Levels Of Immune Complexes Research Articles

Immune complexes as a tool for strongyloidiasis immunodiagnosis in kidney and liver transplant candidate.

Strongyloidiasis is a chronic and asymptomatic infection in immunocompetent patients. Immunocompromised patients, such as organ transplant candidates, can develop severe forms of this disease, and the best way to prevent progression to these forms is early diagnosis. Serological techniques using specific IgG and immune complexes (IC) detection can help in the diagnosis of these patients. This study aimed to detect specific anti-Strongyloides IC and IgG antibodies in kidney transplant (KT) and liver transplant (LT) candidates. A total of 100 blood samples was collected from transplant candidates (50 blood samples each from KT and LT candidates). Serum was obtained and analysed using enzyme-linked immunosorbent assay for IC and IgG detections. The IC levels showed frequencies of 18% and 2% in the KT and LT groups, respectively, whereas anti-Strongyloides IgG was detected in 34% and 12% of KT and LT candidates, respectively. The correlation between IC and IgG detection is poor in KT candidates, while in LT candidates, there is a significant positive correlation. The detection of IC can be an additional tool for the diagnosis of strongyloidiasis, especially when associated with the detection of specific IgG anti-Strongyloides antibodies.

FC049: Nefecon® (Budesonide) is an Epigenetic Modifier in IGA Nephropathy

Abstract BACKGROUND AND AIMS In recent years, the dysregulated expression of microRNAs (miRs)—small molecules of noncoding RNA that epigenetically fine-tune post-transcriptional gene expression—has been increasingly implicated in the pathogenesis of IgA nephropathy (IgAN). Extracellular miRs, contained within extracellular vesicles such as exosomes and microvesicles, are thought to function as important intercellular and interorgan modes of communication in health and disease. In the current study, next-generation sequencing (NGS) and subsequent real-time quantitative polymerase chain reaction (RT-qPCR) validation were performed to identify serum miRs associated with a high risk of future kidney function decline in IgAN. We then went on to determine whether treatment with Nefecon® 16 mg/day for 9 months was capable of modifying the serum levels of miRs associated with high-risk IgAN. This study was supported by a grant from Calliditas Therapeutics AB. METHOD NGS was performed by Qiagen (Germany) on serum from patients with IgAN (10 at high risk and 10 at low risk of progression) or membranous nephropathy (MN, n=10), as well as healthy individuals (HS, n=10). Sequencing data were validated by RT-qPCR using TaqMan miR PCR assays in independent sets of serum samples (20 per cohort). Using the Total Exosome Isolation (from serum) reagent (Thermo Fisher Scientific, UK), extracellular exosomes were isolated from the serum of participants of the NEFIGAN trial from the placebo group (n=40) and Nefecon® 16 mg/day group (n=40) at the start of treatment (SOT) and end of treatment (EOT). RNA was isolated and levels of miRs-483-5p and -122-5p were measured by RT-qPCR. The NEFIGAN trial (NCT01738035) was a randomized, double-blind, placebo-controlled Phase 2b trial designed to assess the safety and efficacy of Nefecon® a novel targeted-release formulation of budesonide, designed to deliver the drug to the distal ileum in patients with IgAN. The trial comprised a 6-month run-in, a 9-month treatment and a 3-month follow-up phase. A total of 48 patients received Nefecon® 16 mg/day, 51 patients received Nefecon® 8 mg/day and 50 patients received placebo. The key result of the study was that Nefecon® 16 mg/day, added to optimized renin–angiotensin system blockade, reduced proteinuria and stabilized estimated glomerular filtration rate in patients with IgAN. These findings have now been replicated in the NefIgArd study, which released data in 2021. RESULTS miRs-483-5p and -122-5p were significantly overexpressed in the serum of patients with IgAN at high risk of progression compared with those who had stable IgAN or HS, but not compared with patients with MN. Both miRs were also found to be significantly increased in extracellular exosomes in high-risk IgAN compared with low-risk IgAN, HS and MN. Interestingly, levels of exosomal miRs-483-5p and -122-5p did not correlate with total serum IgA, IgA1, galactose-deficient IgA1 or IgA–IgG immune complex levels, suggesting a novel mechanism of action. Treatment with 16 mg/day of Nefecon® led to a significant reduction in the exosomal levels of miR-122-5p, while no change in miR-483-5p levels was observed in the treated group. CONCLUSION These data reveal a dysregulation of systemic exosomal miR expression in IgAN, and demonstrate for the first time that it is possible to pharmacologically modify the miR content of circulating exosomes in IgAN. Treatment with Nefecon® 16 mg/day for 9 months selectively downregulated exosomal miR-122-5p, while having no effect on exosomal miR-483-5p levels, arguing against a generalized ‘anti-miR’ effect of Nefecon®. Studies are ongoing to both precisely delineate the cellular source(s) of these exosomes and determine the downstream impact of these changes on glomerular and tubulointerstitial biology.

