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Jul 2020 DOI 10.14302/issn.2692-1537.ijcv-20-3459
As there is no specific treatment yet, the fight against the COVID-19 pandemic is being carried out with great difficulty today. The use of immune plasma is seen as a promising option since there is expectation that it will reduce mortality, as in influenza pandemics experienced in 1918 and 2009. However, the safety and effectiveness of this treatment option against SARS-CoV-2 viruses are not known for certain. In addition, the optimal obtaining methods and protection time of neutralizing antibodies to be used to provide passive immunization are not fully known. Therefore, it would be very useful to investigate the most effective neutralizing antibody collection methods without disrupting the overall structure and effectiveness of the antibodies subject to the use of the convalescent immune plasma. For this purpose, we found it appropriate to prepare a broad review on the structure and properties of antibodies, as well as the principles and storage conditions of antibodies to be used in passive immunization.
Apr 2018 DOI 10.14302/issn.2372-6601.jhor-18-1988
Hematopoietic stem cell transplantation (HSCT) from a mismatched unrelated donor, an haploidentical donor or a cord blood unit (CBU) has become a widely aviable approach if patient lacks a matched related or unrelated donor. However, if the patient has anti-HLA antibodies against antigens present in the mismatched donor or CBU (donor-specific antibodies, DSAs) this option should be disregarded due to the high risk of graft failure. Desensitization can be used to reduce levels of DSAs but this technique has limited results. We report the case of a 62-year-old woman with DSAs against two haploidentical familiar donors who failed desensitization of DSAs. Finally she underwent a HSCT from a 5/10 mismatched unrelated donor which has been successful.
Jan 2015 DOI 10.14302/issn.2372-6601.jhor-14-377
Background Abnormalities of plasma von Willebrand Factor (vWF) system has been described in solid tumors but more information is required to understand the pathophysiological process in haematological malignancies. Objectives This study was carried out to investigate the changes in vWF-related parameters including ADAMTS13 protein level in aggressive haematological malignancies and to identify the prevalence of anti-ADAMTS13 antibody as well as its correlations with vWF-related parameters. Patients/Methods Patient newly diagnosed or having relapse acute leukaemias or aggresive non-Hodgkin lymphomas were recruited into this study. Exclusion criterias include; pregnancy, patient already commenced chemotherapy, sepsis or has background congenital bleeding disorders. Blood specimen was subjected to; blood counts, ADAMTS13 protein, ADAMTS13 antibody detection, vWF:Ag, vWF activity, factor VIII level (FVIII) and vWF: CBA (collagen binding assays) Results and Conclusion A total of 60 subjects with median age at 42.5 (IQR: 23.25-57.5) were included. There were 34(56.7%) lymphomas and 26(43%) acute leukaemias. FVIII, vWF:Ag, wVF activity and vWF:CBA level were elevated whereas ADAMTS13 protein was reduced in majority of patients. Those with lymphomas showed significantly higher levels of FVIII, vWF:Ag, vWF:activity and vWF:CBA compared to the leukaemias. 38(63.3%) of patients showed presence of ADAMTS 13 autoantibody. There was however no correlation between ADAMTS13 protein and vWF-related parameters or with ADAMTS13 autoantibodies. There was a high prevalence of ADAMTS 13 autoantibodies in this cohort despite the absence of thrombotic thrombocytopenic purpura (TTP). The more pronounced changes in vWF-related parameters among aggressive lymphomas compared to acute leukaemias are in tandem with the marginally higher rates of venous thromboembolism in the former.
Mar 2026 DOI 10.14302/issn.2372-6601.jhor-25-5938
Acquired haemophilia (AHA) is a rare coagulation disorder secondary to autoantibodies against coagulation factor, most commonly factor VIII with potential for life threatening bleeding episodes. We report a case of an 88-year-old female presenting with frank haematuria three weeks after catheter insertion. Her background was of Alzheimer’s Dementia, Asthma and Bullous Pemphigoid for which she was on low dose maintenance prednisolone (5mg). Laboratory tests showed haemoglobin 98g/dl and partial thromboplastin time (PTT) of 60s, with corrected prothrombin time 52s. Fibrinogen 5.39. As such coagulation factors were tested which revealed factor VIII of 0%. Her case was complicated by urinary tract sepsis, as such she was treated with oral prednisolone 60mg without immunosuppressive agent usage. A pan-CT scan revealed likely mesothelioma for which she declined further investigation. This case report will describe a rare presentation of AHA associated with bullous pemphigoid and mesothelioma, complicated by infection and frailty.
Sep 2024 DOI 10.14302/issn.2574-4488.jna-24-5219
Primary membranous nephropathy (MN) is due to autoantibodies to phospholipase A2 receptor (PLA2R Ab). It is unclear whether COVID-19 vaccines can trigger flares of glomerular diseases such as primary MN. There have been increasing reports of glomerular diseases presenting or flaring after receipt of COVID-19 vaccines. We present a patient with primary MN who developed nephrotic syndrome after receiving her second mRNA-1273 COVID-19 vaccine with positive PLA2R Ab. Renal biopsy confirmed primary MN. She was treated for her primary MN flare with rituximab in a manner similar to non-vaccine-associated MN, which led to significant reduction in both PLA2R Ab level and proteinuria. This case adds to the growing literature on MN flares after receipt of mRNA COVID-19 vaccines. Close follow-up of patients with primary MN and other glomerular diseases after COVID-19 vaccination is warranted. Further research is needed to determine the pathophysiology behind vaccine-induced MN flares and whether there is a potential association between exposure to SARS-CoV-2 antigens and loss of tolerance to the PLA2R antigen.
