Effects Of Immunosuppressive Therapy Research Articles

Dendritic Cells: A Bridge between Tolerance Induction and Cancer Development in Transplantation Setting.

Dendritic cells (DCs) are a heterogeneous group of antigen-presenting cells crucial for fostering allograft tolerance while simultaneously supporting host defense against infections and cancer. Within the tumor microenvironment, DCs can either mount an immune response against cancer cells or foster immunotolerance, presenting a dual role. In immunocompromised individuals, posttransplant malignancies pose a significant health concern, with DCs serving as vital players in immune responses against cancer cells. Both recipient- and donor-derived DCs play a critical role in the rejection process, infiltrating the transplanted organ and sustaining T-cell responses. The use of immunosuppressive drugs represents the predominant approach to control this immunological barrier in transplanted organs. Evidence has shed light on the immunopharmacology of these drugs and novel strategies for manipulating DCs to promote allograft survival. Therefore, comprehending the mechanisms underlying this intricate microenvironment and the effects of immunosuppressive therapy on DCs is crucial for developing targeted therapies to reduce graft failure rates. This review will delve into the fundamental immunobiology of DCs and provide a detailed exploration of their clinical significance concerning alloimmune responses and posttransplant malignancies.

Splenectomy Before Kidney Transplantation for Hypersplenism: A Case Report

Hypersplenism, although a rare hematological complication seen in chronic kidney disease patients, poses a significant challenge for successful kidney transplantation due to potential complications such as cytopenias and inadequate immunosuppressive therapy. We present a 40-year old end-stage kidney disease patient on dialysis with hypersplenism who underwent a laparoscopic splenectomy prior to high immunological risk renal transplantation. Post-splenectomy, there was a remarkable improvement in cytopenias, and effective immunosuppressive therapy could be administered prior to renal transplantation. Splenectomy remains a valuable strategy for managing hypersplenism, ensuring correction of cytopenias, for optimal immunosuppression prior to kidney transplantation. Pre-transplant vaccination further mitigates the risk infections with capsulated organisms. Our case underscores the importance of a multidisciplinary approach in decision-making and highlights splenectomy as a safe and effective intervention to address cytopenias due to hypersplenism prior to renal transplantation.

Survival in systemic sclerosis associated pulmonary arterial hypertension in the current treatment era-results from a nationwide study.

Pulmonary arterial hypertension (PAH) is a leading cause of mortality in systemic sclerosis (SSc). This nationwide study aims to describe real world treatment characteristics and assess survival rates of patients with SSc-PAH. In this retrospective cohort study, patients with SSc-PAH were identified from Turkish Ministry of Health National Electronic Database (from January 2016 to September 2022), using ICD-10 codes. Data on demographics, treatment characteristics, and death was collected. Kaplan-Meier curves were used to calculate cumulative probabilities of survival at 1, 3, and 5years. Five hundred forty-seven patients (90.7% female) with SSc-PAH were identified. Median age at PAH diagnosis was 59.9 (50.0-67.4) years. During a median follow-up duration of 3.2 (1.5-4.8) years, 199 (36.4%) deaths occurred. Estimated survival rates at 1, 3, and 5years were 90.2%, 73.2%, and 56.6%, respectively. Survival was similar among patients with and without interstitial lung disease (p = 0.20). Patients who used immunosuppressives had better survival than those who did not (p < 0.001). No difference was observed in survival rates according to initial PAH-specific treatment regimen (monotherapy or combination) (p = 0.49). Compared to most of historical cohorts, higher survival rates for SSc-PAH were observed in this study. Early diagnosis of PAH may have contributed to these findings. The impact of immunosuppressive therapy on prognosis of SSc-PAH needs to be further investigated in prospective studies. Key Points • Early diagnosis is pivotal for better outcomes in SSc-PAH. • Implementation of PAH treatment guidelines in routine clinical practice is still poor and should be improved. • Effect of immunosuppressive therapies on disease course has to be defined in SSc-PAH.

