Publications by authors named "Jean-François Augusto"

67 Publications

Spectrum of Kidney Involvement in Patients with Myelodysplastic Syndromes.

Kidney Int Rep 2021 Mar 6;6(3):746-754. Epub 2021 Jan 6.

Service of Nephrology and Hypertension, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.

Introduction: Myelodysplastic syndromes (MDS) are characterized by a high prevalence of associated autoimmune manifestations. Kidney involvement has been rarely reported in MDS patients. We report on the spectrum of kidney pathological findings in MDS patients.

Methods: We retrospectively identified MDS patients who had undergone a kidney biopsy between 2001 and 2019 in nine Swiss and French nephrology centres.

Results: Nineteen patients (median age 74 years [63-83]) were included. At the time of kidney biopsy, eleven (58%) patients had extra-renal auto-immune manifestations and sixteen (84%) presented with acute kidney injury. Median serum creatinine at diagnosis was 2.8 mg/dL [0.6-8.3] and median urinary protein to creatinine ratio was 1.2 g/g [0.2-11]. Acute tubulo-interstitial nephritis (TIN) was present in seven (37%) patients. Immunofluorescence study in one patient with acute TIN disclosed intense IgG deposits along the tubular basement membrane and Bowman's capsule. Other kidney pathological features included ANCA-negative pauci-immune necrotizing and crescentic glomerulonephritis (n = 3), membranous nephropathy (n = 2), IgA nephropathy (n = 1), IgA vasculitis (n = 1), immunoglobulin-associated membrano-proliferative glomerulonephritis type I (n=1), crescentic C3 glomerulopathy (n = 1), fibrillary glomerulonephritis (n = 1) and minimal change disease (n = 1). Eleven (58%) patients received immunosuppressive treatments, among whom one developed a severe infectious complication. After a median follow-up of 7 month [1-96], nine (47%) patients had chronic kidney disease stage 3 (n = 6) or 4 (n = 3) and five (26%) progressed to end-stage kidney disease. Three patients died.

Conclusions: MDS are associated to several autoimmune kidney manifestations, predominantly acute TIN. MDS are to be listed among the potential causes of autoimmune TIN.
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http://dx.doi.org/10.1016/j.ekir.2020.12.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938072PMC
March 2021

Retrospective and Systematic Analysis of Causes and Outcomes of Thrombotic Microangiopathies in Routine Clinical Practice: An 11-Year Study.

Front Med (Lausanne) 2021 26;8:566678. Epub 2021 Feb 26.

Service de Néphrologie-Dialyse-Transplantation, Université d'Angers, Centre Hospitalier Universitaire (CHU) Angers, Angers, France.

Thrombotic microangiopathies (TMAs) are highly suspected in patients showing mechanical hemolytic anemia, thrombocytopenia, and haptoglobin consumption. Primary [thrombotic thrombocytopenic purpura (TTP) and atypical hemolytic uremic syndrome] and secondary TMA are considered. Even if ADAMTS13 measurements and alternative complement pathway explorations have greatly improved the ability to identify primary TMA, their diagnosis remains difficult, and their frequency relative to that of secondary TMA is undetermined. The objectives of the present study were, therefore, to describe the etiologies, management, and the outcomes of patients presenting with TMA in real-life clinical practice. We conducted a retrospective study between 01/01/2008 and 31/12/2018 that included all consecutive patients presenting with biological TMA syndrome at admission or developing during hospitalization. Patients were identified from the laboratory databases, and their medical files were reviewed to confirm TMA diagnosis, to determine etiology, and to analyze their therapeutic management and outcomes. During this period, 239 patients with a full TMA biological syndrome were identified, and the TMA diagnosis was finally confirmed in 216 (90.4%) after the cases were reviewed. Primary TMAs (thrombotic thrombocytopenic purpura or atypical hemolytic uremic syndrome) were diagnosed in 20 of 216 patients (9.3%). Typical HUS was diagnosed in eight patients (3.7%), and the most frequent secondary TMAs were HELLP syndrome (79/216, 36.6%) and active malignancies (30/219, 13.9%). ADAMTS13 measurements and alternative complement pathway analyses were performed in a minority of patients. Multiple factors identified as TMA triggers were present in most patients, in 55% of patients with primary TMA, vs. 44.7% of patients with secondary TMA ( = 0.377). Death occurred in 57 patients (23.4%) during follow-up, and dialysis was required in 51 patients (23.6%). Active malignancies [odds ratio (OR) 13.7], transplantation (OR 4.43), male sex (OR 2.89), and older age (OR 1.07) were significantly associated with death. Secondary TMAs represent many TMA causes in patients presenting a full TMA biological syndrome during routine clinical practice. Multiple factors favoring TMA are present in about half of primary or secondary TMA. ADAMTS13 and complement pathway were poorly explored in our cohort. The risk of death is particularly high in patients with malignancies as compared with patients with other TMA.
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http://dx.doi.org/10.3389/fmed.2021.566678DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952313PMC
February 2021

Anti-Pentraxin Antibodies in Autoimmune Diseases: Bystanders or Pathophysiological Actors?

Front Immunol 2020 16;11:626343. Epub 2021 Feb 16.

Université d'Angers, INSERM, CRCINA, Angers, France.

Pentraxins are soluble innate immunity receptors involved in sensing danger molecules. They are classified as short (CRP, SAP) and long pentraxin subfamilies, including the prototypic long pentraxin PTX3. Pentraxins act mainly as bridging molecules favoring the clearance of microbes and dead cells. They are also involved in many other biological processes, such as regulation of complement activation, inflammation and tissue homeostasis. Autoantibodies directed against pentraxins have been reported in various autoimmune diseases, especially in systemic lupus erythematosus and ANCA-associated vasculitis. In this review, we review the main biological characteristics and functions of pentraxins and summarize data concerning autoantibodies directed against pentraxins in the context of autoimmune diseases and discuss their potential pathological role.
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http://dx.doi.org/10.3389/fimmu.2020.626343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921723PMC
February 2021

Impact of aging on phenotype and prognosis in IgA vasculitis.

Rheumatology (Oxford) 2021 Jan 7. Epub 2021 Jan 7.

Université Paris Descartes, Paris, France.

Objectives: Immunoglobulin A vasculitis (IgAV) is a small-vessel vasculitis most frequently benign in children while the disease is more severe in adults. We aimed to study the impact of age on presentation and outcome of adult IgAV.