Apr 2024 DOI 10.14302/issn.2998-4211.jalr-24-4926
This article has been retracted on 20 March 2025. VIEW THE RETRACTION NOTICE (https://doi.org/10.14302/issn.2998-4211.jalr-25-5855) The research is focused on neuroinflammation a normal physiological process which is known to be associated with neurodegenerative diseases could be the potential targeted therapy via the microglia cells, it starts with defining Alzheimer’s; a neurodegenerative disease which causes deposition of Aβ (amyloid beta) protein in the cerebral cortex as well as NFT (neurofibrillary tangles) in the hippocampus and basal ganglia. The paper then describes process of neuroinflammation, microglia’s role, apolipoprotein E4 gene in relation to Alzheimer’s, which leads to different stem cell research and how pruning microglia as well as targeting microglia receptors in the brain is being used in current research trials, we included multiple meta-analysis showing microglia receptors being targeted currently by emerging drugs like propofol, antibodies CSF1R inhibitor etc, which are currently under trial phase, the research ends with concluding potential diagnostic markers like sirt1 considered to be an anti-aging protein which can be used as therapeutic interventions and Lps effect on Sirt 1. A Microglia initiated target therapy in Neuroinflammation for Alzheimer’s Patients.
Feb 2024 DOI 10.14302/issn.2379-7835.ijn-24-4938
Public health interest in vaccinations and immune protection has increased with the COVID-19 pandemic. Dairy products are an important source of protein and other nutrients, and there are unresolved research questions regarding the potential health impact of dairy products on the enhancement of immune response. A systematic literature review was conducted to synthesize the published literature reporting the effects of dairy interventions on: 1) the vaccine-specific immune response and 2) immunoglobulins in the absence of vaccination. To assess study validity and quality, we used the Academy of Nutrition and Dietetics Quality Criteria Checklist. Sixty-one studies (59 clinical trials, 1 cohort, 1 cross-sectional survey) were included, spanning 1983-2017. Ten trials evaluated the effect of dairy intervention on vaccine-specific IgG, IgA, IgM, vaccine-specific antibody titers, seroprotection rates, or seroconversion rates. Of these, 7 reported significant increases with dairy interventions for post-vaccine tetanus antibodies, mean change in tetanus antibody level, total antibody titers to flagellin from Salmonella Adelaide, mean antibody titers to influenza B, influenza-specific IgA and IgG levels, and seroconversion or seroprotection rates for influenza A and B. Fifty-six studies evaluated dairy’s effects on immunoglobulins without vaccinations. The results were heterogenous, with some studies reporting significant enhancement of immunoglobulins (IgA, IgE, or IgG), while others observed no differences between groups. Clinical relevance of the immunoglobulin changes was not investigated in these studies. Dairy products and their components could enhance the efficacy of vaccines. This review highlights the evidence gaps and provides a potential roadmap for additional research.
Aug 2023
DADA2 (deficiency of adenosine deaminase type 2) is an autoinflammatory autosomal recessive disease resulting from biallelic loss of function mutations in ADA2 gene. Clinical presentation and age of onset vary widely even among related patients, and variability of symptoms and severity manifestations include bone marrow failure, autoinflammation, immunodeficiency and vasculitis. Here, we report a case of young male with adult onset DADA2, who presented with fever, lower limbs skin rash, joint pain, and anemia resembling systemic lupus erythematous (SLE). DADA2 has an extremely variable clinical phenotype. It was described into three categories: inflammatory/vascular, immune dysregulation, and hematologic. However, the data is scant in describing autoimmunity phenotype in DADA2 and further studies are required to investigate the clinical correlation and presence of autoantibodies. We recommend genetic testing in cases with lupus-like disease especially if there is consanguinity between parents and family history of vasculitis.
Aug 2023 DOI 10.14302/issn.2692-1537.ijcv-23-4679
Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-Co V-2) has contributed to control of the coronavirus disease 2019 (COVID-19). On the other side, vaccination of SARS-CoV-2 could trigger autoimmune or inflammatory diseases. We present a 50-year-old female with well-controlled optic neuromyelitis with prednisolone (PSL) maintained at a dose of 2.5 mg/day. She ran a fever and liver injury was indicated 5 weeks after a second COVID-19 vaccination (BNT162b2 mRNA/Pfizer ). Liver biopsy showed accumulation of macrophages around the central veins, identified using anti-CD68 antibodies. As the treatment, cyclosporine A improved liver injury. COVID- 19 vaccination may have triggered liver inflammation due to cytokine storm via macrophage activation in the liver.
