Publications by authors named "Charlotte Laurent"

19 Publications

  • Page 1 of 1

Intensity of de novo DSA detected by Immucor Lifecodes assay and C3d fixing antibodies are not predictive of subclinical ABMR after Kidney Transplantation.

PLoS One 2021 22;16(4):e0249934. Epub 2021 Apr 22.

EFS Normandie, Rouen, France.

De novo donor-specific antibodies (dnDSA) are associated with antibody-mediated rejection (ABMR) and allograft loss. We tested Immucor* (IM) Luminex Single-antigen beads (LSAB) assay and C3d-fixing antibodies in the setting of dnDSA and subclinical (s) ABMR. This retrospective multicentric study included 123 patients biopsied because of the presence of subclinical de novo DSA detected by One Lamda* Labscreen (MFI > 1000). In 112 patients, sera of the day of the biopsy were available and tested in a central lab with IM Lifecodes LSAB and C3d fixing antibodies assays. In 16 patients (14.3%), no DSA was detected using Immucor test. In 96 patients, at least one DSA was determined with IM. Systematic biopsies showed active sABMR in 30 patients (31.2%), chronic active sABMR in 17 patients (17.7%) and no lesions of sABMR in 49 KT recipients (51%). Intensitity criteria (BCM, BCR and AD-BCR) of DSA were not statistically different between these 3 histological groups. The proportion of patients with C3d-fixing DSA was not statistically different between the 3 groups and did not offer any prognostic value regarding graft survival. Performing biopsy for dnDSA could not be guided by the intensity criteria of IM LSAB assay. C3d-fixing DSA do not offer added value.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0249934PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062066PMC
April 2021

Belatacept as maintenance therapy in kidney transplant recipients with ANCA-associated vasculitis.

Clin Exp Rheumatol 2021 Mar 18. Epub 2021 Mar 18.

University of Rennes, CHU Rennes, Inserm, EHESP, Irset (Institut de Recherche en Santé, Environnement et Travail) - UMR_S 1085, Rennes, France.

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March 2021

Preservation of epoxyeicosatrienoic acid bioavailability prevents renal allograft dysfunction and cardiovascular alterations in kidney transplant recipients.

Sci Rep 2021 Feb 12;11(1):3739. Epub 2021 Feb 12.

Department of Pharmacology, Rouen University Hospital, 76000, Rouen, France.

This study addressed the hypothesis that epoxyeicosatrienoic acids (EETs) synthesized by CYP450 and catabolized by soluble epoxide hydrolase (sEH) are involved in the maintenance of renal allograft function, either directly or through modulation of cardiovascular function. The impact of single nucleotide polymorphisms (SNPs) in the sEH gene EPHX2 and CYP450 on renal and vascular function, plasma levels of EETs and peripheral blood monuclear cell sEH activity was assessed in 79 kidney transplant recipients explored at least one year after transplantation. Additional experiments in a mouse model mimicking the ischemia-reperfusion (I/R) injury suffered by the transplanted kidney evaluated the cardiovascular and renal effects of the sEH inhibitor t-AUCB administered in drinking water (10 mg/l) during 28 days after surgery. There was a long-term protective effect of the sEH SNP rs6558004, which increased EET plasma levels, on renal allograft function and a deleterious effect of K55R, which increased sEH activity. Surprisingly, the loss-of-function CYP2C9*3 was associated with a better renal function without affecting EET levels. R287Q SNP, which decreased sEH activity, was protective against vascular dysfunction while CYP2C8*3 and 2C9*2 loss-of-function SNP, altered endothelial function by reducing flow-induced EET release. In I/R mice, sEH inhibition reduced kidney lesions, prevented cardiac fibrosis and dysfunction as well as preserved endothelial function. The preservation of EET bioavailability may prevent allograft dysfunction and improve cardiovascular disease in kidney transplant recipients. Inhibition of sEH appears thus as a novel therapeutic option but its impact on other epoxyfatty acids should be carefully evaluated.
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http://dx.doi.org/10.1038/s41598-021-83274-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881112PMC
February 2021

Protocol Biopsies in Patients With Subclinical De Novo Donor-specific Antibodies After Kidney Transplantation: A Multicentric Study.

Transplantation 2020 08;104(8):1726-1737

Nephrology Kidney Transplantation Dialysis, CHU Rouen, Rouen, France.

