Understanding the dynamics of hydroxychloroquine blood levels in lupus nephritis

Objectives It is unknown if hydroxychloroquine blood level dynamics impact flare rates in lupus nephritis patients. We prospectively evaluated hydroxychloroquine levels to determine which blood-based patterns are more associated with disease activity. Methods In total, 82 lupus nephritis patients under a prescribed hydroxychloroquine dose of 4–5.5 mg/kg actual body weight (maximum 400 mg/day) for ≥3 months were evaluated at baseline and 7 months. Hydroxychloroquine blood levels were determined by liquid chromatography-tandem mass spectrometry. Flare was defined as increase ≥3 in the Systemic Lupus Erythematosus Disease Activity Index 2000 score and/or a change or increase in therapy. Results Overall, 9/82(11%) patients had flares during follow-up and had lower baseline hydroxychloroquine blood levels than those without flares (220.4 (53.5–1471.1) vs. 1006.3 (53.5–2137.8) ng/ml, p = 0.013). The hydroxychloroquine blood level cut-off that best predicted flares was 613.5 ng/ml (odds ratio = 8.67, 95% confidence interval: 1.66–45.18, p = 0.006). For 77 (94%) patients, the 7-month hydroxychloroquine level dynamics was evaluated and revealed: 59/77 (77%) had a persistent pattern of adequate (41/77(53%)) or fluctuating (18/77 (23%)) levels, with a low and comparable risk of flares (2/41 (5%) vs. 1/18 (5%), p = 1.000). The remaining group had persistent low levels (18/77 (23%)) and their flare frequency was significantly higher than the adequate group (5/18 (28%) vs. 2/41 (5%), p = 0.023). The frequencies of adequate/inadequate hydroxychloroquine blood levels in patients were comparable at baseline and 7 months (McNemar’s test, p = 0.480). Conclusion We provide novel evidence that hydroxychloroquine blood-level patterns (persistently low, adequate, or intermittent) have distinct impacts on flare rates in lupus nephritis patients. These findings reinforce the need of routine hydroxychloroquine measurements to maintain the appropriate blood levels.

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Urinary Neutrophil Gelatinase-Associated Lipocalin to Monitor Lupus Nephritis Disease Activity

Biomarker Insights ◽

10.4137/bmi.s27625 ◽

2015 ◽

Vol 10 ◽

pp. BMI.S27625 ◽

Cited By ~ 1

Author(s):

Hani Susianti ◽

Jullyanny W. Wijaya ◽

Ati Rastini ◽

Kusworini Handono ◽

Atma Gunawan ◽

...

Keyword(s):

Lupus Nephritis ◽

Disease Activity ◽

Lupus Erythematosus ◽

Transforming Growth Factor ◽

Activity Index ◽

Disease Activity Index ◽

Transforming Growth Factor Β1 ◽

Sledai Score ◽

Neutrophil Gelatinase Associated Lipocalin ◽

Neutrophil Gelatinase

Background This study was conducted to determine whether there is an association between urinary neutrophil gelatinase-associated lipocalin (uNGAL) and urinary transforming growth factor-β1 (uTGF-β1) with lupus nephritis (LN) disease activity. Methods Urine samples from 18 LN patients were collected every month for six months then examined for uNGAL, uTGF-β1, and renal domain Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score. Results The uNGAL levels were significantly different between active and inactive LN (P < 0.05). uTGF-β1 levels were not different between active and inactive LN (P > 0.05). There was a significant correlation between uNGAL levels and renal domain SLEDAI score (r= 0.417, P < 0.05). There was no correlation between uTGF-β1 levels and renal domain SLEDAI score (r = 0.031, P > 0.05). Conclusion uNGAL is better than uTGF-β1 for differentiation of active and inactive LN. uNGAL can be considered as a biomarker to monitor LN disease activity.

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Intrarenal and Urinary Th9 and Th22 Cytokine Gene Expression in Lupus Nephritis

The Journal of Rheumatology ◽

10.3899/jrheum.140954 ◽

2015 ◽

Vol 42 (7) ◽

pp. 1150-1155 ◽

Cited By ~ 7

Author(s):

Cathy Choi-Wan Luk ◽

Lai-Shan Tam ◽

Bonnie Ching-Ha Kwan ◽

Priscilla Ching-Han Wong ◽

Terry King-Wing Ma ◽

...