Jun 2022 DOI 10.14302/issn.2328-0182.japst-22-4193
The strategy for safe drug discovery and development has limited clinical success as compared to wasted time and resources annually. This is due to the fact that the results of multiphase preclinical trials are less likely to make an accurate early prediction on the safety of test compounds to progress into the clinic as a valuable therapeutic agent. A lot of time and resources has been wasted in the multistage processes of drug discovery and development that does not work at the end of the procedure every year. During pre-marketing stage, for instance, the number of unsuccessful clinical trials are greater than the successful one because of safety issues. A toxicity study at different stages of preclinical and clinical trials is a routine procedure to investigate the undesirable side effects of test compounds being manifested on the natural processes of living things. It deals with the effect and mechanism of toxicity of test compounds that triggers different biological responses on different organ systems. The biological responses that would be manifested as a result of interaction between the receptors and active molecules of a test compound could be desirable pharmacological effect or undesirable side effect or both responses are manifested simultaneously depending on the selectivity or specificity of the molecule of a test compound for its receptor subtype which makes safe drug discovery and development very challenging. The response efficiency of the body (the net outcome of the body’s biological reaction against the side effect) would determine the potency of a test compound to manifest undesirable pharmacologic effect. In other words, the amount of a drug required to cause a biological harm or injury depends on the magnitude of the body’s biological reaction in which the immune response plays a great pharmacological role by neutralizing and harmonizing xenobiotics with the biological molecules. The dose of a test compound at 100 mg/kg body weight, for instance, could be lethal to some of the study animals while it is still non-lethal to some other study animals depending on the response efficiency of the body. The immune system is well connected to each and every biological systems of the body which allows it to detect undesirable side effects being manifested through immunoglobulins signalling and activation mechanisms. This complex communication network helps to localize the diverse side effects of a test compound being manifested on different organ systems into the immune system which makes a toxicity study relatively simple to monitor. The cellular immune system becomes active following the molecule-receptor interaction and start producing antibodies which is also known as immunoglobulins to protect bodily harm and destruction. Under normal biological circumstances, the amount of immunoglobulins produced by the cellular immune system following exposure to a test compound is proportional to the number of harmful molecules interacted with its receptor subtype. Thus, with the reference to the changes in the immune response against the administered dose, it would be able to deal with the diverse undesirable side effects of a test compound being manifested on treated study animals using computational systemic biology.
Dec 2021 DOI 10.14302/issn.2575-1212.jvhc-21-4034
In bovine tuberculosis (bTB), cellular, humoral, or both types of immune responses have been observed. The purpose of this study was to examine the immune status of tuberculous cows based on the differential cytokine gene expression associated with Th1 (IFN-γ, IL-2), or Th2 (IL-4, IL-10) responses. Twenty-three (23) cows belonging to a dairy herd located in a rural region of the State of Hidalgo, México, were selected for the study. Single Intradermal Comparative Cervical Tuberculin (SICCT) Test, Interferon-Gamma (IFN-γ) Release Assay (BOVIGAM), and Enzyme-Linked Immunosorbent Assay (ELISA) were used for detection of cattle infected by M. bovis. Thirteen cows were positive to all the tests (Group 1); ten cows were positive only to ELISA (Group 2), and the remaining Group (Group 3, control) included cows negative to all the tests. Peripheral blood mononuclear cells (PBMC) from animals were in vitro stimulated by bovin purified protein derivative (PPD), avian PPD, and Concanavalin A (Con A) mitogen for 72h. Changes in the levels of expression of mRNA of the respective cytokines was measured by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) using β-actin gene as internal control. In group 1, PPD bovis and Con A-stimulated cells exhibited high production of IFN-γ, IL-2 and IL-4, but not IL-10. In contrast, PPD avium-stimulated cells displayed a low production of cytokine transcripts. In group 2, cells showed a significant production of IL-10 in response to bovine PPD (P< 0.001). In the control group, a high production of IFN-γ and IL-2 was observed only in Con A-stimulated cells. Post-mortem examinations in animals of group 1 showed slight and medium lesions in lymph nodes, whereas in group 2, the lesions were more extensive. Results indicate differences on gene expression levels of cytokines considered to determine balance in Th1/Th2 response among the evaluated groups. In addition, high levels of antibodies against M. bovis and high IL-10 expression in PBMC together are indicators of progressive bTB when both tuberculin test and IFN-γ assay are negative in tuberculous anergic cattle. Inclusion of serology and IL-10 cytokine expression in in the diagnosis checklist improves detection of infected cattle to help control bovine tuberculosis.
Nov 2021 DOI 10.14302/issn.2690-4837.ijip-21-4015
Copper (Cu) has a strong impact on the function of the immune system through several different pathways. These impacts include helping the function of monocytes, neutrophils, and macrophages, and enhancing Natural Killer cells’ activities. Cu also has a role in antimicrobial properties and inflammatory response. It is also important for IL-2 production and response, which is a component of adaptive immune cells. Additionally, Cu has multiple roles in both proliferation and differentiation of T cells and is involved in the production of antibodies. Cu deficiency can even lead to "increased viral virulence"1. Copper has a long history of use in medicine, and has continued to be used for purification of water, including use in hospitals to prevent legionnaires disease. The CDC pre released information on a study completed in March 2020 on the lifespan of COVID-19 on different surfaces which included its lifespan on copper, where it was completely dead within 4 hours. In addition, "Several reports demonstrated that Cu deficiency weakens the human immune response" 2. Given the multiple avenues of impact, it has been suggested that Cu supplementation, within recommended levels, be given to individuals who are low in Cu to help them fight off COVID-19. It is also possible that Cu supplementation, within recommended levels, may help prevent COVID-19 infection, or help individuals who are not low in Cu to fight off COVID-19 infection. However, dosage would have to be carefully managed, as excess levels of Cu can lead to both neurodegenerative and neurodevelopmental diseases.
