Immunometabolism in the pathogenesis of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a typical autoimmune disease characterized by chronic inflammation and pathogenic auto-antibodies. Apart from B cells, dysregulation of other immune cells also plays an essential role in the pathogenesis and development of the disease including CD4+T cells, dendritic cells, macrophages and neutrophils. Since metabolic programs control immune cell fate and function, they are critical checkpoints in an effective immune response and are involved in the etiology of autoimmune disease. In addition, mitochondria and oxidative stress are both involved in cellular metabolism and is also essential in immune response. In this review, apart from the disturbed immune system, we will discuss mitochondrial dysfunction, oxidative stress, abnormal metabolism (including glucose, lipid and amino acid metabolism) of immune cells as well as epigenetic control of metabolism reprogramming to elucidate the underlying pathogenic mechanisms of systemic lupus erythematosus.

Clinical manifestations, immunological features and prognosis of Chinese pediatric systemic lupus erythematosus: A single-center study.

AIM: Since there are only a few reports on pediatric systemic lupus erythematosus (pSLE) in Chinese populations, therefore we retrospectively report the clinical and immunological features as well as renal outcome in Chinese pSLE. METHODS: Patients diagnosed with pSLE at Shanghai Children's Medical Center between 2001 and 2016 were evaluated and clinical data were retrospectively collected. RESULTS: A total of 102 pSLE patients were analyzed. Renal disorder including proteinuria (81.37%) and hematuria (65.69%) were most commonly identified. Class IV was the most common finding on renal biopsy. In lupus nephritis (LN), 67.21%, 78.0%, 86.0% and 94.55% achieved complete remission within 6, 12, 18 and 24 months, respectively. Furthermore, 16.67% of LN patients suffered at least one renal flare. Antinuclear antibodies were detected in nearly all patients (97.62%), followed by anti-double-stranded DNA (anti-dsDNA) antibodies (70.0%) and anti-Sjögren's syndrome A (anti-SSA) antibodies (60.64%). Oral corticosteroid (93.14%) and mycophenolate mofetil (64.71%) was used in the majority of patients. Infection (32.35%) was the main side effect caused by the medications. CONCLUSIONS: Our population-based pSLE cohort indicated that compared to other international cohorts, there was a higher prevalence of LN in Chinese pSLE. Proteinuria was the most frequent manifestation both at disease onset and during the entire clinical course. Class IV LN was the dominant renal pathological type. Nevertheless, there was a favorable renal remission rate and relatively low incidence of renal flare in our cohort. Apart from antinuclear antibodies and anti-dsDNA antibodies, anti-SSA antibodies were most frequently detected. Infection was the leading complication caused by the medications.

Feasibility of diagnosing renal allograft dysfunction by oligonucleotide array: Gene expression profile correlates with histopathology.

BACKGROUND: Effective non-invasive monitoring method to tell histopathology is a big challenge in renal transplantation. METHODS: We used 70-mer long oligonucleotide array with 449 immune related genes to determine gene expression profiles of peripheral blood mononuclear cells (PBMCs) under different immune status including stable renal function (TX), acute tubular necrosis (ATN), biopsy conformed acute rejection (AR), clinical rejection with pathology of borderline changes (BL), clinical rejection without biopsy proven/presumed rejection (PR) and renal dysfunction without rejection (NR). RESULTS: Distinct molecular expression signatures in each group were found to correlate with histopathology. And we concluded that B cell chemokine CXCL13 and mast cell may play a role in renal allograft rejection through significant difference analysis and functional pathway analysis. CONCLUSIONS: It provides a potential non-invasive method for monitoring renal allograft function and immune status of renal transplant recipients.

[Preparation of a novel targeted MR contrast agent Gd-DTPA-Granzyme B monoclonal antibody].

OBJECTIVE: To prepare a novel MRI targeted contrast agent Gd-DTPA-Granzyme B monoclonal antibody (mAb) and to test its reaction conditions. METHODS: The Granzyme B mAb was coupled with DTPA,and then conjugated with Gd. The Gd-DTPA antibody was characterized using MALDI-TOF-MS. Cytotoxicity test was performed with MTT assay, and immune activation was examined with immunohistochemistry. RESULT: MALDI-TOF-MS demonstrated that the molecular weight shifted from granzyme B mAb (133986) to Gd-DTPA-GB mAb (139736), which indicated the conjugation of the antibody with Gd-DTPA. The molar ratio of Gd per IgG molecule was about 20. MTT assay showed that Gd, DTPA, Gd-DTPA and Gd-DTPA-GB mAb groups did not make an impact on cell viability, and there were no significant differences among 4 groups (P>0.05). Immunohistochemistry results showed that compared with the positive control group the targeted contrast agent had a high immune activity. CONCLUSION: The novel contrast agent Gd-DTPA-Granzyme B mAb prepared in this study keeps a good immune activity and has no significant cytotoxicity.

A pilot study of GC/MS-based serum metabolic profiling of acute rejection in renal transplantation.

AIMS: Acute allograft rejection is one of the important complications after renal transplantation, and it is a deleterious factor for long-term graft survival. Rejection is a complex pathophysiologic process, which has been explained by transcriptome and proteome in RNA transcripts and proteins level respectively. How are serum metabolite levels in response to acute rejection? Can metabolite levels in serum be used to diagnose and explain acute renal allograft rejection? METHODS: Gas chromatograph-mass spectrometry (GC-MS) was used to analyze serum metabolome in 22 recipients of acute rejection and 15 stable renal transplant recipients. RESULTS: 46 endogenous metabolites included amino acid, fatty acid, carbohydrate and other intermediate metabolites were identified in 37 recipients. Principal component analysis based on these metabolites discriminated acute rejection group from stable recipients. Among these metabolites, the levels of 17 metabolites were significant higher in rejection group than those in stable group. These included amino acid (phenylalanine, serine, glycine, threonine, valine), carbohydrate (galactose oxime, glycose, fructose), carboxylic acid, lipids and other metabolite such as lactate, urea and myo-inositol. The levels of 5 metabolites of alanine, lysine, leucine, aminomalonic acid and tetradecanoic acid were low in rejection group compared to stable group. The prediction accuracy of acute rejection was 77.3% and stable function was 100% by supervised clustering based on these 22 metabolites. CONCLUSIONS: This study demonstrated that metabolic profile was changed in response to rejection process and renal function can be reflected by serum metabolite levels. This study showed potential capability to diagnose acute rejection by metabolome analysis.