Administration Of Immunosuppressive Drugs Research Articles

Self-limited Polymyalgia Rheumatica-like Syndrome Following mRNA-1273 SARS-CoV-2 Vaccination.

Polymyalgia rheumatica (PMR) is an inflammatory rheumatic disease characterized by stiffness and aching mainly in the shoulders, neck and hip girdles. The underlying pathogenesis of PMR involves myeloid lineage activation with a high expression of pattern recognition receptors. In addition, vaccination against severe acute respiratory syndrome coronavirus 2 with mRNA-1273 functions as both an immunogen and intrinsic adjuvant. It leads to the activation of innate immunity, resulting in antibody production. We herein report the first case of PMR-like syndrome seven days after mRNA-1273 vaccination. Reassuringly, the symptoms, such as pain of the neck, shoulder girdle and pelvic girdle, as well as elevated inflammatory markers were resolved within a month without glucocorticoid or immunosuppressant administration.

Netosis in the pathogenesis of antiphospholipid syndrome and systemic lupus erythematosus

Antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE) are autoimmune diseases. In recent years, APS has been considered as an autoimmune thrombo-inflammatory disease. It has been established that clinical manifestations of APS can persist, progress over time, or debut during an adequate anticoagulant therapy and, in some cases, require administration of immunosuppressive drugs, which indicates the role of autoimmune inflammation in their development. The formation of extracellular neutrophil traps (neutrophil extracellular traps, NETs) is one of the connecting links of inflammation and thrombosis. Netosis is the process by which activated neutrophils in the extracellular space form netlike structures (NETs). This review examines the role of neutrophils and netosis in the pathogenesis of APS and SLE.

Surgical resection of a rapidly growing pulmonary spindle cell carcinoma by robot-assisted thoracoscopic surgery: a case report

BackgroundPulmonary spindle cell carcinoma (PSCC) is an extremely rare tumor that is highly malignant and fast-growing. As chemotherapy and radiation therapy are ineffective, early surgical resection is effective for PSCC.Case presentationA 70-year-old woman with rheumatoid arthritis was referred to our hospital with an abnormal shadow. Chest computed tomography revealed a 33-mm-wide lobular mass in the right upper lobe. She was diagnosed with non-small cell lung cancer by bronchoscopic smear cytology. Although staging evaluation indicated stage IIIB (T3N2M0) disease, she required continued administration of immunosuppressants and prednisolone for rheumatoid arthritis. Therefore, robot-assisted thoracoscopic surgery (RATS) right upper lobectomy followed by lymph node dissection was performed without preoperative chemotherapy and radiotherapy. Pathological findings revealed PSCC.ConclusionsWe report a very rare case of pulmonary spindle cell carcinoma, successfully resected with RATS.

Optimization of an Evaluation Method for Anti-Babesia microti Drug Efficacy

Babesiosis is an emerging zoonotic disease that is typically caused by Babesia microti infection. Clinical treatment of B. microti infection is challenging; hence, it is crucial to find new effective drugs. The current laboratory screening methods for anti-B. microti drugs are not optimized. We conducted drug-suppressive and drug-therapeutic tests to investigate whether use of an immunosuppressant and the target gene-based qPCR are helpful to reduce the number of animals affected and to improve parasite detection in an immunocompetent mouse model. These results were verified by subpassage test. In the drug-suppressive test, no B. microti were observed after immunosuppressant administration or in subpassage mice in the 100 mg/kg robenidine hydrochloride (ROBH) group. The opposite results were observed in the control, 50 mg/kg ROBH, atovaquone (ATO) + azithromycin (AZM), and proguanil hydrochloride (PGH) groups. Significant differences were observed in the EIR and target gene relative values (both P < 0.001) between the control group and any ROBH groups. In the drug-therapeutic test, recrudescence occurred in the 50 mg/kg ROBH, ATO+AZM, and control groups. This was not observed in the 100 mg/kg ROBH group after immunosuppressant administration. Similar findings were observed in the subpassage test. This suggests that a 4-day anti-B. microti drug-suppressive test can be used in preliminary drug screening. Potentially effective drugs can be verified by immunosuppressant test in subsequent drug-therapeutic tests. Thus, a laboratory evaluation method of anti-B. microti drug efficacy was optimized, which is highly accurate and requires a short drug screening time.