Mar 2021 DOI 10.14302/issn.2575-1212.jvhc-21-3767
Antibodies and antibody fragments, especially single-domain antibodies known as nanobodies, are important tools in diagnostics, research, and therapeutics. In a conventional antibody, light and heavy chains contribute to the formation of the antigen binding site. In addition to conventional antibodies, old and new world camels also have heavy-chain antibodies (hcAbs), which lack the light-chain antibodies that usually bind to the antigen, as well as single domain antibodies, the VHH domain, which are the smallest antigen-binding fragments and have high solubility, stability, and specificity. A VHH library against E. coli lipopolysaccharide (LPS) was produced using the camel immune system. E. coli strains from dead camel calves were isolated to extract the LPS and used to immunize a 2-year-old female camel. After isolating mononuclear lymphocytes for RNA extraction and amplification of the VHH gene, the PCR product was cloned into the pF1AT7 Flexi vector and transformed into JM109 E. coli competent cells by heat shock, resulting in a comprehensive VHHs library with 6.9 × 104 cfu/µg. The VHHs were expressed and screened with ELISA and PCR. Eleven colonies were positive by PCR, six of which were sequenced and submitted to Genbank compared with GenBank data to confirm the production of nanobodies with a similarity >90%.
Jul 2020 DOI 10.14302/issn.2575-1212.jvhc-20-3434
Background The mammary glands are the second most common tumor development site in female dogs. One of the ways of staging such tumors is to evaluate the presence or absence of distant metastasis, including in bone marrow. Such findings in human medicine are associated with poor survival of women with breast tumors. However, in veterinary medicine, this clinical staging is used more for patients with lymphomas and mastocytomas. Studies using bone marrow biopsies as a staging method for mammary tumors are scarce. Objectives The present study was to evaluate mammary lesions and bone marrow in 23 female dogs, searching for disseminated tumor cells or metastatic foci. Results: Grade I carcinoma in mixed tumors was the type most observed (22.4%), and there was no statistical difference in relation to tumor size or presence of metastasis in lymph nodes. In the bone marrow of one female dog with carcinosarcoma (4.35%), there was cytoplasmic marking of a probable disseminated tumor cell of epithelial origin, and immunohistochemical evaluation showed presence of cytokeratin-19 antibodies. None of the female dogs presenting reduced cellularity or medullary fibrosis, confirmed through Masson’s trichrome technique, had cell marking in immunohistochemical analyses. Conclusions Bone marrow evaluation can be used as a staging method for mammary gland tumors in female dogs, since disseminated tumor cells present the potential to become secondary lesions and to disseminate to distant foci, thereby causing tertiary metastases over an indeterminate period of time.
Jun 2020 DOI 10.14302/issn.2372-6601.jhor-20-3372
Immune thrombocytopenia currently called under its’ new name, immune thrombocytopenic purpura (ITP) is a disease characterized by thrombocytopenia, in which the body attacks its own platelets due to the disorders in immune system. The pathophysiology of this disease includes increased platelet destruction and most megakaryocyte production in bone marrow. The most common clinical manifestation of ITP is mild or severe progressive bleeding that could result in death. ITP is generally named as primary or secondary ITP according to thrombocytopenia severity, disease duration, bleeding status and secondary occurrence of the disease. Currently for diagnosis, despite the blood count, antiglobulin test and laboratory tests that can detect platelet-bound antibodies, they are not enough for definitive diagnosis. Like the difficulty in diagnosis, ITP treatment is quite complicated which varies depending on age, characteristics and risk of the patient. It is classified as first, second and third-line treatment options. Also, depending on the condition of patients, combined treatment might be an option which increases the complexity of the treatment. Unfortunately, discussions related to different clinical applications in diagnosis and treatments continue recently. For this reason, we considered that preparation of a review containing recent updates in diagnostic approaches and treatment options in ITP will be remarkable and beneficial for physicians interested in this subject.
Mar 2020 DOI 10.14302/issn.2766-8681.jcsr-21-3719
Background Since receiving unexplained pneumonia patients at the Jinyintan Hospital in Wuhan, China in December 2019, the new coronavirus (COVID-19) has rapidly spread in Wuhan, China and spread to the entire China and some neighboring countries. We establish the dynamics model of infectious diseases and time series model to predict the trend and short-term prediction of the transmission of COVID-19, which will be conducive to the intervention and prevention of COVID-19 by departments at all levels in mainland China and buy more time for clinical trials. Methods Based on the transmission mechanism of COVID-19 in the population and the implemented prevention and control measures, we establish the dynamic models of the six chambers, and establish the time series models based on different mathematical formulas according to the variation law of the original data. Findings The results based on time series analysis and kinetic model analysis show that the cumulative diagnosis of pneumonia of COVID-19 in mainland China can reach 36,343 after one week (February 8, 2020), and the number of basic regenerations can reach 4.01. The cumulative number of confirmed diagnoses will reach a peak of 87,701 on March 15, 2020; the number of basic regenerations in Wuhan will reach 4.3, and the cumulative number of confirmed cases in Wuhan will reach peak at 76,982 on March 20. Whether in Mainland China or Wuhan, both the infection rate and the basic regeneration number of COVID-19 continue to decline, and the results of the sensitivity analysis show that the time it takes for a suspected population to be diagnosed as a confirmed population can have a significant impact on the peak size and duration of the cumulative number of diagnoses. Increased mortality leads to additional cases of pneumonia, while increased cure rates are not sensitive to the cumulative number of confirmed cases. Interpretation Chinese governments at various levels have intervened in many ways to control the epidemic. According to the results of the model analysis, we believe that the emergency intervention measures adopted in the early stage of the epidemic, such as blocking Wuhan, restricting the flow of people in Hubei province, and increasing the support to Wuhan, had a crucial restraining effect on the original spread of the epidemic. It is a very effective prevention and treatment method to continue to increase investment in various medical resources to ensure that suspected patients can be diagnosed and treated in a timely manner. Based on the results of the sensitivity analysis, we believe that enhanced treatment of the bodies of deceased patients can be effective in ensuring that the bodies themselves and the process do not result in additional viral infections, and once the pneumonia patients with the COVID-19 are cured, the antibodies left in their bodies may prevent them from reinfection COVID-19 for a longer period of time.