The effect of immunosuppressive therapies on the endothelial host response in critically ill COVID-19 patients

While several effective therapies for critically ill patients with COVID-19 have been identified in large, well-conducted trials, the mechanisms underlying these therapies have not been investigated in depth. Our aim is to investigate the association between various immunosuppressive therapies (corticosteroids, tocilizumab and anakinra) and the change in endothelial host response over time in critically ill COVID-19 patients. We conducted a pre-specified multicenter post-hoc analysis in a Dutch cohort of COVID-19 patients admitted to the ICU between March 2020 and September 2021 due to hypoxemic respiratory failure. A panel of 18 immune response biomarkers in the complement, coagulation and endothelial function domains were measured using ELISA or Luminex. Biomarkers were measured on day 0–1, day 2–4 and day 6–8 after start of COVID-19 treatment. Patients were categorized into four treatment groups: no immunomodulatory treatment, corticosteroids, anakinra plus corticosteroids, or tocilizumab plus corticosteroids. The association between treatment group and the change in concentrations of biomarkers was estimated with linear mixed-effects models, using no immunomodulatory treatment as reference group. 109 patients with a median age of 62 years [IQR 54–70] of whom 72% (n = 78) was male, were included in this analysis. Both anakinra plus corticosteroids (n = 22) and tocilizumab plus corticosteroids (n = 38) were associated with an increase in angiopoietin-1 compared to no immune modulator (n = 23) (beta of 0.033 [0.002–0.064] and 0.041 [0.013–0.070] per day, respectively). These treatments, as well as corticosteroids alone (n = 26), were further associated with a decrease in the ratio of angiopoietin-2/angiopoietin-1 (beta of 0.071 [0.034–0.107], 0.060 [0.030–0.091] and 0.043 [0.001–0.085] per day, respectively). Anakinra plus corticosteroids and tocilizumab plus corticosteroids were associated with a decrease in concentrations of complement complex 5b-9 compared to no immunomodulatory treatment (0.038 [0.006–0.071] and 0.023 [0.000–0.047], respectively). Currently established treatments for critically ill COVID-19 patients are associated with a change in biomarkers of the angiopoietin and complement pathways, possibly indicating a role for stability of the endothelium. These results increase the understanding of the mechanisms of interventions and are possibly useful for stratification of patients with other inflammatory conditions which may potentially benefit from these treatments.

Possible Effects of Immunosuppressive Therapy on Male Fertility and Pregnancy Outcomes After Paternal Exposure in Kidney Transplant Patients

Possible Effects of Immunosuppressive Therapy on Male Fertility and Pregnancy Outcomes After Paternal Exposure in Kidney Transplant Patients

Immunosuppressive strategies in face and hand transplantation: a comprehensive systematic review of current therapy regimens and outcomes.

Recipients of Vascularized Composite Allotransplants require effective immunosuppressive therapy to prevent graft rejection. This systematic review summarizes the current body of literature on immunosuppressive regimens used in face and hand transplants while summarizing their outcome in terms of rejection, renal failure, and infections. A systematic search of electronic databases was conducted to identify relevant studies from 1998 until July 1st, 2023. We included all studies that discussed immunosuppressive strategies in face and hand transplant recipients according to PRISMA. The standard triple maintenance therapy was mostly adjusted due to nephrotoxicity or high incidence of rejection. The most common alternative treatments utilized were sirolimus (25/91; 27.5%) or everolimus (9/91; 9.9%) following hand- and photophoresis (7/45; 15.6%), sirolimus (5/45; 11.1%) or belatacept (1/45; 2.2%) following face transplantation. Episodes of rejection were reported in 60 (65.9%) of hand- and 33 (73%) of face transplant patients respectively. Graft loss of 12 (13.2%) hand and 4 (8.9%) face transplants was reported. Clinical CMV infection was observed in 6 (6.6%) hand and 7 (15.5%) face transplant recipients. Based on the herein presented data, facial grafts exhibited a heightened incidence of rejection episodes and CMV infections. Facial mucosa adds complexity to the immunological graft composition highlighting the need of individualized immunosuppressive regimens and further research.

A brief review of the current status of pig islet xenotransplantation.

