Immune Complex Reaction Research Articles

Lipid Peroxidation Processes in Convalescents after COVID-19: Their Diagnostic Significance and Correction under the Influence of Rehabilitation Treatment

Despite global response to the COVID-19 pandemic, humanity has not been able to completely elimination of the SARS-CoV-2 virus. And although the acute period of COVID-19 is currently relatively mild, there is still a risk of the post-COVID syndrome with persistent multisystem disorders development, which necessitates restorative treatment during the convalescence period. The objective: to assess the severity of oxidative stress and the possible role of immune complex lesions in convalescents after COVID-19 in relation to the severity of the disease and the timing of examination after the acute period, as well as to analyze the dynamics of the detected changes under the influence of rehabilitation treatment. Materials and methods. 91 convalescents after COVID-19 were examined. In patients aged 21 to 67 years, the manifestations of COVID pneumonia were diagnosed during the acute period. Among them, 46 patients had a mild course of COVID-19, 31 persons had a moderate course, and 14 patients had a severe course. Within 1–3 weeks after inpatient treatment 55 patients were admitted to a rehabilitation treatment course, and after 2–3 months – 36 persons. The comparison group included 25 convalescents after community-acquired bacterial pneumonia. As a control for laboratory indicators, 27 practically healthy individuals were examined. During the examination the disorders in the lipid peroxidation (LPO) – antioxidant protection (AOP) system were studied, examining the level of LPO end products – Schiff bases (SB) and the AOP enzyme – catalase in the blood. To quantify the imbalance in the ROS-AOD system, the oxidative stress severity index (OSI) was calculated. The presence of endogenous intoxication was assessed by determining the average mass molecules (AMM) in the blood serum by spectrophotometric method. To assess the development of immune complex lesions, the level of circulating immune complexes (CIC) was determined. The main component of the treatment was the use of haloaerosol therapy (dry aerosol media of rock salt with a given concentration and dispersion) – 18–20 sessions per course. In addition, rehabilitation treatment included a gentle regimen with regular therapeutic physical exercises, the necessary basic bronchodilator and anti-inflammatory therapy (according to indications). Results. Before the treatment in the convalescents there were the signs of pronounced oxidative stress and endotoxemia, which was manifested by a significant increase in the level of BS in the control group and in patients after bacterial pneumonia. These changes were combined with a significant increase in MSM content by 1.3 times and CIC level by 2.1 times, which causes the development of tissue damage and post-covid syndrome. The detected changes did not significantly depend on the timing of the examination and were pronounced even with a mild course of COVID-19. After the course of rehabilitation treatment all patients, regardless of the severity of the disease, had inhibition of lipoperoxidation, which was accompanied by an increase in catalase activity and was confirmed by a significant OSI decrease, a decrease in endotoxemia and CIC level. The positive dynamics of the studied indicators was somewhat more pronounced with a mild course of COVID-19, but by the end of the course of treatment, none of the indicators reached the control level. This fact confirms the pathogenetic significance of the studied processes in the development of post-covid syndrome and determines the need to improve rehabilitation treatment of convalescents after COVID-19. Conclusions. After COVID-19 disease the convalescents have disturbances in the redox balance with the development of oxidative stress, manifestations of endogenous intoxication and immune complex reactions, which do not significantly depend on the severity of the acute period of the disease and persist for a long time, which may be the basis for the development of post-covid syndrome. The rehabilitation therapy based on haloaerosol therapy leads to an improvement in clinical and functional indicators and a decrease in the manifestations of oxidative stress and endotoxemia, but does not provide full compensation for these changes, which determines the need to correct the rehabilitation complex with an emphasis on restoring oxidative homeostasis.

Safety of Crovalimab Versus Eculizumab in Patients With Paroxysmal Nocturnal Haemoglobinuria (PNH): Pooled Results From the Phase 3 COMMODORE Studies.