Feb 2020 DOI 10.14302/issn.2690-6759.jpar-20-3184
Domestic pigeons (Columba liviadomestica) of the order Columbiformes are ubiquitous birds and can be found in virtually every town and city around the globe. Their interaction with humans and domestic animals and wild birds makes them a potential carrier of zoonotic parasites. The present study aimed to detect the prevalence of different zoonotic protozoans that affect different-aged domestic pigeons in different localities in Assiut Governorate, Egypt. A total of 50 fecal samples from 20 young and 30 adult pigeons were collected and examined for identification and estimation of prevalence of Cryptosporidium sp. and Microsporidium sp. using modified Kinyoun acid-fast stain. For detection of the prevalence of Toxoplasma gondii, serum samples from 50 pigeons were examined serologically for the presence of Toxoplasma antibodies by using Latex Agglutination test. The prevalence of Cryptosporidium sp. infection was 20%; 6.7% in adult pigeons and 40 % in young pigeons while that of Microsporidium sp. was 40% both in adult and young pigeons. Mixed infection was detected in only two young pigeons (10%). Regarding Toxoplasma gondii detection, the number of seropositive cases detected by LAT was 29 out of 50 (58%). The positive agglutination titers, among 14 (48.27%) seropositive pigeons ranged between 1:2 -1:128. It was concluded that domestic pigeons may be considered as a reservoir host for Cryptosporidium, Microsporidium, and Toxoplasmagondii human infection which represents a serious human public health problem especially for high risk groups of population living in the same dwellings with pigeons. Moreover, the present pilot results provide a baseline data for planning future researches and control strategies against domestic pigeon's parasites.
Jan 2020 DOI 10.14302/issn.2372-6601.jhor-20-3186
Introduction The anti-HCV RIBA test verifies the presence of anti-HCV serum antibodies detected by the Elisa test. In Côte d'Ivoire, screening for hepatitis C is done exclusively by enzyme immunoassays. In order to reduce the number of HCV positive blood donor exclusions on ELISA, we conducted this study which aimed to demonstrate the value of the RIBA test in confirming diagnosis of viral hepatitis C to blood donors. Methods Our study, which took place from 02 to 23 February 2008 in the laboratory of Abidjan NBTC, focused on 200 sera of blood donors anti-HCV positive (Elisa test) selected according to the ratio. The DECISCAN HCV PLUS confirmation test of BIORAD was used. Results Among the 200 HCV samples positive by EIA, 49% (98/200) were confirmed positive. RIBA gave an indeterminate result in 40% of cases (80/200); and negative in 11% of cases (22/200) corresponding to false ELISA devices. In RIBA 96 samples had a low ELISA ratio of which 21% (20/96) were RIBA negative, and 79% (76/96) were indeterminate. RIBA positive samples (98/200) had a high ratio in 82% of cases (80/98). The presence of NS3 (C33) and NS4 (C100) was noted in 100% of cases (98/98, C2 in 37% (36/98) of cases and C1 in 18% of cases (18/98). RIBA indeterminate noted the presence of NS3 in 98% of cases (78/80) and NS4 in 30% of cases (24/80). Proteins C1, C2 and NS4 are essential for the diagnosis of confirmation of viral hepatitis C by RIBA. Conclusion These results attest to the lower specificity of enzyme immunoassays (ELISAs); hence the benefit of using RIBA confirmatory tests. A significant number of donors are excluded from blood donation in Côte d'Ivoire on the basis of false positive results obtained by the ELISA technique.
Dec 2019 DOI 10.14302/issn.2690-6759.jpar-19-3081
Malaria and typhoid fever are two endemic infectious diseases in developing tropical countries including Burkina Faso. There are two distinct infectious diseases with many similar clinical signs. In each sanitary area, it is important to describe the "typhomalaria" epidemiology to elaborate adequate diagnosis algorithm and efficient treatment protocol. A cross-sectional study was carried out from July to October 2014 in the lab department of University Hospital Souro SANOU, Bobo-Dioulasso. All microscopy positive malaria during the study period was included. Serodiagnosis of Widal and Felix was performed systematically in all Plasmodium spmalaria cases. Titers of antibodies anti-agglutinin O equal or higher than 1/400 and/or 1/800 for anti-agglutinin H antibodies were considered positive for Salmonella sp. A total of 283 malaria cases were included in this study, majority falciparum malaria. In this malaria cases, 91 patients were seropositive for Salmonella sp. "Typhomalaria" co-infection prevalence was 34.3% (CI 95% (28.8%; 40.1%)). The patient with the normal hemoglobin rate had the highest prevalence of co-infection (46.7% versus 30.9; p=0.02). Malaria and typhoid fever co-infection was high (approximately 1/3 of malaria cases) in University hospital of Bobo-Dioulasso. This study revealed the need to explore typhoid fever in malaria confirmed cases, especially in persistent fevers and non-anemic situation despite adapting antimalarial treatment.
