scholarly journals POS0787 BERBERINE MODULATE LUPUS SYNDROME VIA THE REGULATION OF GUT MICROBIOTA IN MRL/LPR MICE

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 646.2-646
Author(s):  
Y. Bao ◽  
J. Ji ◽  
Z. Xue ◽  
Z. Gu

Background:Intestinal flora disorder and immune abnormalities have been reported in systemic lupus erythematosus (SLE) patients1,2. Berberine (BBR) showed significant effects in regulating the intestinal flora, repairing gut barriers and regulating immune cells3,4. While few reports mentioned the abnormal gut microbiota and metabolites in Chinese SLE patients.Objectives:Our investigation tried to illustrate the relationship between gut microbiota, intestinal metabolites and disease activity in Chinese SLE patients. And the effect of BBR to intestinal dysbacteriosis, multiple organ damages and over-activated immune system in MRL/Lpr mice.Methods:16S high-throughput (16S rRNA) sequence, qRT-PCR and gas chromatography technology were used to determine the gut microbiota and metabolites in 104 SLE patients from Affiliated Hospital of Nantong University, China. BBR was orally treated to the MRL/Lpr mice in low, medium and high doses. After 6 weeks treatment, mice were sacrificed. Serum, faeces and organs were collected for further studies.Results:Chinese SLE patients showed higher abundance of Bacteroidetes and lower abundance of Firmcutes. The results of qRT-PCR showed high Firmcutes/Bacteroidetes (F/B) ratio of SLE patients. The F/B ratio was negative correlated with SLE disease activity index (SLEDA) score. Almost all the tested short-chain fatty acids (SCFAs) found statistically significant results in SLE and LN (lupus nephritis) patients, especially the propanoic acid and butyric. BBR altered the relative abundance of Bacteroides and Verrucomicrobia and the butyric acid content in colon of MRL/Lpr mice. The increase of tight junction protein also indicated the gut barrier was repaired by BBR. Treg and Tfr cells in spleen and mesenteric lymph node (MLN) were increased. These results revealed a positive therapeutic effect of berberine on SLE from gut microbiota to immune status.Conclusion:Our study highlights current status of intestinal dysbacteriosis in Chinese patients with SLE and differences in intestinal metabolites among patients with different disease states. The regulation of intestinal flora and the repairment of gut barrier by intestinal metabolites in BBR treated mice seemed to be the factor that directed the immune responses and disease outcomes. The ultimate goal of our study was to determine the beneficial effects of regulating the gut microbiota on the treatment of SLE. The application of berberine is a relatively safe and convenient way. In the coming investigations, we plan to focus on the study of berberine and its metabolites on intestinal function and systemic immunity.References:[1]Guo, M. et al. Alteration in gut microbiota is associated with dysregulation of cytokines and glucocorticoid therapy in systemic lupus erythematosus. Gut microbes11, 1758-1773, doi:10.1080/19490976.2020.1768644 (2020).[2]Mu, Q. et al. Control of lupus nephritis by changes of gut microbiota. Microbiome5, 73, doi:10.1186/s40168-017-0300-8 (2017).[3]Habtemariam, S. Berberine pharmacology and the gut microbiota: A hidden therapeutic link. Pharmacological research155, 104722, doi:10.1016/j.phrs.2020.104722 (2020).[4]Cui, H. et al. Berberine Regulates Treg/Th17 Balance to Treat Ulcerative Colitis Through Modulating the Gut Microbiota in the Colon. Frontiers in pharmacology9, 571, doi:10.3389/fphar.2018.00571 (2018).Figure 1.Disclosure of Interests:None declared

Lupus ◽  
2020 ◽  
pp. 096120332097904
Author(s):  
Eman Ahmed Hafez ◽  
Sameh Abd El-mottleb Hassan ◽  
Mohammed Abdel Monem Teama ◽  
Fatma Mohammed Badr