Keyword(s):

Lupus Nephritis ◽

Disease Activity ◽

Lupus Erythematosus ◽

Activity Index ◽

Mrna Level ◽

Disease Activity Index ◽

Cytokine Gene Expression ◽

Mrna Levels ◽

Active Lupus Nephritis ◽

Histological Activity

Objective.We studied the urinary sediment mRNA level of Th9- and Th22-related cytokines in patients with systemic lupus erythematosus (SLE).Methods.We quantified urinary mRNA levels of interleukin (IL) 9, IL-10, IL-22, and their corresponding transcription factors in 73 patients with active lupus nephritis, 13 patients with hypertensive nephrosclerosis (HTN), and 25 healthy subjects.Results.There was no detectable IL-9 mRNA in all samples. Patients with proliferative lupus nephritis had significantly lower urinary IL-22 mRNA levels than those with nonproliferative nephritis (2.2 ± 5.4 vs 8.6 ± 20.0 copies, p = 0.019), and urinary IL-22 mRNA level inversely correlated with the histological activity index (r = −0.427, p < 0.0001). In contrast, patients with lupus nephritis had significantly higher urinary IL-10 mRNA levels than patients with HTN (7.8 ± 18.5 vs 1.9 ± 4.0 copies, p = 0.012), and urinary IL-10 mRNA levels correlated with its intrarenal mRNA levels (r = 0.337, p = 0.004) and SLE disease activity index (r = 0.277, p = 0.018). Urinary IL-10 mRNA level was significantly lower among patients who achieved complete remission than those with partial remission or no response (4.1 ± 6.5 vs 14.1 ± 28.0 copies, p = 0.036).Conclusion.Urinary IL-22 mRNA level is decreased in patients with SLE with proliferative nephritis, while urinary IL-10 mRNA levels correlates with its intrarenal mRNA level and disease activity. Urinary IL-10 mRNA levels may also predict treatment response. These results suggest that urinary mRNA levels of IL-10 and IL-22 might be used as biomarkers for assessing disease activity and risk stratification in lupus nephritis.

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Antineutrophil Cytoplasmic Antibody in Lupus Nephritis: Correlation with Clinicopathological Characteristics and Disease Activity

Current Rheumatology Reviews ◽

10.2174/1573397116999201208213422 ◽

2020 ◽

Vol 16 ◽

Author(s):

Dina Said ◽

Nearmeen Mohammed Rashad ◽

Nora Said Abdelrahmanc ◽

Ghada Aboelsaud Dawaa

Keyword(s):

Lupus Nephritis ◽

Disease Activity ◽

Lupus Erythematosus ◽

Activity Index ◽

Rapidly Progressive Glomerulonephritis ◽

Disease Activity Index ◽

Antineutrophil Cytoplasmic Antibody ◽

Systemic Lupus ◽

Cross Sectional ◽

Class Iv

Background:: Lupus nephritis (LN) represents 40%–50% of all systemic lupus erythematosus (SLE) patients, and rapidly progressive glomerulonephritis is associated with significant morbidity and mortality. Antineutrophil cytoplasmic antibody (ANCA) might be involved in the pathogenesis of LN. Objective:: We evaluated the role of myeloperoxidase (MPO)-ANCA, proteinase 3 (PR3)-ANCA, and anti-glomerular basement membrane autoantibodies (anti-GBM autoAb) for the diagnosis of LN. Methods:: In this cross-sectional study, 95 SLE patients were divided into 2 subgroups: LN group (n = 60) and non-LN group (n = 35). For further analysis, we subclassified the LN group into ANCA-positive (n = 16) and ANCA-negative (n = 44) LN patients. The entire Non-LN group was ANCA-negative. The SLE disease activity index (SLEDAI) was reported for each patient. Determination of MPO-ANCA, PR3-ANCA, and anti-GBM autoAb was performed using a novel multiplex bead-based technology in all patients. Data analyses were done using SPSS, version 20. Approval was obtained from the institutional review board of Zagazig University (ZU-IRB#6000). Results:: Of 95 patients with SLE, 16 patients (16.84%) had ANCA-positive LN, all of which were MPO-ANCA. There was a positive correlation between MPO-ANCA and SLEDAI, as well as with class IV LN. Receiver operating characteristic analyses revealed that the sensitivity and specificity of MPO-ANCA were 81.3% and 99.8%, respectively, in discriminating LN from systemic lupus without nephritis. Conclusion:: MPO-ANCA level was significantly correlated with SLEDAI, inflammatory markers, kidney function tests, and LN class IV.