Apr 2019 DOI 10.14302/issn.2377-2549.jndc-19-2736
Antibody phage display has become a useful technique for discovering and optimizing target-specific monoclonal antibodies suitable for many applications, including therapeutic ligands, which may act as direct pharmacological compounds or may be used as targeting ligands for controlled drug delivery. Recently, the D2-5-HT1A heteromer, which is formed by the dopamine D2 and serotonin 5-HT1A receptors has attracted attention as a potential target of antipsychotic drugs. Therefore, the aim of the study was to identify scFv monoclonal antibodies that are able to specifically recognize epitopes formed within the heteromer structure. Because both receptors are membrane proteins, it is important to conduct bio-panning experiments in the most natural conditions, in which the presented antigens (D2-5-HT1A heteromers) are in their native form and possibly in their best-preserved spatial structure. It has been shown here that phage display methodology can be successfully used in the preparation of monoclonal antibodies against dimers of membrane proteins. To separate phages specifically binding the D2-5-HT1A heteromer, the selection process using CHO+ cells with overexpression of both receptors was conducted. Phages that were bound to receptor monomers or other CHO-K1 cell surface proteins were eliminated as a result of negative selection by using CHO- cells expressing separate receptor monomers.
Jan 2019 DOI 10.14302/issn.2572-3030.jcgb-18-2527
As remarkable advances have been made in immunotherapies, the overall goal of immunotherapy has become the selection of patients and evaluating the benefits of treatment. One of the major obstacles to develop immunotherapies is the lack of effective immune monitoring. Monitoring of key changes in the immune system during immunotherapy (immunomonitoring) provides important insights into efficacy as well as the immune mechanisms of response at the molecular and cellular levels. Immunomonitoring techniques include traditional immunoassays that use specific antibodies to recognize the analytes of interest, new high-throughput immunoassays that target immune cells and nucleic acids, and less classical immunogenomic approaches that rely on genome-wide profiling and computational analysis on various types of clinical samples. Substantial progress has been made in the application of immunomonitoring strategies to pre-clinical and clinical studies, especially for patients with cancer and infectious diseases. Current and emerging immunoassays performed in clinical practice will be examined herein, and immunogenomic approaches that complement these techniques will be highlighted and compared with traditional methods. Finally, we will discuss several new computational methods for analyzing gene signatures for immunomonitoring, including gene expression data profiling by microarray, the nCounter technique, regular RNA-seq, and single-cell RNA-seq. Novel immunomonitoring techniques, especially immunogenomic approaches, will continue to be developed to facilitate assessment of immunotherapeutic response and predict patient outcomes in cancer and infectious disease.
Aug 2018 DOI 10.14302/issn.2641-9181.ijnr-18-2195
Objectives: An association between the measles virus and Hodgkin lymphoma has been disclosed by our laboratory in Beer-Sheva, starting in 2003. We question the refutation of our study and the absence of interest among experts. Methodology: It was based on immunohistochemistry with commercial, as well as experimental anti-measles antibodies. It relied also on RT-PCR and in situ hybridization evidence of measles virus RNA. Key Results: At this stage (2004), the link between the virus and the lymphoma was essentially descriptive. The first and last response to our challenge appeared in 2007, in the form of doublet articles, in the same issue of a major cancer journal. The two European research groups responding, rejected categorically our findings by proposing different arguments. Major Conclusion: As reservations to these reactions became soon apparent, a series of papers from our laboratory were published. These articles concerned the evidence of a relationship between the measles virus and additional categories of cancers. Different malignancies in which this virus was not expressed at all, were also described. A further study suggested a mechanism by which the measles virus may activate lymphomagenesis in classic Hodgkin lymphoma. To our dismay, and in spite of repeated calls to verify the various results, no further response was obtained from international experts.
Jan 2018 DOI 10.14302/issn.2470-5020.jnrt-17-1926
Since the first description in 2013, 39 cases of anti-DPPX-encephalitis have been described. Main features of this autoimmune encephalitis characterized by antibodies against the potassium-channel-associated regulatory protein DPPX are gastrointestinal symptoms, cognitive dysfunction and signs of CNS hyperexcitability. While the majority of patients responds to immunotherapy relapses are frequent and often successfully treated with rituximab. Here we report another case of anti-DPPX-encephalitis presenting with the above mentioned triad. However, this is the first case of anti-DPPX-encephalitis in the context of a connective tissue disease combined with cerebral arteriopathy along with brain parenchymal lesions that we interpreted as a secondary, CTD-associated cerebral vasculitis. While the latter resolved under immunosuppressive treatment, comprising glucocorticosteroids, cyclophosphamide, rituximab and plasmapheresis, deterioration of the CTD and multiple infectious complications finally led to the patient's death. As histological evidence for cerebral vasculitis is lacking, other differential diagnoses for the observed cerebral arteriopathy, especially reversible cerebral vasoconstriction syndrome, have to be considered.