Methods: We conducted a nationwide retrospective study including 260 IgAV patients. Patients were divided into four quartiles according to the age at IgAV diagnosis: <36; 36≤age < 52; 52≤age < 63 and ≥63 years. Comparison of presentation and outcome were performed according to age of disease onset.

Results: Mean age at diagnosis was 50.1 ± 18 years and 63% were male. IgAV diagnosed in the lowest quartile of age was associated with more frequent joint (p< 0.0001) and gastrointestinal involvement (p= 0.001). In contrast, the oldest patients had more severe purpura with necrotic lesions (p= 0.001) and more frequent renal involvement (p< 0.0001), with more frequent hematuria, renal failure, higher urine protein excretion and more frequent tubulointerstitial lesions. Patients were treated similarly in all groups of age, and clinical response and relapse rates were similar between groups. In the 127 treated patients with follow-up data for >6 months, clinical response and relapse rates were similar between the four groups. Median follow-up was of 17.2 months (9.1-38.3 months). Renal failure at the end of follow-up was significantly more frequent in the highest quartile of age (p= 0.02), but the occurrence of end-stage renal disease was similar in all groups. Last, overall and IgAV-related deaths were associated with increase age.

Conclusion: Aging negatively impacts the severity and outcome of IgAV in adults. Younger patients have more frequent joint and gastrointestinal involvement, while old patients display more frequent severe purpura and glomerulonephritis.
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http://dx.doi.org/10.1093/rheumatology/keaa921DOI Listing
January 2021

Refractory Auto-Immune Thrombotic Thrombocytopenic Pupura Successfully Treated With Caplacizumab.

Front Med (Lausanne) 2020 22;7:549931. Epub 2020 Oct 22.

Service de Néphrologie-Dialyse-Transplantation, Centre Hospitalier Universitaire Angers, Angers, France.

Thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy characterized by mechanical hemolytic anemia, profound thrombocytopenia, and neurological manifestations. Acquired auto-immune TTP, the most prevalent cause of TTP, is induced by the presence of inhibitory anti-ADAMTS13 auto-antibodies. Modern treatment of acquired TTP relies on plasma exchange, rituximab, and steroids. Caplacizumab (Cablivi®), a humanized single-variable domain immunoglobulin that targets the A1 domain of the ultra-large von Willebrand factor, inhibits the interaction between ultra-large vWFand platelets. In two clinical trials, caplacizumab, in addition to conventional treatment, shortened the delay to platelet count normalization in comparison to conventional treatment plus placebo, without increasing significantly hemorrhagic complications. Moreover, caplacizumab was associated with reduced occurrence of a secondary endpoint associating death, TTP recurrence, and major thromboembolic events. Here, we report the off-label use of caplacizumab in a 68-year-old patient with confirmed acquired TTP, severe thrombocytopenia, and generalized tonic-clonic seizures requiring mechanical ventilation and admission in the intensive care unit. Conventional treatment was rapidly started. Despite the intensification of plasma exchange treatment with twice-daily sessions, steroid continuation, and a second rituximab infusion on day 6, thrombotic microangiopathy worsened with thrombocytopenia at 21 g/L on day 8 from admission. We also considered using caplacizumab, which we could obtain and start on day 12 from admission, as it was available under a temporary authorization use in France. As soon as 12 h after caplacizumab initiation, we observed a significant increase of platelet count and improvement of other hemolytic parameters. We observed resolution of encephalopathy and complete recovery of motor paralysis, allowing us to stop mechanical ventilation on day 14. Caplacizumab was maintained for 128 days until day 139 from initial admission. The patient is going well 10 months after initial admission, without any neurological sequelae, and TTP did not relapse. To the best of our knowledge, this is the first reported use of caplacizumab in such a condition. This case report suggests that caplacizumab use may help to reduce the rate of refractory TTP episodes.
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http://dx.doi.org/10.3389/fmed.2020.549931DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649819PMC
October 2020

A regimen with caplacizumab, immunosuppression, and plasma exchange prevents unfavorable outcomes in immune-mediated TTP.

Blood 2021 Feb;137(6):733-742

Centre de Référence des Microangiopathies Thrombotiques, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.

The anti-von Willebrand factor nanobody caplacizumab was licensed for adults with immune-mediated thrombotic thrombocytopenic purpura (iTTP) based on prospective controlled trials. However, few data are available on postmarketing surveillance. We treated 90 iTTP patients with a compassionate frontline triplet regimen associating therapeutic plasma exchange (TPE), immunosuppression with corticosteroids and rituximab, and caplacizumab. Outcomes were compared with 180 historical patients treated with the standard frontline treatment (TPE and corticosteroids, with rituximab as salvage therapy). The primary outcome was a composite of refractoriness and death within 30 days since diagnosis. Key secondary outcomes were exacerbations, time to platelet count recovery, the number of TPE, and the volume of plasma required to achieve durable remission. The percentage of patients in the triplet regimen with the composite primary outcome was 2.2% vs 12.2% in historical patients (P = .01). One elderly patient in the triplet regimen died of pulmonary embolism. Patients from this cohort experienced less exacerbations (3.4% vs 44%, P < .01); they recovered durable platelet count 1.8 times faster than historical patients (95% confidence interval, 1.41-2.36; P < .01), with fewer TPE sessions and lower plasma volumes (P < .01 both). The number of days in hospital was 41% lower in the triplet regimen than in the historical cohort (13 vs 22 days; P < .01). Caplacizumab-related adverse events occurred in 46 patients (51%), including 13 major or clinically relevant nonmajor hemorrhagic events. Associating caplacizumab to TPE and immunosuppression, by addressing the 3 processes of iTTP pathophysiology, prevents unfavorable outcomes and alleviates the burden of care.
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http://dx.doi.org/10.1182/blood.2020008021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986049PMC
February 2021

Incidence and Risk Factors of Venous Thromboembolic Events in Patients with ANCA-Glomerulonephritis: A Cohort Study from the Maine-Anjou Registry.

J Clin Med 2020 Sep 30;9(10). Epub 2020 Sep 30.

Service de Néphrologie-Dialyse-Transplantation, Université d'Angers, CHU Angers, 4 rue Larrey, 49033 Angers CEDEX 09, France.