GRAFT VERSUS HOST DISEASE IN AUTOLOGOUS STEM CELL TRANSPLANT: AN UNCOMMON ENTITY

Identify in literature the graft versus host disease (GVHD) incidence after autologous hematopoietic stem cell transplantation (HSCT). We searched the PubMed database using a broad search strategy to identify studies related to GVHD complication after autologous stem cell transplant. The primary search was conducted using the terms: “GVHD in autologous transplant”, and publication date less than 5 years. 91 free full articles were identified, but 7 were better related to the purpose of the study. Two articles present cases of gastrointestinal tract (GIT) GVHD in recipients of autologous HSCT. Two patients with multiple myeloma had GVHD and the clinical and endoscopic presentations were distinct. Another patient developed severe acute GVHD 93 days post autologous HSCT for Hodgkin's lymphoma. PET and CT findings included characteristic patterns of bowel inflammation with bowel wall thickening, mural stratification, and enhancement with high FDG-uptake of the involved regions, as well as typical extra intestinal findings such as ascites, engorgement of the vasa recti and stranding of the mesenteric fat. A case report of membranous nephropathy succeeding autologous HSCT described that this is a rarely entity (3% post-autologous vs . 97% post-allogeneic HSCT). In autologous HSCT populations, there have been reports of associated glomerular disease, because of any type of immune dysregulation. Based on literature, 6% of all patients with glomerulonephritis after HCT had received Autologous transplants. And the last case report presents a 4-year-old girl with metastatic neuroblastoma who spontaneously developed AGVHD after autologous HSCT. One article said the risk of GVHD in an autologous transplant is zero and the last one related the skin cancer with the delayed immune recovery and persistent immunodeficiency in GVHD. GVHD following stem cell transplantation (SCT) is a common complication in patients that have undergone allogenic SCT but rare in recipients of autologous SCT. With the emergence of autologous HSCT, GVHD and its complications were expected to be eliminated. However, autologous GVHD has been described in some patients, and your prophylaxis mainly consists of post-transplant administration of immunosuppressive drugs and may impair the post-transplant immunologic reconstitution. After the sixth month, immune recovery occurs progressively towards complete recovery, but GVHD may develop. In chronic case, patients with only liver and skin involvement have a better prognosis. Patients with extensive involvement of multiple organs the prognosis may be poor. Recent studies have indicated that two major factors are necessary for the induction of autologous GVHD: the first factor was a disruption of thymic-dependent immune reconstitution and the second one was a failure to reestablish peripheral self-tolerance. On another hand, autologous GVHD has been thought of as an autoimmune syndrome and a milder form of GVHD than its counterpart in allogeneic transplantation, the presence of autoantibodies in relation to the HSCT provides evidence for the involvement of the B cell. The difficulty of finding articles related to the study shows GVHD in autologous HSCT is an uncommon entity, but although this fact, these cases are important to further the understanding of the various presentation of this manifestation and be awake to the possibilities of differential diagnoses.

Dysfunctional Immune Regulation in Autoimmune Hepatitis: From Pathogenesis to Novel Therapies.

Autoimmune hepatitis (AIH) is a chronic inflammatory disorder characterized by hypergammaglobulinemia, presence of serum autoantibodies and histological features of interface hepatitis. AIH therapeutic management still relies on the administration of corticosteroids, azathioprine and other immunosuppressants like calcineurin inhibitors and mycophenolate mofetil. Withdrawal of immunosuppression often results in disease relapse, and, in some cases, therapy is ineffective or associated with serious side effects. Understanding the mechanisms underlying AIH pathogenesis is therefore of paramount importance to develop more effective and well tolerated agents capable of restoring immunotolerance to liver autoantigens. Imbalance between effector and regulatory cells permits liver damage perpetuation and progression in AIH. Impaired expression and regulation of CD39, an ectoenzyme key to immunotolerance maintenance, have been reported in Tregs and effector Th17-cells derived from AIH patients. Interference with these altered immunoregulatory pathways may open new therapeutic avenues that, in addition to limiting aberrant inflammatory responses, would also reconstitute immune homeostasis. In this review, we highlight the most recent findings in AIH immunopathogenesis and discuss how these could inform and direct the development of novel therapeutic tools.

