Cross-sectional study of plasma Axl, ferritin, IGFBP4 and sTNFR2 as biomarkers of disease activity in childhood-onset SLE: A study of the Pediatric Nephrology Research Consortium

Objective To evaluate the performance of 4 plasma protein markers for detecting disease activity in childhood-onset systemic lupus erythematosus (SLE) patients. Methods Eighty-three consecutive pediatric patients fulfilling ≥4 ACR criteria for SLE and twenty-five healthy controls were prospectively recruited for serological testing of 4 protein markers identified by antibody-coated microarray screen, namely Axl, ferritin, IGFBP4 and sTNFR2. SLE disease activity was assessed using SLEDAI-2000 score. Fifty-seven patients had clinically active SLE (SLEDAI score ≥4, or having a flare). Results The plasma concentrations of Axl and ferritin were significantly higher in patients with active SLE than inactive SLE. Plasma Axl levels were significantly higher in active renal versus active non-renal SLE patients. Levels of Axl, ferritin and IGFBP4 correlated significantly with SLEDAI scores. Levels of Axl, IFGBP4 and sTNFR2 inversely correlated with plasma complement C3 levels. Only plasma Axl and ferritin levels correlated with degree of proteinuria. These markers were more specific, but less sensitive, in detecting concurrent SLE activity than elevated anti-dsDNA antibody titer or decreased C3. Ferritin and IGFBP4 levels were more specific for concurrent active lupus nephritis than anti-dsDNA or C3. Plasma ferritin was the best monitor of global SLE activity, followed by C3 then Axl, while both Axl and C3 were best monitors of clinical lupus nephritis activity. Conclusion In childhood-onset SLE patients, plasma ferritin and Axl perform better than traditional yardsticks in identifying disease activity, either global or renal. The performance of these plasma markers should be explored further in longitudinal cohorts of SLE patients.

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Galectin-9 is an easy to measure biomarker for the interferon signature in systemic lupus erythematosus and antiphospholipid syndrome

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2018-213497 ◽

2018 ◽

Vol 77 (12) ◽

pp. 1810-1814 ◽

Cited By ~ 20

Author(s):

Lucas L van den Hoogen ◽

Joël A G van Roon ◽

Jorre S Mertens ◽

Judith Wienke ◽

Ana Pinheiro Lopes ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Antiphospholipid Syndrome ◽

Lupus Erythematosus ◽

Area Under The Curve ◽

Serum Levels ◽

Complement C3 ◽

Tumour Necrosis Factor Receptor ◽

Systemic Lupus ◽

Dsdna Antibody

ObjectiveThe interferon (IFN) signature is related to disease activity and vascular disease in systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) and represents a promising therapeutic target. Quantification of the IFN signature is currently performed by gene expression analysis, limiting its current applicability in clinical practice. Therefore, the objective of this study was to establish an easy to measure biomarker for the IFN signature.MethodsSerum levels of galectin-9, CXCL-10 (IP-10) and tumour necrosis factor receptor type II (TNF-RII) were measured in patients with SLE, SLE+APS and primary APS (PAPS) and healthy controls (n=148) after an initial screening of serum analytes in a smaller cohort (n=43). Analytes were correlated to measures of disease activity and the IFN signature. The performance of galectin-9, CXCL-10 and TNF-RII as biomarkers to detect the IFN signature was assessed by receiver operating characteristic curves.ResultsGalectin-9, CXCL-10 and TNF-RII were elevated in patients with SLE, SLE+APS and PAPS (p<0.05) and correlated with disease activity and tissue factor expression. Galectin-9 correlated stronger than CXCL-10 or TNF-RII with the IFN score (r=0.70, p<0.001) and was superior to CXCL-10 or TNF-RII in detecting the IFN signature (area under the curve (AUC) 0.86). Importantly, in patients with SLE(±APS), galectin-9 was also superior to anti-dsDNA antibody (AUC 0.70), or complement C3 (AUC 0.70) and C4 (AUC 0.78) levels in detecting the IFN signature.ConclusionGalectin-9 is a novel, easy to measure hence clinically applicable biomarker to detect the IFN signature in patients with systemic autoimmune diseases such as SLE and APS.