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SLE Plasma Profiling Identifies Unique Signatures of Lupus Nephritis and Discoid Lupus

Scientific Reports ◽

10.1038/s41598-019-50231-y ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 1

Author(s):

Michael A. Smith ◽

Jill Henault ◽

Jodi L. Karnell ◽

Melissa L. Parker ◽

Jeffrey M. Riggs ◽

...

Keyword(s):

Lupus Nephritis ◽

Disease Activity ◽

Lupus Erythematosus ◽

Activity Index ◽

Disease Activity Index ◽

Complement C3 ◽

Type I ◽

Tissue Remodelling ◽

Organ Systems ◽

Organ Specific

Abstract Systemic lupus erythematosus (SLE) impacts multiple organ systems, although the causes of many individual SLE pathologies are poorly understood. This study was designed to elucidate organ-specific inflammation by identifying proteins that correlate with SLE organ involvement and to evaluate established biomarkers of disease activity across a diverse patient cohort. Plasma proteins and autoantibodies were measured across seven SLE manifestations. Comparative analyses between pathologies and correlation with the SLE Disease Activity Index (SLEDAI) were used to identify proteins associated with organ-specific and composite disease activity. Established biomarkers of composite disease activity, SLE-associated antibodies, type I interferon (IFN), and complement C3, correlated with composite SLEDAI, but did not significantly associate with many individual SLE pathologies. Two clusters of proteins were associated with renal disease in lupus nephritis samples. One cluster included markers of infiltrating leukocytes and the second cluster included markers of tissue remodelling. In patients with discoid lupus, a distinct signature consisting of elevated immunoglobulin A autoantibodies and interleukin-23 was observed. Our findings indicate that proteins from blood samples can be used to identify protein signatures that are distinct from established SLE biomarkers and SLEDAI and could be used to conveniently monitor multiple inflammatory pathways present in different organ systems.

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Monocyte Chemoattractant-1 as a Urinary Biomarker for the Diagnosis of Activity of Lupus Nephritis in Brazilian Patients

The Journal of Rheumatology ◽

10.3899/jrheum.110201 ◽

2012 ◽

Vol 39 (10) ◽

pp. 1948-1954 ◽

Cited By ~ 30

Author(s):

RENATA FERREIRA ROSA ◽

KIOKO TAKEI ◽

NAFICE C. ARAÚJO ◽

SÔNIA M.A. LODUCA ◽

JOSÉ C.M. SZAJUBOK ◽

...

Keyword(s):

Lupus Nephritis ◽

Disease Activity ◽

Lupus Erythematosus ◽

Activity Index ◽

Sandwich Elisa ◽

Disease Activity Index ◽

High Specificity ◽

Control Group ◽

Kidney Involvement ◽

Active Lupus Nephritis

Objective.Monocyte chemotactic protein (MCP-1), involved in the pathogenesis of lupus nephritis (LN), has recently been indicated as a new biomarker of kidney activity in systemic lupus erythematosus (SLE). Our aim was to assess urinary MCP-1 (uMCP-1) as a biomarker of renal activity in patients with SLE and to compare it to other disease activity markers, using the ELISA.Methods.Seventy-five female Brazilian patients with SLE and a control group participated in our study. Patients with SLE were distributed among 3 groups according to kidney involvement and classified according to disease activity based on clinical and laboratory measures such as urinary sediment, proteinuria, kidney function, C3, C4, anti-dsDNA, disease activity index, and renal SLE disease activity index. The serum and uMCP-1 concentrations were measured by sandwich ELISA.Results.In the A-LN group (active lupus nephritis: SLE with kidney involvement), the concentration of uMCP-1 was significantly higher than in other groups. A cutoff point was established using the results of the control group to apply this test in the detection of LN. A-LN had a higher frequency of positive results for uMCP-1 in comparison to the other groups (p < 0.001). To detect disease activity in patients with LN, a new cutoff was determined based on the results of patients with SLE with kidney involvement. Setting specificity at 90%, the sensitivity of the test was 50%.Conclusion.The high specificity makes uMCP-1 a useful test as a predictor of kidney activity in SLE, especially when associated to other measures used in clinical practice.