To evaluate the tolerability of crovalimab versus eculizumab in C5 inhibitor (C5i)-naive and -experienced patients with PNH from COMMODORE 2, 3 and 1 (NCT04434092, NCT04654468 and NCT04432584). Pooled safety data were assessed in the total crovalimab and eculizumab populations and by C5i-naive versus C5i-switched status in patients receiving crovalimab. Analyses include 6.5 months of additional follow-up from the COMMODORE 2 and 1 primary analyses. COMMODORE safety data (crovalimab, 393 patients [naive, 192 patients; switched, 201 patients]; eculizumab, 111 patients) were analysed. The total patient years (PY) were 503.9 and 51.1 in the total crovalimab and eculizumab populations, respectively, with 471 and 581 adverse events (AEs) per 100 PY. Serious infection rates were 8.9 and 13.7 AEs per 100 PY, respectively; no meningococcal infections were reported. Fatal AEs occurred in eight (2%) patients receiving crovalimab (naive, six patients; switched, two patients) and one (1%) receiving eculizumab, all treatment unrelated. In C5i-switched patients, 39 (19%) had transient immune complex reactions (risk when switching between C5i and crovalimab); the majority were Grades 1-2 arthralgia and rash, and 16 (8%) had Grade 3 events. Crovalimab's safety profile was consistent with eculizumab's and was generally comparable between C5i-naive and C5i-switched patients.

The Association between Gut Microbiota and Serum Biomarkers in Children with Atopic Dermatitis.

Background. Currently, it is known that the gut microbiota plays an important role in the functioning of the immune system, and a rebalancing of the bacterial community can arouse complex immune reactions and lead to immune-mediated responses in an organism, in particular, the development of atopic dermatitis (AD). Cytokines and chemokines are regulators of the innate and adaptive immune response and represent the most important biomarkers of the immune system. It is known that changes in cytokine profiles are a hallmark of many diseases, including atopy. However, it remains unclear how the bacterial imbalance disrupts the function of the immune response in AD. Objectives. We attempted to determine the role of gut bacteria in modulating cytokine pathways and their role in atopic inflammation. Methods. We sequenced the 16S rRNA gene from 50 stool samples of children aged 3-12 years who had confirmed atopic dermatitis, and 50 samples from healthy children to serve as a control group. To evaluate the immune status, we conducted a multiplex immunofluorescence assay and measured the levels of 41 cytokines and chemokines in the serum of all participants. Results. To find out whether changes in the composition of the gut microbiota were significantly associated with changes in the level of inflammatory cytokines, a correlation was calculated between each pair of bacterial family and cytokine. In the AD group, 191 correlations were significant (Spearman's correlation coefficient, p ≤ 0.05), 85 of which were positive and 106 which were negative. Conclusions. It has been demonstrated that intestinal dysbiosis is associated with alterations in cytokine profiles, specifically an increase in proinflammatory cytokine concentrations. This may indicate a systemic impact of these conditions, leading to an imbalance in the immune system's response to the Th2 type. As a result, atopic conditions may develop. Additionally, a correlation between known AD biomarkers (IL-5, IL-8, IL-13, CCL22, IFN-γ, TNF-α) and alterations in the abundance of bacterial families (Pasteurellaceae, Barnesiellaceae, Eubacteriaceae) was observed.

Phase 3 randomized COMMODORE 1 trial: Crovalimab versus eculizumab in complement inhibitor-experienced patients with paroxysmal nocturnal hemoglobinuria.