An estimated 1.5 million Americans suffer from Type I diabetes mellitus, and its incidence is increasing worldwide. Islet allotransplantation offers a treatment, but the availability of deceased human donor pancreases is limited. The transplantation of islets from gene-edited pigs, if successful, would resolve this problem. Pigs are now available in which the expression of the three known xenoantigens against which humans have natural (preformed) antibodies has been deleted, and in which several human 'protective' genes have been introduced. The transplantation of neonatal pig islets has some advantages over that of adult pig islets. Transplantation into the portal vein of the recipient results in loss of many islets from the instant blood-mediated inflammatory reaction (IBMIR) and so the search for an alternative site continues. The adaptive immune response can be largely suppressed by an immunosuppressive regimen based on blockade of the CD40/CD154 T cell co-stimulation pathway, whereas conventional therapy (e.g., based on tacrolimus) is less successful. We suggest that, despite the need for effective immunosuppressive therapy, the transplantation of 'free' islets will prove more successful than that of encapsulated islets. There are data to suggest that, in the absence of rejection, the function of pig islets, though less efficient than human islets, will be sufficient to maintain normoglycemia in diabetic recipients. Pig islets transplanted into immunosuppressed nonhuman primates have maintained normoglycemia for periods extending more than two years, illustrating the potential of this novel form of therapy.

Non-invasive molecular biomarkers for monitoring solid organ transplantation: A comprehensive overview.

Solid organ transplantation is a life-saving intervention for individuals with end-stage organ failure. Despite the effectiveness of immunosuppressive therapy, the risk of graft rejection persists in all viable transplants between individuals. The risk of rejection may vary depending on the degree of compatibility between the donor and recipient for both human leucocyte antigen (HLA) and non-HLA gene-encoded products. Monitoring the status of the allograft is a critical aspect of post-transplant management, with invasive biopsies being the standard of care for detecting rejection. Non-invasive biomarkers are increasingly being recognized as valuable tools for aiding in the detection of graft rejection, monitoring graft status and evaluating the efficacy of immunosuppressive therapy. Here, we focus on the importance of molecular biomarkers in solid organ transplantation and their potential role in clinical practice. Conventional molecular biomarkers used in transplantation include HLA typing, detection of anti-HLA antibodies, killer cell immunoglobulin-like receptor genotypes, and anti-MHC class 1-related chain A antibodies, which are important for assessing the compatibility of the donor and recipient. Emerging molecular biomarkers include the detection of donor-derived cell-free DNA, microRNAs (regulation of gene expression), exosomes (small vesicles secreted by cells), and kidney solid organ response test, in the recipient's blood for early signs of rejection. This review highlights the strengths and limitations of these molecular biomarkers and their potential role in improving transplant outcomes.

Cold autoimmune hemolytic anemia

Cold agglutinins are antibodies that recognize antigens on erythrocytes at temperatures below normal body temperature. Antibodies are of IgM nature and bind to “I” or “i” antigens on red blood cells, causing agglutination in red blood cells. This situation results in anemia by creating extravascular hemolysis. If there is no underlying disease, it is called primary or idiopathic cold agglutinin disease (CAD), and if there is, it is called secondary cold agglutinin syndrome (CAS). Primary CAD is an extremely rare disease, with an incidence and prevalence of 1 per million and 16 per million, respectively. It is seen twice more in women than in men, and the median age of diagnosis is 67 (between 30-92 years). The etiology of CAS includes infections, autoimmune and lymphoproliferative diseases. There are cold-related symptoms and symptoms of anemia in the clinic. In treatment, it is necessary to avoid cold in order to reduce cold-induced symptoms and hemolysis. Currently, the most effective treatment for reducing antibody production is rituximab. It can be given alone or in combination with bendamustine, interferon alfa, fludarabine and prednisolone. bortezomib is used when rituximab is ineffective or contraindicated. Plasmapheresis or intravenous immunoglobulin can be given when there is critical hemolysis or when the effectiveness of immunosuppressive therapy may start late. Treatment in CAS is the treatment of the underlying disease.

Mycophenolate mofetil as induction and maintenance immunosuppressive therapy in adult primary central nervous system vasculitis: A prospective observational study.

