Immune Phenomena Research Articles

Inflammation, fibrosis and skeletal muscle regeneration in LGMDR9 are orchestrated by macrophages.

Variable degrees of inflammation, necrosis, regeneration and fibrofatty replacement are part of the pathological spectrum of the dystrophic process in alpha dystroglycanopathy LGMDR9 (FKRP-related, OMIM #607155), one of the most prevailing types of LGMDs worldwide. Inflammatory processes and their complex interplay with vascular, myogenic and mesenchymal cells may have a major impact on disease development. The purpose of our study is to describe the specific immune morphological features in muscle tissue of patients with LGMDR9 to enable a better understanding of the phenotype of muscle damage leading to disease progression. We have analysed skeletal muscle biopsies of 17 patients genetically confirmed as having LGMDR9 by histopathological and molecular techniques. We identified CD206+ MHC class II+ and STAT6+ immune-repressed macrophages dominating the endomysial infiltrate in areas of myofibre regeneration and fibrosis. Additionally, PDGFRβ+ pericytes were located around MHC class II+ activated capillaries residing in close proximity to areas of fibrosis and regenerating fibres. Expression of VEGF was found on many regenerating neonatal myosin+ fibres, myofibres and CD206+ macrophages also co-expressed VEGF. Our results show characteristic immune inflammatory features in LGMDR9 and more specifically shed light on the predominant role of macrophages and their function in vascular organisation, fibrosis and myogenesis. Understanding disease-specific immune phenomena potentially inform about possibilities for anti-fibrotic and anti-inflammatory therapeutic strategies, which may complement Ribitol replacement and gene therapies for LGMDR9 that may be available in the future.

A Literary Aesthetics of War Crime

In order to develop a literary aesthetics of war crime, I examine the phenomenon of moral immunity in military memoir. Using three paradigmatic examples of memoirs of unjust wars characterised by the routine perpetration of war crimes, I argue that moral immunity is achieved by means of three literary devices: literary irresponsibility, ethical peerage, and moral economy. I then employ the proposed literary aesthetics of war crime to provide an answer to the perennial question of the relationship between literature and morality as well as to two specific instantiations of this question, the value interaction debate in literary aesthetics and the ethics of reading in literary theory. My conclusion is that the literary aesthetics of war crime demonstrates both that there is a systematic relationship between aesthetic value and moral value and that there is no systematic relationship between literary ambiguity and moral uncertainty.

Efficacy of Brazilian green propolis (EPP-AF®) as an adjunct treatment for hospitalized COVID-19 patients: A randomized, controlled clinical trial

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) promotes challenging immune and inflammatory phenomena. Though various therapeutic possibilities have been tested against coronavirus disease 2019 (COVID-19), the most adequate treatment has not yet been established. Propolis is a natural product with considerable evidence of immunoregulatory and anti-inflammatory activities, and experimental data point to potential against viral targets. We hypothesized that propolis can reduce the negative effects of COVID-19. MethodsIn a randomized, controlled, open-label, single-center trial, hospitalized adult COVID-19 patients were treated with a standardized green propolis extract (EPP-AF®️) as an adjunct therapy. Patients were allocated to receive standard care plus an oral dose of 400 mg or 800 mg/day of green propolis for seven days, or standard care alone. Standard care included all necessary interventions, as determined by the attending physician. The primary end point was the time to clinical improvement, defined as the length of hospital stay or oxygen therapy dependency duration. Secondary outcomes included acute kidney injury and need for intensive care or vasoactive drugs. Patients were followed for 28 days after admission. ResultsWe enrolled 124 patients; 40 were assigned to EPP-AF®️ 400 mg/day, 42 to EPP-AF®️ 800 mg/day, and 42 to the control group. The length of hospital stay post-intervention was shorter in both propolis groups than in the control group; lower dose, median 7 days versus 12 days (95% confidence interval [CI] −6.23 to −0.07; p = 0.049) and higher dose, median 6 days versus 12 days (95% CI −7.00 to −1.09; p = 0.009). Propolis did not significantly affect the need for oxygen supplementation. In the high dose propolis group, there was a lower rate of acute kidney injury than in the controls (4.8 vs 23.8%), (odds ratio [OR] 0.18; 95% CI 0.03–0.84; p = 0.048). No patient had propolis treatment discontinued due to adverse events. ConclusionsAddition of propolis to the standard care procedures resulted in clinical benefits for the hospitalized COVID-19 patients, especially evidenced by a reduction in the length of hospital stay. Consequently, we conclude that propolis can reduce the impact of COVID-19.