Crovalimab, a novel C5 inhibitor, allows for low-volume, every-4- week, subcutaneous self-administration. COMMODORE 1 (NCT04432584) is a phase 3, global, randomized trial evaluating crovalimab versus eculizumab in C5 inhibitor-experienced patients with paroxysmal nocturnal hemoglobinuria (PNH). Adults with lactate dehydrogenase ≤1.5 × upper limit of normal and receiving approved eculizumab doses for ≥24 weeks were randomized 1:1 to receive crovalimab (weight-based tiered dosing) or continue eculizumab. The original primary study objective was efficacy; however, given the evolving treatment landscape, target recruitment was not met, and all efficacy endpoints became exploratory, with safety as the new primary objective. Exploratory efficacy endpoints included transfusion avoidance, hemolysis control, breakthrough hemolysis, hemoglobin stabilization, FACIT-Fatigue score, and patient preference (crovalimab vs. eculizumab). Eighty-nine patients were randomized (45 to crovalimab; 44 to eculizumab). During the 24-week primary treatment period, adverse events (AEs) occurred in 77% of patients receiving crovalimab and 67% receiving eculizumab. No AEs led to treatment withdrawal or death, and no meningococcal infections occurred. 16% of crovalimab-treated patients had transient immune complex reactions (also known as Type III hypersensitivity events), an expected risk when switching between C5 inhibitors that bind to different C5 epitopes; most were mild/moderate and all resolved without treatment modification. Crovalimab-treated patients had sustained terminal complement activity inhibition, maintained disease control, and 85% preferred crovalimab over eculizumab. Together with phase 3 COMMODORE 2 results in complement inhibitor-naive patients, these data support crovalimab's favorable benefit-risk profile. Crovalimab is a new C5 inhibitor for PNH that is potentially less burdensome than existing therapies for this lifelong disease.

P264 The utility of ANCA in Ulcerative Colitis and Crohn’s Disease: A Retrospective Cohort Study in Taiwan

Abstract Background Inflammatory bowel disease (IBD) includes two chronic idiopathic inflammatory diseases: ulcerative colitis (UC) and Crohn disease (CD). The diagnosis of IBD depends on clinical, endoscopic, histological, radiological and biochemical criteria, which may be invasive, time consuming and usually not accepted by patients with IBD. Antineutrophil cytoplasmic antibodies (ANCAs) is believed to be related to IBD. The aim of this study was to investigate these serological markers and the evidence for their use in the diagnosis and management of IBD in Taiwan. Methods We conducted a retrospective cohort study in adult IBD patients who had received the serum examinations using the medical records of China Medical University Hospital between 1 January 1980 and 31 October. 2023. Results A total of 301 IBD patients (194 with UC, 107 with CD) were included in this current study. A high proportion were male (IBD 70.41%; UC 65.63%, and CD 76.71%). The mean diagnostic age of these enrolled patients was 42.9 years. In our patients, the prevalence of positive anti-HCV Ab is 0.0% in UC patients and 0.96% in CD patients. However, the prevalence of positive HBsAg was 14.5% in UC patients and 9.4% in CD patients. The prevalence of pANCA was 21.2% in UC patients and 1.4% in CD patients, respectively. The prevalence of cANCA was 3.1% in UC patients and 0.0% in CD patients. This pattern of low sensitivity and high specificity for pANCA is also seen in UC patients in various cohort studies. The serum positivity of p-ANCA was significantly higher in UC patients (Figure 1). UC patients with positive p-ANCA were older than CD patients with positive p-ANCA (44.9 vs. 37.3 years). Furthermore, we found that the incidence of positive p-ANCA in UC patients with E1, E2, and E3 at diagnosis was 3.5%, 39.2%, and 57.1%, respectively (Table 1). The serum levels of ANCA-IgG were indeed higher in patients in the severe group than those in the moderate and mild groups. Conclusion Serological biomarkers have been demonstrated to be a series of rapid, non-invasive approaches for assessments of early diagnosis, disease activity and prognosis for IBD. ANCA may be helpful in the early diagnosis of UC and in differentiating it from CD. UC patients with positive ANCA have a higher rate of intestinal mucosal vasculitis than UC patients with negative ANCA. Furthermore, ANCA may also contributes to the pathogenesis of HBV-related systemic vasculitis. Therefore, the management of HBV-related vasculitis includes control the immune complex formation and reaction as well as antiviral agents to reduce the antigenic load resulting in reduction of inflammation. Moreover, effective biomarkers with high sensitivity and specificity need to be investigated in the future.

