Neutrophil extracellular traps are a source of extracellular HMGB1 in lupus nephritis: associations with clinical and histopathological features

Objective This study aimed to analyze the expression of the high mobility group box-1 (HMGB1) protein in neutrophil extracellular traps (NETs) of patients with lupus nephritis (LN) and its association with clinical and histopathological features of the disease. Methods Twenty-three patients with biopsy-confirmed LN and 14 systemic lupus erythematosus (SLE) patients with active disease (SLE Disease Activity Index (SLEDAI) score ≥ 6) and no evidence of LN were included. Clinical and laboratory features were recorded. NETs and the expression of HMGB1 were assessed by confocal microscopy, and serum HMGB1 levels were measured by ELISA. Results In comparison to patients without kidney disease, patients with LN had a higher expression of HMGB1 in spontaneous (57 vs. 30.4; p = 0.027) and lipopolysaccharide (LPS)-induced (55.8 vs. 24.9; p = 0.005) NETs. We found a positive correlation between serum HMGB1 and the expression of HMGB1 in LPS-induced NETs ( r = 0.447, p = 0.017). The expression of HMGB1 in spontaneous NETs correlated with SLEDAI score ( r = 0.514, p = 0.001), anti-dsDNA antibodies ( r = 0.467, p = 0.004), the rate of glomerular filtration descent ( r = 0.543, p = 0.001), and diverse histopathological components of active nephritis in the kidney biopsy, such as the activity index ( r = 0.581, p = 0.004), fibrinoid necrosis ( r = 0.603, p = 0.002), and cellular crescents ( r = 0.486, p = 0.019). Conclusions In patients with SLE, NETs are a source of extracellular HMGB1. The expression of HMGB1 in NETs is higher among patients with LN, which correlates with clinical and histopathological features of active nephritis and suggest a possible role of this alarmin in the pathophysiology of kidney damage in SLE.

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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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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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Therapeutic potential of allogeneic mesenchymal stromal cells transplantation for lupus nephritis

Lupus ◽

10.1177/0961203318804922 ◽

2018 ◽

Vol 27 (13) ◽

pp. 2161-2165 ◽

Cited By ~ 13

Author(s):

J Barbado ◽

S Tabera ◽

A Sánchez ◽

J García-Sancho

Keyword(s):

Lupus Nephritis ◽

Mesenchymal Stromal Cells ◽

Lupus Erythematosus ◽

Stromal Cells ◽

Therapeutic Potential ◽

Activity Index ◽

Disease Activity Index ◽

Controlled Clinical Trial ◽

Allogeneic Mscs

Animal and human studies have suggested the potential of mesenchymal stromal cells (MSCs) to treat systemic lupus erythematosus (SLE). Here, we present the results of compassionate MSC treatments for three SLE patients to provide the proof of concept for a randomized and controlled clinical trial. Three patients of different ethnicities who suffer from chronic SLE, and who presented with class IV active proliferative nephritis confirmed by biopsy, were treated with allogeneic MSCs from healthy donors. Ninety million cells were infused intravenously into each patient during high and very high activity disease flare-ups and follow-up was continued for 9 months. Multi-organic affectation was quantified by the SLE disease activity index (SLEDAI), and indicators of lupus nephritis activity, such as proteinuria, as well as lymphocyte and monocyte antigens and anti-HLA antibodies were measured at 1, 3, 6, and 9 months after treatment. Proteinuria levels improved dramatically during the 1st month after treatment and the ameliorations were sustained throughout the follow-up period. SLEDAI scores revealed early, durable, and substantial remissions that were complete for two patients and partial for the third patient and that permitted medication doses to be reduced 50–90%. These favourable outcomes support completion of the randomized and controlled MSC trial for SLE.