Background: De novo donor-specific antibodies (DSAs) are associated with antibody-mediated rejection (AMR) and allograft loss. Whether monitoring of de novo DSA (dnDSA) paired with systematic kidney biopsy should become routine remains to be established.

Methods: A retrospective multicentric study (9 French kidney transplant units of the Spiesser group) included patients without graft dysfunction biopsied because of the presence of dnDSA (One Lambda, mean fluorescence intensity [MFI], >1000).

Results: One hundred twenty-three patients (85 male/38 female; mean age, 49.5 ± 13.1 y old) were biopsied after the detection of a dnDSA, 65.3 months (median) after kidney transplantation. Graft function was stable within 3 months before biopsy (estimated glomerular filtration rate, 55.3 ± 18.9 mL/min/1.73 m). Fifty-one subclinical AMRs (sAMRs) (41.4%) were diagnosed, of which 32 (26%) active and 19 (15.5%) chronic active sAMR. Seventy-two biopsies revealed no AMR (58.5%). Predictive factors associated with the diagnosis of active sAMR were MFI of immunodominant DSA >4000, MFI of the sum of DSA >6300, age of the recipient <45 years old, and the absence of steroids at biopsy. The presence of proteinuria >200 mg/g was predictive of chronic active sAMR. The decrease of estimated glomerular filtration rate at 5 years post-biopsy was significantly higher in patients with acute sAMR (-25.2 ± 28.3 mL/min/1.73 m) and graft survival significantly lower.

Conclusions: Performing a kidney graft biopsy for the occurrence of dnDSA without renal dysfunction leads to the diagnosis of a sAMR in over 40% of cases. Nevertheless, we did not observe any effect of standard treatment in acute sAMR.
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http://dx.doi.org/10.1097/TP.0000000000003055DOI Listing
August 2020

Autologous hematopoietic stem cell transplantation with reduced-intensity conditioning regimens in refractory Takayasu arteritis: a retrospective multicenter case-series from the Autoimmune Diseases Working Party (ADWP) of the European Society for Blood and Marrow Transplantation (EBMT).

Bone Marrow Transplant 2020 11 22;55(11):2109-2113. Epub 2020 Apr 22.

Sorbonne Université, Service de Médecine Interne and Inflammation-Immunopathology-Biotherapy Department (DMU i3), Hôpital Saint-Antoine, APHP, F-75012, Paris, France.

Autologous hematopoietic stem cell transplantation (AHSCT) has emerged as a promising treatment option in severely affected and refractory patients with autoimmune diseases. This is a retrospective survey of patients reported to the EBMT registry between 1998 and 2019, who received AHSCT for TAK. Data from six patients treated with AHSCT for refractory TAK have been identified, five were female (83%), median age 25 (9-39) years. All patients were pretreated with a median of 6 (4-8) lines of therapy, including steroids (six patients), methotrexate (five patients), cyclophosphamide, mycophenolate mofetil or infliximab (four patients), tocilizumab or etanercept (two patients). Conditioning included cyclophosphamide and rabbit anti-thymocyte globulin in all patients. At 6 months post transplantation, remission was obtained in all cases, which persisted at 12 months in five cases. Four patients reactivated TAK at a median time of 27 (7-52) months after AHSCT, and three resumed disease-modifying therapy. At last follow-up, all patients were alive, two patients were in remission (off-therapy), two patients improved compared with baseline, and two patients were in complete and partial remission, respectively, under immunosuppressive treatment. This retrospective case-series demonstrates that AHSCT has the potential to provide significant clinical responses in TAK patients, but large prospective trials are necessary to confirm these preliminary data.
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http://dx.doi.org/10.1038/s41409-020-0907-4DOI Listing
November 2020

The Detection of Spontaneous Venous Pulsation with Smartphone Video Ophthalmoscopy.

Clin Ophthalmol 2020 3;14:331-337. Epub 2020 Feb 3.

University of Otago, Dunedin, New Zealand.

Purpose: Spontaneous venous pulsation (SVP) has a high negative predictive value for raised intracranial pressure and is a useful sign when assessing patients with headache. The objective was to determine if smartphone-based video ophthalmoscopy can detect SVP.

Patients And Methods: In total 233 patients and 291 eyes were recruited from the Dunedin Hospital eye clinic from July to November 2018. Patients were examined by a clinician and graded for SVP with a slit lamp and 78 Dioptre lens. Videos were taken with a smartphone ophthalmoscope and graded by two separate clinicians blinded to the slit lamp findings.