ImmunoglobulinA vasculitis

The immune-mediated small vessel vasculitis is known as Schoenlein-Henoch purpura predominantly from pediatrics and in these cases occurs more frequently after infections of the upper airways. In adults, immunoglobulinA (IgA) vasculitis often proceeds more severely und recurrently with the classical tetrad of skin manifestations in the sense of leukocytoclastic vasculitis, joint affection, gastrointestinal involvement and IgA nephritis, in contrast to the mostly mild and self-limiting course in children. The background of this systemic vasculitis with formation of IgA immune complexes is considered to be an altered glycosylation of IgA, as this causes the exposure of binding sites for autoantibodies so that an immune complex reaction can be elicited. This ultimately leads to perivascular deposition of IgA and afurther activation of neutrophils. Groundbreaking in the diagnostics is the histological detection of leukocytoclastic vasculitis and in cases of renal manifestations akidney biopsy with characteristic deposits of immune complexes, which cannot be clearly differentiated from IgA nephropathy. The treatment is aimed at the respective manifestation and is mostly based on consensus recommendations due to the lack of randomized studies. In addition to immunosuppressive medication, in the presence of achronic kidney disease general nephroprotection is becoming increasingly more important also by inhibition of sodium-glucose transporter2 (SGLT2). The type and extent of kidney involvement and also rare cardiac manifestations are the main determinants of the prognosis. Continuous medical accompaniment of those affected is necessary due to the possible progression of the disease and the risk of recurrence.

The role of platelets in sepsis: A review.

Sepsis, a life-threatening condition characterized by organ dysfunction, results from a complex series of pathophysiological mechanisms including immune dysfunction, an uncontrolled inflammatory response, and coagulation abnormalities. It is a major contributor to global mortality and severe disease development. Platelets, abundant in the circulatory system, are sensitive to changes in the body's internal environment and are among the first cells to respond to dysregulated pro-inflammatory and pro-coagulant reactions at the onset of sepsis. In the initial stages of sepsis, the coagulation cascade, inflammatory response, and endothelial tissue damage perpetually trigger platelet activation. These activated platelets then engage in complex inflammatory and immune reactions, potentially leading to organ dysfunction. Therefore, further research is essential to fully understand the role of platelets in sepsis pathology and to develop effective therapeutic strategies targeting the associated pathogenic pathways. This review delves into the involvement of platelets in sepsis and briefly outlines the clinical applications of associated biomarkers.

The Role of Invasive Diagnostics of Systemic Connective Tissue Diseases in Respiratory Inflammation

Systemic connective tissue diseases (SCDs) are a group of diseases caused by inadequate autoimmune or immune complex reactions, manifested by damage to various organs and systems. Objective — to present our own experience and to propose an algorithm for the diagnosis of CTDs. Materials and methods. We carried out a clinical analysis of 55 newly diagnosed cases of CTDs in patients who were treated at the Department of Thoracic Surgery and Invasive Diagnostic Methods, from 2010 to 2023. For the purpose of histological verification of the diagnosis, 57 invasive interventions were performed on 55 patients, — 55 video thoracoscopic (VATS) and 2 endobronchial (EVUS) biopsies. Results and discussion. lesions of the cardiovascular system occurred in 30 (54.5%) patients, kidneys — in 26 patients (47.3 %), edematous syndrome — in 31 (56.4 %) patients, hyperthermia — in 22 (40.0 %), anemia — in 23 (41.8 %), increased erythrocyte sedimentation rate — in 34 (61.8 %) cases. As a result of 57 invasive interventions, 79 biopsies of various tissues were obtained: 41 (51.9 %) of the pleura, 25 (31.6 %) of the lung, 11 (13.9 %) of the pericardium, 2 (2.5 %) of the intrathoracic lymph nodes. An algorithm for the diagnosis of SCDs is proposed. Conclusions. Newly diagnosed patients with combined damage to the respiratory, cardiovascular and kidney systems without a history of chronic damage to any of them should be considered as a risk group for further diagnosis of SCDs. The use of VATS biopsies of affected tissues should be the standard of investigation along with immunological confirmation for establishing the type of SCDs. Identification of the type of SCDs should be carried out taking into account clinical manifestations based on the results of pathomorphological examination and serological verification of the diagnosis by specialized specialists.