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HLA-DRB1*04 as a Risk Allele to Systemic Lupus Erythematosus and Lupus Nephritis in the Malay Population of Malaysia

Frontiers in Medicine ◽

10.3389/fmed.2020.598665 ◽

2021 ◽

Vol 7 ◽

Author(s):

Malarvili Selvaraja ◽

Voon Kin Chin ◽

Maha Abdullah ◽

Masita Arip ◽

Syafinaz Amin-Nordin

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Nephritis ◽

Lupus Erythematosus ◽

Activity Index ◽

Disease Activity Index ◽

Systemic Lupus ◽

Mortality And Morbidity ◽

Curative Therapy ◽

Multiple Organs ◽

Increased Risk

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease afflicting multiple organs. Lupus nephritis (LN) is a serious complication of SLE and remains a major cause of mortality and morbidity. Curative therapy remains unavailable as etiology from genetic and environmental factors is still unclear. The present study was conducted to elucidate the link between HLA-DRB1 gene polymorphisms with SLE and LN through clinical and laboratory/biological presentations in a population of Malaysian Malay females with SLE. A total of 100 Malay female SLE patients inclusive of 70 SLE patients without LN and 30 patients with LN were included in this study. HLA-DRB1 allele examination in SLE patients was performed using PCR-SSO, and the alleles' frequencies were compared with 951 publicly available datasets representing Malay healthy controls in Malaysia. Cytokines and free radical levels were detected by ELISA and bead-based multiplexed Luminex assays. The association between HLA-DRB1 alleles with clinical and serological manifestations and immune mediators was analyzed using different statistical approaches whenever applicable. Our study showed that HLA-DRB1*0405, HLA-DRB1*1502, and HLA-DRB1*1602 were associated with the increased risk of SLE while HLA-DRB1*1201 and HLADRB1*1202 alleles were associated with a lower risk of SLE development. Furthermore, HLA-DRB1*04 showed significant association to LN and arthritis while HLA-DRB1*15 was significantly associated with oral ulcer in Malay SLE patients. Association analysis of HLA-DRB1*04 with clinical and biological factors revealed that HLA-DRB1*04 was significantly associated with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores, anti-nuclear antibody (ANA), C-reactive protein (CRP) in the blood, and total protein in the urine. SLE carriers with the HLA-DRB1*04 allele were significantly correlated to the increased levels of cytokines (IFN-y, GM-CSF, IL-17F, IL-18, IL-21, and VEGF) and were significantly showing negative correlation to IL-5 and free radicals (LPO and catalase enzyme) levels compared to SLE carriers without HLA-DRB1*04 allele. The results suggested that disease severity in SLE may be determined by HLA-DRB1 alleles. The risk of HLA-DRB1*04 allele with LN was supported by the demonstration of an intense inflammatory response in Malay SLE patients in Malaysia. More studies inclusive of a larger and multiple SLE cohorts in the future are warranted to validate these findings.

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Η σημασία νεότερων βιολογικών δεικτών στην εκτίμηση της νεφρίτιδας του νεανικού συστηματικού ερυθηματώδους λύκου

10.12681/eadd/40300 ◽

2017 ◽

Author(s):

Άρτεμις-Ωραιάνθη Κουτσονικολή

Keyword(s):

