scholarly journals Serum A08 C1q antibodies are associated with disease activity and prognosis in Chinese patients with lupus nephritis

2016 ◽  
Vol 90 (6) ◽  
pp. 1357-1367 ◽  
Author(s):  
Yun Pang ◽  
Ying Tan ◽  
Yongzhe Li ◽  
Jianchun Zhang ◽  
Yongbing Guo ◽  
...  
2018 ◽  
Vol 15 (1) ◽  
pp. 2-6 ◽  
Author(s):  
Chi Chiu Mok

The Treat-to-Target (T2T) principle has been advocated in a number of inflammatory and non-inflammatory medical illnesses. Tight control of disease activity has been shown to improve the outcome of rheumatoid arthritis and psoriatic arthritis as compared to the conventional approach. However, whether T2T can be applied to patients with lupus nephritis is still under emerging discussion. Treatment of lupus nephritis should target at inducing and maintaining remission of the kidney inflammation so as to preserve renal function and improve survival in the longterm. However, there is no universal agreement on the definition of remission or low disease activity state of nephritis, as well as the time points for switching of therapies. Moreover, despite the availability of objective parameters for monitoring such as proteinuria and urinary sediments, differentiation between ongoing activity and damage in some patients with persistent urinary abnormalities remains difficult without a renal biopsy. A large number of serum and urinary biomarkers have been tested in lupus nephritis but none of them have been validated for routine clinical use. In real life practice, therapeutic options for lupus nephritis are limited. As patients with lupus nephritis are more prone to infective complications, tight disease control with aggressive immunosuppressive therapies may have safety concern. Not until the feasibility, efficacy, safety and cost-effectiveness of T2T in lupus nephritis is confirmed by comparative trials, this approach should not be routinely recommended with the current treatment armamentarium and monitoring regimes.


Lupus ◽  
2016 ◽  
Vol 25 (11) ◽  
pp. 1230-1236 ◽  
Author(s):  
R Gupta ◽  
A Aggarwal ◽  
S Sinha ◽  
L Rajasekhar ◽  
A Yadav ◽  
...  

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 999.1-999
Author(s):  
M. Abreu ◽  
O. Monticielo ◽  
V. Fernandes ◽  
A. Cristovão Maiorano ◽  
F. Dos Santos Beserra ◽  
...  

Background:Lupus nephritis (LN) is one of the most serious organic manifestations of systemic lupus erythematosus (SLE). Ethnicity can contribute to disparities in the prevalence and disease activity of LN.Objectives:To assess the prevalence of LN in Brazilian patients with SLE and to determine factors associated with LN activity across the country.Methods:This cross-sectional study (GSK Study 207353) was carried out through face-to-face interviews and review of medical records (12-month study period). Adult patients with SLE (American College of Rheumatology [ACR] criteria, 1997) were included. Five SLE reference teaching centres were selected: North (NO), Northeast (NE), Midwest (CO), Southeast (SE), and South (SU). Patients with another disease whose morbidity surpassed SLE were excluded. LN was defined as reported in the medical record or history of confirmed renal biopsy; disease activity by pre-defined changes in SLE Disease Activity Index (SLEDAI) or the patient’s kidney disease during the study. Activity was assessed during (T0), 6 months before (T6), and 12 months before (T12) the interview. Systemic Lupus International Collaborating Clinics/ACR Damage Index score mapped damage accrual. Two pairings were performed, aiming to discriminate factors associated with LN and its activity, respectively. Matching technique was used to select similar individuals based on propensity scores, obtained from a logistic regression model. A bootstrapping method explored characteristic variables associated with the risk of progressing to LN.Results:Overall, 300 Brazilian patients with SLE were included in the study. Two groups were paired: LN group (N=150) and non-LN group (N = 141). The prevalence of LN in the paired sample (N=291) was 51.5%, with a disparity between centres (p<0.001; Figure 1A). Most patients were female (LN: 92.7%; non-LN: 94.3%) and the mean (standard deviation [SD]) age for the LN and non-LN groups was 39.46 (11.86) and 43.96 (12.18), respectively. History of serositis was associated with the presence of LN (42 [28.0%] vs 21 [14.9%] non-LN; p=0.010). Type IV histological class predominated in both groups, with no disparity between centres. Social disparities were noted between groups. Non-active workers prevailed among the LN group (115 [76.7%] vs 98 [69.5%] for non-LN, p=0.024).When pairing for disease activity at T12, 73 (50.3%) patients with LN (N=145) had active disease. There was regional disparity in terms of disease activity (Figure 1B), with a predominance of active LN in the NO (28 [68.3%]) and SU (16 [55.2%], p=0.026). Type IV histological class was the component most associated with active LN (active: 32 [43.8%]; non-active: 11 [15.3%], p<0.001). Variation in SLEDAI during the study period discriminated between active and non-active LN. The mean (SD) SLEDAI score at T12 was substantially higher in those with active LN compared with non-active LN (7.18 [4.83] vs 2.47 [4.63], p<0.001). As for the pattern of care, corticosteroids users prevailed in those with active LN (62 [84.9%] vs 45 [62.5%] for non-active LN, p=0.004). There was no disparity in the use of immunosuppressants, with the exception of cyclophosphamide use, noted among 16 (21.9%) patients with active LN and 6 (8.3%) patients with non-active LN (p=0.041). Psychotropic or anticonvulsant use was higher in patients with non-active LN (32 [44.4%] vs 17 [23.3%] patients with active LN, p=0.012). Consultation with a neurologist was verified in 15 (20.8%) patients with non-active LN and 6 (8.2%) with active LN (p=0.055). Hospitalisation occurred in 17 patients with non-active (23.6%) and active (23.3%) LN.Conclusion:Disparities in the prevalence of LN and its activity were evident between the regions across Brazil, highlighting differences in clinical factors, regional factors, and patterns of care.Funding:GSKFigure 1.Prevalence of A) LN among regional centres, comparing them to disease activity profile and prescriptive practice, and B) Active and non-active LN according to prescriptive practiceCQ, chloroquine; HCQ, hydroxychloroquine*At T12Acknowledgements:Medical writing assistance was provided by Helen Taylor, Fishawack Indicia Ltd., UK, part of Fishawack Health, and was funded by GSK.Disclosure of Interests:Mirhelen Abreu Grant/research support from: GSK, Amgen, Biogen, Libbs, Odirlei Monticielo Speakers bureau: GSK, AbbVie, UCB, Roche, Novartis, Consultant of: GSK, AbbVie, Janssen, Vander Fernandes Speakers bureau: Janssen, Novartis, Roche, AbbVie, Pfizer, Grant/research support from: Novartis, GSK, Pfizer, Alexandre Cristovão Maiorano: None declared, Fernando dos Santos Beserra: None declared, Flavia Lamarao Employee of: GSK, Nathalie David Shareholder of: GSK, Employee of: GSK, Bruna de Veras Employee of: GSK, Blanca Bica: None declared, Domingos Sávio Nunes de Lima Grant/research support from: GSK, Marta Maria das Chagas Medeiros: None declared