TREATMENT OF HERPES ASSOCIATED ERYTHEMA MULTIFORME (HAEM)

Introduction: Herpes Associated Erythema Multiforme (HAEM) is Erythema multiforme (EM) caused herpes virus infection. EM a caused by an acute hypersensitivity reaction that occurs in the mucocutaneous area. HAEM is hypersensitivity reaction that occurs due to a hypersensitivity reaction to the herpes virus. Case: 17 year old male complaints of itching and dry on his lips since 5 days ago. patient said that ± 7 days ago he had a fever which lasted for 2 days then after the fever went down his lips felt itchy and dry. On clinical examination, desquamation with yellowish brown crusts was found on the vermilion of the upper and lower lips. Case Treatment: patient is given Aloclair® Gel and Becomzet®. Patient is referred for a complete blood count, Total IgE and IgM and IgG HSV-1 antibody testing. The patient was then given hydrocortisone cream 2.5% used 3 times a day. The patient recovered 10 days after the first visit. Discussion: HAEM is triggered by an immunological response in which an immune complex reaction occurs as a result of an immune response to certain antigens such as the herpes simplex virus or certain types of drugs. In cases of HAEM the herpes virus that triggers it is usually HSV-1 & HSV-2. Diagnosis is confirmed by Total IgE and HSV-1 Antibody Tests. Conclucion: Management of cases of HAEM can be successfully determined by establishing the correct diagnosis which requires investigations so that we can rule out the differential diagnosis and provide appropriate treatment

Persistent Exhausted T-Cell Immunity after Severe COVID-19: 6-Month Evaluation in a Prospective Observational Study.

Severe COVID-19 can result in a significant and irreversible impact on long-term recovery and subsequent immune protection. Understanding the complex immune reactions may be useful for establishing clinically relevant monitoring. Hospitalized adults with SARS-CoV-2 between March/October 2020 (n = 64) were selected. Cryopreserved peripheral blood mononuclear cells (PBMCs) and plasma samples were obtained at hospitalization (baseline) and 6 months after recovery. Immunological components' phenotyping and SARS-CoV-2-specific T-cell response were studied in PBMCs by flow cytometry. Up to 25 plasma pro/anti-inflammatory cytokines/chemokines were assessed by LEGENDplex immunoassays. The SARS-CoV-2 group was compared to matched healthy donors. Biochemical altered parameters during infection were normalized at a follow-up time point in the SARS-CoV-2 group. Most of the cytokine/chemokine levels were increased at baseline in the SARS-CoV-2 group. This group showed increased Natural Killer cells (NK) activation and decreased CD16high NK subset, which normalized six months later. They also presented a higher intermediate and patrolling monocyte proportion at baseline. T cells showed an increased terminally differentiated (TemRA) and effector memory (EM) subsets distribution in the SARS-CoV-2 group at baseline and continued to increase six months later. Interestingly, T-cell activation (CD38) in this group decreased at the follow-up time point, contrary to exhaustion markers (TIM3/PD1). In addition, we observed the highest SARS-CoV-2-specific T-cell magnitude response in TemRA CD4 T-cell and EM CD8 T-cell subsets at the six-months time point. The immunological activation in the SARS-CoV-2 group during hospitalization is reversed at the follow-up time point. However, the marked exhaustion pattern remains over time. This dysregulation could constitute a risk factor for reinfection and the development of other pathologies. Additionally, high SARS-CoV-2-specific T-cells response levels appear to be associated with infection severity.

Leukocytoclastic vasculitis in association with linear epidermal basement membrane zone immunoglobulin deposition: Linear vasculitis.