Contribution of Coronavirus-Specific Immunoglobulin G Responses to Complement Overactivation in Patients with Severe Coronavirus Disease 2019.

BackgroundExcessive complement activation has been implicated in the pathogenesis of coronavirus disease 2019 (COVID-19), but the mechanisms leading to this response remain unclear.MethodsWe measured plasma levels of key complement markers, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA and antibodies against SARS-CoV-2 and seasonal human common cold coronaviruses (CCCs) in hospitalized patients with COVID-19 of moderate (n = 18) and critical severity (n = 37) and in healthy controls (n = 10).ResultsWe confirmed that complement activation is systemically increased in patients with COVID-19 and is associated with a worse disease outcome. We showed that plasma levels of C1q and circulating immune complexes were markedly increased in patients with severe COVID-19 and correlated with higher immunoglobulin (Ig) G titers, greater complement activation, and higher disease severity score. Additional analyses showed that the classical pathway was the main arm responsible for augmented complement activation in severe patients. In addition, we demonstrated that a rapid IgG response to SARS-CoV-2 and an anamnestic IgG response to the nucleoprotein of the CCCs were strongly correlated with circulating immune complex levels, complement activation, and disease severity.ConclusionsThese findings indicate that early, nonneutralizing IgG responses may play a key role in complement overactivation in severe COVID-19. Our work underscores the urgent need to develop therapeutic strategies to modify complement overactivation in patients with COVID-19.

Нейроендокринно-імунний супровід діуретичного ефекту бальнеотерапії на курорті Трускавець

Мета: виявити супутні зміни параметрів нейроендокринно-імунного комплексу і мікробіоценозу товстого кишечника, що супроводжують діуретичний ефект бальнеотерапії на курорті Трускавець. Результати. У спостереженні за 22 чоловіками, хворими на хронічний пієлонефрит в поєднанні з холециститом, виявлено, що 10–12-денний курс бальнеотерапії (пиття біоактивної води «Нафтуся», аплікації озокериту, мінеральні ванни) збільшує добовий діурез на 28 % (p < 0,001). Це поєднується із збільшенням екскреції фосфатів на 103 % (p < 0,001), кальцію — на 76 % (p < 0,01), креатиніну — на 32 % (p < 0,02), сечової кислоти — на 29 % (p < 0,001), сечовини — на 21 % (p < 0,01), магнію — на 19 % (p = 0,05) при відсутності суттєвих змін екскреції хлориду, калію і натрію. При цьому знижується рівень у плазмі креатиніну на 14 % (p < 0,001) і сечовини на 11 % (p < 0,01). Лейкоцитурія зменшується на 16 % (p < 0,02). Екскреторно-депураційний і протизапальний ефекти бальнеотерапії супроводжуються відчутною модуляцією параметрів нейроендокринно-імунного комплексу. Зокрема, зменшується як абсолютна, так і відносна щільність спектральної потужності (PSD) δ- і α-ритмів (p < 0,05–0,01), і підвищується відносна PSD β-ритму (p < 0,05–0,02) базальної електроенцефалограми. Разом з тим знижуються індекси варіабельності ритму серця: (VLF + LF)/HF — на 34 % (p < 0,05) і LF/HF — на 32 % (p > 0,05) за рахунок підвищення PSD HF більшою мірою, ніж LF. Базальний рівень у плазмі кортизолу знижується на 20 % (p < 0,01), тестостерону — на 15 % (p = 0,01), натомість підвищується рівень трийодтироніну — на 4 % (p < 0,05) і особливо кальцитонінової активності — на 92 % (p < 0,001), розрахованої за екскрецією з сечею фосфатів і кальцію. Лейкоцитарний індекс адаптації Поповича зростає на 46 % (p < 0,02). Стосовно параметрів фагоцитарної функції нейтрофілів констатовано підвищення зниженого індексу кілінгу ними Staphylococcus aureus на 19 % (p < 0,001) і Escherichia coli на 18 % (p < 0,01) за відсутності змін початково нормальних фагоцитарних індексів. Мікробне число стосовно Staphylococcus aureus залишається нормальним, а початково підвищена на 15 % інтенсивність фагоцитозу Escherichia coli знижується на 8 % (p < 0,05). Стосовно параметрів імунітету виявлено значуще підвищення рівня в крові лише CD16+ лімфоцитів (+17 %, p < 0,01) при відсутності змін рівнів CD3+CD4+ і CD3+CD8+ Т-лімфоцитів і CD19+ В-лімфоцитів. Не змінюються суттєво ні рівні в сироватці Ig G, M, A, ні циркулюючих імунних комплексів. Імунотропний ефект супроводжується редукцією проявів дисбактеріозу: вміст Bifidumbacter зростає на 19 % (p < 0,02), Lactobacter — на 20 % (p < 0,05), а Escherichia coli — на 48 % (p < 0,01), при цьому доля штамів з ослабленими ферментативними властивостями зменшується на 47 % (p < 0,001), з гемолітичними властивостями — на 77 % (p < 0,01). Висновок. Бальнеотерапія на курорті Трускавець чинить відчутний діуретичний ефект, що поєднується з активацією екскреторної і депураційної функцій нирок та бактерицидної функції нейтрофілів, редукцією дисбактеріозу товстого кишечника, лейкоцитурії і нейроендокринних проявів стресу.