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 346.2-347
Author(s):  
G. Silverman ◽  
D. Azzouz ◽  
Z. Chen ◽  
J. Deng ◽  
Z. Li ◽  
...  

Background:From a cross-sectional cohort, we have identified a candidate human gut anaerobic pathobiont,Ruminococcus gnavus(RG) of the familyLachnospiraceaethat was linked to active Lupus nephritis (LN)(1). Based on 16S rRNA amplicon analysis, LN patients displayed increased fecal RG abundance, concordant with serum IgG anti-RG antibody responses that appeared intertwined with anti-dsDNA responses implicated in renal pathogenesis. Indeed, monocolonization of germ-free mice is reported to result in generalized inflammation and expansions of Th17 cells. However, RG at low levels are also prevalent in healthy adults, and the temporal dynamics of RG representation within Lupus microbiota ecosystems have not been investigated. Also, genomic sequences of few RG strains have been reported, and these vary greatly in genome structure, gene representation and sequence, which may have broad implications for adaptation to a host with systemic inflammation and/or factors that contribute to immune activation in a susceptible host.Objectives:To investigate the relationships betweenin vivoRG expansions and disease activity that often wax and wane overtime, we initiated longitudinal studies in Lupus patients and controls. As representation of RG strains alone might alter pathogenic potential, we also sought to characterize RG strains from active LN patients.Methods:From our cohort, patients were characterized for demographics, clinical disease activity, and serologies including standard autoantibody and complement levels, and anti-bacterial responses of interest. High throughput 16S rRNA amplicon libraries from fecal samples were analyzed using QIIME 2 and DADA2 (1). Also, individual RG colonies were isolated and subjected to whole genome sequencing. Species and strains were then assigned in part based on multi-locus sequence typing and reference guided genomic assemblies.Results:16S rRNA analysis of 34 samples, at 2-4 timepoints from 14 SLE patients, documented highly conserved patterns of gut community representation overtime in 10/14 patients, based in part on unsupervised hierarchical cluster analysis. Notably, independent of vacillations in clinical disease activity of up to 8 SLEDAI points, conserved microbiome phylogenetic abundance/composition was documented at a family level, and the level of amplicon sequence variants that approximate identification of individual species. In pilot studies, from two active lupus nephritis patients hundreds of fecal bacterial colonies were isolated, with initial assignments by 16S rRNA sequence. From highly redundant whole genome sequence analysis, these Lupus-patient fecal colonies were found to distribute into only four distinct RG strains, which differed from reported strains.Conclusion:Our findings suggest that many Lupus patients have little or no detectable perturbations in representation of theLachnospiraceaefamily or abundance of RG species overtime. Moreover, this seeming microbiota stability was documented even in patients with dramatic changes in disease activity. However, these approaches are inadequate to detect shifts between RG strains. In pilot studies we have isolated and characterized the genomes of four unique RG strains from active LN patients, which include variations in gene content and sequence that may have implications for the host-commensal relationship and immune activation. Broadening of these studies to larger number of SLE patients and healthy subjects, with metagenomic surveys of strain representation in genomic shotgun libraries are currently in progress, in coordination with murine colonization testing for immune modulatory properties of individual strains.References:[1]Azzouzet al.Ann Rheum Dis2019 78(7):947-56Disclosure of Interests: :Gregg Silverman Consultant of: Work with industry is unrelated to the topic in this abstract, Doua Azzouz: None declared, Ze Chen: None declared, Jing Deng: None declared, Zhi Li: None declared, David Fenyo: None declared, Alexander Alekseyenko: None declared