New phenomena for clinicians, model of Candida albicans mobilization before and after biofilm formation in the intestinal mucosa of Wistar rats (Rattus norvegicus)

Background and Aim: The virulence and antifungal resistance of Candida albicans are recently known for their ability to form biofilm. This research aimed to construct an in vivo model of C. albicans biofilm in Wistar rats' intestinal mucosa and study their mobilization while in a planktonic and biofilm formation. In this study, there was one treatment group that was treated with three antibiotics, immunosuppressants, and C. albicans. Materials and Methods: This study was divided into control and treatment groups. The data sampling was conducted after C. albicans inoculation. The C. albicans biofilm formation stage was monitored with colony-forming units method calculation every week post-inoculation and then observed by the confocal laser scanning microscope. Results: The planktonic C. albicans overgrowth occurred up to 14 days after inoculation. The formation and maturation of C. albicans biofilm in the intestinal mucosa started in the 28th and 35th-day post-inoculation, respectively. The density of planktonic C. albicans in the stool was dramatically decreased on the 35th day. Before the biofilm formation, the planktonic Candida was carried away by food scraps to be released as a stool. However, there were minuscule or no planktonic Candida observed in the stool during and after biofilm formation. Instead, they were attached to the caecum's mucosa as a biofilm. Conclusion: We have proved that the planktonic C. albicans with its mobile nature were carried into the stool along with the rest of the feed, as we observed a lot of C. albicans cells found in the stool. Meanwhile, on day 28 after administration of antibiotics and immunosuppressants, no C. albicans was found in the stool samples, and at the same time, we observed C. albicans cells and their matrix attached to the intestinal mucosa as a biofilm.

Effect of Cancer Treatment on the Worsening of Periodontal Disease and Dental Caries: A Preliminary, Retrospective Study.

To investigate the effect of cancer treatment on the worsening of dental caries and periodontal disease. Fifty-three adult cancer patients who underwent panoramic radiography before cancer treatment and 1-2 years later were enrolled in this study. They received professional oral care, including oral hygiene instruction, scaling and root planing, professional mechanical tooth cleaning, and dental treatment or extraction of any tooth with the source of infection. Age, sex, smoking habit, probing pocket depth, alveolar bone loss, oral hygiene, number of teeth, leukocytes, haemoglobin, and albumin counts, cancer treatment, the administration of immunosuppressants, worsening of dental caries, and alveolar bone loss after 1-2 years were examined. Factors related to the worsening of dental caries and alveolar bone loss were analysed using logistic regression analysis. Dental caries and periodontal disease worsened in 20.8% of the patients. Smoking habit and chemotherapy were independent risk factors for the worsening of dental caries, while alveolar bone loss greater than 1/3 and chemotherapy were independent risk factors related to worsening periodontal disease. Anticancer drug treatment is an exacerbating factor for dental caries and periodontal disease.

P-MU005. Myopathy in primary Sjögren’s syndrome in Dr. Moewardi Hospital Indonesia

Introduction . Myopathies are disorders affecting skeletal muscle. There is a term 'overlap syndrome' when myopathies are associated with another well-defined connective tissue disease. Sjögren’s syndrome is one of the connective tissue disease characterized by hypo- function of salivary and lacrimal glands and possible systemic multi-organ manifestations. Although muscular manifestations are very common with Sjögren’s syndrome, true myopathy is very rare. Myopathy inflammatory has been reported in less than 3% of patients. The aim of the case report is to report a case of myopathy in primary Sjögren’s syndrome in Dr. Moewardi hospital Surakarta. Results . 22 years old female, with the weakness of all four extremities, arthralgia, myalgia, and shortness of breath due to respiratory failure. The weakness was heavier in the proximal. Schirmer’s test ≤5 mm/5 min in left eye. From the results of laboratory examination obtained increased CK, SGOT, and SGPT. From cerebrospinal fluid examination, no dissociation of cytoalbumin was found. There was a positive (strong) result on La / SS-B antigen. Muscle biopsy showed hyalinized muscle. Plasmapheresis was performed on this patient. The patient received intravenous methylprednisolone, azathioprine, and folic acid therapy. The patient did not improve after the plasmapheresis and immunosuppressant administration. Conclusion . Skeletal muscle involvement in primary Sjögren’s syndrome is a relatively rare complication. Some signs, symptoms, and laboratory results support the appearance of myopathy in this case. Muscle biopsy is the gold standard examination for diagnosed myopathy. In Sjögren’s syndrome, the type of myopathy that is often found is myositis. In this case, there was a hyalinized muscle that supports myopathy but no inflammatory cells were found on the muscle biopsy. Myopathy in Sjögren’s syndrome responded favorably to high- dose steroids. In this case, there was no improvement after immunosuppressant administration.