Results: Only 272 eyes of 215 patients were included, as others failed in the inclusion criteria for overall video quality. Sensitivity was calculated as how likely the presence of SVP on video was indicative of the presence of SVP on slit lamp. Sensitivity was 84.77% for Observer 1, with 128 videos graded as positive for SVP on video ophthalmoscopy of the 151 identified as positive on slit lamp examination. Sensitivity was 76.82% for Observer 2 with 116 videos correctly identified. The false positive rate was calculated as the number of videos graded positive for SVP that had been graded as negative on slit lamp examination. This was 10.74% for observer 1 and 31.40% for observer 2.

Conclusion: This study demonstrates that SVP is detected by video ophthalmoscopy. This may be a useful triage, telemedicine and referral tool to be used for patients with headache in a primary care setting.
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http://dx.doi.org/10.2147/OPTH.S238897DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7006856PMC
February 2020

Combination vasodilator therapy improves skin microvascular blood but do not restore endothelial function in systemic sclerosis.

Autoimmun Rev 2020 Mar 7;19(3):102467. Epub 2020 Jan 7.

Assistance Publique - Hôpitaux de Paris (AP-HP), Hôpital Saint-Antoine, Service de réanimation médicale, 75571 Paris Cedex 12, France; Sorbonne Université, Université Pierre-et-Marie Curie, Paris 6, France. Electronic address:

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http://dx.doi.org/10.1016/j.autrev.2020.102467DOI Listing
March 2020

Ipilimumab-induced renal granulomatous arteritis: a case report.

BMC Nephrol 2019 10 11;20(1):366. Epub 2019 Oct 11.

Nephrology department, Rouen University Hospital, 147 avenue du Maréchal Juin 76230 Bois Guillaume, Rouen, France.

Background: Immune Checkpoint Inhibitors (ICPIs) are promising new drugs in treatment of advanced tumours targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death protein-1 (PD1) or its ligand (PDL-1). Ipilimumab is a monoclonal antibody targeting the CTLA-4 receptor used in treatment of metastatic melanoma. By increasing activity of the immune system, ICPIs lead to immune-related adverse events, such as dermatitis, colitis or hepatitis. ICPIs-related kidney adverse events are rare and acute tubulointerstitial nephritis with or without granuloma have mainly been reported.

Case Presentation: We report a case of acute kidney injury in a patient with melanoma treated by ipilimumab. Kidney biopsy revealed acute interlobular and juxtaglomerular granulomatous arteritis, which has not yet been reported in patients treated by ICPIs. Kidney function partially recovered after ipilimumab discontinuation and oral prednisone. Unfortunately, the patient died a few months later from progression of his melanoma.

Conclusion: This case highlights a new mechanism of acute kidney injury related to ICPIs and supports the interest of kidney biopsy in case of ICPIs related acute renal failure.
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http://dx.doi.org/10.1186/s12882-019-1552-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6788031PMC
October 2019

PET/MRI in large-vessel vasculitis: clinical value for diagnosis and assessment of disease activity.

Sci Rep 2019 08 27;9(1):12388. Epub 2019 Aug 27.

AP-HP, Sorbonne Université, Hôpital Saint-Antoine, Service de Médecine Interne and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), F-75012, Paris, France.

Diagnosis of large vessel vasculitis (LVV) and evaluation of its inflammatory activity can be challenging. Our aim was to investigate the value of hybrid positron-emission tomography/magnetic resonance imaging (PET/MRI) in LVV. All consecutive patients with LVV from the Department of Internal Medicine who underwent PET/MRI were included. Three PET/MRI patterns were defined: (i) "inflammatory," with positive PET (>liver uptake) and abnormal MRI (stenosis and/or wall thickening); (ii) "fibrous", negative PET (≤liver uptake) and abnormal MRI; and (iii) "normal". Thirteen patients (10 female; median age: 67-years [range: 23-87]) underwent 18 PET/MRI scans. PET/MRI was performed at diagnosis (n = 4), at relapse (n = 7), or during remission (n = 7). Among the 18 scans, eight (44%) showed an inflammatory pattern and three (17%) a fibrous pattern; the other seven were normal. The distribution of the three patterns did not differ between patients with Takayasu arteritis (TA, n = 10 scans) and those with giant cell arteritis (GCA, n = 8 scans). PET/MRI findings were normal in 2/10 (20%) TA scans vs. 5/8 (62%) GCA scans (p = 0.3). Median SUV was 4.7 [2.1-8.6] vs. 2 [1.8-2.6] in patients with active disease vs. remission, respectively (p = 0.003). PET/MRI is a new hybrid imaging modality allowing comprehensive and multimodal analysis of vascular wall inflammation and the vascular lumen. This technique offers promising perspectives for the diagnosis and monitoring of LVV.
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http://dx.doi.org/10.1038/s41598-019-48709-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6711961PMC
August 2019

HIV-associated vasculitis. Part II: histologic and angiographic diagnostic reconfirmation after an uncontrolled HIV infection and fatal outcome.