Viral Infections and Cutaneous Drug-Related Eruptions.

In the general population, up to 10% of children treated by antibiotics have cutaneous adverse drug reaction, but allergy is confirmed in less than 20% of patients. Most of the non-allergic reactions are probably due to virus, such as enterovirus acute infection or Ebstein-Barr Virus (EBV) acute infection or reactivation. Especially in children, viruses have the propensity to induce skin lesions (maculopapular rash, urticaria) due to their skin infiltration or immunologic response. In drug-related skin eruptions, a virus can participate by activating an immune predisposition. The culprit antibiotic is then the trigger for reacting. Even in severe drug-induced reactions, such as Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome, viruses take part in immune phenomena, especially herpes viruses. Understanding the mechanisms of both virus- and drug-induced skin reaction is important to develop our clinical reflection and give an adaptive care to the patient. Our aim is to review current knowledge on the different aspects and potential roles of viruses in the different type of drug hypersensitivity reactions (DHR). Although major advances have been made those past year, further studies are needed for a better understanding of the link between viruses and DHR, to improve management of those patients.

A Case Report of Central Nervous System Graft-Versus-Host Disease and Literature Review

As an adverse immune phenomenon, graft-versus-host disease often occurs after allogeneic hematopoietic stem cell transplantation. The incidence of acute and chronic graft-versus-host disease is about 40–60% and the mortality rate can reach 15%, which is a potentially fatal disease. There are rare GvHD cases involving the central nervous system. We reported a rare case of diffuse white matter changes after haploid bone marrow transplantation, summarizing its clinical manifestations and diagnosis and treatment in conjunction with the literature.

Characterization of antibody-dependent cellular cytotoxicity induced by the plasma from persons living with HIV-1 based on target cells with or without CD4 molecules

Antibody-dependent cellular cytotoxicity (ADCC) is essential for reducing the reservoir of latent virus in persons living with HIV-1 (PLWH). This study evaluated the plasma's ADCC activity from treatment-naïve PLWH based on target cells with or without CD4 molecules. We found that the distribution of plasma activities to mediate ADCC is different between 8E5 cells (CD4-) and NL4-3-infected CEM.NKR.CCR5 cells (CD4+). There was no correlation between the IgG-binding ability and ADCC activity. The binding ability of the 8E5 cells (2.2%) to A32 antibody was significantly lower than that of CEM.NKR.CCR5 cells (69.3%). After incubating the 8E5 cells with CD4-mimetic compound, it did not increase the binding ability with the A32 antibody. After incubation with CD4+ T cells, the binding ability of the 8E5 cells for the A32 antibody increased significantly, which implies that the conformation of the Env protein open and expose the CD4-induced epitopes. The effect of the ADCC in plasma directly applied to 8E5 cells was positively correlated with that of the NL4-3-infected CEM.NKR.CCR5 cells. In conclusion, ADCC induction in plasma was general in the treatment-naïve PLWH. The ADCC activity levels differed when target cells with or without CD4 molecules were evaluated; When designing experiments on ADCC, full consideration should be given to this immune phenomenon.

TLR Agonists as Mediators of Trained Immunity: Mechanistic Insight and Immunotherapeutic Potential to Combat Infection.