To observe the clinical and angiographic effectiveness of mycophenolate mofetil (MMF) as induction and maintenance immunosuppressive therapy in primary central nervous system vasculitis (PCNSV). In this open-label prospective study done at a tertiary care neurology centre, adult patients with PCNSV, diagnosed by Calabrese's criteria, were recruited from 2017 to 2021 and treated with glucocorticoids, MMF and standard of care. Patients were followed-up and clinical and angiographic changes were recorded. Total 26 patients were recruited with median age 39years (34-49) with a slight female predilection (61.5%). Angiographic diagnoses were: small vessels disease 11.5%; large vessels disease 42.3% and both in 46.2%. Median duration of follow-up was 24.5months (14.25-38). Proportion of patients with severe disability (modified Rankin Score (mRS) 4-6) at baseline was 73.08% (19/26) which reduced to 7.69% (2/26) (p < 0.001). At the last follow-up mRS = 0 was achieved in 38.5% (10/26) and mRS of ≤ 1 was achieved in 69.2% (18/26). Median time to achieve a mRS ≤ 1 was 12months (95% CI: 6.8-17.2). Angiography was repeated in 16 patients after a median duration of 13months (10.5-19.7), out of which 10 (62.5%) showed improvement and 5 (31.2%) showed non-progression of lesions. MMF may be an effective immunosuppressive therapy in adult PCNSV as both induction and maintenance. Serial DSA of brain may be useful to monitor the effect of treatment. Key Points • Mycophenolate mofetil is effective as induction and maintenance immunosuppressive therapy in PCNSV. • Repeat angiogram may be useful to monitor treatment response in PCNSV.

Ocular Myasthenia Gravis: A Current Overview.

Ocular myasthenia gravis (OMG) is a neuromuscular disease characterized by autoantibody production against post-synaptic proteins in the neuromuscular junction. The pathophysiological auto-immune mechanisms of myasthenia are diverse, and this is governed primarily by the type of autoantibody production. The diagnosis of OMG relies mainly on clinical assessment, the use of serological antibody assays for acetylcholine receptors (AchR), muscle-specific tyrosine kinase (MusK), and low-density lipoprotein 4 (LPR4). Other autoantibodies against post-synaptic proteins, such as cortactin and agrin, have been detected; however, their diagnostic value and pathogenic effect are not yet clearly defined. Clinical tests such as the ice test and electrophysiologic tests, particularly single-fiber electromyography, have a valuable role in diagnosis. The treatment of OMG is primarily through cholinesterase inhibitors (pyridostigmine), and steroids are frequently required in cases of ophthalmoplegia. Other immunosuppressive therapies include antimetabolites (azathioprine, mycophenolate mofetil, methotrexate) and biological agents such as B-cell depleting agents (Rituximab) and complement inhibitors (eculizumab). Evidence is scarce on the effect of immunosuppressive therapy on altering the natural course of OMG. Clinicians must be vigilant of a myasthenic syndrome in patients using immune-check inhibitors. Reliable and consistent biomarkers are required to assess disease severity and response to therapy to optimize the management of OMG. The purpose of this review is to summarize the current trends and the latest developments in diagnosing and treating OMG.

Lupus nephropathy beyond immunosuppression: Searching for nephro and cardioprotection.

Renal involvement in systemic lupus erythematosus (SLE) represents one of the most frequent organ manifestations, often leading to end-stage kidney disease (ESKD). Several therapies have been tested in patients with lupus nephritis (LN) to prevent further organ damage. The effectiveness of immunosuppressive therapy as a treatment for LN is abundant, supported by multiple clinical trials that have shown its efficacy in preventing the development of chronic kidney disease (CKD). In addition to immunosuppressive therapy, several traditional and recent therapies aimed at nephroprotection in patients with proteinuric chronic kidney disease are gaining importance in the setting of LN. Thus, immunosuppressive therapy should be accompanied by nephro- and cardioprotective measures to control cardiovascular risk factors and proteinuria to ensure a better renal prognosis. Despite this, the literature on these specific measures is relatively scarce, with recommendations focused on the blockade of the renin-angiotensin-aldosterone system (RAAS). This review explores the pharmacological options available for cardiovascular and renal protection outside the usual treatment schemes.