Objective Lupus nephritis (LN) is closely associated with hyperuricemia, and uric acid is considered a risk factor for renal involvement in systemic lupus erythematosus (SLE). This study aimed to examine the association between serum uric acid (SUA) level and LN development and progression in SLE patients with normal renal function. Methods A total of 60 SLE patients with normal renal function from Ain Shams University Hospital were selected and assigned to group 1 (30 patients with LN) and group 2 (30 patients without LN). All patients were subjected to history taking, clinical examination, disease activity assessment based on SLE disease activity index (SLEDAI) and renal SLEDAI (SLEDAI-R) scores, and laboratory investigations, including as SUA, complete blood count, blood urea nitrogen (BUN), serum creatinine, creatinine clearance, urine analysis, protein/creatinine ratio, 24-h urinary protein excretion, Antinuclear antibodies (ANA), anti-dsDNA antibody, and serum complement (C3, C4). Results Disease duration, SLEDAI score, and SUA level were higher in group 1 than in group 2 (p < 0.001). SUA level was positively correlated with SLEDAI and SLEDAI-R scores, proteinuria, urinary casts, renal biopsy class, disease activity and chronicity indices, BUN level, and serum creatinine level but was negatively correlated with creatinine clearance (p < 0.05). SUA was a predictor of LN development in SLE patients (sensitivity, 83.3%; specificity, 70%). Conclusion SUA is associated with the development of lupus nephritis in patients with normal kidney function also SUA in-dependently correlated with disease activity and chronicity in LN.


Lupus ◽  
2017 ◽  
Vol 26 (13) ◽  
pp. 1448-1456 ◽  
Author(s):  
K C Maloney ◽  
T S Ferguson ◽  
H D Stewart ◽  
A A Myers ◽  
K De Ceulaer

Background Epidemiological studies in systemic lupus erythematosus have been reported in the literature in many countries and ethnic groups. Although systemic lupus erythematosus in Jamaica has been described in the past, there has not been a detailed evaluation of systemic lupus erythematosus patients in urban Jamaica, a largely Afro-Caribbean population. The goal of this study was to describe the clinical features, particularly disease activity, damage index and immunological features, of 150 systemic lupus erythematosus subjects. Methods 150 adult patients (≥18 years) followed in rheumatology clinic at a tertiary rheumatology hospital centre (one of two of the major public referral centres in Jamaica) and the private rheumatology offices in urban Jamaica who fulfilled Systemic Lupus International Collaborating Clinics (SLICC) criteria were included. Data were collected by detailed clinical interview and examination and laboratory investigations. Hence demographics, SLICC criteria, immunological profile, systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K) and SLICC/American College of Rheumatology (ACR) damage index (SDI) were documented. Results Of the 150 patients, 145 (96.7%) were female and five (3.3%) were male. The mean age at systemic lupus erythematosus onset was 33.2 ± 10.9. Mean disease duration was 11.3 ± 8.6 years. The most prevalent clinical SLICC criteria were musculoskeletal, with 141 (94%) of subjects experiencing arthralgia/arthritis, followed by mucocutaneous manifestations of alopecia 103 (68.7%) and malar rash 46 (30.7%), discoid rash 45 (30%) and photosensitivity 40 (26.7%). Lupus nephritis (biopsy proven) occurred in 42 (28%) subjects and 25 (16.7%) met SLICC diagnostic criteria with only positive antinuclear antibodies/dsDNA antibodies and lupus nephritis on renal biopsy. The most common laboratory SLICC criteria were positive antinuclear antibodies 136 (90.7%) followed by anti-dsDNA antibodies 95 (63.3%) and low complement (C3) levels 38 (25.3%). Twenty-seven (18%) met SLICC diagnostic criteria with only positive antinuclear antibodies/anti-dsDNA antibodies and lupus nephritis on renal biopsy. Mean SLEDAI score was 6.9 ± 5.1 with a range of 0–32. Organ damage occurred in 129 (86%) patients; mean SDI was 2.4 ± 1.8, with a range of 0–9. Conclusion These results are similar to the clinical manifestations reported in other Afro-Caribbean populations; however, distinct differences exist with respect to organ involvement and damage, particularly with respect to renal involvement, which appears to be reduced in our participants.


Reumatismo ◽  
2018 ◽  
Vol 70 (4) ◽  
pp. 241-250 ◽  
Author(s):  
W.A. Wan Asyraf ◽  
M.S. Mohd Shahrir ◽  
W. Asrul ◽  
A.W. Norasyikin ◽  
O. Hanita ◽  
...  