Clinical, pathology-associated and molecular biomarkers of hidradenitis suppurativa/acne inversa

Hidradenitis suppurativa/acne inversa is ascarring disease of the intertrigines that is now intensively researched. Improved pathogenetic understanding has led to the introduction of tumor necrosis factor alpha (TNF‑α) inhibition, which represents amajor advance over traditional broad immunosuppression and antibiotic administration. In addition, awide range of newer and promising treatments is or is about to be clinically evaluated. These include various specific antibodies against cytokines and the complement system and small molecules. Successful use of the individual drugs depends on the stratification of suitable patient groups with the help of clinically relevant biomarkers. While molecular investigations have shown anumber of possible biomarkers and/or therapeutic target molecules, the detection of robust predictive biomarkers is still in its initial phase. In summary, the therapeutic options for hidradenitis suppurativa/acne inversa are improving through the introduction of new drugs, possibly in combination with surgical interventions, whereby the possibilities for predictive therapeutic decisions through the discovery of biomarkers would revolutionize the chances of therapeutic success.

Exposure to dexamethasone modifies transcriptomic responses of free-living stages of Strongyloides stercoralis.

Hyperinfection and disseminated infection by the parasitic nematode Strongyloides stercoralis can be induced by iatrogenic administration of steroids and immunosuppression and lead to an elevated risk of mortality. Responses of free-living stages of S. stercoralis to the therapeutic corticosteroid dexamethasone (DXM) were investigated using RNA-seq transcriptomes of DXM-treated female and male worms. A total of 17,950 genes representing the transcriptome of these free-living adult stages were obtained, among which 199 and 263 were differentially expressed between DXM-treated females and DXM-treated males, respectively, compared with controls. According to Gene Ontology analysis, differentially expressed genes from DXM-treated females participate in developmental process, multicellular organismal process, cell differentiation, carbohydrate metabolic process and embryonic morphogenesis. Others are involved in signaling and signal transduction, including cAMP, cGMP-dependent protein kinase pathway, endocrine system, and thyroid hormone pathway, as based on Kyoto Encyclopedia of Genes and Genomes analysis. The novel findings warrant deeper investigation of the influence of DXM on growth and other pathways in this neglected tropical disease pathogen, particularly in a setting of autoimmune and/or allergic disease, which may require the clinical use of steroid-like hormones during latent or covert strongyloidiasis.

Spk-9001: Adeno-Associated Virus Mediated Gene Transfer for Hemophilia B Achieves Sustained Factor IX with Minimal Immune Response

