Brief report on the relation between complement C3a and anti dsDNA antibody in systemic lupus erythematosus

Cai, Yaohua; Deng, Jun; Chen, Zhaolin; Mei, Heng; Tang, Liang V.; Luo, Shanshan; Hu, Yu Lin

doi:10.1038/s41598-022-10936-z

Cited by 5 publications

(2 citation statements)

References 15 publications

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“…the serum C3a concentrations that we observed in the FD patients are not only much higher than in healthy controls but markedly higher than the C3a levels determined in two immune-complex mediated diseases, in which complement activation has previously been demonstrated, i.e. systemic lupus erythematosus (32) or antiphosphlipd syndrome (33) and similar to C3a levels observed in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculits (34).…”

Section: Discussionsupporting

confidence: 60%

Complement activation and cellular inflammation in Fabry disease patients despite enzyme replacement therapy

Laffer,

Lenders,

Ehlers-Jeske

et al. 2024

Front. Immunol.

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Defective α-galactosidase A (AGAL/GLA) due to missense or nonsense mutations in the GLA gene results in accumulation of the glycosphingolipids globotriaosylceramide (Gb3) and its deacylated derivate globotriaosylsphingosine (lyso-Gb3) in cells and body fluids. The aberrant glycosphingolipid metabolism leads to a progressive lysosomal storage disorder, i. e. Fabry disease (FD), characterized by chronic inflammation leading to multiorgan damage. Enzyme replacement therapy (ERT) with agalsidase-alfa or -beta is one of the main treatment options facilitating cellular Gb3 clearance. Proteome studies have shown changes in complement proteins during ERT. However, the direct activation of the complement system during FD has not been explored. Here, we demonstrate strong activation of the complement system in 17 classical male FD patients with either missense or nonsense mutations before and after ERT as evidenced by high C3a and C5a serum levels. In contrast to the strong reduction of lyso-Gb3 under ERT, C3a and C5a markedly increased in FD patients with nonsense mutations, most of whom developed anti-drug antibodies (ADA), whereas FD patients with missense mutations, which were ADA-negative, showed heterogenous C3a and C5a serum levels under treatment. In addition to the complement activation, we found increased IL-6, IL-10 and TGF-ß1 serum levels in FD patients. This increase was most prominent in patients with missense mutations under ERT, most of whom developed mild nephropathy with decreased estimated glomerular filtration rate. Together, our findings demonstrate strong complement activation in FD independent of ERT therapy, especially in males with nonsense mutations and the development of ADAs. In addition, our data suggest kidney cell-associated production of cytokines, which have a strong potential to drive renal damage. Thus, chronic inflammation as a driver of organ damage in FD seems to proceed despite ERT and may prove useful as a target to cope with progressive organ damage.

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Section: Discussionsupporting

confidence: 60%

Complement activation and cellular inflammation in Fabry disease patients despite enzyme replacement therapy

Laffer,

Lenders,

Ehlers-Jeske

et al. 2024

Front. Immunol.

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“…Exclusion criteria included concurrent pregnancy, use of hormonal or other medications in the recent 1 month. We defined SLE group patients based on the Systemic Lupus International Collaborative Clinics (SLICC) classification criteria [ 25 ]. We defined controls from the same hospital as healthy population without clinical and laboratory evidence of SLE or other dysfunction, a total of 113 eligible healthy individuals were recruited in this survey.…”

Section: Methodsmentioning

confidence: 99%

Association of Perfluoroalkyl and polyfluoroalkyl substances (PFASs) exposures and the risk of systemic lupus erythematosus: a case–control study in China