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Assessment of SLEDAI Score in Children with Lupus Nephritis Class III-IV in Vietnam National Children’s Hospital

VNU Journal of Science Medical and Pharmaceutical Sciences ◽

10.25073/2588-1132/vnumps.4238 ◽

2020 ◽

Vol 36 (2) ◽

Author(s):

Duong Thi Thanh Binh ◽

Nguyen Thu Huong ◽

Nguyen Thi Kien ◽

Pham Van Dem ◽

Tran Minh Dien

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Nephritis ◽

Disease Activity ◽

Lupus Erythematosus ◽

Activity Index ◽

Disease Activity Index ◽

Class Iii ◽

Systemic Lupus ◽

Sledai Score ◽

Pediatric Systemic Lupus Erythematosus

This study describes clinical, paraclinical characteristics and treatment response in children with nephritis class II-IV caused by systemic lupus erythematosus and validates SLEDAI for the evaluation of disease activity and the appropriate treatment strategy. A cross-sectional descriptive study was carried out on 40 children, 37 girls (92%) and 3 boys (8%), with an average age of 11.7 years with lupus nephritis class III- IV in Vietnam National Children’s Hospital in 2019. The study results show that the average score of SLEDAI in the children with pericardial and pleural effusions was 20.94 ± 4.09; high blood pressure, 20.89 ± 4.23; and gross hematuria, 20.29 ± 5.03, which were higher than those in children without these manifestations with p< 0.05. The most common kidney manifestations were nephrotic-range nephritis with renal failure (40%) and Glomerulonephritis (35%), corresponding to an average SLEDAI score of 24.25 ± 5.52 and 24.33 ± 3.2, respectively (p = 0.001). SLEDAI had an inverse correlation with the C3 complement value (r -0.315, p <0.05). The average SLEDAI score decreased gradually from 18.75 ± 4.22 to 3.38 ± 3.95 points (p <0.001) after 12 months of treatment. The study concludes that SLEDAI score was higher in patients with pleural and/or pericardial effusions, hypertension and gross hematuria, nephrotic-range nephritis with kidney failure or glomerulonephritis. SLEDAI score corresponded with the C3 complement value and the average SLEDAI score decreased gradually with treatment. Keywords: Lupus Nephritis class III- IV, SLEDAI. References [1] George Bertsias, Ricard Cervera và Dimitrios T Boumpas, Systemic Lupus Erythematosus: Pathogenesis and Clinical Features<sample chapter 20_mod 17_Systemic Lupus nephritis 2012.pdf> (2012), EULAR Textbook on Rheumatic Diseases, EULAR, 476-505.[2] D.M. Levy and S. Kamphuis, Systemic lupus erythematosus in children and adolescents. Pediatr Clin North Am59(2) (2012)345-64.[3] Thai Thien Nam, 2018, Lupus in National Children,s Hospital, [4] C.Bombardier, M.B. Hurwitz et al, Derivation of the SLEDAI: A disease activity index for lupus patients. The committee on prognosis studies in SLE, Arthritis Rheum 35(6) (1992) 630-640.[5] R. Shamim, S. Farman, S. Batool et al, Association of systemic lupus erythematosus disease activity index score with clinical and laboratory parameters in pediatric onset systemic lupus erythematosus. Pak J Med Sci. 36(3) (2020) 467-472.[6] Le Thuy Hang, Assesment of SLEDAI score and panthology in children with lupus nephritis, 2016, Pediatrician thesis, Hanoi Medical University.[7] S.K.S.M. Nazri, K.K. Wong and W.Z.W.A. Hamid, Pediatric systemic lupus erythematosus. Retrospective analysis of clinico-laboratory parameters and their association with Systemic Lupus Erythematosus Disease Activity Index score, Saudi Med J. 39(6) (2018) 627-631. [8] Nguyen Thuy Duong, clinical, paraclinical and pathology characteristics in children with nephritis caused by systemic lupus erythematosus, 2011, Master thesis, Hanoi Medical University.[9] S.N. Wong, W.K. Chan, J.Hui et al, Membranous lupus nephritis in Chinese children--a case series and review of the literature. Pediatr Nephrol, 24(10)(2009) 1989-1996.[10] N.T.N. Dung, H.T. Loan, S. Nielsen et al, Juvenile systemic lupus erythematosus onset patterns in Vietnamese children: a descriptive study of 45 children. Pediatric Rheumatology Online Journal, 10 (2010) 38-48.[11] T. Pusongchai, J. Jungthirapanich, S. Khositseth, Pediatric Systemic Lupus Erythematosus in Thammasat University Hospital, J Med Assoc Thai. 93(12) (2010) 283-290.