Based on the recent evidence of association between hyperprolactinemia and systemic lupus erythematosus disease activity (SLEDAI), a study was conducted to analyze the association of hyperprolactinemia with lupus nephritis disease activity. In this cross-sectional study, the analysis was conducted on SLE patients who visited the University Kebangsaan Malaysia Medical Centre (UKMMC) Nephrology Clinic from August 2015 till February 2016. The disease activity was measured using the SLEDAI score, with more than 4 indicating active lupus nephritis. Basal resting prolactin level was analyzed in 43 patients with lupus nephritis, in 27.9% of them had raised serum prolactin. The median of serum prolactin level at 0 minutes was 19.91 ng/mL (IQR: 15.95-22.65 ng/ mL) for active lupus nephritis, which was significantly higher compared to the median of serum prolactin level of 14.34 ng/mL (IQR: 11.09-18.70 ng/mL) for patients in remission (p=0.014). The serum prolactin level positively correlated with SLEDAI (rhos: 0.449, p=0.003) and the UPCI level in lupus nephritis patients (rhos: 0.241, p=0.032). The results were reproduced when the serum prolactin was repeated after 30 minutes. However, the serum prolactin levels at 0 minutes were higher than those taken after 30 minutes (p=0.001). An assessment of serum IL-6 levels found that the active lupus nephritis patients had a higher median level of 65.91 pg/ mL (IQR: 21.96-146.14 pg/mL) compared to the in-remission level of 15.84 pg/mL (IQR: 8.38-92.84 pg/mL), (p=0.039). Further correlation analysis revealed that there was no statistical correlation between the interleukin (IL)-6 levels with serum prolactin, SLEDAI and other lupus nephritis parameters. An ROC curve analysis of serum prolactin at 0 minutes and serum prolactin after 30 minutes and IL-6 levels for prediction of SLE disease activity provided the cutoff value of serum prolactin at 0 minutes, which was 14.63 ng/mL with a sensitivity of 91.7% and specificity of 58.1% and AUC of 0.74 (p=0.015). This study concurred with the previous findings that stated that hyperprolactinemia is prevalent in SLE patients and correlated with clinical disease activity and UPCI level. The baseline of the fasting serum prolactin level was found to be a sensitive biomarker for the evaluation of lupus nephritis disease activity.


2018 ◽  
Author(s):  
Tim Dierckx ◽  
Sylvie Goletti ◽  
Laurent Chiche ◽  
Laurent Daniel ◽  
Bernard Lauwerys ◽  
...  

Objective: Glycoprotein acetylation (GlycA) is a novel biomarker for chronic inflammation, associated to cardiovascular risk. Serum GlycA levels are increased in several inflammatory diseases, including systemic lupus erythematosus (SLE). We investigated the relevance of serum GlycA measurement in SLE and lupus nephritis (LN). Methods: GlycA was measured by NMR in 194 serum samples from patients and controls. Comparisons were performed between groups. Clinical and biological parameters were tested for correlation with GlycA levels. The predictive value of GlycA to differentiate proliferative from non-proliferative LN was determined using logistic regression models. Results: GlycA was correlated to C-reactive protein (CRP), neutrophil count, proteinuria and the SLE disease activity index (SLEDAI), and inversely with serum albumin. GlycA was higher in active (n=105) than in quiescent (n=39) SLE patients, in healthy controls (n=29), and in patients with non-lupus nephritis (n=21), despite a more altered renal function in the latter. In patients with biopsy-proven active LN, GlycA was higher in proliferative (n=32) than non-proliferative (n=11) LN, independent of renal function and proteinuria level. Logistic regression models showed that, in univariate models, GlycA outperforms traditional biomarkers. A bivariate model using GlycA and BMI better predicted the proliferative status of LN than a model comprising CRP, renal function (eGFR), serum albumin, proteinuria, C3 consumption and the presence of anti-dsDNA antibodies. Conclusion: Serum GlycA is elevated in SLE, and correlates with disease activity and LN. Serum GlycA, which summarizes different inflammatory processes, could be a valuable biomarker to discriminate proliferative from non-proliferative LN and should be tested in large, prospective cohorts.


2011 ◽  
Vol 31 (1) ◽  
pp. 29-34 ◽  
Author(s):  
Mohamed N. Farres ◽  
Dina S. Al-Zifzaf ◽  
Alaa A. Aly ◽  
Nermine M. Abd Raboh

2019 ◽  
Vol 41 (1) ◽  
pp. 31-34 ◽  
Author(s):  
Dina F. Elessawi ◽  
Geilan A. Mahmoud ◽  
Wael S. El-Sawy ◽  
Hala F. Shieba ◽  
Shimaa M. Goda

Folia Medica ◽  
2014 ◽  
Vol 56 (4) ◽  
pp. 245-252 ◽  
Author(s):  
Maria E. Tsanyan ◽  
Sergey K. Soloviev ◽  
Stefka G. Radenska-Lopovok ◽  
Anna V. Torgashina ◽  
Ekaterina V. Nikolaeva ◽  
...  