(1) Introduction: The incidence of venous thromboembolisms (VTE) has not been extensively analyzed in patients with antineutrophil cytoplasmic antibody (ANCA)-glomerulonephritis (ANCA-GN). Thus, the aim of the present study was to assess the frequency and the risk factors of VTE in patients with ANCA-GN. (2) Methods: Patients from the Maine-Anjou ANCA-associated vasculitis (AAV) registry with a biopsy showing pauci-immune glomerulonephritis were included. VTE events, site, and interval from AAV diagnosis were analyzed. (3) Results: 133 patients fulfilled the inclusion criteria of the study and were analyzed. VTE episodes were diagnosed in 23/133 (17.3%) patients at a median delay of 3 months from ANCA-GN diagnosis. Patients with VTE had lower serum albumin ( = 0.040), were less frequently on statin therapy ( = 0.009) and had less frequently proteinase-3 (PR3)-ANCAs ( = 0.078). Univariate analysis identified higher age ( = 0.022), lower serum albumin ( = 0.030), lack of statin therapy ( = 0.009), and rituximab treatment ( = 0.018) as significant risk factors of VTE. In multivariate analysis, only lack of statin therapy (HR 4.873; = 0.042) was significantly associated with VTE. (4) Conclusion: Patients with ANCA-GN are at high risk of VTE, especially within the first months following AAV diagnosis. Our results suggest that statin therapy is associated with a lower risk of VTE in ANCA-GN patients.
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http://dx.doi.org/10.3390/jcm9103177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7599765PMC
September 2020

Severe polyuria secondary to acyclovir induced-proximal tubulopathy.

Therapie 2020 Aug 28. Epub 2020 Aug 28.

Néphrologie dialyse transplantation, CHU Angers, 49933 Angers, France.

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http://dx.doi.org/10.1016/j.therap.2020.08.001DOI Listing
August 2020

Ifosfamide nephrotoxicity in adult patients.

Clin Kidney J 2020 Aug 31;13(4):660-665. Epub 2019 Dec 31.

Department of Nephrology, Dialysis, Transplantation, Georges Pompidou European Hospital, Paris, France.

Background: Ifosfamide, a widely prescribed antineoplasic agent, is frequently associated with kidney dysfunction. Its nephrotoxicity is well documented in children, but data are lacking in adult patients.

Methods: The aim of this retrospective study was to describe the clinical, biological and histological characteristics of ifosfamide nephrotoxicity.

Results: We report 34 patients (median age: 41 years) admitted in six French nephrology departments for kidney failure and/or tubular dysfunction. Fifteen patients (44.1%) received cisplatin as part of their chemotherapy. In 6 patients (17.7%), ifosfamide nephrotoxicity was revealed by a proximal tubular dysfunction (PTD), in 5 patients (14.4%) by an acute kidney injury (AKI), in 6 patients (17.7%) by a chronic kidney disease (CKD) and in 17 patients (49.7%) by an association of PTD and AKI. Fourteen renal biopsies (41.2%) were performed and revealed acute tubular necrosis (85.7%), vacuolation (78.6%) and nuclear atypias (71.4%) of renal epithelial cells, interstitial inflammation (71.4%) and fibrosis (57.1%). Electron microscopy showed mitochondrial enlargement and dysmorphic changes suggestive of mitochondrial toxicity. Ten patients (29.4%) progressed to Stage 5 CKD, six (17.6%) required haemodialysis and six patients died during a median follow-up period of 31 months. Risk factors for Stage 5 CKD were age and cisplatin co-administration.
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http://dx.doi.org/10.1093/ckj/sfz183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7467602PMC
August 2020

High Incidence of Amoxicillin-Induced Crystal Nephropathy in Patients Receiving High Dose of Intravenous Amoxicillin.

J Clin Med 2020 Jun 27;9(7). Epub 2020 Jun 27.

Service de Néphrologie-Dialyse-Transplantation, Université d'Angers, CHU Angers, 49000 Angers, France.

Background: Amoxicillin (AMX)-induced crystal nephropathy (AICN) is considered as a rare complication of high dose intravenous (IV) AMX administration. However, recently, its incidence seems to be increasing based on French pharmacovigilance centers. Occurrence of AICN has been observed mainly with IV administration of AMX and mostly under doses over 8 g/day. Given that pharmacovigilance data are based on declaration, the real incidence of AICN may be underestimated. Thus, the primary objective of the present study was to determine the incidence of AICN in the current practice.

Materials And Methods: We conducted a retrospective study between 1 January 2015 and 31 December 2017 in Angers University Hospital. Inclusion criteria were age over 18 years-old and IV AMX administration of at least 8 g/day for more than 24 h. Patients admitted directly into the intensive care units were excluded. Medical records of patients that developed Kidney Disease:Improving Global Outcome (KDIGO) stage 2-3 acute kidney injury (AKI) were reviewed by a nephrologist and a specialist in pharmacovigilance. AICN was retained if temporality analysis was conclusive, after exclusion of other causes of AKI, in absence of other nephrotoxic drug administration.

Results: A total of 1303 patients received IV AMX for at least 24 h. Among them, 358 (27.5%) were exposed to AMX doses of at least 8 g/day and were included. Patients were predominantly males (68.2%) with a mean age of 69.1 years-old. AMX was administered for a medical reason in 78.5% of cases. Patients received a median dose of AMX of 12 g/day (152.0 mg/kg/day). Seventy-three patients (20.4%) developed AKI, 42 (56.8%) of which were KDIGO stage 2 or 3. Among the latter, AICN diagnosis was retained in 16 (38.1%) patients, representing an incidence of 4.47% of total patients exposed to high IV AMX doses. Only female gender was associated with an increased risk of AICN. AMX dose was not significantly associated with AICN development.

Conclusion: This study suggests a high incidence of AICN in patients receiving high IV AMX doses, representing one third of AKI causes in our study. Female gender appeared as the sole risk factor for AICN in this study.
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http://dx.doi.org/10.3390/jcm9072022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409099PMC
June 2020

The Presence of Renal IgG Deposits in Necrotizing Crescentic Glomerulonephritis Associated with ANCA Is Not Related to Worse Renal Clinical Outcomes.

Kidney Dis (Basel) 2020 Mar 21;6(2):98-108. Epub 2019 Nov 21.

Department of Nephrology - Hypertension, Dialysis, Transplantation, CHRU, Tours, France.