EXPRESSION OF SYNAPTOFYSIN AND VEGF IN THE SENSOMOTOR CORTEX DURING THE CAROTID ARTERY LIGATION, THE BRAIN ANTIGEN SENSITIZATION AND THEIR COMBINATIONS.

The aim: To study changes of the expression of synaptophysin (Syn) and vascular endothelial growth factor (VEGF) in neurons of the sensorimotor cortex (SMC) to reveal after unilateral ligation of the carotid artery, sensitization with brain antigen and their combination. Materials and methods: Experimental animals - Wistar rats (260-290 g). Experimental models: mobilization of the left common carotid artery, ligation of the indicated artery, sensitization with cerebral antigen, combination of sensitization with cerebral antigen and ligation of the carotid artery. Methods: immunohistochemistry, quantitative densitometric assessment. Results: Dyscirculatory disorders of cerebral blood supply during unilateral mobilization or ligation of the common carotid artery, sensitization with cerebral antigen lead in rats to a transient decrease in synaptophysin expression and phase changes in VEGF expression in the SMC from the lesion side. These changes occur in the absence of morphological changes in the cerebral cortex. Conclusions: The absence of morphological changes in the SMC in the short term (10-30 days) after minor trauma to the common carotid artery (separation from the bed and n.vagus) or its ligation is accompanied by a transient decrease in Syn expression and some increase in VEGF, which may reflect a violation of synaptic function and the general metabolic activity of neurons. Sensitization with a brain antigen, leading to an increase in the level of anti-brain antibodies and immune complexes in the blood of rats, can act as an independent damaging factor for the brain, and also potentiates and prolongs changes caused by impaired blood circulation.

Serological Measurement of Poly-IgA Immune Complex Levels in IgA Nephropathy and IgA Vasculitis.

Both IgA nephropathy and IgA vasculitis, formerly known as Henoch-Schӧnlein purpura, are immune deposition diseases. IgA nephropathy is caused by the deposition of aberrantly formed poly-IgA complexes from blood circulation to the kidney glomerulus; IgA vasculitis is characterized by IgA-dominant immune deposits to small vessels of the skin and other organs, including the kidney. Therefore, measuring the disease-causing poly-IgA contents in the plasma is needed to study these conditions. However, while clinical tests for the level of total plasma IgA are routinely performed, methods for specific detection of poly-IgA contents are unavailable in clinical medicine. In this protocol, we describe a practical solution for measuring poly-IgA in patient samples. The new method is based on the biological selectivity of IgA Fcα receptor I (FcαRI/CD89) toward poly-IgA species, in contrast to its relatively low affinity for normal monomeric IgA. By devising recombinant CD89 ectodomain as the "capturing" probe, we validated the feasibility of the assay for measuring plasma poly-IgA levels in a 96-well format. The methodology was able to differentiate plasma samples of IgA nephropathy, or related IgA vasculitis, from those of other autoimmune kidney disease types or from healthy controls. Moreover, the measured poly-IgA indices not only correlated with the severity of IgA nephropathy, but the levels also trended lower following corticosteroid or immunosuppressant treatments of patients. Therefore, we anticipate the new assay will provide useful measurements of the IgA nephropathy disease activity index for stratifying disease severity or for evaluating treatment response. Graphical abstract.

Poly-IgA Complexes and Disease Severity in IgA Nephropathy.