Despite advances in critical care medicine, infection remains a significant problem that continues to be complicated with the challenge of antibiotic resistance. Immunocompromised patients are highly susceptible to development of severe infection which often progresses to the life-threatening condition of sepsis. Thus, immunotherapies aimed at boosting host immune defenses are highly attractive strategies to ward off infection and protect patients. Recently there has been mounting evidence that activation of the innate immune system can confer long-term functional reprogramming whereby innate leukocytes mount more robust responses upon secondary exposure to a pathogen for more efficient clearance and host protection, termed trained immunity. Toll-like receptor (TLR) agonists are a class of agents which have been shown to trigger the phenomenon of trained immunity through metabolic reprogramming and epigenetic modifications which drive profound augmentation of antimicrobial functions. Immunomodulatory TLR agonists are also highly beneficial as vaccine adjuvants. This review provides an overview on TLR signaling and our current understanding of TLR agonists which show promise as immunotherapeutic agents for combating infection. A brief discussion on our current understanding of underlying mechanisms is also provided. Although an evolving field, TLR agonists hold strong therapeutic potential as immunomodulators and merit further investigation for clinical translation.

Behavioral Immunity and Social Distancing in the Wild: The Same as in Humans?

The COVID-19 pandemic imposed new norms on human interactions, perhaps best reflected in the widespread application of social distancing. But social distancing is not a human invention and has evolved independently in species as dissimilar as apes and lobsters. Epidemics are common in the wild, where their spread is enhanced by animal movement and sociality while curtailed by population fragmentation, host behavior, and the immune systems of hosts. In the present article, we explore the phenomenon of behavioral immunity in wild animals as compared with humans and its relevance to the control of disease in nature. We start by explaining the evolutionary benefits and risks of sociality, look at how pathogens have shaped animal evolution, and provide examples of pandemics in wild animal populations. Then we review the known occurrences of social distancing in wild animals, the cues used to enforce it, and its efficacy in controlling the spread of diseases in nature.

Update on Post-Streptococcal Reactive Arthritis: Narrative Review of a Forgotten Disease.

This topical review attempts to build the concepts of PSRA as an independent entity and discuss prevalent diagnostic criteria. It utilizes a search strategy to collate all clinical features of PSRA reported from across the world and also discusses laboratory and treatment options in brief. There are several immune-mediated diseases described after acute streptococcal infections. Post-streptococcal reactive arthritis (PSRA) is a sterile, self-limiting arthritis that occur as an immune sequelae to streptococcal infection. Though PSRA resembles the arthritis of acute rheumatic fever superficially, it is a separate entity in its own right. It is different from classical reactive arthritis too. It was being recognized worldwide and more frequently in the recent past, possibly due to heightened awareness amongst clinicians. However, research on this enigmatic immune phenomenon is limited. Most acceptable hypotheses suggest molecular mimicry sensitizing the immune system towards synovial peptides such as keratin, vimentin and laminin, leading to arthritis in a genetically predisposed individual. There is still much to be learnt from this unique disease about the vagaries of the immune system.

The Immune Overreaction Phenomena in Severe Sars-cov-2 Human Infections

The immunology of Sars-cov-2 human infection is known to be complex. One of the facets of its complexity is the occurrence of immune over reaction phenomena in its severe forms. Such forms stands as a challenge for laboratory diagnostics and clinicians due its further complexity. The objective of the present mini-review was to explore these immune over-reaction phenomena [IORP ]among the severe infection forms .The noted IORP in severe covid-19 were as; two,the innate immno-thrombi [microthrombi] and the hyper-cytokine-mia[cytokine storm],one cross-road IORP as an unrestrained activation of complement system and two adaptive IORP as an autoimmune phenocopy[ Neutralizing autoantibody producing B cell autoimmune pheno-copy of the type I Interferons ] as well as the Viral sensor [ Dynamics of the MAIT immune cells ]. These phenomena are resolved on reaching the possible case recovery. Keywords: Adaptive ,cross-road ,innate ,immune ,over-reaction, phenomena ,sars-cov-2. DOI: 10.7176/JHMN/85-09 Publication date: January 31 st 2021