Cutaneous leukocytoclastic vasculitis (LCV) has a distinctive clinical and light microscopic presentation; however, the etiologic basis of LCV is varied. Most cases are attributable to immune complex deposition within a vessel wall and represent an Arthus type III immune complex reaction. The prototypic immunoreactant profile is characterized by granular deposits of components of complement activation in concert with immunoglobulin within the cutaneous vasculature. We encountered nine patients with vasculitic and/or vesiculobullous clinical presentations exhibiting an LCV in association with an immunoreactant profile characterized by homogeneous linear deposits of immunoglobulin along the dermal epidermal junction in a fashion resembling an autoimmune vesiculobullous disease. Among the clinical presentations were palpable purpura, urticarial vasculitis, and vesiculobullous eruptions with supervening purpura. Two patients with Crohn disease presented with classic palpable purpura with biopsy-proven LCV, and direct immunofluorescence (DIF) studies demonstrated linear immunoglobulin G (IgG) with floor localization on the salt-split skin assay. Four patients with systemic lupus erythematosus (SLE) showed purpuric vesiculobullous lesions, with evidence of a neutrophilic interface dermatitis and LCV in three of the four. The remaining patient had urticarial nonbullous lesions showing small-vessel vasculitiswith a neutrophilic interface dermatitis. In all of the patients with SLE, DIF studies showed linear immunoglobulin deposits within the basement membrane zone (BMZ). These constellation of findings clinically, light microscopically, and by immunofluorescence were those of a vasculitic presentation of bullous systemic lupus erythematosus. Two patients had linear IgA disease, which was drug induced in one and paraneoplastic in the other, and the dominant morphology on biopsy in both cases was an LCV. One patient microscopically demonstrated drug-associated and eosinophilic enriched LCV with DIF studies showing striking linear deposits of IgG suggestive of bullous pemphigoid, which was consistent with a vasculitic presentation of drug-induced bullous pemphigoid. In all cases, typical granular vascular immunoglobulin and complement deposition compatible with immune complex mediated vasculitis was observed. It is likely that local immune complexes derived from BMZ antigen bound to antibody are pathogenically relevant. We propose the designation of linear vasculitis for this unique scenario of LCV and linear immunoglobulin epidermal BMZ staining, which in some cases represents a vasculitic presentation of conventional autoimmune vesiculobullous disease.

Transcriptome Analysis of Greenfin Horse-Faced Filefish (Thamnaconus septentrionalis) Gills in Response to Amyloodinium ocellatum (AO) Infection

The greenfin horse-faced filefish (Thamnaconus septentrionalis) is susceptible to recurrent Amyloodinium ocellatum (AO) infestation over the grow-out production cycle. This parasite breeds mainly on the gills, causing hypoxia in the fish body, and leading to many deaths. The host-parasite response drives a complex immune reaction, which is poorly understood. To generate a model for host-parasite interaction and the pathogenesis of AO in greenfin horse-faced filefish, an RNA-seq approach, differential gene expression, GO, and KEGG analyses were employed. Overall, 624 new genes and 2076 differentially expressed genes (DEGs) were detected, including 942 upregulated and 1134 downregulated genes in the gills. Compared with the control group, the expression of leptin a, GTPase IMAP family member 4, and NLR family CARD domain-containing protein 3 was significantly higher in the AO-infected group. Conversely, cell wall integrity and stress response component 1-like, and hepcidin-like were significantly downregulated in the gills of AO-infected fish. GO and KEGG enrichment analysis indicated that DEGs were significantly enriched in signaling pathways associated with viral protein interaction with cytokine and cytokine receptor and cytokine–cytokine receptor interaction. Collectively, this transcriptomic study provides novel molecular insights into the pathology caused by AO infestation and alternative theories for future research implementing strategies to control and manage AO.

Diverse Roles of Immune Cells in Transplant Rejection and Immune Tolerance

Organ transplant rejection (OTR) is a complex immune reaction involving multiple cells, and it determines graft survival and patient prognosis. At present, most transplant recipients are administered a combination of immunosuppressive and biological agents to protect them from OTR. However, immunosuppressive agents negatively impact the immune system of the patients, causing them to suffer from serious complications, such as chronic infection and malignant tumors. Therefore, a thorough understanding of the mechanisms involved in immune tolerance and immune rejection with regard to organ transplant (OT) is essential for developing better treatment options and improving patient outcomes. This article reviews the role of immune cells in OTR and organ transplant tolerance (OTT), including the novel cell therapies that are currently under clinical trials for transplant recipients.

Multicolor Flow Cytometry and High-Dimensional Data Analysis to Probe Complex Questions in Vaccinology.