He,

Qu,

Tian

et al. 2023

Environ Health

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Perfluoroalkyl and polyfluoroalkyl substances (PFASs) may have a role in impaired health. However, the data on the association between PFASs and Systemic lupus erythematosus (SLE) have been limited. We designed a population-based case–control study in China and evaluated the association. 100 normal persons (Control) and 100 SLE patients (Case) were obtained from 113 controls and 125 cases according to matching conditions. Serum samples were collected by venipuncture for UHPLC-MRM-MS Analysis to obtain the concentration of five PFASs in participants. Demographic characterization description was performed for the two groups of participants, the PFASs concentration distribution of the two groups was described and compared, then divided into three tiers (< 50th, 50th ~ 75th, > 75th) for subsequent analysis. Conditional logistic regression models were utilized to calculate the odds ratios (ORs) and 95% CIs for SLE. Relationship between changes in the concentration of PFASs and the risk of SLE assessed by restricted cubic spline. As the highest serum levels of the five PFASs tested in this study population, the highest perfluoroundecanoic acid (PFUnA) quartile had a 2.78-fold (95%CI: 1.270, 6.10) compared with the lowest quartile of PFUnA exposure, other types of PFASs also showed high association with SLE as well as PFASs mixture. Additionally, the exposure of PFASs exist a dose–response relationship (ptrend < 0.05). This risk association remained be found after adjusting the covariates in model 1 (adjustment of BMI) and in model 2(adjustment of BMI, smoking, drinking, hypertension and leukocyte). The restricted cubic spline illustrated a gradual increase in the possible risk of SLE with the increasing exposure of PFASs components levels. Our study firstly revealed that PFASs are risk factors for SLE and PFASs exposures are associated with SLE risk in a dose − response manner. Evidence from larger and more adequately powered cohort studies is needed to confirm our results.

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Serological Profiles of Systemic Lupus Erythematosus in Humanized Mice and Pristane-Induced Lupus Models

Syahrul Chilmi,

Dimas Ikhsan Airlangga,

Hani Susianti

et al. 2024

FMI

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Highlights:1. This study compared the serological markers of pristane-induced mice to humanized mouse models of lupus achieved by transplanting stem cells from lupus patients, which is a novel method in Indonesia.2. This study will allow for more accurate research into the pathophysiology of the disease and the development of new lupus treatment strategies. Abstract More studies related to systemic lupus erythematosus (SLE) therapy are urgently needed because of the current insufficiency in treatment effectiveness. However, due to ethical limitations, researchers use experimental animals as a substitute for conducting studies on humans. Models commonly used to study lupus include the pristane-induced mouse model and the recently developed humanized mouse model. The second model involves implanting human immune cells into immunodeficient mice. This study compared the serologic profiles of lupus antibodies, the antinuclear antibodies (ANA) and anti-double stranded DNA (anti-dsDNA), in both mouse models. The aim was to determine which one is more promising for use as a lupus animal model. Thirty BALB/c mice (Mus musculus) were used as subjects and divided into three groups: K1, K2, and K3. K1 served as the control group, consisting of healthy mice that received a placebo. The K2 mice were intraperitoneally injected with 0.5 cc of pristane. The K3 mice were transplanted with stem cell cultures from SLE patients, resulting in humanized mice with immune deficiencies. The mice were observed for 16 weeks, during which the ANA and anti-dsDNA levels in their serum were obtained for analysis using the Kruskal-Wallis test (p<0.05). The comparison revealed differences in the average ANA and anti-dsDNA levels among the three groups. K3 had the highest ANA and anti-dsDNA levels, followed by K1 and K2. The Kruskal-Wallis test indicated that the differences were not significant in the mean levels of ANA (p=0.156) and anti-dsDNA (p=0.061). In conclusion, the humanized mouse model has higher ANA and anti-dsDNA antibody levels compared to the pristane-induced mouse model, albeit without a significant difference. This suggests a positive picture of the humanized mouse model of lupus, making it an invaluable tool for studying the disease and testing potential therapeutic interventions.

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Brief report on the relation between complement C3a and anti dsDNA antibody in systemic lupus erythematosus

Cited by 5 publications

References 15 publications

Complement activation and cellular inflammation in Fabry disease patients despite enzyme replacement therapy

Complement activation and cellular inflammation in Fabry disease patients despite enzyme replacement therapy

Association of Perfluoroalkyl and polyfluoroalkyl substances (PFASs) exposures and the risk of systemic lupus erythematosus: a case–control study in China

Serological Profiles of Systemic Lupus Erythematosus in Humanized Mice and Pristane-Induced Lupus Models

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