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1496.3-1496
Author(s):  
R. Wakiya ◽  
K. Ueeda ◽  
H. Shimada ◽  
S. Nakashima ◽  
M. Mahmoud Fahmy Mansour ◽  
...  

Background:Systemic lupus erythematosus(SLE) patients, especially patients with lupus nephritis have poor vascular endothelial function and increased cardiovascular(CV) mortality.Meanwhile, several studies showed hydroxychloroquine(HCQ) has effect on reduction in lipids and thrombosis(1), but the mechanism is unclear.Objectives:We examined effect of HCQ on adipocytokine expression in SLE patients.Methods:52 SLE patients with low disease activity started with HCQ were analyzed before and 3 months after HCQ treatment. 21 SLE patients has past history of lupus nephritis. Serum S100 proteins and adipocytokines were measured by ELISA, and serum inflammatory ctytokine levels were evaluated by Multiplex assay (TNF-α, IL-6, VEGF-A).Results:Serum adiponectin level was increased significantly 3 months after HCQ treatment compared with those at baseline (mean change 1.35, Figure 1). SLE patients who achieved LLDAS had a greater increase than those who did not. Additionally, the changes of serum adiponectin levels were associated with those of TNF-α, IL-6, VEGF-A and S100A9 protein, which plays an important role of SLE pathogenesis.Figure 1.Serum adiponectin levels at baseline were compared with levels after 3 months of HCQ treatment. Serum adiponectin levels significantly decreasing during HCQ treatment in SLE patients. For statistical analyses *p<0.0001,Pvalue: Wilcoxon signed-rank testConclusion:A HCQ could reduce the risk factors for atherosclerosis along with control of SLE disease activity.References:[1]Wallace DJ, et al. Cholesterol-lowering effect of hydroxychloroquine in patients with rheumatic disease: reversal of deleterious effects of steroids on lipids. Am J Med. 1990; 89: 322-6.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.


2001 ◽  
Vol 59 (4) ◽  
pp. 1520-1528 ◽  
Author(s):  
Angela Yee Moon Wang ◽  
Peter Poon ◽  
Fernand Macmound Lai ◽  
Lymee Yu ◽  
Paul Cheung Lung Choi ◽  
...  

2011 ◽  
Vol 38 (11) ◽  
pp. 2301-2308 ◽  
Author(s):  
YING-QIAN MO ◽  
LIE DAI ◽  
DONG-HUI ZHENG ◽  
LANG-JING ZHU ◽  
XIU-NING WEI ◽  
...  

Objective.The efficacy of B cell depletion in the treatment of patients with rheumatoid arthritis (RA) has revitalized interest in the pathogenic role(s) of B cells in RA. We evaluated the distribution of synovial B lineage cells and their correlation with histologic disease activity and joint destruction in RA.Methods.Synovial tissue samples were obtained by closed-needle biopsy from 69 Chinese patients with active RA, from 14 patients with osteoarthritis (OA), and from 15 with orthopedic arthropathies (OrthA) as disease controls. Serial tissue sections were stained immunohistochemically for CD79a (pro-B cell to plasma cell), CD20 (B cells), CD38 (plasma cells), CD21 (follicular dendritic cells), CD68 (macrophages), CD3 (T cells), and CD34 (endothelial cells). Densities of positive-staining cells were determined and correlated with histologic disease activity (Krenn 3-component synovitis score) and radiographic joint destruction (Sharp score).Results.Mean sublining CD79a-positive cell density was significantly higher in RA than in OA (p <0.001) or OrthA (p = 0.003). Receiver operating characteristic curve analysis showed that CD79a-positive cell density differentiated RA well from OA [area under the curve (AUC) = 0.79] or OrthA (AUC = 0.75). Spearman’s rank order correlation showed significant correlations between sublining CD79a-positive cell density and the synovitis score (r = 0.714, p < 0.001), total Sharp score (r = 0.490, p < 0.001), and the erosion subscore (r = 0.545, p < 0.001), as well as the joint space narrowing subscore (r = 0.468, p = 0.001) in RA.Conclusion.Synovial CD79a-positive B cells may be a helpful biomarker for histologic disease activity in RA and may be involved in the pathogenesis of joint destruction in RA.


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