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Serum complement levels as prognostic marker for monitoring treatment response in lupus nephritis

BIRDEM Medical Journal ◽

10.3329/birdem.v11i2.53129 ◽

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 ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Nephritis ◽

Disease Activity ◽

Treatment Response ◽

Lupus Erythematosus ◽

Treatment Initiation ◽

Complement C3 ◽

P Value ◽

Serum Complement ◽

Systemic Lupus

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

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Soluble TNF-R1, VEGF and other cytokines as markers of disease activity in systemic lupus erythematosus and lupus nephritis

Lupus ◽

10.1177/0961203319845487 ◽

2019 ◽

Vol 28 (6) ◽

pp. 713-721 ◽

Cited By ~ 4

Author(s):

Z Adhya ◽

M El Anbari ◽

S Anwar ◽

A Mortimer ◽

N Marr ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Nephritis ◽

Disease Activity ◽

Lupus Erythematosus ◽

Response To Therapy ◽

Complement C3 ◽

Systemic Lupus ◽

Multiplex Bead ◽

Urine Markers ◽

Serum And Urine

Background Current non-invasive methods of assessing disease activity in systemic lupus erythematosus (SLE) are of limited sensitivity and specificity. Testing includes acute phase markers, autoantibodies and complement levels. Although measurements of dsDNA antibodies and complement C3/C4 levels are routine, they remain of limited value. Improved blood and urine markers may help in early detection of flare, distinction between flare and chronic damage, and monitoring response to therapy. Methods A total of 87 patients with SLE were tested for the following cytokines in serum and urine: monocyte chemoattractant protein 1 (MCP-1), regulated upon activation, normal T cell expressed and secreted (RANTES), soluble tumour necrosis factor receptor 1 (sTNF-R1), interferon-inducible protein 10 (IP-10), monocyte inhibitory protein 1α (MIP-1α) and vascular endothelial growth factor (VEGF). Patients attending the Lupus Unit at St Thomas’ Hospital, London, UK were divided into active lupus nephritis (LN), inactive LN and non-renal SLE groups based on their renal pathology and SLE disease activity index (SLEDAI). Cytokine testing was performed using the FIDIS multiplex bead assay. Results The mean level of serum sTNF-R1 was higher in the active LN group compared with both inactive LN and non-renal SLE groups ( p < 0.001). For urine measurements there were significant differences between active LN and non-renal SLE for VEGF ( p = 0.016), after statistical correction for multiple testing. Both urinary and serum sTNF-R1 and IP-10 levels correlated with SLEDAI scores ( p < 0.001), while serum VEGF correlated weakly with SLEDAI ( p = 0.025). The optimum combination for differentiating active from inactive LN patients was serum VEGF, sTNF-R1, MCP-1 and glomerular filtration rate plus urinary sTNF-R1 and protein-creatinine ratio. Conclusion These results indicate that for active LN, sTNF-R1 could be a useful serum cytokine marker, with potential for VEGF in the urine. This study has confirmed the ability of the multiplex bead technique to detect cytokines in a good analytical range, including very low and high levels, in both serum and urine. Combining serum and urine markers provided additional sensitivity in distinguishing active from inactive LN.

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Urinary C3d is elevated in patients with active Lupus nephritis and a fall in its level after 3 months predicts response at 6 months on follow up

Lupus ◽

10.1177/0961203320950019 ◽

2020 ◽

Vol 29 (13) ◽

pp. 1800-1806

Author(s):

Sujata Ganguly ◽

Sanjukta Majumder ◽

Sandeep Kumar ◽

Ranjan Gupta ◽

Hafis Muhammed ◽

...