Extracellular Vesicle-Associated TWEAK Contributes to Vascular Inflammation and Remodeling During Acute Cellular Rejection

Acute cellular rejection (ACR) is a leading cause of graft loss and death after heart transplantation despite effective immunosuppressive therapies. The identification of factors that impair graft vascular barrier function or promote immune cell recruitment during ACR could provide new therapeutic opportunities for the treatment of patients who receive transplants. In 2 ACR cohorts, we found theextracellular vesicle-associated cytokine TWEAK to be elevated during ACR. Vesicular TWEAK promoted expression of proinflammatory genes and the release of chemoattractant cytokines from human cardiac endothelial cells. We conclude that vesicular TWEAK is a novel target with potential therapeutic implications in ACR.

SARS-CoV-2 post-vaccination adverse reports: A review

Acute respiratory infection caused by the SARS-CoV-2 coronavirus was the cause of the pandemic announced in March 2020. To prevent this disease, various vaccines have been developed and introduced into mass use, including on an innovative gene platform. The aim of the review is to analyze foreign literature on post-vaccination complications with the use of foreign vaccines, as well as whole-virion vaccines for the period 2021 — January 2023. The sources used in the publication were obtained from the Medline database, as well as articles in peer-reviewed journals and official reports. Post-vaccination complications are associated with specific damage to organs or systems either directly by the vaccine itself or indirectly as a result of exacerbation of the chronic process. The pathogenesis of post-vaccination complications depends on the composition of the vaccine. All complications were grouped by organs and systems. Vaccines containing SARS-CoV-2 antigens can activate autoimmune reactions due to homology, as well as activation of existing reactions in predisposed patients, which is confirmed by the effectiveness of immunosuppressive therapy. Innovative platforms using gene technologies are so complex and profoundly active that they can be introduced into broad medical practice only after a thorough and comprehensive study of the effects and mechanisms. Scientific achievements should follow the ethical principles of healing, and above all primum non nocere. Experts around the world emphasize the need for continued monitoring of people’s condition in order to protect their health and assess the long-term safety of drugs.

Reasons for misdiagnosis of polymyositis in patients with dysferlinopathy: a clinical case

Differential diagnosis of inflammatory myopathies with hereditary muscular dystrophies accompanied by a secondary inflammatory process is a time‑consuming clinical and pathomorphological task. In particular, false diagnosis of polymyositis in patients with dysferlinopathy reaches 25 % of cases.A 40‑year‑old female patient with a limb‑girdle phenotype of dysferlinopathy, initially diagnosed as polymyositis, is presented. The reasons that led to the erroneous diagnosis were: sporadic case; subacute onset; proximal muscle weakness; myalgia, which stopped on the glucocorticosteroid therapy; high levels of creatine phosphokinase (up to 17 times); the presence of lymphocytic‑macrophage infiltrate in the muscle biopsy and the absence of magnetic resonance imaging data in primary examination of the patient.The refractoriness of clinical and laboratory signs to complex immunosuppressive therapy was the reason for revising the muscle biopsy with typing of the inflammatory infiltrate. The predominantly unexpressed perivascular infiltrate was characterized by the predominance of macrophages and, to a lesser extent, CD4+, which indicated the secondary nature of the inflammation in the muscle observed in some hereditary muscular dystrophies. When conducting an immunohistochemical reaction, the absence of the dysferlin protein in the sarcoplasmic membrane was revealed.Whole‑exome sequencing (NGS) revealed a mutation in exon 39 of the DYSF gene (p.Gln1428Ter) in the heterozygous state, which leads to the appearance of a stop codon and premature termination of protein translation. MLPA method registered 3 copies of exons 18, 19, 20, 22, 24 of the DYSF gene.Thus, this clinical example reflects the main methodological errors and possible effects of immunosuppressive therapy in patients with dysferlinopathy.