Clin Exp Rheumatol 2019 Mar-Apr;37 Suppl 117(2):151-152. Epub 2019 May 9.

Vasculitis Research Unit, Department of Autoimmune Diseases, Hospital Clínic of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Spain.

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June 2019

Splinter haemorrhages, splenic infarcts, and pulmonary embolism in granulomatosis with polyangiitis.

Vasc Med 2019 06 14;24(3):263-264. Epub 2018 Nov 14.

1 Service de médecine interne, Centre de référence maladies auto-immunes et systémiques rares, Hôpital Cochin, AP-HP, Paris, France.

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http://dx.doi.org/10.1177/1358863X18807541DOI Listing
June 2019

Comparison of Two Luminex Single-antigen Bead Flow Cytometry Assays for Detection of Donor-specific Antibodies After Renal Transplantation.

Transplantation 2019 03;103(3):597-603

Laboratory of Histocompatibility, EFS Normandie, Rouen, France.

Background: Defining the clinical relevance of donor-specific HLA antibodies (DSA) detection by Luminex single-antigen (LSA) flow beads assay is critical in monitoring posttransplant outcome.

Methods: Sera of kidney transplanted patients were tested by LSA1 and LSA2 with One Lambda Labscreen (test 1) and Immucor Lifecodes (test 2), at the time of a graft biopsy. The first group (G1, n = 50) had a biopsy highly suggestive of humoral rejection, and the second (G2, n = 50) had no criteria of rejection. Positivity criteria for DSA was mean fluorescence intensity greater than 500 for test 1, whereas specificity assignation respected the provider's recommendations for test 2.

Results: In G1, we identified at least 1 DSA in 44 patients with test 1, and in 39 patients with test 2. In G2, test 1 identified at least 1 DSA in 16 (32%) patients and test 2 in 7 (14%) patients. Sensitivity and specificity for antibody-mediated rejection diagnosis was 88% and 68%, respectively, with One Lambda, and 78% and 86%, respectively, with Immucor. Correlation and agreement were found in class I and II between intensity parameters of the 2 manufacturers. The use of the sum of the intensity of DSA improved the sensitivity and specificity of the 2 tests.

Conclusions: We report the first comparative study of the 2 Luminex assays available for detecting DSA in the postkidney transplant setting. Although there is a good correlation and reliability between the 2 assays, significant differences exist. Positivity criteria for DSA determination differ and interpretation should take these specificities into account.
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http://dx.doi.org/10.1097/TP.0000000000002351DOI Listing
March 2019

Dropped head syndrome with proximal myopathy revealing AL amyloidosis.

Joint Bone Spine 2018 12 11;85(6):779-781. Epub 2018 Apr 11.

Department of rheumatology, Henri-Mondor hospital, AP-HP, 94010 Créteil, France.

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http://dx.doi.org/10.1016/j.jbspin.2018.03.011DOI Listing
December 2018

Steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT): Characteristics, treatment and outcome in 251 cases from the literature.

Autoimmun Rev 2016 Dec 15;15(12):1129-1133. Epub 2016 Sep 15.

Service de médecine interne, UPMC, DHU i2B AP-HP, Hôpital Saint Antoine, 75012 Paris, France. Electronic address:

Background: Steroid-responsive encephalopathy and associated autoimmune thyroiditis (SREAT) is characterized by encephalopathy and the presence of antithyroid antibodies. We describe the clinical presentation, outcome and treatments for SREAT by a systematic review of the literature.

Methods: MEDLINE via PubMed, Web of Science and the Cochrane Library were searched for articles published until 2015. Inclusion criteria were unexplained encephalopathy with antithyroid antibodies.