Abstract Aim: TO assess the effects of rituximab (RTM) therapy on clinical and morphologic activity of lupus nephritis (LN). Material and methods: The study included 45 patients with confirmed diagnosis of systemic lupus erythematosus (SLE), unaffected by previously received standard therapy with glucocorticoids (GCs) and cytostatics. The disease activity was assessed using Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI 2K); to assess the LN activity we used the SLICC RA/RE index. Forty-five patients with LN were given puncture renal biopsy prior to prescribing RTM; 16 patients had repeated renal biopsy 1 year and more after beginning the anti-B-cell therapy. LN was graded histologically in accordance with the WHO classification (2003) with indices of activity (AI) and chronicity (CI). Results: The predominant number of patients had class III - IV of LN. The repeated renal biopsies demonstrated that LN had undergone a transition into a more favourable morphologic class, which was associated, in most of these cases, with a positive therapeutic effect. The follow-up dynamics showed a statistically significant reduction of AI (p=0.006), and no statistically significant changes in the CI (p = 0.14). Conclusion: The long-term follow-up in the study has showed that repeated courses of anti-B-cell therapy with RTM have a positive effect both on SLE activity and generally on the renal process. The reduction of the morphologic class of LN as assessed in the repeated renal biopsies is a convincing proof for this. Eleven out of 16 patients experienced transition of the morphologic class into a more favourable type, which in most cases was combined with lower AI (p = 0.006). We found no evidence of increase in the CI (p = 0.14).


2021 ◽  
Vol 11 (2) ◽  
pp. 97-102
Author(s):  
Saiful Bahar Khan ◽  
Rafi Nazrul Islam ◽  
Md Saif Bin Mizan ◽  
AKM Shahidur Rahman ◽  
Shah Md Zakir Hossain ◽  
...  

Background: Lupus nephritis (LN) is one of the most common and serious manifestations of systemic lupus erythematosus (SLE) that causes significant morbidity and mortality. Certain biomarkers for LN are sometimes able to assess treatment response in lupus nephritis. This study aimed to compare serum complement levels (C3 and C4) as markers of treatment response of LN and their relation to the LN class in renal biopsy. Methods: This prospective observational study was conducted in the Department of Nephrology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from July 2018 to August 2019. Twenty seven patients who were diagnosed with LN after kidney biopsy were included in this study. Serum complement levels (C3 and C4), 24 hours urinary total protein (24-hr UTP) and anti-double-stranded DNA (anti-ds DNA) were measured in all patients at baseline, 3 months and 6 months after treatment initiation. These biomarker values before and after treatment were compared between the proliferative and non-proliferative LN patients. Results: Serum C3 levels were significantly different between patients with proliferative LN (Class III and Class IV) and non-proliferative LN (Class V) at baseline (0.47 ± 0.32 g/l versus 0.89 ± 0.43 g/l, p=0.009) and levels changed significantly 6 months after treatment initiation (p<0.001) and likewise for serum C4 levels (0.10 ± 0.06 g/l versus 0.24 ± 0.26 g/l, p=0.040). The values of 24-hr UTP and anti-ds-DNA were significantly different 6 months after treatment with p value <0.05 in both groups but C3 (p<0.001) and renal Systemic Lupus Erythematosus Disease Activity Index (rSLEDAI) (p<0.001) were only significant in the proliferative group. On the other hand, after 6 months treatment, C4 levels became relatively higher but that was not significant in both groups (p>0.05). Conclusion: After 6 months of treatment, serum C3 and C4 levels increased towards normal in both LN groups. Serum C3 and C4 levels in patients with LN correlate with disease activity. Therefore, serum complement (C3 and C4) levels may be utilized as serological biomarkers for treatment response of LN. Birdem Med J 2021; 11(2): 97-102


2015 ◽  
Vol 42 (2) ◽  
pp. 68
Author(s):  
Asmaa Shaaban ◽  
NadiaAbd El-Salam Elkadery ◽  
HebatallahAhmed El-Shamy ◽  
RanaAhmed El-Hilaly ◽  
NesrineAly Mohamed ◽  
...  

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