Levamisole-Induced immune phenomenon and its various clinical manifestations in children: Two case reports along with review of literature

In literature, levamisole-induced immune manifestations were described mostly in association with its use in treatment of rheumatoid arthritis, malignancies, and recently, in relation to the use of illicit cocaine contaminated with levamisole among adults. Even though levamisole has been proven to be an inexpensive, safer, and effective drug with minimal side effects among children, it is not possible to undermine its potential side effects. The objective of this study was to describe levamisole-induced immune phenomenon and its manifestation in children. We describe two children with levamisole-induced immune phenomenon, leading to limb ischemia resulting in a gangrene and autoamputation of toes in the first child and an isolated microscopic hematuria in the second child along with a thorough review of available knowledge on this rare manifestation in children. Increased awareness of these rare but severe manifestations will remind clinicians to keep a high index of suspicion, its early recognizing, and withdrawal of offending drug before severe morbidity occurs in those children on levamisole.

Genetically Corrected Autologous Stem Cells Engraft, But Host Immune Responses Limit Their Utility in Canine α-L-iduronidase Deficiency

Canine alpha-L-iduronidase (alpha-ID) deficiency, a model of the human storage disorder mucopolysaccharidosis type I (MPS I), is an ideal system in which to evaluate the clinical benefit of genetically corrected hematopoietic stem cells. We performed adoptive transfer of genetically corrected autologous hematopoietic cells in dogs with alpha-ID deficiency. Large volume marrow collections were performed on five alpha-ID-deficient dogs. Marrow mononuclear cells in long-term marrow cultures (LTMCs) were exposed on three occasions during 3 weeks of culture to retroviral vectors bearing the normal canine alpha-ID cDNA. Transduced LTMC cells from deficient dogs expressed enzymatically active alpha-ID at 10 to 200 times the levels seen in normal dogs. An average of 32% of LTMC-derived clonogenic hematopoietic cells were provirus positive by polymerase chain reaction and about half of these expressed alpha-ID. Approximately 10(7) autologous gene-modified LTMC cells/kg were infused into nonmyeloablated recipients. Proviral DNA was detected in up to 10% of individual marrow-derived hematopoietic colonies and in 0.01% to 1% of blood and marrow leukocytes at up to 2 to 3 years postinfusion. Despite good evidence for engraftment of provirally marked cells, neither alpha-ID enzyme nor alpha-ID transcripts were detected in any dog. We evaluated immune responses against alpha-ID and transduced cells. Humoral responses to alpha-ID and serum components of the culture media (fetal bovine and horse sera and bovine serum albumin) were identified by enzyme-linked immunosorbent assay. Cellular immune responses to autologous alpha-ID but not neo(r) transduced cells were demonstrated by lymphocyte proliferation assays. To abrogate potential immune phenomena, four affected dogs received posttransplant cyclosporine A. Whereas immune responses were dampened in these dogs, alpha-ID activity remained undetectable. In none of the dogs engrafted with genetically corrected cells was there evidence for clinical improvement. Our data suggest that, whereas the alpha-ID cDNA may be transferred and maintained in approximately 5% of hematopoietic progenitors, the potential of this approach appears limited by the levels of provirally derived enzyme that are expressed in vivo and by the host's response to cultured and transduced hematopoietic cells expressing foreign proteins.

Vaccination against β-Amyloid as a Strategy for the Prevention of Alzheimer's Disease.