Vaccines induce a highly complex immune reaction in secondary lymphoid organs to generate immunological memory against an antigen or antigens of interest. Measurement of postimmunization immune responses generated by specialized lymphocyte subsets requires time-dependent sampling, usually of the blood. Several T and B cell subsets are involved in the reaction, including CD4 and CD8 T cells, T follicular helper cells (Tfh), and germinal center B cells alongside their circulating (c) counterparts; cTfh and antibody secreting cells. Multicolor flow cytometry of peripheral blood mononuclear cells (PBMC) coupled with high-dimensional analysis offers an opportunity to study these cells in detail. Here we demonstrate a method by which such data can be generated and analysed using software that renders multidimensional data on a two dimensionalmap to identify rare vaccine-induced T and B cell subsets.

M035 GROWTH HORMONE HYPERSENSITIVITY REACTION IN AN 8-YEAR-OLD CHILD: A CASE REPORT

Hypersensitivity reactions to recombinant human growth hormone (rhGH) are uncommon and rarely reported. Reported reactions in the literature include local erythema, generalized pruritus, and urticaria, with both IgE-mediated (Type I) and type III immune complex reactions being implicated. Reactions are thought to be caused by preservatives, buffers, or the GH molecule itself.

Host-Parasite Interaction of Atlantic salmon (Salmo salar) and the Ectoparasite Neoparamoeba perurans in Amoebic Gill Disease.

Marine farmed Atlantic salmon (Salmo salar) are susceptible to recurrent amoebic gill disease (AGD) caused by the ectoparasite Neoparamoeba perurans over the growout production cycle. The parasite elicits a highly localized response within the gill epithelium resulting in multifocal mucoid patches at the site of parasite attachment. This host-parasite response drives a complex immune reaction, which remains poorly understood. To generate a model for host-parasite interaction during pathogenesis of AGD in Atlantic salmon the local (gill) and systemic transcriptomic response in the host, and the parasite during AGD pathogenesis was explored. A dual RNA-seq approach together with differential gene expression and system-wide statistical analyses of gene and transcription factor networks was employed. A multi-tissue transcriptomic data set was generated from the gill (including both lesioned and non-lesioned tissue), head kidney and spleen tissues naïve and AGD-affected Atlantic salmon sourced from an in vivo AGD challenge trial. Differential gene expression of the salmon host indicates local and systemic upregulation of defense and immune responses. Two transcription factors, znfOZF-like and znf70-like, and their associated gene networks significantly altered with disease state. The majority of genes in these networks are candidates for mediators of the immune response, cellular proliferation and invasion. These include Aurora kinase B-like, rho guanine nucleotide exchange factor 25-like and protein NDNF-like inhibited. Analysis of the N. perurans transcriptome during AGD pathology compared to in vitro cultured N. perurans trophozoites, as a proxy for wild type trophozoites, identified multiple gene candidates for virulence and indicates a potential master regulatory gene system analogous to the two-component PhoP/Q system. Candidate genes identified are associated with invasion of host tissue, evasion of host defense mechanisms and formation of the mucoid lesion. We generated a novel model for host-parasite interaction during AGD pathogenesis through integration of host and parasite functional profiles. Collectively, this dual transcriptomic study provides novel molecular insights into the pathology of AGD and provides alternative theories for future research in a step towards improved management of AGD.

The Reaction and Type of Hypersensitivity

The purpose of the study is to analyze the reaction and types of hypersensitivity. The study discusses the reaction of hypersensitivity occurs in individuals who have previously been exposed to an antigen that has created an immune response to it (sensitization). there are 4 groups of hypersensitivity reactions, namely Type I (anaphylactic reaction), type II (cytotoxic reaction), type III (immune complex reaction), type IV (slow type reaction). Hypersensitivity reactions can occur in two situations. first, the response to foreign antigens (microbes and non-infectious environmental antigens) which can cause tissue damage, especially if the reaction is repeated and uncontrolled. Second, the immune response can act directly against self-antigens (autologs) as a result of failure to tolerate self (self-tolerance).

Arthus Reaction as an Adverse Event Following Tdap Vaccination.