Poly-IgA immune complex formation and glomerular deposition play a key role in IgA nephropathy. Our study sought to develop a new methodology for one-step serologic detection of poly-IgA levels. A novel ELISA method using recombinant CD89 as a "capturing" probe was established for detecting poly-IgA immune complex in plasma. We applied semiquantitative measurements of these poly-IgA indices in patients recruited at Peking University First Hospital who had IgA nephropathy or other kidney disease types, as compared with healthy controls. The longitudinal trend of the poly-IgA index and the association with pathologic parameters and treatment responses were evaluated. Finally, we analyzed the molecular composition of poly-IgA complexes in patients by mass spectrometry. Recombinant CD89-mounted ELISA plates specifically captured plasma poly-IgA. The levels of poly-IgA immune complex (26.7 [interquartile range (IQR) 17.1-42.6] U/ml) in IgA nephropathy were significantly higher than those in healthy controls (15.5 [IQR 10.7-20.0] U/ml; P<0.001) or in controls with non-IgA nephropathy disease (14.8 [IQR 10.5-21.9] U/ml; P<0.001). Higher levels of poly-IgA immune complex were associated with lower eGFR and worse kidney outcome. Accuracy parameters and concordant statistics showed good discrimination between IgA nephropathy and healthy controls based on poly-IgA index levels (area under the curve [AUC], 0.78; 95% confidence interval [95% CI], 0.72 to 0.83; P<0.001), significantly outperforming galactose-deficient IgA1 levels (AUC, 0.70; P=0.05). Corticosteroid and immunosuppressant treatments lowered poly-IgA indices. After a recombinant CD89-directed workflow in conjunction with mass spectrometry, we also analyzed the molecular composition of IgA immune complex in patients with IgA nephropathy. Higher level of recombinant CD89-bound poly-IgA immune complex was associated with the severity of the disease and with treatment response to steroids and immunosuppressants.

Antibodies to neurofilament light as potential biomarkers in multiple sclerosis

Background and objectiveThe concentration of neurofilament light (NfL) protein in cerebrospinal fluid (CSF) and blood is widely considered as a quantitative measure of neuro-axonal injury. Immune reactivity to NfL released...

Clinical and immunological changes in patients with chronic inflammatory diseases of the upper respiratory tract at different periods after administration of influenza vaccine. Message 1. The influence of parenteral influenza vaccination on the clinical condition and indicators of systemic humoral immunity in patients with chronic inflammatory diseases of the upper respiratory tract

Topicality: Today, as an assessment of the effectiveness of vaccination against influenza infection is to determine the level of antibodies against influenza virus hemagglutinin, which is determined by the reaction of inhibition of hemagglutination. It is known that the effect of vaccination with modern drugs is short-lived, compared with what remains after the disease. Therefore, there is a need for further vaccinations, which are carried out without taking into account the state of immunity in those who will be vaccinated. This raises the question of the appropriateness of this approach in individuals who, according to this indicator, can already be considered protected from influenza infection and how often such patients occur in clinical practice. Material and methods: From the autumn-winter period of 2019 to November 2020, 32 donors and 32 patients with chronic inflammatory diseases of the upper respiratory tract chronic inflammatory diseases of the upper respiratory tract of both sexes who were not vaccinated for 1 year before the study were examined. Among these patients, 11 were diagnosed with chronic rhinosinusitis, 9 with chronic tonsillitis, and 12 with chronic pharyngitis. All patients with chronic inflammatory diseases of the upper respiratory tract underwent a complete otolaryngological examination prior to influenza vaccination and were monitored for another 36 weeks thereafter. Attention was paid to their general clinical condition, cases of exacerbations of chronic inflammatory diseases of the upper respiratory tract and the number of episodes of acute respiratory viral infections during the year before vaccination according to the anamnesis and for the observation period during the post-vaccination period. Samples of serum venous blood of donors, as well as persons with chronic inflammatory diseases of the upper respiratory tract were obtained at the initial examination, and in vaccinated patients 3, 12 and 36 weeks after vaccination and stored at -20°C (Ardo, Italy) until the simultaneous detection of antibodies (Ab) to influenza A and B viruses by hemagglutination inhibition reaction with human erythrocytes 0 group. Trivalent influenza inactivated split vaccine Vaxigrip (France) was used both for vaccination and in the determination of Ab in the blood for influenza viruses. In all examinations, the titer of anti-influenza Ab and the content of immune complexes were determined in the sera of patients, and the content of total IgE was measured in patients with chronic inflammatory diseases of the upper respiratory tract before and after 12 and 36 weeks. Statistical processing of the obtained results was performed in accordance with the recommendations of Glantz. Results: In 41% of those examined protectively significant titers of antibodies to hemagglutinins of vaccine strains of influenza virus vaccine Vaxigrip were detected in the blood. Parenteral vaccination of patients with chronic inflammatory diseases of the upper respiratory tract against influenza helped to improve the course of their underlying clinical disease and reduce their incidence of acute respiratory viral infections within 36 weeks after vaccination. The effect of increasing the level of antibodies to hemagglutinins of influenza virus remained at the limit of 3 months and decreased. Influenza vaccination in patients with chronic inflammatory diseases of the upper respiratory tract with the presence of most of them at the time of vaccination of clinically significant protective titers of antibodies to hemagglutinins vaccine strains of viruses led to an increase in blood in the long term of the vaccination process levels of immune complex and total IgE relative to their initial level, while these indicators did not exceed the limits of their physiological values. Conclusion: Single parenteral influenza vaccination leads to a short-term increase in the blood of specific projective antibodies, improving the clinical condition of patients with inflammatory diseases of the upper respiratory tract, increasing the level of immune complexes and total IgE.