Introduction: Classical pauci-immune necrotizing crescentic glomerulonephritis (CGN) associated with antineutrophil cytoplasmic autoantibodies (ANCA) is characterized by the absence of renal immunoglobulin (Ig) deposits. However, IgG deposits can sometimes be present. We wanted to assess whether necrotizing CGN with IgG deposits is associated with a more severe presentation and outcome than necrotizing CGN without IgG deposits.

Methods: Between November 2008 and August 2013, we retrospectively identified 158 patients from four centers who had necrotizing CGN due to primary ANCA-associated systemic vasculitis. Glomerular IgG deposits were found in 18 (11%) patients (group 1). For each patient in group 1, we selected 2 patients with classical pauci-immune necrotizing CGN with the nearest date of diagnosis in the same center (group 2, = 36). We assessed clinical, biological, and pathological characteristics in both groups.

Results: Baseline characteristics were similar in both groups, and most patients had ANCA-associated vasculitis with antibodies to myeloperoxidase (74%). Deposits displayed moderate to strong staining in 9 patients. As compared with group 2, group 1 exhibited a higher frequency of interstitial fibrosis/tubular atrophy lesions ( = 0.024) and lower frequency of acute tubular necrosis ( = 0.046). Nevertheless, after a mean follow-up of 30 and 26 months for group 1 and group 2, respectively, IgG deposits did not affect the renal prognosis or probability of relapse. Finally, the groups did not differ in renal or patient survival.

Conclusions: IgG deposits, detected in 11% of patients with ANCA-associated necrotizing CGN, did not affect renal or patient outcomes.
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http://dx.doi.org/10.1159/000503969DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7154286PMC
March 2020

Renal biopsy in very elderly patients (over 80 years): clinical presentation, histological diagnosis, and long-term outcome.

Int Urol Nephrol 2020 Apr 29;52(4):721-729. Epub 2020 Feb 29.

CHU Angers, Service de Néphrologie-Dialyse-Transplantation, Université Angers, 4 rue Larrey, 49933, Angers Cedex 9, France.

Purpose: Data regarding the long-term outcome of very elderly (VE) patients undergoing renal biopsy (RB) are lacking. The objective of this study was to analyse the outcome of VE patients undergoing RB.

Methods: All patients over 65 years that underwent native RB between 2004 and 2016 in our center were included. Among the 206 included patients, those over 80 years (VE, 46 patients) were analysed and compared to those aged 65-80 years (160 patients). The outcomes of the VE group were analysed.

Results: Baseline characteristics, renal presentation, safety of RB and RB-related diagnosis were not different between VE patients and 65-80-year-old patients. Survival of VE patients was 73.1, 50.6 and 21.8% at 2, 4 and 6 years after RB, significantly poorer than those of 65-80-year-old group. Early death (< 1 year) occurred in 10 VE patients, was associated with a higher proteinuria-to-creatininuria ratio and tended to be associated with a more frequent dialysis need at RB. Of the 46 VE patients, 31 (67.4%) were diagnosed with a potentially reversible kidney disease, of whom 17 (40%) were started on immunosuppressive regimens. Survival of patients with a reversible kidney disease tended to be better than those with other diseases.

Conclusion: RB appears as a safe and valuable procedure to assess diagnosis of kidney disease in VE patients. Our data suggest that RB is critical for the identification and treatment decision of patients with potentially reversible diseases and may translate in clinical improvement.
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http://dx.doi.org/10.1007/s11255-020-02403-3DOI Listing
April 2020

T Cell Dysregulation in Non-silicotic Silica Exposed Workers: A Step Toward Immune Tolerance Breakdown.

Front Immunol 2019 22;10:2743. Epub 2019 Nov 22.

Service de Néphrologie-Dialyse-Transplantation, CHU d'Angers, Angers, France.

Chronic silica exposure can lead to silicosis, complicated or not by autoimmune diseases (AID). The pathophysiology of silica-induced AID remains not fully understood, especially immune mechanisms that may develop in patients without yet established silicosis. We conducted a prospective clinical study to analyze the impact of crystalline silica (CS) on T cell phenotype and regulatory T cells (Tregs) frequency, as well as on auto-antibodies development in non-silicotic workers exposed to CS. Workers with moderate to high exposure level to CS and aged between 30 and 60 years-old were considered for inclusion. Peripheral blood mononuclear cells were analyzed by flow cytometry. Auto-antibodies were screened in serum by immunofluorescence. Blood from 42 and 45 healthy subjects (HC) was used as control for T cell phenotype and serum analyses, respectively. Among the 63 included workers exposed to CS, 55 had full data available and were analyzed. Ten were exposed to CS for <5 years, 18 for 5-10 years and 27 for more than 10 years. The frequency of Tregs (CD4CD25CD127FoxP3) was significantly lower in CS exposed workers as compared to HC. We found an increased expression of the activation marker HLA-DR on T cells (CD3, CD4, and CD8) of CS exposed workers as compared to HC. Tregs to activated T cells ratio was also lower in exposed subjects. In the latter, HLA-DR expression level and Tregs frequency were significantly associated with CS exposure duration. Serum autoantibody detection was significantly higher in CS exposed workers as compared to HC. Especially, among workers exposed more than 10 years, antinuclear antibodies and ANCA were detected in 44 and 22% among them, as compared to 5 and 2.5% in HC, respectively. This work shows that CS exposure is associated with a decrease of Tregs frequency, an increase of T cell activation status, and a tolerance breakdown against auto-antigens. These results show that alterations of the T cell compartment can be detected early over the course of CS exposure, preceding silicosis development or AID onset.
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http://dx.doi.org/10.3389/fimmu.2019.02743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883424PMC
November 2020

Complement alternative pathway in ANCA-associated vasculitis: Two decades from bench to bedside.

Autoimmun Rev 2020 Jan 15;19(1):102424. Epub 2019 Nov 15.