▪Background: Data from earlier hemophilia B (HB) AAV-mediated liver gene transfer trials demonstrated a dose-dependent, capsid-specific immune response that may result in clearance of transduced hepatocytes and loss of transgene expression (Manno et al. 2006, Mingozzi et al. 2007). This has not posed major safety concerns, but may limit efficacy. Prior work incorporated the use of steroids to abort this immune response and maintain factor IX (FIX) expression (Nathwani et al 2014). The percent of transgene expression lost increased with number of elapsed days from transaminase elevation to steroid initiation. Once vector responsiveness to steroids is established, the need for steroids is not a limitation in and of itself but highlights the requirement to reliably and expeditiously recognize an immune response and initiate steroids. Here we present our immunomonitoring data following infusion of SPK-9001, an AAV vector designed to achieve therapeutic FIX:C at a low vector dose to minimize capsid-specific T cell responses.Method: Ten HB subjects were infused with 5 x 1011 vg/kg SPK-9001, containing a transgene cassette encoding FIX-Padua that confers ~8-12 - fold higher specific activity than wild-type factor IX (Simioni et al. 2009, Crudele et al. 2016). T cell responses to the SPK-9001 AAV capsid and transgene product were monitored post-infusion using a validated interferon-γ enzyme-linked immunospot (ELISpot) assay, with a threshold for positivity of > 50 spot forming units (SFU) per 106 PBMC.Results: As of 7/26/17, 10 subjects are 26 -78 weeks post SPK-9001 infusion with mean sustained FIX:C of 33.8±18.1% (mean±SD). There were no vector or procedure-related adverse events. All subjects discontinued prophylaxis and had a significant reduction in the annualized bleeding rate (p<0.0001). No patients exhibited a significant T cell response to the transgene product, including the Padua mutation site. T cell responses against the viral capsid generally fell into 3 categories: 5 subjects had no detectable response to capsid; 3 subjects had a transient T cell response that peaked at week 2 that quickly resolved without intervention; 2 subjects demonstrated a T cell response that persisted for longer than 3 weeks. The persistent T cell responses observed in the 2 subjects correlated with an asymptomatic increase of liver transaminases. One subject was administered a course of prednisone starting on day 56, after which FIX:C levels stabilized and T cell reactivity quickly returned to baseline levels. An orthogonal peptide matrix approach identified 1 candidate AAV epitope, SEYQLPYVL, which is a MHC Class I predicted binder for the subject's HLA-B*18 haplotype according to bioinformatics prediction algorithms. This epitope is highly conserved across AAV serotypes. In response to grade I transaminase toxicity, the second subject was administered steroids starting on day 36. Concurrent ELISPOT values were elevated (1260 SFU/106 PBMC), but not associated with a decline in FIX:C and the subject maintained FIX:C in the normal range. Like the subject's LFTs, the ELISPOT response markedly decreased with steroids while his FIX:C remained stable at ~80%. This subject continues to demonstrate a low-positivity to AAV capsid peptides through 32 weeks and off steroids, but the persistent T cell response has not been associated with a decline in FIX:C or impact on overall efficacy. Further ELISPOT analysis on this subject identified 4 AAV T cell epitopes that are predicted binders for 2 of this subject's alleles, HLA-A*03 and HLA-B*07.Conclusion:We report consistent levels of sustained plasma FIX:C of 33.8±18.1% (mean±SD) in 10 subjects to date. Observed T cell responses to the AAV capsid occurred in 2/10 subjects that required steroid intervention. The early administration of immunosuppression and subsequent decrease in T cell response in the absence of a corresponding loss in FIX:C suggests that prompt recognition of a capsid immune response and early steroid intervention is critical. Furthermore, persistence of detectable T cell responses late in the time-course, with no association with a diminution in FIX:C, may suggest that circulating T cells may be present long after transduced hepatocytes cease presenting capsid peptides. Preliminary data suggest that our validated method for assessing T cell responses can detect responses that require management with steroids to ensure continuous FIX expression. DisclosuresHui:Spark Therapeutics: Employment, Equity Ownership. Liu:Spark Therapeutics: Employment. Patel:Spark Therapeutics: Employment. Chen:Spark Therapeutics: Employment. George:Pfizer: Consultancy; Spark Therapeutics: Other: Principal Investigator of Ongoing Phase I/II Gene Therapy Trials for Hemophilia A and B. Rasko:Genea: Equity Ownership; Novartis: Other: Clinical trials, Speakers Bureau; Spark: Equity Ownership, Other: clinical trials, Speakers Bureau; Rarecyte: Consultancy, Equity Ownership; President-Elect International Society for Cellular Therapy: Membership on an entity's Board of Directors or advisory committees; IMAGO Biosciences: Consultancy, Equity Ownership. Ducore:Octapharma: Research Funding; Bayer, Shire, HemaBiologics, Bioverativ, Octapharma, Spark Therapeutics: Other: Advisory board. Dasen:Spark Therapeutics: Employment. Carr:Spark Therapeutics: Employment. Anguela:Spark Therapeutics: Employment, Equity Ownership, Patents & Royalties. High:Spark Therapeutics: Employment, Equity Ownership, Patents & Royalties.