Value of Plasma Squamous Cell Carcinoma Antigen-IgM Immune Complexes (SCCA-IgM IC) as a Novel Biomarker for Monitoring Hepatocellular Carcinoma Treatment Outcome

Abstract Background Assessment of the levels of Squamous Cell Carcinoma Antigen-IgM Immune Complexes (SCCA-IgM IC) as a serum biomarker to assess the prognosis and treatment outcome of HCC after locoregional treatment Aim of the work Evaluation of plasma squamous cell carcinoma antigen-IgM immune complex (SCCA-IgM IC) level as a biomarker to predict response to treatment with radiofrequency ablation (RF) and/or trance arterial chemoembolization (TACE) in HCC patients. Patients and Methods This study was conducted at the Internal Medicine department, Faculty of Medicine, Ain Shams University, during the period from July 2016 to November 2018 on 60 sequentially recruited patients with HCC undergoing locoregional treatment (RF and/or TACE). Patients were divided into two groups, Group A: 40 patients underwent TACE, Group B: 20 patients Underwent RF, all patients were followed up at 3 and 6 months post treatment. Patients who were excluded, those with HCC with late stage of the BCLC (Barcelona clinic liver cancer) staging system, patients with decompensated liver disease (Child-Pugh C), Hepato-renal syndrome or renal insufficiency, patients who had history of organ transplant or previously treated HCC. Results SCCA IgM IC serum level was significantly lower in patients without recurrence post TACE than patients with HCC recurrence at 3 and 6 months post treatment. SCCA IgM IC showed promising results especially when combining with AFP in diagnosis and monitoring of treatment response of HCC Conclusion the use of SCCA IgM IC in combination with AFP serum level may prove to be useful in assessing prognosis of HCC locoregional treatment

Humoral response to neurofilaments and dipeptide repeats in ALS progression.

ObjectiveTo appraise the utility as biomarkers of blood antibodies and immune complexes to neurofilaments and dipeptide repeat proteins, the products of translation of the most common genetic mutation in amyotrophic lateral sclerosis (ALS).MethodsAntibodies and immune complexes against neurofilament light, medium, heavy chains as well as poly‐(GP)‐(GR) dipeptide repeats were measured in blood samples from the ALS Biomarkers (n = 107) and the phenotype–genotype biomarker (n = 129) studies and in 140 healthy controls. Target analyte levels were studied longitudinally in 37 ALS cases. Participants were stratified according to the rate of disease progression estimated before and after baseline and C9orf72 genetic status. Survival and longitudinal analyses were undertaken with reference to matched neurofilament protein expression.ResultsCompared to healthy controls, total neurofilament proteins and antibodies, neurofilament light immune complexes (p < 0.0001), and neurofilament heavy antibodies (p = 0.0061) were significantly elevated in ALS, patients with faster progressing disease (p < 0.0001) and in ALS cases with a C9orf72 mutation (p < 0.0003). Blood neurofilament light protein discriminated better ALS from healthy controls (AUC: 0.92; p < 0.0001) and faster from slower progressing ALS (AUC: 0.86; p < 0.0001) compared to heavy‐chain antibodies and light‐chain immune complexes (AUC: 0.79; p < 0.0001 and AUC: 0.74; p < 0.0001). Lower neurofilament heavy antibodies were associated with longer survival (Log‐rank Chi‐square: 7.39; p = 0.0065). Increasing levels of antibodies and immune complexes between time points were observed in faster progressing ALS.ConclusionsWe report a distinctive humoral response characterized by raising antibodies against neurofilaments and dipeptide repeats in faster progressing and C9orf72 genetic mutation carriers ALS patients. We confirm the significance of plasma neurofilament proteins in the clinical stratification of ALS.

Immunoglobulin G Immune Complexes May Contribute to Neutrophil Activation in the Course of Severe Coronavirus Disease 2019.

Severe COVID-19 is associated with an overactive inflammatory response mediated by macrophages. Here, we analyzed the phenotype and function of neutrophils in COVID-19 patients. We found that neutrophils from severe COVID-19 patients express high levels of CD11b and CD66b, spontaneously produce CXCL8 and CCL2 and show a strong association with platelets. Production of CXCL8 correlated with plasmatic concentrations of LDH and D-dimer. Whole blood assays revealed that neutrophils from severe COVID-19 patients show a clear association with IgG immune complexes. Moreover, we found that sera from severe patients contain high levels of immune complexes and activate neutrophils through a mechanism partially dependent on FcγRII (CD32). Interestingly, when integrated in immune complexes, anti-SARS-CoV-2 IgG antibodies from severe patients displayed a higher pro-inflammatory profile compared with antibodies from mild patients. Our study suggests that IgG immune complexes might promote the acquisition of an inflammatory signature by neutrophils worsening the course of COVID-19.