Combination Therapy to Enable AAV Re-Dosing and Mitigate Transgene Immunity in Liver-Targeted Gene Therapy

Liver directed gene delivery with AAV has made tremendous strides in the last decade and is poised to cure disorders such as hemophilia A and B. Although AAV is typically considered to be relatively innocuous, immunogenicity to the vector, its genome, and encoded transgene has resulted in innate and adaptive immunotoxicities as well as loss of the transgene product, which not only limit efficacy, but also raise important safety concerns. A major impediment to patient re-dosing with AAV is the formation of high-titer neutralizing antibodies (NAb) to the viral capsid following first administration. The right combination of immunosuppressive (IS) drugs have the capacity to control NAb formation, as well as mitigate innate and adaptive immune responses to both the vector and the transgene product. We tested hepatic gene delivery with AAV8 in C57BL/6 mice (n=8-10), using a dose (1X1011 vg/kg) that was previously shown to induce CD8+ T cells to the model transgene, ovalbumin (OVA). We compared (i) B cell depletion with α-CD20, 2 X 250μg doses spaced 3 weeks apart), (ii) α-CD20 combined with the mTOR inhibitor rapamycin (α-CD20+rapa, oral gavage with 4mg/kg rapa, 3X/week/5 weeks), (iii) α-CD20 combined with an antibody to B cell activating factor (α-CD20+α-BAFF, 2 X 60μg doses spaced 10 days apart), a cytokine that we confirmed to be crucial for B cell survival [(J Clin Invest 2021, 15;131(8)]. IS therapies administered concurrent with AAV8 gene therapy caused a high frequency of animals (40 - 75%) to develop transgene immunity (H-2 Kb SIINFEKL tetramer+), corresponding with loss of OVA expression in the liver and in circulation. OVA-CD8+ T cells had a short-lived effector memory phenotype in blood and spleen, characterized as CD44+CD62L-CCR7-KLRG1+CX3CR1+. Interestingly, there were much higher frequencies of OVA-CD8+ T cells in the liver, even when they were undetectable in blood and spleen, and their presence in the liver did not completely correlate with loss of OVA expression. In line with this observation, OVA-CD8+ T cells in the liver expressed multiple exhaustion markers PD1, 2B4, LAG3, TIM3, highly upregulated transcription factors TBet, STAT3, and BATF, but not TCF1, and did not express KLRG1 and CX3CR1 expression. All control and IS treated groups of animals developed NAb (IgM and IgG2c, equivalent to IgG1 in human) to the AAV8 vector, which precluded re-administration with the same AAV serotype (5X1012 vg/kg of AAV8-hFIX). In contrast, when IS therapies were initiated 3 weeks prior to AAV8 gene therapy (1X1011 vg/kg), we were successfully able to re-administer AAV8-hFIX (n=6-10) to 70% of α-CD20, 75% of α-CD20+rapa, and 80% of α-CD20+α-BAFF treated animals without transgene immunity development. Re-administration was unsuccessful in animals that did not receive immune modulation. We then tested pre-IS therapy with a clinically relevant primary administration dose (5X1012 vg/kg of AAV8-OVA). We were able to re-administer AAV8-hFIX to 44% of α-CD20, 88% of α-CD20+rapa, and 67% of α-CD20+α-BAFF treated animals. Mice that were precluded from re-dosing with AAV8-hFIX in the IS treatment groups had high circulating BAFF levels, which correlated with the development of α-AAV8 IgM NAbs. To validate this finding and mitigate α-AAV8 IgM NAbs, we extended α-BAFF injections for an additional 4 weeks in the α-CD20+α-BAFF group (n=10). Extending α-BAFF treatment prevented both BAFF and IgM production, allowing not only successful re-dosing in 100% of animals but also higher circulating FIX levels (12901 ± 686.7ng/mL) as compared to mice that only received AAV8-FIX (9725 ± 415.5 ng/mL). Finally, we tested the practicality of α-CD20+extended α-BAFF treatment in the event of delayed AAV8 re-dosing, once immune compartments have completely repopulated (~14 weeks based on flow cytometry analysis). We were successfully able to re-dose 100% of α-CD20+extended α-BAFF pre-IS treated mice with AAV8-FIX following a delayed re-administration schedule (15 weeks). FIX expression levels remained stable until the last timepoint tested (16 weeks post re-dosing). We conclude that timing and duration of IS, vector dose and transgene immunogenicity are important considerations in developing effective IS therapies. We propose that pre-IS therapy with αCD20+ extended αBAFF is an effective candidate to enable re-dosing with clinically relevant doses of AAV.