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Lupus Erythematosus ◽

Activity Index ◽

High Mobility ◽

Disease Activity Index ◽

Systemic Lupus Erythematosus Disease ◽

Systemic Lupus ◽

Neutrophil Gelatinase Associated Lipocalin ◽

Neutrophil Gelatinase

Εισαγωγή. Η νεφρίτιδα αποτελεί τον καθοριστικότερο παράγοντα της συνολικής βαρύτητας και πρόγνωσης του παιδιατρικού Συστηματικού Ερυθηματώδους Λύκου (πΣΕΛ). Η ανεύρεση νέων βιολογικών δεικτών, ειδικών για τη νεφρίτιδα του πΣΕΛ, θα επιτρέψει τη μη επεμβατική εκτίμηση της πορείας της και τη στοχευμένη θεραπεία. Τα επιστημονικά δεδομένα για τους παιδιατρικούς ασθενείς, ιδιαιτέρως για ομοιογενείς καυκάσιους πληθυσμούς, είναι ακόμη ελλειπή. Σκοπός. Να διερευνηθεί η σχέση των αντισωμάτων έναντι των νουκλεοσωμάτων (αντι-NCS) ορού, των αντισωμάτων έναντι της βασικής μεμβράνης του σπειράματος (αντι-GBM) ορού, των αντισωμάτων έναντι του παράγοντα C1q του συμπληρώματος (αντι-C1q) ορού, της πρωτεΐνης High-Mobility Group Box-1 (HMGB1) ορού και ούρων και της Neutrophil Gelatinase-Associated Lipocalin (NGAL) ούρων με: (α) την παρουσία νεφρίτιδας στον πΣΕΛ και (β) με την ενεργότητα του πΣΕΛ και της νεφρίτιδας ειδικότερα, σε έναν αμιγώς καυκάσιο πληθυσμό ασθενών από τη βόρεια Ελλάδα. Υλικό-Μέθοδοι. Ελήφθησαν δείγματα ορού και ούρων από 22 ασθενείς με πΣΕΛ και νεφρίτιδα, 20 ασθενείς με πΣΕΛ χωρίς νεφρίτιδα, 15 ασθενείς με νεφρίτιδα άλλης αυτοάνοσης αιτιολογίας (IgA νεφροπάθεια, νεφρίτιδα πορφύρας Henoch-Schönlein, μεταλοιμώδη νεφρίτιδα ή μεμβρανώδη σπειραματονεφρίτιδα) και 26 υγιείς μάρτυρες. Ο προσδιορισμός των βιολογικών δεικτών έγινε με τη μέθοδο ELISA. Η ενεργότητα του πΣΕΛ και της νεφρίτιδας του πΣΕΛ εκτιμήθηκε με το εργαλείο SLEDAI-2K (Systemic Lupus Erythematosus Disease Activity Index-2000). Αποτελέσματα. Α. Βιολογικοί δείκτες ορού. Τα επίπεδα των αντι-NCS, των αντι-GBM, των αντι-C1q και της HMGB1 βρέθηκαν στατιστικώς σημαντικά υψηλότερα στους ασθενείς με νεφρίτιδα του πΣΕΛ συγκριτικά με τους υγιείς μάρτυρες αλλά και συγκριτικά με τους ασθενείς με νεφρίτιδα άλλης αυτοάνοσης αιτιολογίας. Κατά τη σύγκριση των επιπέδων των βιολογικών δεικτών ορού μεταξύ των ασθενών με νεφρίτιδα του πΣΕΛ και των ασθενών με πΣΕΛ χωρίς νεφρίτιδα, τα αντι-NCS, τα αντι-GBM και η HMGB1 παρουσίαζαν στατιστικώς σημαντικά υψηλότερες τιμές στους ασθενείς με νεφρίτιδα, ενώ για τα αντι-C1q δεν παρατηρήθηκαν στατιστικώς σημαντικές διαφορές. Τα επίπεδα της HMGB1 παρουσίασαν υψηλή θετική συσχέτιση με την ενεργότητα της νεφρίτιδας του πΣΕΛ. Τα επίπεδα της HMGB1 και των αντι-C1q παρουσίασαν μέτρια θετική συσχέτιση με την ενεργότητα του πΣΕΛ συνολικά. Β. Βιολογικοί δείκτες ούρων. Τα επίπεδα της NGAL και της HMGB1 ήταν στατιστικώς σημαντικά υψηλότερα στους ασθενείς με νεφρίτιδα του πΣΕΛ συγκριτικά με τους ασθενείς με πΣΕΛ χωρίς νεφρίτιδα. Επιπλέον, τα επίπεδα της NGAL παρουσίασαν μέτρια θετική συσχέτιση και τα επίπεδα της HMGB1 υψηλή θετική συσχέτιση με την ενεργότητα της νεφρίτιδας του πΣΕΛ. Συμπεράσματα. Σε αυτόν τον ομοιογενή πληθυσμό Καυκάσιων ασθενών με πΣΕΛ, τα αντι-NCS, τα αντι-GBM, η HMGB1 ορού και ούρων και η NGAL ούρων προέκυψαν ως πιθανοί χρήσιμοι βιολογικοί δείκτες, ενδεικτικοί της νεφρικής προσβολής. Επιπλέον, τα αντι-NCS, τα αντι-GBM και η HMGB1 ορού δεν φαίνεται να παρουσιάζουν αύξηση σε νεφρίτιδες άλλης αυτοάνοσης αιτιολογίας. Η HMGB1 ορού και ούρων και η NGAL ούρων προέκυψαν ως πιθανοί χρήσιμοι βιολογικοί δείκτες παρακολούθησης της ενεργότητας της νεφρίτιδας του πΣΕΛ. Τα αντι-C1q και η HMGB1 ορού προέκυψαν ως πιθανοί χρήσιμοι βιολογικοί δείκτες παρακολούθησης της ενεργότητας του πΣΕΛ συνολικά.

