RESUMO
The detection of the antibody of Epstein-Barr virus (EBV) is critical for the diagnosis of nasopharyngeal carcinoma (NPC). An accurate and scalable point-of-care detection method would support the screening, diagnosis, and monitoring of NPC patients. In this study, firstly, we made an antibody enrichment element, antigen-MNPs, which can screen out specific antibodies in a complex sample. Secondly, signal-amplifying elements were synthesized by labelling inorganic quantum dots (QDs) and anti-antibodies on the surface of flop-ferritin. A sandwich structure is formed among antigen-MNPs, target-antibodies, and anti-antibodies-flop-ferritin@QDs. The antibodies are quantified by fluorescence intensity with a limit of detection (LOD) as low as 10-11 g mL-1. Moreover, the method can detect different types of antibodies and was employed to examine 10 sera from NPC patients and 10 sera from healthy individuals. The result indicates that the simultaneous detection of anti-EBNA-IgG and anti-EBNA-IgA provides an efficient route for early diagnosis of NPC.
Assuntos
Infecções por Vírus Epstein-Barr , Nanopartículas , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/diagnóstico , Herpesvirus Humano 4 , Infecções por Vírus Epstein-Barr/diagnóstico , Neoplasias Nasofaríngeas/diagnóstico , Anticorpos Antivirais , Imunoensaio , Anticorpos Anti-Idiotípicos , Imunoglobulina ARESUMO
Molecular therapies, including anti-IgE, biologicals and small molecules are increasingly used for treatment of asthma. The effectiveness of these therapies may be increased with biomarkers. Aim of this study was to assess the value of measuring cumulative IgE levels specific for respiratory allergens to increase the efficacy of anti-IgE therapy for severe bronchial asthma. One hundred and thirty seven patients with severe asthma were recruited from 2016 to 2022. Standard empirical allergy diagnosis (i.e., anamnesis, skin testing, allergen-specific IgE measurement), blood eosinophil counting, measurement of total IgE and of cumulative IgE-specific for respiratory allergens by Phadiatop™ were performed. Thirty four patients with severe allergic asthma, for whom all three diagnostic methods were performed, were then used to analyze the efficacy of anti-IgE treatment in patients stratified in two groups according to cumulative IgE levels specific for respiratory allergens determined by Phadiatop™. Group #1 patients (n = 8) had cumulative specific IgE values ≥ 0.35 and < 1.53 PAU/l while in group #2 patients (n = 26) they were ≥ 1.53 PAU/l. Treatment with Omalizumab was performed for at least 12 months. The level of asthma control (ACT questionnaire), the number of asthma exacerbations, the quality of life (AQLQ questionnaire), the need for systemic corticosteroids, and the respiratory function (FEV1) was determined by "before-after" analysis for each group, followed by a comparison of the dynamics between groups. In group 2 patients with an initial allergen-specific IgE level ≥ 1.53 kUA/L, the efficacy of Omalizumab treatment was better regarding asthma control, number of exacerbations, and quality of life than in group 1 patients. Our study provides evidence that measuring cumulative levels of IgE specific for respiratory allergens could be a useful screening method for detecting an allergic phenotype of severe asthma and may serve as biomarker to enhance the success of IgE-targeted therapy.