Foremost Concepts in Mechanisms of De Novo Post-Liver Transplantation Malignancy

In liver transplant patients, solid tumors and post-transplant lymphoproliferative disorders (PTLD) have emerged as significant long-term mortality causes. Additionally, it is assumed that de novo malignancy (DNM) after liver transplantation (LT) is the second-leading cause of death after cardiovascular complications. Well-established risk factors for PTLD and solid tumors are calcineurin inhibitors (CNIs), tacrolimus (TAC), and cyclosporine, the cornerstones of all immunosuppressive (IS) therapies used after LT. The loss of immunocompetence facilitated by the host immune system due to prolonged IS therapy leads to cancer development, including in LT patients. Hindering DNA repair mechanisms, promoting tumor cell invasiveness, and hampering apoptosis are critical events in tumorigenesis and tumor growth in LT patients resulting from IS administration. This paper aims to overview the refined mechanisms of IS-induced tumorigenesis after LT and the loss of immunocompetence facilitated by the host immune system due to prolonged IS therapy. In addition, we also discuss in detail the mechanisms of action in different types of IS regimen used after LT, and their putative effect on DNM.

Dermatologists' attitude towards psoriasis treatment during the COVID-19 pandemic.

BackgroundThe COVID-19 pandemic introduced new challenges in several dimensions in healthcare services. Herein, we describe the real-life strategies and therapeutic options adopted by dermatologists regarding their patients with psoriasis being treated with or with an indication for systemic therapy during the first COVID-19 lockdown period in Portugal.MethodsThe study involves a web-based survey on the clinical management of systemic therapy for psoriasis during the COVID-19 pandemic administered to Portuguese dermatologists. The survey consisted of 55 questions (4 open-ended questions; 51 closed-ended questions), grouped into 6 sections.ResultsA total of 60 dermatologists voluntarily participated in this survey. Nearly 63% of the participants opted for suspending biologics during the COVID-19 lockdown period and 23.3% increased the time between drug administrations. Eighty percent of the participants agreed that biologics did not change the probability of acquiring COVID-19 and 58.4% believed that these drugs decreased or did not change the severity of the disease. Approximately one-third of the participants opted not to prescribe a biological agent in patients despite clinical indication over the duration of the pandemic. Nearly 25% of the participants opted for suspending traditional immunosuppressant administration. Virtual appointments were an option for 93.3% of the participants.ConclusionThe COVID-19 pandemic has significantly affected the management of patients with psoriasis being treated with or with an indication for systemic therapy. Some of the decisions made during the first lockdown period were contrary to what we know today. These decisions might have had a significant impact on patients’ quality of life and on future therapeutic success. An adequate interpretation and analysis of the available data will be extremely important to an insightful adaptation of the clinical practice in future confinement or restrictive scenarios.

A rare case of knee joint mucormycosis with pathological fracture after COVID-19 infection

Abstract Mucormycosis is a fungal infection that generally occurs in patients with some degree of immunosuppression, such as patients with malignancies, diabetes, HIV infection, or patients who require the administration of immunosuppressive drugs. The final diagnosis is established by collecting some tissue from the infectious process and isolating the fungus using lab cultures. The treatment of mucormycosis is complex and consists of trying to reduce risk factors, rigorous surgical debridement, and specific antifungal treatment. We present the case of a 54-year-old male patient with a background of SARS-COV2 infection (moderate form), that started 3 months prior to presentation to our hospital, initially treated at home. The patient presented to the Orthopaedics Department of the University Emergency Hospital of Bucharest with pain and total functional impotence in his left knee as a result of a trauma that occurred about 2 months before the presentation to the hospital, at that moment with progressive worsening of the symptoms. Clinical and imaging examination established the diagnosis of pathological supra-intercondylar fracture of the left femur. The purpose of this case report is to present the risk of infection with an opportunistic agent as a result of immunosuppression induced by COVID-19 or its treatment with immunosuppressive agents necessary to combat the inflammatory process. The patient presented with a moderate form of COVID-19 treated at home with nonsteroidal anti-inflammatory drugs and antibiotics to prevent a bacterial superinfection. Mucormycosis remained a challenging situation for the physician, regardless of his medical specialty, both in terms of diagnosis and treatment. In this case, COVID-19 is one of the risk factors that contributed to the appearance of mucormycosis.

Comparing IRF-4 Gene Expression Between Acute T cell- Mediated Rejection and Stable Renal Transplant Recipients.