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Multitarget Therapy: An Effective and Safe Therapeutic Regimen for Lupus Nephritis

Journal of Pharmacy & Pharmaceutical Sciences ◽

10.18433/jpps30526 ◽

2019 ◽

Vol 22 ◽

pp. 365-375

Author(s):

Tianbiao Zhou ◽

Xialan Zhang ◽

Wenshan Lin ◽

Shujun Lin

Keyword(s):

Lupus Nephritis ◽

Lupus Erythematosus ◽

Activity Index ◽

Therapy Group ◽

Meta Analysis ◽

Disease Activity Index ◽

Biomedical Literature ◽

Cochrane Library ◽

Negative Rate ◽

Multitarget Therapy

Introduction: We evaluated the effectiveness and safety of various multitarget therapies for inducing remission in lupus nephritis patients. Methods: Randomized controlled trials (RCT) were identified and extracted from the Embase, PubMed, Chinese Biomedical Literature Database (CBM), and the Cochrane Library until Oct 31, 2018, investigations meeting inclusion criteria were extracted, and data were analyzed by meta-analysis. The total remission (TR; complete to partial remission), complete remission (CR), albumin, proteinuria levels, negative rate of anti-double-stranded DNA antibody (ds-DNA), negative rate of anti-nuclear antibody (ANA), and systemic lupus erythematosus disease activity index (SLE-DAI) were calculated using the software of RevMan 5.3. Results: Eleven RCTs were included and analyzed. The multitarget therapy group exhibited a higher value of CR (OR=3.06, 95%CI: 2.35-3.99, P﹤0.00001) as well as TR (OR=3.83, 95%CI: 2.77-5.31, P﹤0.00001) than those in the cyclophosphamide (CYC) group. In addition, multitarget therapies had more albumin (WMD=3.50, 95%CI: 1.04-5.95, P=0.005), greater albumin increases (OR=1.96, 95%CI: 0.63-3.29, P=0.004) and higher negative rates of ds-DNA (OR=2.13, 95%CI: 1.51-3.01, P﹤0.0001) and ANA (OR=2.82, 95%CI: 1.77-4.50, P﹤0.0001) when compared with the CYC group. This group also had less proteinuria levels (WMD=-0.55, 95%CI: -0.79 to -0.30, P﹤0.0001), lower degrees of SLE-DAI (OR=-1.80, 95%CI:-2.78 to -0.81, P=0.0004), and a lower adverse reaction rate. For example, gastrointestinal syndrome, irregular menstruation and leucopenia happened less frequently in the multitarget therapy group. However, hypertension was more prevalent in the multitarget therapy group. Conclusions: Multitarget therapy is an effective and safe intervention for inducing remission in lupus nephritis patients.