Service de Néphrologie-Dialyse-Transplantation, Université d'Angers, CHU Angers, Angers, France; CRCINA, INSERM, Université de Nantes, Université d'Angers, Angers, France. Electronic address:

Anti-neutrophil cytoplasmic autoantibodies (ANCA)-associated vasculitides (AAVs) are small vessel vasculitides involving predominantly ear-nose-throat, kidneys, lungs and nerves. AAVs are life-threatening diseases, especially in their most severe forms such as necrotizing crescentic glomerulonephritis (GN) and/or intra-alveolar hemorrhage. Unlike immune complex GN or anti-glomerular basement membrane GN, AAVs are classified as pauci-immune GN. However, based on recent insights from animal models, the view of AAVs as a complement-unrelated disease has been challenged. Indeed, complement activation, and especially complement alternative pathway (cAP) activation, has been shown to be determinant in AAV pathogenesis through C5a generation, a potent chemoattractant for neutrophils with priming capacities. Here, we review in vitro and in vivo data supporting the role of cAP in murine models and in human AAVs. These findings, together with the need to eradicate glucocorticoid toxicity, led to the development of an anti-C5aR molecule, CCX168, also known as avacopan. Its development and future opportunities are also discussed.
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http://dx.doi.org/10.1016/j.autrev.2019.102424DOI Listing
January 2020

Hyperphosphatemia and Multiple Myeloma: Keep Calm and Control First.

Am J Med 2020 05 9;133(5):e197-e198. Epub 2019 Nov 9.

Service de Médecine Intensive Réanimation, et Médecine Hyperbare, Centre Hospitalier Universitaire d'Angers, France. Electronic address:

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http://dx.doi.org/10.1016/j.amjmed.2019.10.022DOI Listing
May 2020

Immune thrombotic thrombocytopenic purpura in older patients: prognosis and long-term survival.

Blood 2019 12;134(24):2209-2217

Service d'Hématologie, AP-HP.6, Paris, France; and.

Older age is associated with increased mortality in immune thrombotic thrombocytopenic purpura (iTTP). Yet, data are scarce regarding iTTP occurring among older patients. To assess clinical features and long-term impact of iTTP on mortality in older patients (>60 years old), characteristics and prognoses of adult iTTP patients enrolled in the French Reference Center for Thrombotic Microangiopathies registry between 2000 and 2016 were described according to age (<60 years old or ≥60 years old). Long-term mortality of iTTP older survivors was compared with that of non-iTTP geriatric subjects. Comparing, respectively, older iTTP patients (N = 71) with younger patients (N = 340), time from hospital admission to diagnosis was longer (P < .0001); at diagnosis, delirium (P = .034), behavior impairment (P = .045), renal involvement (P < .0001), and elevated troponin level (P = .025) were more important whereas cytopenias were less profound (platelet count, 22 × 103/mm3 [9-57] vs 13 × 103/mm3 [9-21], respectively [P = .002]; hemoglobin level, 9 g/dL [8-11] vs 8 g/dL [7-10], respectively [P = .0007]). Short- and mid-term mortalities were higher (P < .0001) and increased for every 10 years of age range. Age ≥60 years, cardiac involvement, increased plasma creatinine level, and total plasma exchange volume were independently associated with 1-month mortality. Compared with a non-iTTP geriatric population, older survivors showed an increased long-term mortality (hazard ratio = 3.44; P < .001). In conclusion, older iTTP patients have atypical neurological presentation delaying the diagnosis. Age negatively impacts short-term but also long-term mortality.
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http://dx.doi.org/10.1182/blood.2019000748DOI Listing
December 2019

Clinico-pathological considerations in a 48-years-old female with acute kidney injury: is it lupus nephritis, ANCA-associated vasculitis or something else?

BMC Nephrol 2019 08 27;20(1):334. Epub 2019 Aug 27.

Service de Néphrologie-Dialyse-Transplantation, Université d'Angers, CHU Angers, 4 rue Larrey, 49033 Angers CEDEX 09, Angers, France.

Background: The value of ANCA positivity in the setting of systemic lupus erythematous and their pathogenicity remains uncertain.

Case Presentation: We report the case of a 48-year-old female with rapidly progressive kidney failure, arthro-myalgia and weight loss. Auto-immune screening showed anti-dsDNA antibodies, complement consumption and triple ANCA positivity. A first kidney biopsy done at presentation highlighted class IV-G glomerulonephritis with elective extra-capillary involvement and mainly C1q glomerular deposition at immunofluorescence study. After three months of a regimen combining steroids and cyclophosphamide, a second biopsy was performed and showed class IV-G glomerulonephritis with mainly endocapillary proliferation.

Conclusion: This case is atypical in view of immunological profile and kidney histopathological presentation and evolution and gives rise to discussion in view of recent data on ANCA value in lupus nephritis, and suggests that different auto-immune pathways may be involved in lupus nephritis.
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http://dx.doi.org/10.1186/s12882-019-1531-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6712693PMC
August 2019

Patients with ANCA-Associated Glomerulonephritis and Connective Tissue Diseases: A Comparative Study from the Maine-Anjou AAV Registry.

J Clin Med 2019 Aug 14;8(8). Epub 2019 Aug 14.

CHU Angers, Service de Néphrologie-Dialyse-Transplantation, Université d'Angers, 49100 Angers, France.

Background And Objectives: The overlap between antineutrophil cytoplasmic antibody (ANCA) associated glomerulonephritis (ANCA-GN) and connective tissue diseases (CTD) has been reported mainly as case series in the literature. Frequency of this association, as well as presentation and outcomes are unknown.

Materials And Methods: Patients from the Maine-Anjou ANCA-associated vasculitides (AAV) registry with ANCA-GN diagnosed between 01/01/2000 and 01/01/2018, ANCA positivity, and at least six months of follow-up, were included.

Results: 106 out of 142 patients fulfilled the inclusion criteria and were analyzed. CTD was present at ANCA-GN diagnosis in 16 (15.1%) patients. The most common CTD were rheumatoid arthritis, Sjogren syndrome and systemic sclerosis. Compared to the control group, females were more represented in the CTD group (75%, = 0.001). Renal presentation was comparable between groups, including the pathological analysis of renal biopsies. Patients of CTD group presented a higher rate of non-renal relapse (25% versus 7.7%, = 0.037), and experienced more frequently a venous thrombotic event (31.2% versus 10%, = 0.021). No difference between groups was observed according to major outcomes.

Conclusion: Association between CTD and ANCA-GN is not a rare condition and predominantly affects females. While AAV presentation is not significantly different, CTD patients experience more frequently non-renal relapse and venous thrombotic events.
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http://dx.doi.org/10.3390/jcm8081218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6723780PMC
August 2019

Extracorporeal photopheresis for the treatment of graft rejection in 33 adult kidney transplant recipients.