Nov 2017 DOI 10.14302/issn.2471-2175.jdrt-17-1760
Metastatic melanoma is a very deadly type of skin cancer with poor prognosis and low 5-year survival rates. Until recently, patients with metastatic melanoma had very few treatment options, which only included dacarbazine and aldesleukin. In 2011, the first checkpoint blocker, ipilimumab was approved for the treatment of unresectable metastatic melanoma but its success was eclipsed by low response rates and high incidence of adverse events. Later in 2014, anti-PD-1 antibodies, nivolumab and pembrolizumab were approved for the treatment of metastatic melanoma. With comparatively high response rates and manageable safety profile, PD-1 blockers were remarkably successful in the treatment of melanoma and also other cancer subtypes such as non-small cell lung cancer and metastatic urothelial carcinoma. This article highlights the success of anti-PD-1 antibodies, discusses the mechanism of PD-1:PD-L1/2 pathway, responses of melanoma patients to PD-1 blockers and the research on improving response rates to PD-1 blockers.
Nov 2017 DOI 10.14302/issn.2575-1212.jvhc-17-1764
Leishmaniasis treatment monitoring is an important problem, since patient’s frequently present clinical signs improvements with positive indirect immunofluorescence (IFI) titers of anti-Leishmania antibodies, thus making difficult the clinician understand the therapy efficacy. The study aimed 1) to identify over a short period of 30 days, which of the main changes on the serum proteinogram fractions in patients treated with meglumine antimoniate and allopurinol, can be pointed as indicator to classify patients as slower or faster responsive to treatment. A sample of 56 dogs (n=56) with leishmaniasis diagnosis was followed-up for clinical condition, proteinograms and titers of anti-Leishmania antibodies during the treatment period considering three different time points: M0 (diagnosis moment), M1 (15 days after therapy start), and M2 (30 days after therapy start). Two groups of patients were considered according to their clinical condition evolution rate: faster recovery group (FRG) and slower recovery group (SRG). Statistical significant results were considered for p-value <0.05. Statistically significant differences in proteinogram variations between FRG and SRG were registered for TPs (p= 0.03), and for the fractions β (p=0.04), γ (p=0.04), amongst M0 and M2.The PT, β and γ-globulin fractions of proteinogram, in association with patient clinical assessment evolution should be considered as an indicator and a simple way to appoint the efficacy response of the patients to the therapy.
Aug 2017 DOI 10.14302/issn.2575-1212.jvhc-17-1555
The study was carried out to investigate the occurrence of contagious bovine pleuropneumonia CBPP in Khartoum state. One-hundred twenty-two pneumonic lung tissue samples were collected from different slaughterhouses (116 samples most of which from local breed cattle) and from the field (six samples from cross breed cattle). Two-hundred and fifty-seven serum samples were collected randomly from cattle in different areas of the state. Tissue samples were cultivated using the standard mycoplasma procedures. Mmm was isolated from three pneumonic lungs collected from the field while no isolates were recovered from slaughterhouse samples. Histopathological sections from the positive samples revealed the typical picture of the CBPP which include fibrinonecrotic pneumonia within filtration of inflammatory cells and fibrin and distention of interlobular septae. One hundred and eight out of 257 serum samples were found positive for antibodies against Mmmusing complement fixation test (CFT). Findings of this study confirmed the presence of CBPP in Khartoum state by the isolation and identification of the causative agent.
Aug 2017 DOI 10.14302/issn.2575-1212.jvhc-17-1661
Serum samples from wild and domestic South American Camelids (SAC) from Argentina, collected before (2008), during (2009) and after (2010) the 2009 H1N1 influenza pandemic were tested by hemagglutination-inhibition assay (HIA) to evaluate the seroprevalence of antibodies (Ab) against different subtypes of influenza A viruses: A(H1N1)pdm09, A/sw/Argentina/SIV/2009(H3N2) and A/eq/Argentina/97(H3N8). For A(H1N1), an ELISA using a recombinant H1-hemmaglutinin from a reference strain (HA0 PuertoRico/8/1934) was also conducted. Serum samples from Guanacos (126), vicugnas (21) and llamas (100) from Jujuy, Mendoza and Río Negro provinces were analyzed; no clinical signs of respiratory disease were detected, reason for which no nasal swabs were obtained. No seropositive reactors to H3N2 nor H3N8 variants were detected, nevertheless high incidence of Ab reactive to A(H1N1)pdm09 were found by HIA; results which were confirmed by ELISA. The Ab seropositive animals to H1-like IAV found in llamas from Jujuy, and Mendoza (2009) were 78% and 86% by HIA and ELISA, respectively. Thirty-seven samples taken over the three years from guanacos kept in captivity in Rio Negro showed 62% of seropositive animals, while wild guanacos from Mendoza sampled in 2010 showed 36% seropositive animals to H1-like IAV, by both techniques. Finally, wild vicugnas from Jujuy, sampled in 2008 showed 38% and 52% seropositive animals to H1-like IAV by HIA and ELISA, respectively. Our results could indicate the potential role of these species as a reservoir of this zoonotic viral agent of high impact in Public Health, and may suggest that SAC populations might have been infected with an influenza strain antigenically related to H1 IAV. . Surprisingly, for llama and guanaco populations sampled over time in Jujuy and Río Negro, respectively, the HIA and ELISA geometric mean Ab titers (GMT) for 2008 were significantly higher than the ones of 2010. In addition, HIA and ELISA Ab titers found in domestic llamas were significantly higher than those detected in wild vicugnas sampled during that year (2008) in Jujuy. New field campaigns are in progress to collect serum samples and nasal swabs in order to isolate and characterize the virus responsible for triggering H1 reactive Abs. These findings remark the need to better understand the dynamics and ecology of influenza A virus within Sacs populations.