Keyword(s):

Lupus Nephritis ◽

Disease Activity ◽

Lupus Erythematosus ◽

Degradation Products ◽

Activity Index ◽

Complement C3 ◽

Induction Treatment ◽

Significant Fall ◽

Active Lupus Nephritis ◽

Active Lupus

Introduction Complement activation is central to the pathogenesis of lupus nephritis (LN). Low serum complement C3 and C4, are traditionally used as markers of lupus disease activity in general and LN in particular. In this study we prospectively measured plasma and urine C3d and C4d, degradation products of C3 and C4 corrected to creatinine in a cohort of biopsy proven LN in a longitudinal fashion for its correlation with disease activity. Methods Twenty eight biopsy proven active lupus nephritis (AN) were recruited along with four inactive nephritis (IN) and 10 healthy controls (HC). Plasma and urine were collected at baseline, prior to induction treatment and 3 months later. Clinical measures of disease activity, Systemic lupus erythematosus disease activity index 2000 (SLEDAI 2K), renal SLEDAI, serum C3, C4 and antibodies to ds DNA, urine protein and creatinine excretion (UP/UC) were collected. Plasma and urine C3d and C4d were measured using ELISA and normalized to spot urine creatinine value. Results Twenty eight AN of median age of 26.5 (20–31.50) years and disease duration of 3 (0.7–5) years were enrolled. The median urinary C3d/creatinine before treatment was 388.20 (48.98–1296) ng/mg which fell significantly to 62.69 (28.04–502.4) ng/mg at 3 months followup (p-0.01). The baseline values for the active renal disease was significantly different from IN group (9.9 (4.5–46.53 ng/mg) p-0.00). Treatment responders (partial and complete) at 6 months showed a significant fall in urinary C3d at 3 months whereas non responders had a non significant change in value. There was a significant correlation of urine C3d/creatinine with SLEDAI2K (r-0.433, p-0.00), renal SLEDAI (r-0.356, p-0.00), UP/UC ratio (r-0.489, p-<0.0001) but no significant correlation with C3 or C4. There was a significant fall in the median values of plasma C3d from 791.1 (516.0.00–1550.43) µg/ml to 338.52 (211.35–525.82) (p-0.00) µg/ml at the end of 3 months. The values showed a significant correlation with SLEDAI 2K, renal SLEDAI, UP/UC along with a significant negative correlation with C3 and C4. Conclusion Urinary C3d/creatinine levels and plasma C3d levels can be used as biomarker of disease activity and treatment response.

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Concomitance of IgM and IgG anti-dsDNA Antibodies Does Not Appear to Associate to Active Lupus Nephritis

The Open Rheumatology Journal ◽

10.2174/1874312901307010101 ◽

2013 ◽

Vol 7 (1) ◽

pp. 101-104 ◽

Cited By ~ 7

Author(s):

Briele Keiserman ◽

Maria Rita Ronchetti ◽

Odirlei Andre Monticielo ◽

Mauro Waldemar Keiserman ◽

Henrique Luiz Staub

Keyword(s):

Lupus Nephritis ◽

Lupus Erythematosus ◽

Cross Sectional Study ◽

Sectional Study ◽

Cross Sectional ◽

Dsdna Antibody ◽

Active Lupus Nephritis ◽

Duration Of Disease ◽

Dsdna Antibodies ◽

Active Lupus

Previous reports proposed that the IgM anti-dsDNA antibody is protective for lupus nephritis. In this cross-sectional study, we aimed to compare clinical features of systemic lupus erythematosus (SLE) patients positive for IgG anti-dsDNA alone with those presenting both IgG and IgM anti-dsDNA. Anti-dsDNA antibodies, urinary examination and complement levels were assessed in the day of appointment. IgG and IgM anti-dsDNA antibodies were detected by indirect immunofluorescence. Fifty-eight SLE patients (93.1% female, 81% European-derived, mean age 42.8±14.7 years, mean duration of disease 10.9±8 years) positive for IgG anti-dsDNA entered the study. Of those, 15 were also positive for the IgM anti-dsDNA isotype. The group with both isotypes showed significant less frequency of active nephritis (sediment changes and proteinuria) when compared to patients with IgG anti-dsDNA alone (6.7% versus 34.9%, p=0.046). These data suggest a nephroprotective role for IgM anti-dsDNA and a distinct biologic behavior for this isotype in SLE.