Rapamycin alleviates renal damage in mice with systemic lupus erythematosus through improving immune response and function

This study aimed to explore the therapeutic effect and mechanism of rapamycin (RAPA) on systemic lupus erythematosus (SLE) in BALB/C mice induced by pristane. The mice were randomly divided into 5 groups (n = 6): control, model, saline, RAPA (1 mg/kg) and RAPA (2 mg/kg). All groups were injected with pristane except control. HE staining revealed 1 mg/kg and 2 mg/kg RAPA treatments obviously alleviated pathological changes in the kidney of SLE mice such as glomeruli enlargement, hyperplasia of mesangial cells, epithelial and endothelial cells, infiltration of inflammatory cells, and edema-like degeneration of renal tubules. Compared with control group, body weights and anti-ribosomal P-protein antibody (ARPA) level of the mice in model group and saline group decreased (P < 0.05), while immune complex deposition and levels of anti-dsDNA antibody, anti-smRNP antibody and urine protein in model group and saline group increased (P < 0.05). However, compared with model group and saline group, body weights of the mice in RAPA (1 mg/kg) group and RAPA (2 mg/kg) group increased (P < 0.05), while immune complex deposition and levels of anti-dsDNA antibody, anti-smRNP antibody, ARPA, and urine protein in RAPA (1 mg/kg) group and RAPA (2 mg/kg) group decreased (P < 0.05). Compared with control group, the proportion of dentritic cells (DC) in the kidney and peripheral blood decreased while the proportion of Th1, Th2 and Th17 cells in the spleen, kidney and peripheral blood increased in model group and saline group (P < 0.05). Compared with model group and saline group, 1 mg/kg and 2 mg/kg RAPA treatments boosted the proportion of DC in the kidney and peripheral blood, reduced the proportion of Th1 and Th17 cells in the spleen, kidney and peripheral blood, and lessened the proportion of Th2 cells in the kidney and peripheral blood (P < 0.05). In conclusion, RAPA alleviated renal damage in SLE mice through improving immune response and function.

Immunomodulatory effect of d-carvone in swiss albino mice with benzo(a)pyrene-induced lung cancer

Background: Globally, lung cancer is the second most cause of deaths, which accounts for approximately 29% of the cancer cases worldwide. d-Carvone is considered a vital constituent of many essential oils with immense pharmacological benefits. Objective: In this study, we examined the immunomodulatory effect of d-carvone in the Swiss albino mice model against benzo(a)pyrene (BaP)-induced lung carcinoma. Materials and Methods: BaP was orally administered to the mice (50 mg/kg body weight [bw] for 4 weeks [twice a week]). Post-BaP administration, d-carvone (20 mg/kg bw) was orally administered to the mice (20 mg/kg bw). We calculated the tumor incidence and performed the following measurements: lung and bw, hematological parameters, immune complexes (phagocytic and avidity indexes, nitroblue tetrazolium reduction, soluble immune complex levels, immunocompetent cells (leukocytes, lymphocytes, and neutrophils), immunoglobin (Ig) levels (IgG, IgA, and IgM), level of xenobiotics and enzymes that point toward hepatic dysfunction, carcinoembryonic antigen (CEA), and proinflammatory cytokines (PICs) in experimental and normal mice. The level of oxidative stress in the experimental animals was investigated. The lung tissues of investigational animals were examined for the histopathological changes. Results: According to the results, there was an increased level of lipid peroxidation and decreased level of antioxidant activity in the lung tumor samples. The counts of lymphocytes, polymorphonuclear cells, and macrophages were notably decreased and increased, respectively, by the d-carvone post-treatment. Moreover, BaP-induced inflammation that is indicated by the increased in the level of PICs and CEA proteins in lung samples. d-Carvone attenuated the levels of PICs and CEA. Conclusion: The results of this study reveal that d-carvone prevented the cells against BaP-induced inflammation in lung cancer without causing adverse effects.

CLINICAL AND NEUROLOGICAL PECULIARITIES AND THE LEVEL OF AUTOANTIBODIES TO NEUROSPECIFIC ANTIGENS IN PATIENTS WITH CHRONIC HEMOBLASTOSIS

