Urinary microbiome profiling as a non-invasive tool for identifying biomarkers in systemic lupus erythematosus and lupus nephritis.

Bacteriome alterations have been implicated in the pathogenesis of systemic lupus erythematosus (SLE). However, the relationship between SLE and the urinary microbiome remains underexplored. This study aimed to characterize the urinary microbiome of SLE patients using 16S rRNA sequencing and to investigate its correlations with clinical parameters through integrative analyses. Urine sediment samples were collected from individuals with SLE and lupus nephritis (LN) (n = 20), SLE without LN (n = 22), and healthy controls (HCs) (n = 23). DNA was extracted and subjected to 16S rRNA sequencing to profile the urinary microbiome. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the diagnostic efficacy of urinary microbiota, while Spearman's correlation analysis was employed to identify links between specific microbial taxa and clinical parameters. Functional predictions of bacterial roles were performed using Picrust2. The urinary microbiota diagnostic model exhibited excellent performance in distinguishing SLE patients from HCs. Spearman's analysis revealed significant correlations between the urinary microbiome and clinical parameters. Specifically, Sphingomonas and Lachnospiraceae genera showed positive correlations with vitamin D levels, cylinderuria, and proteinuria, while Pedobacter, Aquabacterium, Delftia, and Achromobacter displayed negative correlations with proteinuria and albumin-to-creatinine ratio (ACR). Functional predictions indicated that the urinary microbiome might influence immune regulation through modulation of signaling pathways and metabolic processes. Our study is the first to reveal dysbiosis in the urinary microbiome of patients with SLE. Certain bacterial taxa in the urinary microbiome were identified as potential diagnostic biomarkers for SLE. Furthermore, the functional implications of these bacterial communities suggest their involvement in immune modulation, highlighting the potential for further investigation into their roles in SLE pathogenesis and diagnosis.

Shi B ，Chen F ，Gong J ，Khan A ，Qian X ，Xu Z ，Yang P ... -  《Frontiers in Cellular and Infection Microbiology》

The diagnostic and predictive potential of lncRNA CASC2 targeting miR-155 in systemic lupus erythematosus patients with nephritis complication.

Lupus nephritis (LN) is a serious problem that results from systemic lupus erythematosus (SLE) complications. Recent studies have highlighted that non-coding RNA (ncRNA) dysregulation is a notable feature in patients with SLE. As a result, this research was designed to investigate lncRNA CASC2 and miR-155 levels as non-invasive diagnostic biomarkers in SLE patients, including those with and without nephritis, and to investigate their effectiveness in assessing disease severity and predicting LN. Our study included 60 patients with SLE who were subclassified into (30 non-LN and 30 LN groups), along with 30 control subjects. Quantification of lncRNA CASC2 and miR-155 in serum samples from the Egyptian population was carried out with real-time polymerase chain reaction (RT-PCR). The disease activity index (SLEDAI) for SLE was evaluated, and the analysis of the receiver operating characteristic (ROC) curve was implemented. Increased levels of lncRNA CASC2 were observed in SLE patients compared to healthy controls, with even higher levels observed in the LN group versus the non-LN patients' group. Conversely, miR-155 was noted to be down-regulated in SLE patients relative to controls, and its levels were lower in the LN group relative to the non-LN patients' group. The elevated expression of lncRNA CASC2 and reduced expression of miR-155 were both correlated to the severity of the disease. The current study illustrated that both lncRNA CASC2 and miR-155 could act as valuable non-invasive diagnostic biomarkers for SLE and predicting LN among SLE patients, as well as their abilities to detect the disease severity and progression.

Mohamed NR ，El-Fattah ALA ，Shaker O ，Sayed GA ... -  《Scientific Reports》

Microbiome-producing SCFAs are associated with preterm birth via trophoblast function modulation.

Meng L ，Meng M ，Zhang R ，Wubulikasimu A ，Peng H ，Zhang L ，Chang X ，Ai G ，Zou G ，He Q ，Wang K ，Liu M ，Duan T ... -  《mBio》

Clinico-serological associations of urinary activated leukocyte cell adhesion molecule in systemic lupus erythematosus and lupus nephritis.

Lupus nephritis (LN) is one of the major complications associated with Systemic Lupus Erythematosus (SLE). Activated leukocyte cell adhesion molecule (ALCAM or CD166) is a promising urine biomarker that binds to CD6, a receptor found on lymphocytes. This binding results in T-cell activation, proliferation, and recruitment, which causes tissue inflammation and may explain the pathophysiology of LN. Investigate the urinary ALCAM level in SLE, study its relationship to disease activity, and clarify the association with LN activity and histopathology. A case-control study was performed on 60 patients with SLE and 20 matched controls. The SLE disease activity index (SLEDAI) and the activity of renal disease (rSLEDAI) were evaluated. Renal biopsy and uALCAM levels were also investigated. Urinary ALCAM levels were higher significantly in active LN patients than inactive LN patients, active and inactive non-LN SLE, and the control group (p < 0.001). The cut-off value for identifying active and inactive LN was above 270 ng/mg (p < 0.001). ALCAM levels were greater in proliferative (class III, IV, and IV/V) than in non-proliferative (class II and V) LN (p < 0.001). ALCAM exhibited high positive correlations with SLEDAI and rSLEDAI (p < 0.001 each) and negative significant correlations with C3 (p < 0.001) and C4 (p = 0.005). Urinary ALCAM is a sensitive biomarker evaluating LN in SLE patients. Levels above 270 ng/mg can help distinguish between active and inactive LN. ALCAM levels are correlated positively with SLEDAI and rSLEDAI but have a negative correlation with C3 and C4. Key Points • Urinary ALCAM shows promise as a biomarker for evaluating kidney dysfunction in SLE patients. • It is a non-invasive marker that can differentiate between proliferative and non-proliferative LN. • A urinary ALCAM level above 270 ng/mg can indicate active LN, while lower levels indicate inactive LN. • Urinary ALCAM levels are correlated positively with SLEDAI and rSLEDAI scores but correlated negatively with C3 and C4.

Amer AS ，Abdel Moneam SM ，Hashaad NI ，Yousef EM ，Abd El-Hassib DM ... -  《-》

Identification of amino acids metabolomic profiling in human plasma distinguishes lupus nephritis from systemic lupus erythematosus.

Guo ZS ，Lu MM ，Liu DW ，Zhou CY ，Liu ZS ，Zhang Q ... -  《-》