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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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Four Anti-dsDNA Antibody Assays in Relation to Systemic Lupus Erythematosus Disease Specificity and Activity

The Journal of Rheumatology ◽

10.3899/jrheum.140677 ◽

2015 ◽

Vol 42 (5) ◽

pp. 817-825 ◽

Cited By ~ 29

Author(s):

Helena Enocsson ◽

Christopher Sjöwall ◽

Lina Wirestam ◽

Charlotte Dahle ◽

Alf Kastbom ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Lupus Erythematosus ◽

Good Choice ◽

Systemic Lupus ◽

Cross Sectional ◽

Exact Test ◽

Reference Limit ◽

Specificity And Sensitivity ◽

Dsdna Antibody

Objective.Analysis of antibodies against dsDNA is an important diagnostic tool for systemic lupus erythematosus (SLE), and changes in anti-dsDNA antibody levels are also used to assess disease activity. Herein, 4 assays were compared with regard to SLE specificity, sensitivity, and association with disease activity variables.Methods.Cross-sectional sera from 178 patients with SLE, of which 11 were followed consecutively, from a regional Swedish SLE register were analyzed for immunoglobulin G (IgG) anti-dsDNA by bead-based multiplex assay (FIDIS; Theradig), fluoroenzyme-immunoassay (EliA; Phadia/Thermo Fisher Scientific), Crithidia luciliae immunofluorescence test (CLIFT; ImmunoConcepts), and line blot (EUROLINE; Euroimmun). All patients with SLE fulfilled the 1982 American College of Rheumatology and/or the 2012 Systemic Lupus International Collaborating Clinics (SLICC-12) classification criteria. Healthy individuals (n = 100), patients with rheumatoid arthritis (n = 95), and patients with primary Sjögren syndrome (n = 54) served as controls.Results.CLIFT had the highest SLE specificity (98%) whereas EliA had the highest sensitivity (35%). When cutoff levels for FIDIS, EliA, and EUROLINE were adjusted according to SLICC-12 (i.e., double the reference limit when using ELISA), the specificity and sensitivity of FIDIS was comparable to CLIFT. FIDIS and CLIFT also showed the highest concordance (84%). FIDIS performed best regarding association with disease activity in cross-sectional and consecutive samples. Fisher’s exact test revealed striking differences between methods regarding associations with certain disease phenotypes.Conclusion.CLIFT remains a good choice for diagnostic purposes, but FIDIS performs equally well when the cutoff is adjusted according to SLICC-12. Based on results from cross-sectional and consecutive analyses, FIDIS can also be recommended to monitor disease activity.

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Differences in Rituximab Use Between Pediatric Rheumatologists and Nephrologists for the Treatment of Refractory Lupus Nephritis and Renal Flare in Childhood-Onset Sle

10.21203/rs.3.rs-383675/v1 ◽

2021 ◽

Author(s):

Mileka Gilbert ◽

Beatrice Goilav ◽

Joyce J. Hsu ◽

Paul J. Nietert ◽

Esra Meidan ◽

...

Keyword(s):