The purpose of this study was to determine the level of autoantibodies to neurospecific antigens and their relationship with clinical manifestations of the nervous system lesions in chronic hematological malignancies. Materials and methods. The study included 86 patients with chronic hemoblastosis divided into 3 groups: group 1 consisted of patients with chronic lymphoid leukaemia (n = 30), group 2 involved patients with chronic myeloid leukaemia (n = 30), group 3 included patients with multiple myeloma (n = 26). 21 inpatients of the neurological hospital without immunological and hematological disorders were selected as a control group. We investigated the anamnestic data on the presence of a clinical diagnosis of the nervous system lesions before and after the establishing a cancerous hematological diagnosis, carried out a complete neurological examination of the patients with chronic hematoblastosis to determine main neurological syndromes. The level of peripheral blood autoantibodies to neurospecific antigens was evaluated by the enzyme immunoassay. The level of circulating immune complexes was determined by the method of selective precipitation of antigen-antibody complexes. The findings of the study were statistically processes by using Microsoft Excel 2019 and IBM SPSS Statistics 26.0 software. The data obtained were processed by descriptive statistics methods. The study has demonstrated that encephalopathy (70%) and radiculopathy (40%) develop statistically significantly more often in the patients with chronic lymphoid leukaemia. The patients with chronic myeloid leukaemia are found to have encephalopathy (43%) and polyneuropathy (20%). The development of multiple myeloma is statistically significantly accompanied by the occurrence of radiculopathy (50%) and polyneuropathy (53%). Conclusion. The nervous system lesions are found considerably frequent in the patients with chronic hematological malignancies. The development of secondary encephalopathy in the patients with chronic lymphoid leukaemia may develop as a consequence of paraneoplastic syndrome due to the excessive production of cytokines and plasminogen activators. The predominance of radiculopathy in chronic myeloid leukaemia can be reliably explained by the high severity of the proliferative syndrome with a tendency to the production of localized chlorine, which can compress the corresponding roots of the peripheral nerves. However, peripheral lesions of nervous system are more typical for patients with multiple myeloma that may be due to hyperparaproteinemia combined with the chemotherapy of the underlying disease. Along with this, chronic lymphoid leukaemia and chronic myeloid leukaemia cause an increase in the circulating immune complexes level. Immunological changes indicate significant damage to nerve fibres and considerably rapid destruction of neurons in all forms of chronic hemoblastosis.

FcγRIIA expression accelerates nephritis and increases platelet activation in systemic lupus erythematosus

AbstractSystemic lupus erythematosus (SLE) is an autoimmune inflammatory disease characterized by deposits of immune complexes (ICs) in organs and tissues. The expression of FcγRIIA by human platelets, which is their unique receptor for immunoglobulin G antibodies, positions them to ideally respond to circulating ICs. Whereas chronic platelet activation and thrombosis are well-recognized features of human SLE, the exact mechanisms underlying platelet activation in SLE remain unknown. Here, we evaluated the involvement of FcγRIIA in the course of SLE and platelet activation. In patients with SLE, levels of ICs are associated with platelet activation. Because FcγRIIA is absent in mice, and murine platelets do not respond to ICs in any existing mouse model of SLE, we introduced the FcγRIIA (FCGR2A) transgene into the NZB/NZWF1 mouse model of SLE. In mice, FcγRIIA expression by bone marrow cells severely aggravated lupus nephritis and accelerated death. Lupus onset initiated major changes to the platelet transcriptome, both in FcγRIIA-expressing and nonexpressing mice, but enrichment for type I interferon response gene changes was specifically observed in the FcγRIIA mice. Moreover, circulating platelets were degranulated and were found to interact with neutrophils in FcγRIIA-expressing lupus mice. FcγRIIA expression in lupus mice also led to thrombosis in lungs and kidneys. The model recapitulates hallmarks of human SLE and can be used to identify contributions of different cellular lineages in the manifestations of SLE. The study further reveals a role for FcγRIIA in nephritis and in platelet activation in SLE.

Accumulation of antinuclear associated antibodies in circulating immune complexes is more prominent in SLE patients from Sudan than Sweden

The role of anti-nuclear autoantibody (ANA) specificities in immune complexes (IC) formation has been studied to a limited extent in SLE, and not at all in African SLE patients. We compared ANA in IC from Sudanese and Swedish SLE patients. We included 93 Sudanese and 332 Swedish SLE patients fulfilling the 1982 ACR criteria. IC were captured using C1q-coated beads. ANA specificities were quantified in sera and IC. Results were related to modified SLEDAI. Whereas serum levels of anti-Sm, anti-dsDNA and anti-ribosomal P were higher in Swedish patients, IC levels of most ANA specificities were higher among Sudanese patients. This difference was especially prominent for anti-chromatin antibodies, which remained after adjustment for age, disease duration and treatment. Total levels of C1q-binding IC correlated with levels of specific ANA in IC, with highest correlations for anti-chromatin antibodies among Sudanese patients. Whereas occurrence of anti- SSA/Ro60, anti-histone and anti-U1RNP in both serum and IC associated with high SLEDAI score, anti-dsDNA in IC but not in serum associated with high SLEDAI. ANA, especially antibodies targeting chromatin, accumulate more in IC from Sudanese SLE patients. If the autoantibody fraction forming IC is pathogenically important, this might explain the generally described severe SLE in black populations.