Introduction. Renal transplant rejection is one of the clinical challenges, which usually requires administration of immunosuppressive drugs causing serious side effects. Therefore, invention of effective and specific therapeutics is necessary to control undesired immune responses particularly T-cell reactions to allograft. Interferon Regulatory Factor-4 (IRF-4) due to its implication on T cells differentiation and function might be targeted to treat T cell-mediated cellular rejection (TCMR). The aim of this study was to investigate the association between IRF-4 gene expression and acute TCMR, as well as to examine the correlation between IRF-4 gene expression and cellular expression of Programmed cell death-1 (PD-1) and Helios molecules. Methods. Peripheral blood samples were obtained from 30 patients with biopsy proven acute TCMR and 30 stable recipients. IRF-4 gene expression was quantified using RT-PCR, and cellular expression of PD-1 and Helios were evaluated with flowcytometry. Results. IRF-4 gene expression was significantly increased in acute TCMR patients compared with stable recipients (P < .05). Helios protein expression was slightly decreased in TCMR group but this was not statistically significant. There was a negative correlation between IRF-4 gene expression and PD-1 as well as Helios frequency in the whole studied population. Conclusion. IRF-4 expression increases in acute TCMR which might also lead to a diminished expression of downstream immunoregulatory molecules such as PD-1 and Helios. Therefore, specific inhibition of IRF-4 may be helpful in managing acute TCMR.

Patient response with lupus erythematosus to treatment with Yamamoto New Scalp Acupuncture (YNSA)

It is estimated that 5 million people worldwide have some form of Lupus. It is an autoimmune, idiopathic and until now incurable disease, which affects, especially women in reproductive period. In the West, its treatment is educational, essentially medication, with administration of anti-inflammatories, antimalarials and immunosuppressants. For Traditional Chinese Medicine (TCM), Lupus is above all a syndromic imbalance, which varies according to its manifestation. The set of these disorders is classified as deterioration of the Spleen (Pi) and Heart (Xin), weakening of the Fire and the Door of Life. Treatment by MTC occurs with the administration of herbal medicines, diet therapies, acupuncture, massage, moxibustion, Qi Gong, magnetotherapy, wind therapy, flowers and others. YNSA (Yamamoto Neue Schädelakupunktur) is a somatotopic scalp therapy that, among other advantages, has access points to the 12 main meridians, bilaterally. Usually used in case of pain, neurological disorders and surgical conditions, it has its own diagnostic methods that also serve to monitor the treatment. Ryodoraku is the most sensitive and reproducible current diagnostic tool for identifying the average circulating energy in the meridians. This research aimed to identify the usefulness of YNSA in the treatment of lupus patients. In this process, the energy evolution of a patient with lupus considered severe was monitored, over 23 applications of YNSA. It was compared with the results of acupuncture with those of allopathy. With YNSA, in addition to relaxation and pain control, there was greater energy adequacy. The relevant gains over the 23 applications of YNSA, reaching three times the initial energy pattern, have almost completely retreated to exclusive treatment with allopathy. In effect, chloroquine diphosphate brought much more losses than gains.

How Can Immuno suppression After Organ Transplantation be Made More Effective and Safer? – A Review on Liposomal Formulations with Consideration of Archaeal Tetraetherlipid

Immune-suppressive agents such as methylprednisolone and cyclosporine exert tremendous side effects, because of high dosage and long-term application required for immune suppression after organ transplantation. Major side effects of methylprednisolone include bleeding of the gastro-intestinal tract, hypertension, and osteoporosis, whereas cyclosporine is nephrotoxic. Liposomes are phospholipid particles that allow delivery of drugs preferentially to the reticuloendothelial system. They can be prepared from phospholipids such as lecithin from soybean or egg yolk, other specific or modified lipids or from membrane-spanning tetraether lipid (TEL), which can be extracted and purified from archaeal cell membranes. One advantage in the use of liposomal application is reduced toxicity of many drugs. We report on various liposomal preparations of cyclosporine, methylprednisolone (L-MPL) and its palmitate derivative (L-MPLP). It has been documented that liposomal cyclosporine A (L-CsA), 1.75 mg/kg/day for seven days has potential for use as an immune-suppressive agent in rats with increased efficacy and decreased nephrotoxicity compared to commercially available forms of intravenous CsA. Liposomal methylprednisolone (L-MPL) 2 mg/kg, intravenously (IV), twice a week shows significantly prolonged cardiac allograft survival in rats and tissue-selective sequestration of the drug in comparison with the same dosage regimen of methylprednisolone in solution, administered daily. We report on organ distribution of L-MPLP in rats after intraperitoneal (IP) administration. Conclusion: Liposomal preparations of immunosuppressants have significantly higher immune-suppressive potential and lower toxicity than non-liposomal preparations. Bipolar TEL can be extracted, fractionated and purified from archaea to form stable liposomes which are extremely resistant, even to gastric fluid. Hence, TEL liposomes allow (besides IV and IP) for oral administration of immuno suppressants after organ transplantation with pharmacological and toxicological advantages as common liposomal phospholipid bilayer preparations.