Early clinical course of biopsy-proven IgA vasculitis nephritis

BackgroundIgA vasculitis (IgAV) is the most common form of systemic vasculitis in childhood and frequently involves the kidney. A minority of patients with IgA vasculitis nephritis (IgAVN), especially those presenting with heavy proteinuria and/or kidney failure at onset, are at risk of chronic end-stage kidney disease. For deciding upon treatment intensity, knowledge of the short-term clinical course of IgAVN is needed to improve treatment algorithms.MethodsFor this retrospective multicenter study, the medical records of 66 children with biopsy-proven IgAVN were reviewed. Age, gender, medical history and therapeutic interventions were recorded. Laboratory data included serum creatinine, albumin, urinary protein excretion (UPE) and glomerular filtration rate (eGFR). Threshold values were determined for each parameter, full remission was defined as no proteinuria and eGFR > 90 ml/min/1.73m2.ResultsMedian age at onset of IgAVN was 8.9 years. 14.1% of the children presented with nephrotic syndrome, 50% had an eGFR below 90 ml/min/1.73 m2 and 51.5% showed cellular crescents in renal histology. The treatment regimens varied notably. Forty-four patients were treated with immunosuppression; 17 patients with crescents or nephrotic syndrome were treated with corticosteroid (CS) pulse therapy. After 6 months, UPE had decreased from 3.7 to 0.3 g/g creatinine and the proportion of patients with a decreased eGFR had fallen from 50.0% to 35.5%. Thirteen children (26.5%) achieved full remission within 6 months.ConclusionsIn most patients with IgAVN proteinuria decreases slowly and kidney function improves, but full remission is reached only in a minority after 6 months. Persistent heavy proteinuria in the first two months rarely developed into long-term proteinuria. Therefore, decisions for more intense treatment should take into account the course of UPE over time.For a comparison of treatment effects, patient numbers were too small. Prospective, randomized controlled trials are necessary to clarify risk factors and the effect of immunosuppressive therapies.

An uncommon case of complete AV block

BackgroundGranulomatosis with polyangiitis (GPA) is a rare systemic inflammatory disorder characterized by vasculitis of the small vessels, as well as necrotizing granulomatous lesions, affecting mainly upper and lower respiratory tracts, lungs and kidneys. Cardiac involvement has traditionally been a rare manifestation of GPA, with misleading clinical presentation until late stages. Cardiac conducting tissue involvement is a rare and potentially life-threatening complication.Case presentationWe report the case of a 45-year-old man diagnosed with GPA with typical symptoms, but also complete atrioventricular (AV) block at the onset of the disease. The echocardiogram was unremarkable but the cardiac magnetic resonance (CMR) showed evidence of inflammation of the basal and septal ventricle walls. Despite effective immunosuppressive therapy, a permanent pacemaker was required for recurring complete AV block.DiscussionConduction system abnormalities are a rare manifestation of GPA, due to granulomatous lesions within the conduction system, or arteritis of the atrioventricular nodal artery. Patients are often asymptomatic, so careful and regular screening for cardiac involvement in this multi-system condition is required, often with echocardiogram, electrocardiogram (ECG) monitoring and CMR. Early immunosuppressive treatment may reverse a complete AV block but a pacemaker implantation may sometimes be necessary.

Proceedings of the 28th European Paediatric Rheumatology Congress (PReS 2022)

Proceedings of the 28th European Paediatric Rheumatology Congress (PReS 2022)

Parvovirus B19 infection and anemia after kidney transplantation: a report of two cases

Post-transplantation anemia is common among renal transplant recipients (RTR). The most frequent causes are erythropoietin deficiency, acute allograft rejection, iron deficiency, hemolytic anemia, adverse effects of immunosuppressive therapy, and virus infection. Human parvovirus B19 (HPV B19) can cause persistent viremia and erythropoietin-resistant erythroid aplasia in immunosuppressed patients. This case report describes two male renal transplant recipients who infected HPV B19 after kidney transplantation with severe anemia. Rapid and severe anemia that did not respond to blood transfusion. Adjustment of immunosuppressive drugs and intravenous immunoglobulin treatment resolved severe anemia after two months. In conclusion, when anemia develops rapidly and severely in renal transplant recipients in the absence of rejection and hemolysis, parvovirus B19 infection should be considered.