The content of nonspecific immune complexes and the level of oxidative processes in the organs of the goldfish of the Don River

The study of the content of immune complexes, products of lipid peroxidation and antioxidant activity in the goldfish Carassius auratus inhabiting the r. Don. Fish were caught in the water area of the city of Kalacha-na-Donu, about 13 lock of the Volga-Don canal and downstream. Analysis of the results showed insignificant differences in size and weight parameters. A visual examination on the body of crucians living downstream revealed reddening of the skin and ulcers near the caudal, abdominal and dorsal fins, indicating symptoms of peptic ulcer disease. Significant differences in the content of nonspecific immune complexes and the level of malondialdehyde between fish caught at different stations were recorded. The high content of immune complexes in the kidney and spleen extracts of the crucian carp inhabiting the area of the 13 gateway indicates a violation of the mechanisms for the elimination of these complexes. An increase in the level of immune complexes indicates the presence of pathological and autoimmune processes in fish. The highest indicators of malondialdehyde were recorded in the organs of fish living in the area of the 13th lock and downstream of the river. The increased content of malondialdehyde indicates a high level of lipid peroxidation processes and a decrease in the level of antioxidants in the studied tissues. However, the low values of the constant of inhibition of substrate oxidation in fish organs from different stations indicates the activity of antioxidant structures in the studied tissues. The study showed that crucians from different parts of the Don River differed in the content of immune complexes and the level of malondialdehyde in the organs.

Upregulation of FoxO3a expression through PI3K/Akt pathway attenuates the progression of lupus nephritis in MRL/lpr mice

FoxO3a plays key roles in inflammation and autoimmunity, and the PI3K-Akt-FoxO3a pathway has been proposed to modulate diverse biological processes. The aim of the present study, using lupus murine models, was to investigate whether FoxO3a contributes to the pathogenesis of lupus nephritis. LY294002 was used as an inhibitor of PI3K/AKT signaling pathway. FoxO3a-targeted small interfering RNA (siRNA) was also used for in vivo intervention. Female MRL/lpr mice were separately injected with LY294002, LY294002+siFoxO3a, and LY294002+siControl for 8 weeks. C57BL/6 mice were normal controls. Disease development, including serum creatinine (CRE), blood urea nitrogen (BUN), proteinuria, and renal pathological changes, was monitored. Levels of anti-dsDNA antibodies and immune complex (IC) deposition in the kidney were also measured. The expression of proteins was evaluated. We found that significant downregulation of FoxO3a was detected in the kidney of MRL/lpr mice as compared with normal control mice. Blockade of p-FoxO3a activation by LY294002 suppressed PI3K/Akt/FoxO3a pathway and the subsequent upregulation of FoxO3a in the nucleus resulting in the severity of inflammation and fibrosis in the kidney of MRL/lpr mice. Also, improved kidney function and decreased circulating anti-dsDNA antibodies were due to the upregulation of FoxO3a. Opposite results were obtained by specific siRNA silencing of Foxo3a in vivo. In conclusion, our research demonstrated that the upregulation of FoxO3a expression through inhibiting PI3K/Akt pathway attenuates murine lupus nephritis (LN). Thus, our results suggest that targeting of FoxO3a can be considered as a novel strategy for the treatment of LN.

Dynamics of immunological reactivity indices in patients with laryngal papillomatosis at different periods after complex treatment with antivirus qudrivalent vaccine "Gardasil"

The aim of the study is to determine di­sorders of immune homeostasis in patients with laryngeal papillomatosis at different periods after complex treatment with the inclusion of the “Gardasil” quadrivalent vaccine in the adjuvant therapy. Studies of the immunity state were conducted in 26 patients with laryngeal papillomatosis (LP) before, 2-12 and 13-29 months after complex treatment, consisting of surgical removal of papillomas and anti-relapse therapy, including inhalation of Laferobion, taking a vitamin-mineral complex and a course of vaccination with antiviral “Gardasil” quadrivalent vaccine according to which the second and third injections were administered in 2 and 6 months after the first. Significant disorders of cellular and humoral immunity indices in patients with LP were revealed in the form of multidirectional changes in the functional activity of natural killer cells, a decrease in the total number of T lymphocytes, mainly due to CD4 + subpopulation, increase in circulating immune complexes level in blood serum and concentration of secretory IgA in the secretion of the oropharynx. Disbalance in the patient’s cytokine system resulted in increased γ-IFN and TNF-α serum levels, an increase in spontaneous production of interferon and inhibition of stimulated production of λ - and γ-interferon by blood cells in vitro. Complex treatment with the use of the “Gardasil” quadrivalent antiviral vaccine in the postoperative period contributed to the normalization of most immunological reactivity indices that were altered in patients. The results indicate the prospects of using the antiviral vaccine as part of adjuvant antirelapse therapy after surgical treatment of LP patients and indicate the advisability of long-term clinical and immunological monitoring at different periods after vaccination.