Applying Immunomodulation to Promote Longevity of Immunoisolated Pancreatic Islet Grafts.

Islet transplantation is a promising therapy for insulin-dependent diabetes, but large-scale application is hampered by the lack of a consistent source of insulin-producing cells and need for lifelong administration of immunosuppressive drugs, which are associated with severe side effects. To avoid chronic immunosuppression, islet grafts can be enveloped in immunoisolating polymeric membranes. These immunoisolating polymeric membranes protect islet grafts from cell-mediated rejection while allowing diffusion of oxygen, nutrients, and insulin. Although clinical trials have shown the safety and feasibility of encapsulated islets to control glucose homeostasis, the strategy does up till now not support long-term graft survival. This partly can be explained by a significant loss of insulin-producing cells in the immediate period after implantation. The loss can be prevented by combining immunoisolation with immunomodulation, such as combined administration of immunomodulating cytokines or coencapsulation of immunomodulating cell types such as regulatory T cells, mesenchymal stem cells, or Sertoli cells. Also, administration of specific antibodies or apoptotic donor leucocytes is considered to create a tolerant microenvironment around immunoisolated grafts. In this review, we describe the outcomes and limitations of these approaches, as well as the recent progress in immunoisolating devices. Impact statement Immunoisolation by enveloping islets in semipermeable membranes allows for successful transplantation of islet grafts in the absence of chronic immunosuppression, but the duration of graft survival is still not permanent. The reasons for long-term final graft failure is not fully understood, but combining immunoisolation with immunomodulation of tissues or host immune system has been proposed to enhance the longevity of grafts. This article reviews the recent progress and challenges of immunoisolation, as well as the benefits and feasibility of combining encapsulation approaches with immunomodulation to promote longevity of encapsulated grafts.

Short-Term Outcomes of Total Hip Arthroplasty after Liver Transplantation.

BackgroundIdiopathic osteonecrosis of the femoral head (ONFH) frequently occurs after liver transplantation (LT) because of lifelong administration of corticosteroids or immunosuppressants and often requires total hip arthroplasty (THA). This study examines patient characteristics and short-term outcomes of THA after LT.MethodsWe observed 9 hips in 7 patients who underwent THA from August 2015 to December 2017 for ONFH after LT (group L). Cementless implants were inserted in all hips. Medical records were retrospectively reviewed to reveal reasons for LT, type of donor, and period from LT to THA. Preoperative laboratory data, operative time, intraoperative blood loss, complication rates, and Harris Hip Score were compared with a control group of 27 cementless THAs in 27 patients with ONFH.ResultsCausative diseases were liver cirrhosis (n = 4), type B fulminant hepatitis (n = 1), congenital biliary atresia (n = 1), and iatrogenic biliary tract injury (n = 1). Four livers were from living donors and 3 from cadavers. Mean time from LT to THA was 10.4 (1-20) years. Preoperative blood test showed a significant decrease in platelet count (178 vs 268 [∗103/μl]) and rise in total bilirubin (1.1 vs 0.7 [mg/dL]) in group L. There was no significant difference in operative time (86 vs 100 [minutes]), but intraoperative blood loss (303 vs 163 [mL]) increased significantly in group L. There were no significant differences in complication incidence or Harris Hip Score between the 2 groups.ConclusionTHA after LT requires caution because risks for bleeding increase. However, short-term outcomes appear to be equivalent to normal THA.