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Susceptibility of BAFF-var allele carriers to severe SLE with occurrence of lupus nephritis

10.21203/rs.2.13758/v3 ◽

2019 ◽

Author(s):

Justa Friebus-Kardash ◽

Marten Trendelenburg ◽

Ute Eisenberger ◽

Camillo Ribi ◽

Carlo Chizzolini ◽

...

Keyword(s):

Lupus Nephritis ◽

Disease Activity ◽

Lupus Erythematosus ◽

Activity Index ◽

Immunosuppressive Agents ◽

Disease Activity Index ◽

University Hospital ◽

Study Entry ◽

Organ Manifestations ◽

The University

Abstract Background: Dysregulation of the B-cell activating factor (BAFF) system is involved in the pathogenesis of systemic lupus erythematosus (SLE). Increased serum concentrations of BAFF are related to lupus nephritis and disease activity among SLE patients. Recently, a variant of the BAFF-encoding gene, BAFF-var, was identified to be associated with autoimmune diseases, in particular SLE, and to promote the production of soluble BAFF. The present study aimed to assess the prevalence of BAFF-var in a cohort of 195 SLE patients and to analyze the association of the BAFF-var genotype (TNSF13B) with various manifestations of SLE. Methods: A cohort of 195 SLE patients from Central Europe, including 153 patients from the Swiss SLE Cohort Study and 42 patients from the University Hospital Essen, Germany, underwent genotyping for detection of BAFF-var allele. Results: Of the 195 patients, 18 (9.2%) tested positive for BAFF-var variant according to the minor allele frequency of 4.6%. The presence of BAFF-var was associated with the occurrence of lupus nephritis (p=0.038) (p=0.03 and p=0.003). Among various organ manifestations of SLE, the presence of BAFF-var was associated with the occurrence of lupus nephritis (p=0.038; odds ratio [OR], 2.4; 95% confidence interval [CI], 0.89-6.34) and renal activity markers such as proteinuria and hematuria (p=0.03; OR, 2.4; 95% CI, 0.9-6.4 for proteinuria; p=0.003; OR, 3.9; 95% CI, 1.43-10.76 for hematuria). SLE patients carrying the BAFF-var allele exhibited increased disease activity at study entry, as determined by the physician's global assessment (PGA: p=0.002; OR, 4.8; 95% CI, 1.54-14.93) and the SLE Disease Activity Index (p=0.012; OR, 3.5; 95% CI, 1.12-11.18). Consistent with that, the percentage of patients treated with immunosuppressive agents at study entry was higher among those carrying the BAFF-var allele than among those tested negative for BAFF-var (p=0.006; OR, 3.7; 95% CI, 1.27-10.84). Conclusions: Our results indicate an association between the BAFF-var genotype and increased severity of SLE. Determining the BAFF-var status of SLE patients may improve the risk stratification of patients for whom the development of lupus nephritis is more likely and thus may be helpful in the follow-up care and treatment of SLE patients.

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Anti-dsDNA, anti-nucleosome and anti-C1q antibodies as disease activity markers in patients with systemic lupus erythematosus

Srpski arhiv za celokupno lekarstvo ◽

10.2298/sarh1408431z ◽

2014 ◽

Vol 142 (7-8) ◽

pp. 431-436 ◽

Cited By ~ 10

Author(s):

Valentina Zivkovic ◽

Aleksandra Stankovic ◽

Tatjana Cvetkovic ◽

Branka Mitic ◽

Svetislav Kostic ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Nephritis ◽