Simple SummaryImmunization against β-amyloid has been explored as a vaccination strategy for Alzheimer’s disease for over 20 years. No vaccine has been licensed so far, and immunotherapy has come under considerable criticism following the negative results of several phase III clinical trials. In this narrative review, we illustrate the working hypothesis behind immunization against β-amyloid as a vaccination strategy for Alzheimer’s disease, and the outcome of the active immunization strategies that have been tested in humans. On the basis of the lessons learned from preclinical and clinical research, we discuss roadblocks and current perspectives in this challenging enterprise in translational immunology.Vaccination relies on the phenomenon of immunity, a long-term change in the immunological response to subsequent encounters with the same pathogen that occurs after the recovery from some infectious diseases. However, vaccination is a strategy that can, in principle, be applied also to non-infectious diseases, such as cancer or neurodegenerative diseases, if an adaptive immune response can prevent the onset of the disease or modify its course. Immunization against β-amyloid has been explored as a vaccination strategy for Alzheimer’s disease for over 20 years. No vaccine has been licensed so far, and immunotherapy has come under considerable criticism following the negative results of several phase III clinical trials. In this narrative review, we illustrate the working hypothesis behind immunization against β-amyloid as a vaccination strategy for Alzheimer’s disease, and the outcome of the active immunization strategies that have been tested in humans. On the basis of the lessons learned from preclinical and clinical research, we discuss roadblocks and current perspectives in this challenging enterprise in translational immunology.

Targeting the RNA-Binding Protein HuR Alleviates Neuroinflammation in Experimental Autoimmune Encephalomyelitis: Potential Therapy for Multiple Sclerosis

Multiple sclerosis (MS) is a chronic autoimmune inflammatory and neurodegenerative disease of the central nervous system characterized by demyelination, axonal loss, and motor dysfunction. Activated microglia are associated with the destruction of myelin in the CNS. Activated microglia produce cytokines and proinflammatory factors, favoring neuroinflammation, myelin damage, and neuronal loss, and it is thought to be involved in the disease pathogenesis. The present study investigated the role of post-transcriptional regulation of gene expression on the neuroinflammation related to experimental autoimmune encephalomyelitis (EAE) in mice, by focusing on HuR, an RNA-binding protein involved in inflammatory and immune phenomena. Spinal cord sections of EAE mice showed an increased HuR immunostaining that was abundantly detected in the cytoplasm of activated microglia, a pattern associated with its increased activity. Intrathecal administration of an anti-HuR antisense oligonucleotide (ASO) decreased the proinflammatory activated microglia, inflammatory infiltrates, and the expression of the proinflammatory cytokines IL-1β, TNF-α, and IL-17, and inhibited the activation of the NF-κB pathway. The beneficial effect of anti-HuR ASO in EAE mice corresponded also to a decreased permeability of the blood–brain barrier. EAE mice showed a reduced spinal CD206 immunostaining that was restored by anti-HuR ASO, indicating that HuR silencing promotes a shift to the anti-inflammatory and regenerative microglia phenotype. Mice that received anti-HuR ASO exhibited improved EAE-related motor dysfunction, pain hypersensitivity, and body weight loss. Targeting HuR might represent an innovative and promising perspective to control neurological disturbances in MS patients.