Assuntos
Antiasmáticos , Asma , Hipersensibilidade , Corticosteroides/uso terapêutico , Alérgenos/uso terapêutico , Antiasmáticos/efeitos adversos , Anticorpos Anti-Idiotípicos , Anticorpos Monoclonais Humanizados/uso terapêutico , Asma/diagnóstico , Asma/tratamento farmacológico , Asma/prevenção & controle , Biomarcadores , Humanos , Imunoglobulina E , Imunossupressores/uso terapêutico , Omalizumab/uso terapêutico , Qualidade de Vida , Resultado do TratamentoRESUMO
Idiotype-based therapeutics have failed to deliver their promise, necessitating rethinking of the concept and its potential to develop a viable immunotherapy method. The idiotype based hypothesis is discussed in this paper in order to produce effective anti-idiotype vaccinations. Polyclonal anti-idiotype reagents have been shown to be more successful in animal models, and a better understanding of the immune response in humans supports the idea that polyclonal anti-idiotype vaccines will be more effective than monoclonal-based anti-idiotype vaccines. This innovative approach can be used to produce therapeutic antibodies in a Biotech-standard manner. The idiotype network has been tweaked in the lab to provide protection against a variety of microbiological diseases. Antibodies to image-idiotype antigens, both internal and non-internal, can elicit unique immune responses to antigens. The current outbreak of severe acute respiratory syndrome 2 (SARS-2) has presented a fantastic chance to use idiotype/anti-idiotype antibodies as a protective regimen, which might be used to treat COVID-19 patients. The development of various effective vaccinations has been crucial in the pandemic's management, but their effectiveness has been limited. In certain healthy people, the development of viral variations and vaccinations can be linked to rare off-target or hazardous effects, such as allergic responses, myocarditis and immune-mediated thrombosis and thrombocytopenia. Many of these occurrences are most likely immune-mediated. The current analysis reveals successful idiotype/anti-idiotype antibody uses in a variety of viral illnesses, emphazising their importance in the COVID-19 pandemic.
Assuntos
COVID-19 , Vacinas , Humanos , Animais , Anticorpos Monoclonais/uso terapêutico , Pandemias/prevenção & controle , Idiótipos de Imunoglobulinas , Anticorpos Anti-Idiotípicos/uso terapêuticoRESUMO
Cytokines like IL-17A have been consistently found to be elevated in psoriatic lesional skin, and therapeutic antibodies to IL-17 have demonstrated efficacy in treating psoriatic skin and joint disease. However, results about the circulating cytokines in psoriasis patients remained controversial. Anticytokine autoantibodies (ACAAs) were detected in various autoimmune diseases but remained largely unknown in psoriasis. We aimed to investigate the serum levels of cytokines and ACAAs in psoriasis patients. The study included 44 biologics-naive psoriasis patients and 40 healthy controls. Serum cytokines and the corresponding autoantibodies were measured by multiplex bead-based technology. The bioactivity of serum IL-17A was determined by IL-8 production in primary keratinocytes. Herein, we found serum levels of IL-12B (median: 6.16 vs. 9.03, p = 0.0194) and Th17 cytokines (IL-17A: median: 0.32 vs. 1.05, p = 0.0026; IL-22: median: 4.41 vs. 4.41, p = 0.0120) were increased in psoriasis patients. More interestingly, bioactive IL-17A was identified in a proportion of patients and positively correlated with disease severity. A few of cytokines were closely associated with each other and formed into a distinct panel in psoriasis. Of 13 anticytokine antibodies, anti-IL-22 was moderately lower (median: 262.8 vs.190.5, p = 0.0418), and anti-IL-15 was slightly higher (median: 25.5 vs. 30.5, p = 0.0069) in psoriasis than controls. None of ACAAs was related to disease severity. Consequently, the ratios of antibodies to cytokines varied with the pattern of cytokines. In summary, our finding suggested that the levels of circulating bioactive IL-17A were associated with disease activity in psoriasis patients. In contrast, the titers of ACAAs were not significantly altered nor correlated with disease severity. However, the functionality of ACAAs remains to be further demonstrated in vitro in future studies.
Assuntos
Produtos Biológicos , Psoríase , Anticorpos Anti-Idiotípicos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Autoanticorpos , Produtos Biológicos/uso terapêutico , Citocinas , Humanos , Interleucina-17 , Interleucina-8 , Psoríase/tratamento farmacológicoRESUMO
Immunoglobulin G4-related disease (IgG4-RD) has recently been well recognized and Kuttner tumor is known to be a chronic sclerosing sialadenitis, representing the focal manifestation of IgG4-RD, in the submandibular gland (SMG). This study is to evaluate the immunologic features of IgG4-related Kuttner tumor in the SMG. We retrospectively chose 13 patients who were confirmed as having Kuttner tumor by surgical biopsy between May 2012 and January 2019. The fine-needle aspiration cytology, serum antibody levels (anti-Ro antibodies, anti-La antibodies), IgG serum levels (total IgG and IgG4), and immunohistochemical findings for IgG and IgG4-positive plasma cells were reviewed. The cytologic results found that 7 of the 9 cases were reported as chronic sialoadenitis, and the other 3 as benign lymphoproliferative lesion. The serum levels of autoantibodies, Sjögren-syndrome-related antigen A/Ro-Ab and Sjögren-syndrome-related antigen A/Ro-La, showed all normal values of serum level. The serum level of IgG was increased in only 4 among the cases. However, the IgG4 levels were significantly increased in 11 among the cases. In all the patients who received resection of SMG, immunohistochemical findings showed all positive for IgG4-RD, with elevated numbers of IgG and IgG4-positive plasma cells. The evaluation of IgG4 serum level should be very informative for the diagnosis of this tumor before surgery. Fine-needle aspiration cytology with ultrasound guidance are not conclusive in this study. The immunological study including IgG4 serum level should be required for proper diagnosis and treatment, with clinical features of the Kuttner tumor. The level of evidence was IV.
