

“Although expression of most immunoglobulin-related proteins were elevated in SLE patients, interestingly, we found that these levels decreased slightly in the HA group compared to LAs,” they wrote. “This suggests that immunoglobulin-related immune responses, which were activated in SLEs, might be specifically suppressed in the HAs group.”

The authors also said that disease activity in SLE appeared to be affected by an imbalance of lipid metabolism, particularly sphingolipid metabolism, and that the imbalance was accompanied by dysregulated apolipoproteins.

“This suggests that sphingolipid metabolism may participate in the pathogenesis of SLE and supports the hypothesis that dysregulated lipid metabolism occurs in SLE,” they wrote.

The investigators noted that their study was a single-center study with a relatively small sample size. They added that some of the patients in their cohort had been receiving treatment for SLE for more than a month, which may have affected the results. Still, they said their findings, particularly if confirmed in a larger study, should help scientists better understand how to develop future therapies.

“Overall, this study provides novel insights into SLE as well as valuable clues for deciphering the pathogenesis of SLE and its underlying mechanisms,” they concluded.

Reference:

Huang X, Luu LDW, Jia N, et al. Multi-platform omics analysis reveals molecular signatures for pathogenesis and activity of systemic lupus erythematosus. Front Immunol. Published online April 19, 2022. doi:10.3389/fimmu.2022.833699