Transfus Apher Sci 2019 Aug 22;58(4):515-524. Epub 2019 Jul 22.

Service de Néphrologie, CHU Clermont-Ferrand, Clermont-Ferrand, France; Université Clermont Auvergne, Clermont-Ferrand, France.

Background - Extracorporeal photopheresis (ECP) has shown encouraging results in the prevention of allograft rejection in heart transplantation. However, the role of ECP in kidney transplant (KT) rejection needs to be determined. Methods - This multicentre retrospective study included 33 KT recipients who were treated with ECP for allograft rejection (23 acute antibody-mediated rejections (AMRs), 2 chronic AMRs and 8 acute cellular rejections (ACRs)). The ECP indications were KT rejection in patients who were resistant to standard therapies (n = 18) or in patients for whom standard therapies were contraindicated because of concomitant infections or cancers (n = 15). Results - At 12 months (M12) post-ECP, 11 patients (33%) had a stabilization of kidney function with a graft survival rate of 61%. The Banff AMR score (g + ptc + v) was a risk factor for graft loss at M12 (HR 1.44 [1.01-2.05], p < 0.05). The factorial mixed data analysis identified 2 clusters. Patients with a functional graft at M12 tended to have cellular and/or chronic rejections. Patients with graft loss at M12 tended to have acute rejections and/or AMR; higher serum creatinine levels; DSA levels and histologic scores of AMR; and a longer delay between the rejection and ECP start than those of patients with functional grafts. Conclusions - ECP may be helpful to control ACR or moderate AMR in KT recipients presenting concomitant opportunistic infections or malignancies when it is initiated early.
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http://dx.doi.org/10.1016/j.transci.2019.06.031DOI Listing
August 2019

CD45RC Expression of Circulating CD8 T Cells Predicts Acute Allograft Rejection: A Cohort Study of 128 Kidney Transplant Patients.

J Clin Med 2019 Aug 1;8(8). Epub 2019 Aug 1.

Service de Néphrologie-Dialyse-Transplantation, CHU Angers, 49000 Angers, France.

Predictive biomarkers of acute rejection (AR) are lacking. Pre-transplant expression of CD45RC on blood CD8 T cells has been shown to predict AR in kidney transplant (KT) patients. The objective of the present study was to study CD45RC expression in a large cohort of KT recipients exposed to modern immunosuppressive regimens. CD45RC expression on T cells was analyzed in 128 KT patients, where 31 patients developed AR, of which 24 were found to be T-cell mediated (TCMR). Pre-transplant CD4 and CD8 CR45RC T cell proportions were significantly higher in patients with AR. The frequency of CD45RC T cells was significantly associated with age at transplantation but was not significantly different according to gender, history of transplantation, pre-transplant immunization, and de novo donor specific anti-Human Leucocyte Antigen (HLA) antibody. Survival-free AR was significantly better in patients with CD8 CD45RC T cells below 58.4% (p = 0.0005), but not different according to CD4 T cells (p = 0.073). According to multivariate analysis, CD8 CD45RC T cells above 58.4% increased the risk of AR 4-fold (HR 3.96, p = 0.003). Thus, pre-transplant CD45RC expression on CD8 T cells predicted AR, mainly TCMR, in KT patients under modern immunosuppressive therapies. We suggest that CD45RC expression should be evaluated in a prospective study to validate its usefulness to quantify the pre-transplant risk of AR.
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http://dx.doi.org/10.3390/jcm8081147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6723395PMC
August 2019

Pre-transplant CD45RC expression on blood T cells differentiates patients with cancer and rejection after kidney transplantation.

PLoS One 2019 29;14(3):e0214321. Epub 2019 Mar 29.

LUNAM Université, Angers, France.

Background: Biological biomarkers to stratify cancer risk before kidney transplantation are lacking. Several data support that tumor development and growth is associated with a tolerant immune profile. T cells expressing low levels of CD45RC preferentially secrete regulatory cytokines and contain regulatory T cell subset. In contrast, T cells expressing high levels of CD45RC have been shown to secrete proinflammatory cytokines, to drive alloreactivity and to predict acute rejection (AR) in kidney transplant patients. In the present work, we evaluated whether pre-transplant CD45RClow T cell subset was predictive of post-transplant cancer occurrence.

Methods: We performed an observational cohort study of 89 consecutive first time kidney transplant patients whose CD45RC T cell expression was determined by flow cytometry before transplantation. Post-transplant events including cancer, AR, and death were assessed retrospectively.

Results: After a mean follow-up of 11.1±4.1 years, cancer occurred in 25 patients (28.1%) and was associated with a decreased pre-transplant proportion of CD4+CD45RChigh T cells, with a frequency below 51.9% conferring a 3.7-fold increased risk of post-transplant malignancy (HR 3.71 [1.24-11.1], p = 0.019). The sensibility, specificity, negative predictive and positive predictive values of CD4+CD45RChigh<51.9% were 84.0, 54.7, 89.8 and 42.0% respectively. Confirming our previous results, frequency of CD8+CD45RChigh T cells above 52.1% was associated with AR, conferring a 20-fold increased risk (HR 21.7 [2.67-176.2], p = 0.0004). The sensibility, specificity, negative predictive and positive predictive values of CD8+CD45RChigh>52.1% were 94.5, 68.0, 34.7 and 98.6% respectively. Frequency of CD4+CD45RChigh T cells was positively correlated with those of CD8+CD45RChigh (p<0.0001), suggesting that recipients with high AR risk display a low cancer risk.

Conclusion: High frequency of CD45RChigh T cells was associated with AR, while low frequency was associated with cancer. Thus, CD45RC expression on T cells appears as a double-edged sword biomarker of promising interest to assess both cancer and AR risk before kidney transplantation.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0214321PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6440623PMC
December 2019

OX40L/OX40 axis impairs follicular and natural Treg function in human SLE.

JCI Insight 2018 12 20;3(24). Epub 2018 Dec 20.

CNRS-UMR 5164 Immuno ConcEpT, Bordeaux University, Bordeaux, France.