Repeat administration of tetanus toxoid-containing vaccines has rarely been associated with Arthus phenomenon, an immune-complex reaction. In the US, since 2013, tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccines (Tdap) have been recommended for administration during each pregnancy. Separately, in 2019, one Tdap was approved for repeat administration in adults in the US. We aimed to describe trends in spontaneously reported Arthus reactions following Tdap in the US and to assess the risk of this phenomenon in persons receiving Tdap repeatedly. We reviewed Arthus reports in the Vaccine Adverse Events Reporting System (VAERS), 1990–2018. Reporting rates were estimated using Tdap doses distributed data. A systematic literature review was conducted in MEDLINE for any Arthus cases reported in Tdap clinical trials and observational studies published between 2000 and 2019. We found 192 Arthus reports in VAERS after any vaccine, of which 36 occurred after Tdap and none were reported during pregnancy. The Arthus reporting rate was estimated at 0.1 per million doses distributed. We identified eight published studies of Tdap administration within five years after a previous dose of tetanus toxoid-containing vaccine; no Arthus cases were reported. We conclude that Arthus reaction following Tdap is extremely rare. Increasing frequency of repeat Tdap administration in adults in the US did not result in a detectable increase in reporting rates of this phenomenon, confirming the favorable safety profile of Tdap.

Level of immune complex reactions in non-psychothotic mental disorders in combatants

The level of immune complex reactions in combatants with non-psychotic mental disorders was studied. A clinical-psychopathological and clinical-biochemical examination of 95 combatants with non- psychotic mental disorders were conducted. In the clinical picture of prolonged depressive reaction, there was a decrease in mood, feelings of sadness, anxiety, anhedonia, asthenic manifestations, detachment, lack of hope, guilt of the survivor. Mixed anxiety-depressive reaction was characterized by low mood, feelings of depression, helplessness, insecurity, feelings of despair, sadness, isolated obsessive fears, doubts about the correctness of decisions and actions that are closely related to anxious thinking in relation to their assessment in the eyes of others. Post-traumatic stress disorder was manifested by low mood, anxiety, internal tension with inability to relax, danger, anxiety, flashback effects, symptoms of intrusion, asthenia, irritability, propensity to affective reactions. It was found that in the examined patients there was an increase in the concentration of circulating immune complexes, mainly due to the most pathogenic fractions of medium and low molecular weight and suppression of phagocytic activity of monocytes. Changes in immune complex reactions were most pronounced in post-traumatic stress disorder.

Risk Factors For The Presence Of Artemisinin Antibodies Amongst Patients Undergoing Treatment For Malaria In Benin City, Nigeria

Artemisinin have being used for the control of malaria worldwide for over a decade and its listing by WHO as the first-line drug for treatment of both severe and uncomplicated malaria and the observed treatment failure have warranted the need to screening malaria patients for the presence of antibodies to malaria. In our locality where there is unregulated use of antimicrobials, the need to ascertain the prevalence of antibodies to artemisinin and evaluate the potential risk factors cannot be overemphasised, hence this study. Blood specimens were collected from 400 randomised patients undergoing treatment for malaria in Benin City, Nigeria. Data on socio-demography were collected with the aid of a well-structured questionnaire. Artemisinin antibodies were detected by drug absorption mechanism (DAM) and immune complex reaction (IMC) methods. ABO, rhesus blood group, and haemoglobin (Hb) phenotype were determined by using standard technique. A total of 112(28.00%) out of the 400 participants had artemisinin antibodies. Gender, marital status, level of education, residential area and living arrangement did not significantly affect the prevalence of artemisinin antibodies whereas age and ethnicity significantly affected the prevalence of artemisinin antibodies (p=0.0244 and 0.0001 respectively). Duration of the last artemisinin used and the mostly used brand of artemisinin as well as the ABO and rhesus blood groups and haemoglobin phenotypes did not significantly affect the production of artemisinin antibodies. Although of all the risk factors age and ethnicity were identified as the only risk factors for the development of artemisinin, we therefore advocate the prudent use of artemisinin-containing antimalarial and concerted efforts in combating self-medication with this drugs to avoid the development of resistance.