Disease Activity ◽

Lupus Erythematosus ◽

Activity Index ◽

Disease Activity Index ◽

Clinical Activity ◽

Systemic Lupus ◽

Active Lupus Nephritis ◽

Sensitivity Specificity

Introduction. In spite of the growing number of reports on the study of anti-nucleosome and anti-C1q antibodies, there are still controversies on their significance as disease activity markers in patients with systemic lupus erythematosus (SLE) and their use in everyday clinical practice. Objective. Our aim was to assess the presence of anti-dsDNA, anti-nucleosome and anti-C1q antibodies in SLE patients, as well as to establish their sensitivity, specificity, positive and negative predictive value, and their correlation with SLE and lupus nephritis clinical activity. Methods. The study enrolled 85 patients aged 45.3?9.7 years on the average, with SLE of average duration 10.37?7.99 years, hospitalized at the Institute ?Niska Banja? during 2011, and 30 healthy individuals as controls. Disease activity was assessed using Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). In all examinees the levels of anti-dsDNA, anti-nucleosome and anti-C1q antibodies were measured using the ELISA method with Alegria Test Strips Orgentec (Germany). Results. Patients with active lupus nephritis had a higher presence of anti-C1q antibodies and higher co-positivity of anti-dsDNA, anti-nucleosome, and anti-C1q antibodies compared to those with inactive lupus nephritis (77.77% vs. 21.74%; p<0.01). SLE patients with SLEDAI ?11 had a higher presence of antinucleosome (93.75% vs. 64.15%; p<0.01) and anti-C1q antibodies (46.87% vs. 22.64%; p<0.05), as well as a higher mean level of anti-nucleosome antibodies (107.79?83.46 U/ml vs. 57.81?63.15 U/ml; p<0.05), compared to those with SLEDAI of 0-10. There was a positive correlation between the SLEDAI and the level of anti-dsDNA (r=0.290; p<0.01), anti-nucleosome (r=0.443; p<0.001), and anti-C1q antibodies (r=0.382; p<0.001). Only anti-C1q antibodies demonstrated correlation with proteinuria (r=0.445; p<0.001). Conclusion. Anti-nucleosome and anti-C1q antibodies demonstrated association with SLE and lupus nephritis activity, suggesting their potential usefulness in making predictions about lupus nephritis and assessment of disease activity.

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Susceptibility of BAFF-var allele carriers to severe SLE with occurrence of lupus nephritis

10.21203/rs.2.13758/v1 ◽

2019 ◽

Author(s):

Justa Friebus-Kardash ◽

Marten Trendelenburg ◽

Ute Eisenberger ◽

Camillo Ribi ◽

Carlo Chizzolini ◽

...

Keyword(s):

Lupus Nephritis ◽

Disease Activity ◽

Lupus Erythematosus ◽

Activity Index ◽

Immunosuppressive Agents ◽

Disease Activity Index ◽

University Hospital ◽

Study Entry ◽

Organ Manifestations ◽

The University

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Lupus nephritis is linked to disease-activity associated expansions and immunity to a gut commensal

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2018-214856 ◽

2019 ◽

Vol 78 (7) ◽

pp. 947-956 ◽

Cited By ~ 59

Author(s):

Doua Azzouz ◽

Aidana Omarbekova ◽

Adriana Heguy ◽

Dominik Schwudke ◽

Nicolas Gisch ◽

...

Keyword(s):

Lupus Nephritis ◽

Disease Activity ◽

Lupus Erythematosus ◽

Activity Index ◽

Disease Activity Index ◽

Structural Features ◽

Class Iii ◽

Discovery Cohort ◽

Cross Sectional ◽

Faecal Samples

Background/PurposeTo search for a transmissible agent involved in lupus pathogenesis, we investigated the faecal microbiota of patients with systemic lupus erythematosus (SLE) for candidate pathobiont(s) and evaluated them for special relationships with host immunity.MethodsIn a cross-sectional discovery cohort, matched blood and faecal samples from 61 female patients with SLE were obtained. Faecal 16 S rRNA analyses were performed, and sera profiled for antibacterial and autoantibody responses, with findings validated in two independent lupus cohorts.ResultsCompared with controls, the microbiome in patients with SLE showed decreased species richness diversity, with reductions in taxonomic complexity most pronounced in those with high SLE disease activity index (SLEDAI). Notably, patients with SLE had an overall 5-fold greater representation of Ruminococcus gnavus (RG) of the Lachnospiraceae family, and individual communities also displayed reciprocal contractions of a species with putative protective properties. Gut RG abundance correlated with serum antibodies to only 1/8 RG strains tested. Anti-RG antibodies correlated directly with SLEDAI score and antinative DNA levels, but inversely with C3 and C4. These antibodies were primarily against antigen(s) in an RG strain-restricted pool of cell wall lipoglycans. Novel structural features of these purified lipoglycans were characterised by mass spectrometry and NMR. Highest levels of serum anti-RG strain-restricted antibodies were detected in those with active nephritis (including Class III and IV) in the discovery cohort, with findings validated in two independent cohorts.ConclusionThese findings suggest a novel paradigm in which specific strains of a gut commensal may contribute to the immune pathogenesis of lupus nephritis.

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