Tuberculosis with Immune Thrombocytopenia an Unusual Association

Introduction Tuberculosis (TB) and is the leading infectious cause of death in adult's worldwide.TB can have a wide variety of presentations manifestation. Hematological manifestations of tuberculosis have different forms and one of the rare associated is TB with isolated thrombocytopenia. ITP is relatively common autoimmune bleeding disorder.. However, ITP is very rarely associated with TB with only a few cases reported. Isolated Thrombocytopenia in TB is multifactorial and could be explained by different mechanisms as follows Immune-mediated platelet destruction through antiplatelet antibodies as mycobacterium TB may share antibodies with platelets or platelet-associated immunoglobulin, Tuberculosis-induced hemophagocytosis, Defective platelet production due to bone marrow (BM) infiltration, Hypersplenism, intravascular coagulation, anti-tuberculous treatment (ATT) induced thrombocytopenia. Methodology We reviewed the literature using PubMed, google scholar and English language articles only. We have included all the reported cases of tuberculosis and immune thrombocytopenia if it is associations or initial presentations using the keyword: tuberculosis. Pulmonary tuberculosis, immune thrombocytopenia, Idiopathic thrombocytopenia purpura and we excluded drug induced thrombocytopenia. Our review identified forty-two cases in total, in our review Baseline and clinical characteristics are provided. Results Of the forty-two cases identified, more than one quarter of cases (n=12) were from India; the remainder of the reported cases from thirteen different countries. Gender was nearly equally distributed (males n= 21, females n=20, one case unknown); age ranged from 4 to 74 years. The most reported sites of TB as follows; lung (n=20), disseminated (n=8), lymph nodes (n=6), abdomen (n=4), mediastinum (n=2), spleen (n=1) and knee (n=1). Bone marrow aspiration and biopsy done in 27 cases, three of them (7%) found granuloma and 14 (32%) found to have normal to hyprecellular marrow with increased number of megakaryocytes. Of the forty-two cases, ITP was the first presentation of TB with or without typical TB symptoms and signs in more than three quarters of the cases (n=33), while ITP was discovered in TB patients in routine investigations without obvious bleeding symptoms or signs in only four cases. Hemorrhagic symptoms were reported in most of the cases (n=31), skin manifestations (petechiae/purpura/ecchymosis) being the most common (n=28). The therapeutic approach to TB-associated ITP showed significant heterogeneity with Anti tuberculous treatment and first- and/or second-line treatment for ITP given with or without platelets transfusion. Most of the cases (n=36) achieved full recovery with Anti-tuberculous treatment(ATT) and IVIG ± Steroids. Of the 42 cases, six cases were treated with blood and platelet transfusion for thrombocytopenia which did not normalize the platelet count as thrombocytopenia as expected as this is most likely an immune mediated phenomenon. Conclusion Unfortunately, there are no clear guidelines for management of TB-associated ITP and is anecdotal or observational at best. This highlights the importance of conducting prospective and standardized studies in the future. We found that Anti tuberculous treatment could have play pivotal role in management of ITP in TB Patients. Figure Disclosures No relevant conflicts of interest to declare.

FOXP3 in Melanoma with Regression: Between Tumoral Expression and Regulatory T Cell Upregulation.

Cutaneous melanoma is a significant immunogenic tumoral model, the most frequently described immune phenomenon being tumor regression, as a result of the interaction of tumoral antigens and stromal microenvironment. We present a retrospective cohort study including 52 cases of melanoma with regression. There were evaluated correlations of the most important prognostic factors (Breslow depth and mitotic index) with FOXP3 expression in tumor cells and with the presence of regulatory T cells and dendritic cells in the tumoral stroma. FOXP3 expression in tumor cells seems an independent factor of poor prognosis in melanoma, while regression areas are characterized by a high number of dendritic cells and a low number of regulatory T cells. FOXP3 is probably a useful therapeutical target in melanoma, since inhibition of FOXP3-positive tumor clones and of regulatory T cells could eliminate the ability of tumor cells to escape the immune defense of the host.

S2803 Bizarre Bariatric Complication With Small Bowel Obstruction in a COVID-19 Patient With Acute Abdomen