Tregs are impaired in human systemic lupus erythematosus (SLE) and contribute to effector T cell activation. However, the mechanisms responsible for the Treg deficiency in SLE remain unclear. We hypothesized that the OX40L/OX40 axis is implicated in Treg and regulatory follicular helper T (Tfr) cell dysfunction in human SLE. OX40L/OX40 axis engagement on Tregs and Tfr cells not only specifically impaired their ability to regulate effector T cell proliferation, but also their ability to suppress T follicular helper (Tfh) cell-dependent B cell activation and immunoglobulin secretion. Antigen-presenting cells from patients with active SLE mediated Treg dysfunction in an OX40L-dependent manner, and OX40L-expressing cells colocalized with Foxp3+ cells in active SLE skin lesions. Engagement of the OX40L/OX40 axis resulted in Foxp3 downregulation in Tregs, and expression in SLE Tregs correlated with the proportion of circulating OX40L-expressing myeloid DCs. These data support that OX40L/OX40 signals are implicated in Treg dysfunction in human SLE. Thus, blocking the OX40L/OX40 axis appears to be a promising therapeutic strategy.
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http://dx.doi.org/10.1172/jci.insight.122167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6338386PMC
December 2018

Histologically proven acute tubular necrosis in a series of 27 ICU patients.

J Crit Care 2018 12 24;48:130-134. Epub 2018 Aug 24.

Département de Médecine Intensive Réanimation et Médecine hyperbare, CHU Angers, Université d'Angers, Angers, France. Electronic address:

Purpose: Since renal biopsy is rarely performed for identifying acute tubular necrosis in ICU patients, there is little information on the real histopathological abnormalities observed in such situations.

Materials And Methods: The clinical data of 27 patients with a confirmed diagnostic of acute tubular necrosis issued from two recent series gathering 125 patients who had renal biopsy during their ICU stay were reviewed. They were divided into sepsis (n = 14) and non-sepsis (n = 13) groups. Histopathologic lesions were reanalyzed and semi-quantitatively graded by a pathologist without knowledge of clinical characteristics of the patients.

Results: SAPS2 and SOFA scores were identical in the two groups. Half of the patients had neither sepsis nor shock. The histopathological score was higher in the septic than in the non-septic group: 9 [IC; 9-11] vs 7 [IC 5.25-8.75]; p = 0.01. There was no striking histopathological difference between septic and non-septic patients. However, the cytotoxic edema score was higher (3 [1; 3] vs 1 [0; 1]; p = 0.006), and interstitial infiltration with polymorphonuclears was more frequent (p = 0.02) in septic than in non-septic patients.

Conclusions: Septic and non-septic ICU patients with ATN had similar histopathologic features but lesions were more severe than in septic than in non-septic patients.
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http://dx.doi.org/10.1016/j.jcrc.2018.08.029DOI Listing
December 2018

Serum Magnesium after Kidney Transplantation: A Systematic Review.

Nutrients 2018 Jun 6;10(6). Epub 2018 Jun 6.

LUNAM Université, 49180 Angers, France.

Magnesium (Mg) status has recently drawn close attention in chronic kidney disease and in kidney transplant recipients. This review aims to evaluate the body of evidence linking hypomagnesemia to clinical consequences in these specific populations. After a brief summary of the main mechanisms involved in Mg regulation and of Mg status in end-stage renal disease, the review focuses on the relationship between hypomagnesemia and cardiovascular risk in kidney transplant recipients. A body of evidence in recent studies points to a negative impact of hypomagnesemia on post-transplant diabetes mellitus (PTDM) and cardiovascular risk, which currently represent the main threat for morbidity and mortality in kidney transplantation. Deleterious biological mechanisms induced by hypomagnesemia are also discussed. While data analysis enables us to conclude that hypomagnesemia is linked to the development of PTDM, studies prospectively evaluating the impact of hypomagnesemia correction after kidney transplantation are still lacking and needed.
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http://dx.doi.org/10.3390/nu10060729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6024843PMC
June 2018

Early post-transplant serum IgA level is associated with IgA nephropathy recurrence after kidney transplantation.

PLoS One 2018 25;13(4):e0196101. Epub 2018 Apr 25.

LUNAM Université, Angers, France.

IgA nephropathy (IgAN), the most frequent primary glomerulonephritis, affects young patients and is associated with a high risk of progression to end-stage renal disease. Consequently, patients with IgAN constitute an important proportion of candidates for kidney transplantation. Several studies showed a significant risk of IgAN recurrence on kidney graft, but the risks factors for recurrence remain to be accurately evaluated. Indeed, early identification of at risk patients may allow the optimization of treatment and the reduction of recurrence rate on the graft. In the present work, we studied the relationship between post-transplant serum IgA (sIgA) levels and the risk of IgAN recurrence after kidney transplantation. Recipients with IgAN had higher levels of sIgA as compared to patients with other nephropathies (p<0.05). The prevalence of IgAN recurrence was 20.8% during the period of analysis (mean follow-up of 6 ± 3.2 years). Serum IgA levels at M6, M12 and M24 post-transplant were significantly higher in patients with IgAN recurrence as compared to those without (p = 0.009, p = 0.035 and p = 0.029, respectively). Using receiver operating curve (ROC), sIgA at M6 and M12 post-transplant were significantly associated with IgAN recurrence (AUC = 0.771, p = 0.004 and AUC = 0.767, p = 0.016, respectively), while serum creatinine and proteinuria were not. Serum IgA level at month 6 was significantly associated with the occurrence of post-transplant IgA recurrence, whether it was analyzed as a continuous or a categorical variable. After successive adjustment on age, gender and proteinuria, sIgA remained a significant risk factor of post-transplant IgAN recurrence. Finally, survival free of IgAN recurrence was significantly better in patients with sIgA<222 mg/dL at month 6 as compare to IgAN patients with sIgA≥222 mg/dL (p = 0.03). Thus, the present work supports a link between post-transplant sIgA levels and IgAN recurrence and suggests that sIgA may be a valuable predictive biomarker of IgAN recurrence in kidney transplant recipients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0196101PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5919069PMC
July 2018

IgE in lupus pathogenesis: Friends or foes?

Autoimmun Rev 2018 Apr 7;17(4):361-365. Epub 2018 Feb 7.