Results: We found reports of 251 patients (median age 52years [range 18-86], 73% females, 80 [32%] with preexisting thyroiditis). Patients presented encephalitis signs with convulsions (n=117; 47%), confusion (n=115, 46%), speech disorder (n=91, 37%), memory impairment (n=107, 43%), gait disturbance (n=67, 27%) and persecutory delusions (n=61, 25%). Twenty-eight patients (11%) presented progressive memory impairment and 26 (10%) isolated psychiatric disorders. In serum, 34% of patients were positive for anti-thyroid peroxidase (TPO) antibodies, 7% for anti-thyroglobulin (TG) antibodies, and 69% both. Thyroid-stimulating hormone levels were usually normal, at 2 UI/ml [0.001-205]. Cerebrospinal fluid from 10/53 patients (19%) was positive for anti-TPO antibodies, 2/53 (4%) anti-TG antibodies and 28 (53%) both. Electroencephalography findings were abnormal for 82% of patients, showing diffuse slowing consistent with encephalopathy (70%) or epileptic activity (14%). The first-line treatment was steroids in 193 patients and other immunosuppressive drugs in 10 cases. At a median follow-up of 12months [range 0.2-110], 91% of patients showed complete or partial neurological response, with anti-TPO and -TG antibody titers at 347 UI/ml [0-825,000] and 110 UI/ml [0-50,892], respectively. During follow-up, 40 patients (16%) experienced at least one relapse. Relapse was more frequent in patients with initial coma (26% vs 13%, p=0.08).

Conclusion: The diagnosis of SREAT should be suspected in case of encephalopathy without obvious cause, to quickly start corticosteroid treatment. The exact modalities of treatment must be defined.
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http://dx.doi.org/10.1016/j.autrev.2016.09.008DOI Listing
December 2016

Applying risk analysis to predict posterior capsule rupture during cataract surgery in New Zealand.

Clin Exp Ophthalmol 2016 Dec 7;44(9):861-864. Epub 2016 Jun 7.

The University of Auckland, Auckland, New Zealand.

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http://dx.doi.org/10.1111/ceo.12770DOI Listing
December 2016

Minimization of maintenance immunosuppressive therapy after renal transplantation comparing cyclosporine A/azathioprine or cyclosporine A/mycophenolate mofetil bitherapy to cyclosporine A monotherapy: a 10-year postrandomization follow-up study.

Transpl Int 2016 Jan;29(1):23-33

Service de Néphrologie-Hémodialyse-Transplantation rénale, CHU de Poitiers, Poitiers, France.

Long-term outcomes in renal transplant recipients withdrawn from steroid and submitted to further minimization of immunosuppressive regimen after 1 year are lacking. In this multicenter study, 204 low immunological risk kidney transplant recipients were randomized 14.2 ± 3.7 months post-transplantation to receive either cyclosporine A (CsA) + azathioprine (AZA; n = 53), CsA + mycophenolate mofetil (MMF; n = 53), or CsA monotherapy (n = 98). At 3 years postrandomization, the occurrence of biopsy for graft dysfunction was similar in bitherapy and monotherapy groups (21/106 vs. 26/98; P = 0.25). At 10 years postrandomization, patients' survival was 100%, 94.2%, and 95.8% (P = 0.25), and death-censored graft survival was 94.9%, 94.7%, and 95.2% (P = 0.34) in AZA, MMF, and CsA groups, respectively. Mean estimated glomerular filtration rate was 70.4 ± 31.1, 60.1 ± 22.2, and 60.1 ± 19.0 ml/min/1.73 m(2), respectively (P = 0.16). The incidence of biopsy-proven acute rejection was 1.4%/year in the whole cohort. None of the patients developed polyomavirus-associated nephropathy. The main cause of graft loss (n = 12) was chronic antibody-mediated rejection (n = 6). De novo donor-specific antibodies were detected in 13% of AZA-, 21% of MMF-, and 14% of CsA-treated patients (P = 0.29). CsA monotherapy after 1 year is safe and associated with prolonged graft survival in well-selected renal transplant recipient (ClinicalTrials.gov number: 980654).
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http://dx.doi.org/10.1111/tri.12627DOI Listing
January 2016

[Henoch-Schoenlein purpura]

Rev Prat 2016 01;66(1):53

Service de médecine interne, DHUi2B.

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January 2016

[Travel memories].

Nephrol Ther 2015 Jul 4;11(4):250-1. Epub 2015 May 4.

Service de néphrologie, hémodialyse, transplantation rénale, CHU de Rouen, 76031 Rouen, France.

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http://dx.doi.org/10.1016/j.nephro.2015.02.002DOI Listing
July 2015