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Interleukin-34 as a marker for subclinical proliferative lupus nephritis

Lupus ◽

10.1177/0961203320914976 ◽

2020 ◽

Vol 29 (6) ◽

pp. 607-616

Author(s):

Asmaa SM Abdel-Rehim ◽

Nesrine A Mohamed ◽

Marwa M Shakweer

Keyword(s):

Lupus Nephritis ◽

Lupus Erythematosus ◽

Activity Index ◽

Renal Involvement ◽

Clinical Manifestations ◽

Surrogate Marker ◽

Disease Activity Index ◽

Class Iii ◽

Group I ◽

Dsdna Antibodies

Background Lupus nephritis (LN) is an ominous manifestation of systemic lupus erythematosus (SLE). Clinical renal affection is present in about 70% of lupus patients, and more patients have histological evidence of renal involvement without clinical manifestations. This study aimed to investigate the potential role of serum interleukin-34 (IL-34) as an early marker for the detection of silent LN. Methods Thirty-three lupus patients with silent LN (group I), 37 patients with clinical LN (group II) and 20 controls were included. The SLE Disease Activity Index (SLEDAI), IL-34, anti-dsDNA antibodies and renal biopsy were assessed in all patients. Results Serum IL-34 levels were significantly higher in all lupus patients compared to healthy controls ( p < 0.001) and showed a significant positive correlation with SLEDAI score. SLE patients with positive anti-dsDNA antibodies had more active disease according to SLEDAI and higher levels of IL-34 than those with negative anti-dsDNA antibodies. In both studied groups, serum IL-34 levels were significantly higher in patients with proliferative LN (class III and class IV) than those with non-proliferative lupus (class II and class V) and controls. Yet, in both groups, IL-34 was not useful in differentiating active from chronic renal affection. Conclusion In lupus patients with insignificant proteinuria, serum levels of IL-34 distinguished the different histological classes of subclinical LN. Serum IL-34 may be used as a surrogate marker for early renal affection in silent LN, especially the proliferative type.

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Systemic erythematosus lupus and pregnancy outcomes in a Colombian cohort

Lupus ◽

10.1177/09612033211061478 ◽

2021 ◽

pp. 096120332110614

Author(s):

Valeria Erazo-Martínez ◽

Ivana Nieto-Aristizábal ◽

Isabella Ojeda ◽

Michelle González ◽

Cristian C Aragon ◽

...

Keyword(s):

Lupus Nephritis ◽

Pregnant Women ◽

Lupus Erythematosus ◽

Preterm Labor ◽

Activity Index ◽

Perinatal Outcomes ◽

Disease Activity Index ◽

Obstetric Outcomes ◽

Maternal Complications ◽

Fetal Survival

Objective Pregnant women with SLE have higher probabilities of maternal complications. SLE during pregnancy has alternating patterns of remission and flare-ups; however, most pregnant SLE patients tend to worsen with associated poor obstetric and perinatal outcomes. This study aimed to describe obstetric outcomes in pregnant women with SLE. Methods This retrospective study was performed between 2011 and 2020 at a highly complex referral health center in Cali, Colombia. Pregnant women with a diagnosis of SLE were included. Demographic, clinical, and laboratory features and obstetric and fetal outcomes, including intensive care unit (ICU) characteristics, were evaluated. Results Forty-eight pregnant women with SLE were included. The median age was 29 (25–33.7) years. The SLE diagnosis was made before pregnancy in 38 (79.1%) patients, with a median disease duration of 46 (12–84) months. Thirteen (27.1%) patients had lupus nephritis. Preterm labor (34, 70.8%), preeclampsia (25, 52%), and preterm rupture of membranes (10, 20.8%) were the most common obstetric complications. A relationship between a greater systemic lupus erythematosus pregnancy disease activity index (SLEPDAI) and the development of hypertensive disorders during pregnancy was established (preeclampsia = p < 0.0366; eclampsia = p < 0.0153). A relationship was identified between lupus nephritis (LN) and eclampsia ( p < 0.01), preterm labor ( p < 0.045), and placental abruption ( p < 0.01). Seventeen (35.4%) patients required ICU admission; 52.9% of them were due to AID activity, 17.6% for cardiovascular damage, 11.7% for septic shock, and 5.8% for acute kidney failure. Fetal survival was 89.5% ( N = 43/48). Among the live births, two (4.2%) newborns were diagnosed with neonatal lupus, and two (4.2%) were diagnosed with congenital heart block. One maternal death was registered due to preeclampsia and intraventricular hemorrhage. Conclusions This study is the first to describe SLE during pregnancy in Colombia. SLE was the most prevalent AID in this cohort, and complications included preterm labor, preeclampsia, and postpartum hemorrhage. A higher SLEPDAI and lupus nephritis predicted adverse maternal outcomes.