ImmunoConcEpT, CNRS-UMR 5164 and Université de Bordeaux, 146 rue Léo Saignat, 33076 Bordeaux, France; Centre Hospitalier Universitaire de Bordeaux, FHU ACRONIM, Place Amélie Raba Léon, 33076 Bordeaux, France. Electronic address:

Systemic lupus erythematosus (SLE) is a complex autoimmune disease involving multiple immunological pathways. Recently, several studies have suggested an implication of Immunoglobulin E (IgE) in the pathophysiology of SLE. In the Lyn and FcγIIB.Yaa lupus mouse models, autoreactive IgE activate basophils, and promote a Th2 environment with, subsequently, production of autoantibodies by plasma cells. Autoreactive IgE has been also shown to play a role in the activation of human plasmacytoid dendritic cells (pDCs), in synergy with IgG, which results in an increase of interferon-alpha (IFN-α) production. In contrast, a protective effect of total non-autoreactive IgE has also been suggested, through a decreased ability of FcεRI-triggered pDCs to secrete IFN-α. This review summarizes in a comprehensive manner the emerging recent literature in the field, and propose new concepts to reconcile the observations.
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http://dx.doi.org/10.1016/j.autrev.2017.11.027DOI Listing
April 2018

Infectious complications of a rituximab-based immunosuppressive regimen in patients with glomerular disease.

Clin Kidney J 2017 Aug 10;10(4):461-469. Epub 2016 Nov 10.

Department of Nephrology, Hopital Europeen Georges Pompidou, Paris, France.

Background: Recent years have seen increasing use of rituximab (RTX) for various types of primary and secondary glomerulopathies. However, there are no studies that specifically address the risk of infection related to this agent in patients with these conditions.

Methods: We reviewed the outcomes of all patients who received RTX therapy for glomerular disease between June 2000 and October 2011 in eight French nephrology departments. Each case was analysed for survival, cause of death if a non-survivor and/or the presence of infectious complications, including severe or opportunistic infection occurring within the 12 months following RTX infusion.

Results: Among 98 patients treated with RTX, 25 presented with at least one infection. We report an infection rate of 21.6 per 100 patient-years. Five patients died within 12 months following an RTX infusion, of whom four also presented with an infection. The median interval between the last RTX infusion and the first infectious episode was 2.1 months (interquartile range 0.5-5.1). Most infections were bacterial (79%) and pneumonia was the most frequent infection reported (27%). The presence of diabetes mellitus (P = 0.006), the cumulative RTX dose (P = 0.01) and the concomitant use of azathioprine (P = 0.03) were identified as independent risk factors. Renal failure was significantly associated with an increased infection risk by bivariate analysis (P = 0.03) and was almost significant by multivariate analysis (P = 0.05). Nephrotic syndrome did not further increase the risk of infection and/or death.

Conclusion: The risk of infection after RTX-based immunosuppression among patients with glomerulopathy must be considered and patients should receive close monitoring and appropriate infection prophylaxis, especially in those with diabetes and high-dose RTX regimens.
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http://dx.doi.org/10.1093/ckj/sfw101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5570029PMC
August 2017

Characteristics and Management of IgA Vasculitis (Henoch-Schönlein) in Adults: Data From 260 Patients Included in a French Multicenter Retrospective Survey.

Arthritis Rheumatol 2017 09;69(9):1862-1870

Department of Nephrology, Hôpital Saint Louis, AP-HP, Université Paris Descartes, Paris, France.

Objective: Data on adult IgA vasculitis (Henoch-Schönlein) (IgAV) are scarce. This survey was designed to better define the clinical spectrum of IgAV and efficacy of treatments in a French patient population.

Methods: Data on clinical characteristics, histologic features, and treatment response from 260 patients with IgAV included in a French multicenter retrospective survey were analyzed. Efficacy data were compared using different statistical models.

Results: The mean ± SD age of the patients with IgAV at diagnosis was 50.1 ± 18 years, and 63% of patients were male. Baseline manifestations included purpura (100%), arthralgias/arthritis/myalgia (61%), glomerulonephritis (70%), and/or gastrointestinal involvement (53%). Thirty percent of patients showed renal failure at baseline. In univariate analysis, the response to therapy was 80% (64 of 80) in patients treated with corticosteroids (CS) alone, compared to 77% (23 of 30) in patients treated with CS plus cyclophosphamide (CYC) and 59% (10 of 17) in patients treated with colchicine (P = 0.17). Multivariable analysis showed that treatment with CS or CS plus CYC was more effective than colchicine in achieving a response. Efficacy differences were demonstrated using different statistical models: in the multivariable logistic regression model, odds ratio (OR) 3.68, 95% confidence interval (95% CI) 1.10-12.33 (P = 0.03); in the inverse probability weighting on propensity score model, OR 3.75, 95% CI 1.28-10.99 (P = 0.02). The efficacy of CS plus CYC as compared to CS alone was discordant according to the analytic method used. Analysis with the multivariable logistic regression model did not demonstrate a difference between CS plus CYC and CS alone (OR 0.88, 95% CI 0.29-2.67; P = 0.82). In contrast, inverse probability weighting on propensity score showed that CS plus CYC was more effective than CS alone (OR 1.79, 95% CI 1.00-3.20; P = 0.049).

Conclusion: This series constitutes the largest series of adults with IgAV reported in the literature so far. It provides data on clinical and histologic presentation and therapeutic efficacy, suggesting that CS alone appears to be a reasonable first-line therapy in patients with IgAV, while the benefit of adding CYC to CS remains uncertain.
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http://dx.doi.org/10.1002/art.40178DOI Listing
September 2017

Anti-pentraxin antibodies in autoimmune systemic diseases: Focus on anti-pentraxin-3 autoantibodies.

Int Rev Immunol 2017 05 4;36(3):145-153. Epub 2017 May 4.

b Angers University Hospital , University of Angers , Angers , France.

Pentraxins are soluble pattern recognition molecules implicated not only in the opsonization and removal of microorganisms but also in the clearance of modified self (i.e., dying cells). Pentraxins can be classified into short pentraxins (C-reactive protein and serum amyloid-P component) and long pentraxins with pentraxin-3 (PTX3), the prototypic one of the latter. Pentraxins are involved in various physiological or pathophysiological processes such as inflammation and autoimmunity. A breakdown in immune tolerance to pentraxins has been reported in various autoimmune diseases. In the present review, we analyzed the current knowledge concerning anti-pentraxin antibodies, with a special focus on anti-PTX3 autoantibodies.
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http://dx.doi.org/10.1080/08830185.2017.1284210DOI Listing
May 2017