Aug 2017
Objectives: To identify the clinical epidemiological characteristics of patients with juvenile idiopathic arthritis (JIA) monitored at the Lucidio Portella Children’s Hospital (HILP) in northeastern Brazil and to ascertain the frequency and forms of presentation, the most affected joints, the most common joint involvement for each form, the frequencies of positive rheumatoid factor (RF+) and positive antinuclear antibodies (ANA+) in the various forms of presentation, and the most common complications. Methods: A study was conducted with 74 medical records of patients with JIA monitored at HILP between January 2010 and January 2013. Descriptive statistics were used for statistical analysis. Results: JIA was predominant in females with a mean age at onset of 5.2 years and a median disease duration of two years. The most frequent initial form of presentation was oligoarticular (63.5) arthritis, and the most affected joint was the knee (86.4%). The knee was most affected by oligoarticular arthritis, the wrist, knee, and ankle were affected by RF+ polyarticular arthritis, and the knee, ankle, and cervical spine were affected by systemic arthritis. RF+ was observed in 8.5% of the oligoarticular arthritis cases. ANA+ were present in 27.7% of the oligoarticular cases, in 22.2% of the systemic arthritis cases, and in 11.1% of the RF+ polyarticular arthritis . The most common complications were deformities (20.3%) and uveitis (14.9%). Conclusion: The findings for JIA patients in a referral hospital in northeastern Brazil were consistent with the literature regarding most of the evaluated criteria.
Jul 2017 DOI 10.14302/issn.2577-2279.ijha-17-1538
Status thymico-lymphaticus had ever been explained as a cause of sudden death usually in children, but few cases were reported in adults. We sought to determine the relationship between thymic hypertrophy and sudden unexpected death in adult (SUDA), and associated macroscopic and microscopic findings. Adult post mortems from 1984 to 2014 were reviewed and 23 thymic hypertrophy patients without SUDA, 33 thymic hypertrophy patients with SUDA and 172 SUDAs without thymic hypertrophy entered. The data of thymus, lymph nodes, spleen, heart, aorta, and adrenal glands were collected for macroscopic and histological analysis. Ten antibodies were used and applied to 3 children and 46 adult thymus specimens. We found, as an independent factor, thymic hypertrophy increased significantly the risk of SUDA (6.9 folds) in both male and female. What’s more, SUDAs associated with thymic hypertrophy were quite younger (22.5 years) than those without it. A majority of patients with hypertrophic thymus had a variable number of accompanied anomalies described as the typical characteristics of status thymico-lymphaticus, but no macroscopic and microscopic findings related to SUDA in patients with thymic hypertrophy. Cytokeratins (CKs) showed distinctly different immunohistochemical expression patterns in individuals who had different death causes and disease background. Instead of a disease entity “status thymico-lymphaticus” is a systematic abnormality with thymic hypertrophy as a feature involving mainly immune and/or cardiovascular system, probably caused by gene mutations.
Jan 2016 DOI 10.14302/issn.2379-8572.joa-15-814
Background and Objective: The etiological factors for nasal polyps include infection, inflammation or an imbalance of a metabolic pathway. This study was designed to compare serum Helicobacter pyloriantibodies and H. pylori–DNAs between cases of nasal polyp and controls (nasal fracture). Patients and Methods: This case control study was carried out in ENT Department of Rasul Hospital in Tehran (2007-2008), upon nasal polyp tissues in 62 cases and inferior nasal turbinate mucosa in 25 controls. H. pylori–DNAs were searched by qualitative polymerase chain reaction (PCR) and serum specific H. pylori antibodies (ELISA IgG and IgA). Comparative tests were performed for the 2 groups, and P value < 0.05 was considered as statistically significant. Results: The mean age of cases and controls were 37.5 ± 13.7 and 31 ± 11.5 years, respectively. H. pylori–DNA was found in 32.3% (20/62) of the cases and 4% (1/25) of the controls (P value = 0.005). Serum H. pylori antibody (IgA) was found in 14.5% (9/62) of the cases and 4% (1/25) of the controls (P value = 0.27). However, previous immunity (IgG) was higher in 71% of the cases and 32% of the controls (P = 0.001). Conclusion: H. pylori infection may play a key role in the formation of nasal polyps. We recommend the PCR as the best method of searching for H. pylori infection. However, from the data obtained in this investigation it could not be determined whether or not H. pylori play a pathogenic role. Long-term antibiotics treatment in cases with nasal polyp, especially in cases with severe chronic rhinosinusitis where patients do not respond to surgery or steroids, may be useful. More randomized controlled trial (RCT) studies are necessary to validate the role of H. pylori infection in nasal polyp and the effect of antibiotics for eradication of H. pylori infection.