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Role of micro-RNA132 and its long non coding SOX2 in diagnosis of lupus nephritis

Lupus ◽

10.1177/09612033211067166 ◽

2022 ◽

pp. 096120332110671

Author(s):

Rasha F Ahmed ◽

Olfat Gamil Shaker ◽

Hend M abdelghany ◽

Nilly Helmy Abdallah ◽

Samar Hisham Elsayed ◽

...

Keyword(s):

Lupus Nephritis ◽

Lupus Erythematosus ◽

Molecular Mechanisms ◽

Activity Index ◽

Disease Activity Index ◽

Clinical Indicators ◽

Sox2 Expression ◽

Micro Rnas ◽

Patient Groups

Background The skin and the kidney are commonly affected in systemic lupus erythematosus (SLE) with similar molecular mechanisms. Although clinical indicators of renal injury in SLE are fairly uncontroversial, few biomarkers are reliable. The role of micro-RNAs (mi-RNAs) in lupus nephritis (LN) pathogenesis has been investigated to help in early diagnosis. Purpose The aim of work is to evaluate miRNA132 and SOX2 expressions in SLE Egyptian patients; with and without nephritis, and the relation between miRNA132 and its long non-coding gene SOX2 in both patients groups. Research Design This is a case-control study involving 100 SLE patients with and without LN (LN and non-LN groups), and 50 age-and sex-matched healthy controls. The study was carried out to detect miRNA132 and SOX2 expression by quantitative Real-Time Polymerase chain reaction methods. The SLE disease activity index (SLEDAI) was assessed. Results SLEDAI increased in LN compared to non-LN. Micro-RNA132 expression was significantly increased in patient groups compared to controls ( p<0.01) and increased in LN more than non-LN group ( p<0.001). SOX2 significantly decreased in patient groups compared to controls ( p<0.001), and was more in LN compared to non-LN group ( p<0.001). There was a negative correlation between miRNA132 and SOX2 expression in both patient groups ( p<0.001). Conclusion miRNA132 and SOX2 may play a role in SLE activity and help in the early non-invasive diagnosis of LN.

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Understanding the dynamics of hydroxychloroquine blood levels in lupus nephritis

Lupus ◽

10.1177/0961203320912832 ◽

2020 ◽

Vol 29 (6) ◽

pp. 560-568 ◽

Cited By ~ 3

Author(s):

Tatiana N Pedrosa ◽

Sandra G Pasoto ◽

Nadia E Aikawa ◽

Emily FN Yuki ◽

Eduardo F Borba ◽

...

Keyword(s):

Lupus Nephritis ◽

Disease Activity ◽

Blood Level ◽

Lupus Erythematosus ◽

Activity Index ◽

Disease Activity Index ◽

Blood Levels ◽

Persistent Pattern ◽

Liquid Chromatography Tandem Mass ◽

Group 5

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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