INTRODUCTION: Gastrointestinal emergencies in the novel coronavirus pandemic present as acute abdomen in 4-5% of patients as gathered from emerging studies. Nausea, abdominal pain, diarrhea, rectal bleeding, dysgeusia, anorexia and jaundice have been recorded in these patients. Additionally there are cases with hemorrhagic gastritis, ischemia of bowel, and hepatitis often due to systemic immune complex phenomenon and thrombosis. We report a rare case of small bowel obstruction in a Covid-19 patient with a dislodged and migrated EG junction stent, initially placed to circumvent a leak at a prior gastrojejunal (GJ) bypass surgical revision, and then presenting to the emergency room with acute abdomen. CASE DESCRIPTION/METHODS: A 54 year old woman underwent a routine laparoscopic GJ revision in 2/2020 after which she developed a GJ leak 2 weeks later warranting an esophageal stent placement . She was then discharged home, at the height of the Covid-19 outbreak in a pandemic hotspot. She developed a small intra abdominal abscess post op 2 weeks warranting hospitalization for drainage and discharged on antibiotics. 2 months later, she presented with nausea, malaise, vomiting and diarrhea followed by worsening RLQ pain. An Abdominal CT w/ contrast revealed an impacted stent in the distal ileum with localized perforation and obstruction. After reporting generalized body aches and malaise at presentation, PCR testing revealed a positive Covid19 status. She underwent a successful emergency laparoscopic stent retrieval and repair, with no post op complications. DISCUSSION: Covid19 gastrointestinal emergencies are common, and varied with a favorable prognosis in respect to initial presentation. Our patient had subtle nausea, emesis and enteritis, as noted in 10–20% of patients with similar Covid presentation, which likely led to stent dislodgement and distal migration with subsequent bowel obstruction. Fortunately, her clinical course was mild so she was managed with optimal laparoscopic retrieval and supportive medical therapy after which she was successfully discharged from the hospital. Our case is unique in that an acute Covid19 case presenting concomitantly with post bariatric stent migration and bowel obstruction was successfully managed in a standard fashion during the height of a pandemic in a hotspot with stifling restrictions in place for routine emergencies. Though the exposure risk is high for medical staff, all such patients should be optimally managed like any Covid negative patients for optimal outcomes.Figure 1.: Migrated esophageal stent in the right lower quadrant.

EP01 Post COVID-19 reactive arthritis

Case report - IntroductionWe present what we believe to be the first reported case of post COVID-19 reactive arthritis, in a previously medically well 16-year-old with no past or family history of inflammatory arthritis.Case report - Case descriptionOur patient was a previously medically fit 16-year-old of Caucasian origin who tested positive for COVID-19 in late March 2020. She developed with a 4-day illness with fever, cough, and myalgia from which she made a full and uncomplicated recovery.Ten days later she developed a new erythematous itchy rash on her legs, trunk, and face and a progressive polyarthralgia affecting her MCPs, wrists, shoulders, hips, and knees. The rash typically lasted for 2 days at one site and was non-scarring. This was associated with a low-grade fever. There were no associated mouth ulcers, photosensitivity, alopecia, Raynaud’s, GI disturbance or respiratory symptoms. She had no relevant family history of autoimmunity, psoriasis or inflammatory bowel disease or travel history and had been prescribed no new medications.On examination, she had an erythematous rash on the face in a non malar distribution. She had multiple tender joints without definite synovitis. Cardiovascular, respiratory, gastroenterology and neurological examinations were unremarkable.Investigations revealed a normal full blood count and CRP<1 with normal liver and renal function tests. Her urinalysis was unremarkable. Immunology was negative for ANA, ANCA and rheumatoid factor. Immunoglobulins were normal. Two weeks later her symptoms were fully resolved.Case report - DiscussionCoronaviruses are single-stranded RNA viruses with nearly 30 strains recognised to infect humans. They induce both an innate and adaptive immune system response. It is hypothesised that a dysregulated innate system response, leading to a prolonged adaptive response triggers damaging inflammation and a potential cytokine storm. This is associated with poor outcome during primary viral infection. Variations in this immune response, with different underlying HLA genotypes could lead to other post infectious immune mediated phenomena, such as Paediatric Multisystem Inflammatory Syndrome - Temporally associated with COVID-19.There is a European registry collating data about patients with known rheumatic diseases who are admitted with COVID-19. There is emerging data regarding Paediatric Inflammatory Multisystem Syndrome - Temporally associated with SARS-CoV-2 (PIMS-TS). There is a growing suggestion that a subgroup of patients is developing a COVID-19 associated post viral fatigue syndrome. We suggest that a registry to collect information on de novo autoimmune diseases presenting post COVID-19 is also commenced.Case report - Key learning pointsCOVID-19 infection is associated with a wide variety of sequalae, including rheumatological ones.Classic post viral Reactive arthritis has been seen. A registry to collect information on de novo autoimmune presentations would be highly informative.

Immune-Related Hub Genes and the Competitive Endogenous RNA Network in Alzheimer's Disease.