Lupus Nephritis ◽

Lupus Erythematosus ◽

Treatment Options ◽

Pediatric Nephrology ◽

Response To Treatment ◽

Induction Treatment ◽

Childhood Onset ◽

Renal Flare ◽

Treatment Plans

Abstract Background: Consensus treatment plans have been developed for induction therapy of newly diagnosed proliferative lupus nephritis (LN) in childhood-onset systemic lupus erythematosus. However, patients who do not respond to initial therapy, or who develop renal flare after remission, warrant escalation of treatment. Our objective was to assess current practices of pediatric nephrologists and rheumatologists in North America in treatment of refractory proliferative LN and flare.Methods: Members of Childhood Arthritis and Rheumatology Research Alliance and the American Society for Pediatric Nephrology were surveyed in November 2015 to assess therapy choices (other than modifying steroid dosing) and level of agreement between rheumatologists and nephrologists for proliferative LN patients. Two cases were presented: 1) refractory disease after induction treatment with corticosteroid and cyclophosphamide and 2) nephritis flare after initial response to treatment. Survey respondents chose treatments for three follow up scenarios for each case that varied by severity of presentation. Treatment options included cyclophosphamide, mycophenolate mofetil, rituximab, and others, alone or in combination.Results: Treatment choices between nephrologists and rheumatologists were highly variable. A majority (>50%) consensus of either nephrologists or rheumatologists on treatment choice was only achieved in two of six total follow up scenarios for refractory LN or flare. Rheumatologists in comparison to nephrologists chose more therapy options that contained rituximab in five of six scenarios. These differences were statistically significant (p < 0.05). Conclusions: Therapy choices for pediatric rheumatologists and nephrologists in the treatment of refractory LN or LN flare were highly variable with rheumatologists more often choosing rituximab. Further investigation is necessary to delineate the reasons behind this finding. This study highlights the importance of collaborative efforts in developing consensus treatment plans for pediatric LN.

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P0352P-SELECTIN BLOCKADE AMELIORATES RENAL HYPOXIA OF LUPUS NEPHRITIS IN MRI/LPR MICE

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0352 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Xiao Li

Keyword(s):

Lupus Nephritis ◽

Normal Saline ◽

Lupus Erythematosus ◽

Periodic Acid ◽

Tubulointerstitial Fibrosis ◽

Complement C3 ◽

Bold Mri ◽

Renal Tubulointerstitial Fibrosis ◽

Dsdna Antibody ◽

Tubulointerstitial Lesions

Abstract Background and Aims Lupus nephritis is one of the most common and severe complications of systemic lupus erythematosus, of which poor prognosis is indicated by aggravated renal hypoxia and tubulointerstitial fibrosis. Cell adhesion molecules play a key role in the progression of lupus nephritis tubulointerstitial lesion, including P-selectin, which mediates the rolling of leukocytes and subsequent adhesion and infiltration and then initiates the inflammatory immune response and ischemia and hypoxia injury. However, the effects and mechanisms of P-selectin in lupus nephritis remain to be investigated, and a noninvasive measurement of lupus nephritis tubulointerstitial hypoxia and fibrosis remains to be explored. Method Thirty-four MRL/lpr mice were randomly divided into the following three groups: MRL/lpr, saline, and anti–P-selectin, which consisted of no treatment, treatment with normal saline, and treatment with anti–P-selectin monoclonal antibody (mAb) from 12 to 16 weeks of age, respectively. Ten male C57BL/6 mice of the same age served as normal controls. Twenty-four-hour urinary protein, urinary albumin–creatinine ratio, and periodic acid–Schiff were used to assess kidney damage; Western blot or immunohistochemical staining of the hypoxia probe HypoxyprobeTM-1, hypoxia-inducible factor 1α (HIF-1α), and CD31 were used to evaluate hypoxia in renal tissue; and NADPH oxidase subunit gp91phox and p22phox were used to examine renal oxidative stress. The correlation between kidney injury and blood oxygen level–dependent magnetic resonance imaging (BOLD-MRI) was calculated to assess the clinical value of BOLD-MRI. Results P-selectin is upregulated in lupus nephritis. Blocking P-selectin with mAb alleviated renal tubulointerstitial fibrosis, renal hypoxia, and peritubular capillary loss, without alteration of the levels of lupus activity indicators, anti-dsDNA antibody, or complement C3. BOLD-MRI showed that the reduced R2* values in the renal cortex and medulla of lupus mice were increased when treated with anti–P-selectin mAb as compared with those treated with normal saline, which were negatively correlated with HypoxyprobeTM-1 hypoxia probe and the expression of HIF-1α. Conclusion Early intervention of lupus nephritis with anti–P-selectin mAb can significantly improve the hypoxic state of the kidney and reduce the severity of tubulointerstitial lesions. BOLD-MRI techniques are noninvasive and can dynamically evaluate the changes in renal lesions and intrarenal oxygenation levels before and after treatment in lupus nephritis.

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