The pathogenesis of Alzheimer's disease (AD) involves various immune-related phenomena; however, the mechanisms underlying these immune phenomena and the potential hub genes involved therein are unclear. An understanding of AD-related immune hub genes and regulatory mechanisms would help develop new immunotherapeutic targets. The aim of this study was to explore the hub genes and the mechanisms underlying the regulation of competitive endogenous RNA (ceRNA) in immune-related phenomena in AD pathogenesis. We used the GSE48350 data set from the Gene Expression Omnibus database and identified AD immune-related differentially expressed RNAs (DERNAs). We constructed protein-protein interaction (PPI) networks for differentially expressed mRNAs and determined the degree for screening hub genes. By determining Pearson's correlation coefficient and using StarBase, DIANA-LncBase, and Human MicroRNA Disease Database (HMDD), the AD immune-related ceRNA network was generated. Furthermore, we assessed the upregulated and downregulated ceRNA subnetworks to identify key lncRNAs. In total, 552 AD immune-related DERNAs were obtained. Twenty hub genes, including PIK3R1, B2M, HLA-DPB1, HLA-DQB1, PIK3CA, APP, CDC42, PPBP, C3AR1, HRAS, PTAFR, RAB37, FYN, PSMD1, ACTR10, HLA-E, ARRB2, GGH, ALDOA, and VAMP2 were identified on PPI network analysis. Furthermore, upon microRNAs (miRNAs) inhibition, we identified LINC00836 and DCTN1-AS1 as key lncRNAs regulating the aforementioned hub genes. AD-related immune hub genes include B2M, FYN, PIK3R1, and PIK3CA, and lncRNAs LINC00836 and DCTN1-AS1 potentially contribute to AD immune-related phenomena by regulating AD-related hub genes.

Significance of Anti-Nuclear Antibodies and Cryoglobulins in Patients with Acute and Chronic HEV Infection.

Background: Hepatitis E virus (HEV) has been associated with immunological phenomena. Their clinical significance, however, still needs to be clarified, that is, whether cryoglobulins or autoantibodies impact overt disease in HEV-infected individuals. To better understand, we analyzed these different immune phenomena in three cohorts, each representing different types of HEV infection. Methods: The cohorts included: (i) immunocompetent patients with acute hepatitis E, (ii) immunosuppressed patients with chronic hepatitis E, and (iii) individuals with asymptomatic HEV infection. Together, they consisted of 57 individuals and were studied retrospectively for the presence of anti-nuclear antibodies (ANAs), cryoglobulins, and serum total IgG. They were then compared with a control cohort of 17 untreated patients with chronic hepatitis B virus (HBV) infection or hepatitis C virus (HCV) infection. Results: Thirteen (23%) were immunocompetent patients with acute hepatitis E (median alanine aminotransferase (ALT) = 872 U/L), 15 (26%) were immunosuppressed patients with chronic hepatitis E (median ALT = 137 U/L), and 29 (51%) were blood donors with asymptomatic HEV infection (median ALT = 35 U/L). Overall, 24% tested positive for elevated ANA titers of >1:160, and 11% presented with a specific ANA pattern. ANA detection was not associated with the type of HEV infection, IgG levels, sex, or age. All individuals tested negative for anti-mitochondrial antibodies, anti-neutrophil cytoplasmic antibodies, liver-kidney microsomal antibodies, anti-myeloperoxidase-, and anti-proteinase-3 antibodies. Five patients (9%) tested positive for cryoglobulins. Notably, cryoglobulinemia was present in overt hepatitis E (Groups (i) and (ii); one acute and four chronic HEV infections), but was not present in any of the asymptomatic blood donors (p = 0.02). The frequency of cryoglobulins and elevated ANAs did not differ significantly between HEV and HBV/HCV patients. Conclusion: In line with findings on HBV and HCV infections, we frequently observed detection of ANAs (24%) and cryoglobulins (9%) in association with HEV infections. The presence of cryoglobulins was limited to patients with overt hepatitis E. We add to the findings on the immune phenomena of hepatitis E.