Assuntos
Doença Relacionada a Imunoglobulina G4 , Sialadenite , Anticorpos Anti-Idiotípicos , Autoanticorpos , Doença Crônica , Humanos , Imunoglobulina G , Doença Relacionada a Imunoglobulina G4/patologia , Estudos Retrospectivos , Sialadenite/diagnósticoRESUMO
Celiac disease (CeD) is a chronic gluten-induced enteropathy with plethoric manifestations. The typical manifestations of CeD such as chronic diarrhea and malabsorption are widely recognized, however, many patients have atypical manifestations like iron deficiency anemia, idiopathic short stature, hypertransaminesemia or infertility, etc. These patients often present to the primary care physicians and/or non-gastrointestinal specialties. However, due to a lack of awareness among the healthcare professionals about the various atypical manifestations, many patients are not screened for CeD. In this review, we have summarized the available literature about the prevalence of CeD in various gastrointestinal (chronic diarrhea) and non-gastrointestinal conditions (iron deficiency anemia, short stature, cryptogenic hypertransaminesemia, cryptogenic cirrhosis or idiopathic ataxia etc.) where the diagnosis of CeD should be con-sidered. In addition, we also discuss special scenarios where screening for CeD should be considered even in absence of symptoms such as patients with type 1 diabetes, Down's syndrome, and first-degree relatives of patients with CeD. Further, we discuss the diagnostic performance and limitations of various screening tests for CeD such as IgA anti-tissue transglutaminase antibodies, anti-endomysial antibodies and anti-deamidated gliadin antibodies. Based on the current recommendations, we propose a diagnostic algorithm for patients with suspected CeD.
Assuntos
Anemia Ferropriva , Doença Celíaca , Anticorpos Anti-Idiotípicos , Autoanticorpos , Doença Celíaca/diagnóstico , Doença Celíaca/epidemiologia , Atenção à Saúde , Diarreia , Gliadina , Humanos , Imunoglobulina A , Proteína 2 Glutamina gama-Glutamiltransferase , TransglutaminasesRESUMO
We conducted a retrospective data analysis of 26 patients with chronic spontaneous urticaria (CSU), 12 of whom had been treated with anti-IgE therapy (omalizumab). The subcohort of patients treated with omalizumab displayed more severe and prolonged courses of disease. In addition, they had often undergone various inpatient therapies, frequently presenting with concomitant angioedema. Collecting the Urticaria Activity Scores from the seven daily values for wheals and itching (UAS7) proved an important and suitable instrument for the determination and assessment of the course of therapy in the dermatological office. Elaborate laboratory screenings, however, seem far less indicative of the severity, prognosis and course of the disease. Omalizumab proved to be a viable and well-tolerated treatment option. One third of the patients were completely free of all symptoms, another third showed very good improvement, whereas the last third showed no improvement at all, even when omalizumab and/or concomitant therapies were escalated.
Assuntos
Antialérgicos , Urticária , Antialérgicos/uso terapêutico , Anticorpos Anti-Idiotípicos , Doença Crônica , Humanos , Imunossupressores/uso terapêutico , Omalizumab/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento , Urticária/tratamento farmacológicoRESUMO
Interleukins 4 (IL-4) and 21 (IL-21) belong to the common gamma chain cytokine family which are highly involved in the progression of autoimmune diseases. While IL-4 is well known to be involved in the suppression of apoptosis of autoreactive B cells, the role played by IL-21 remains unclear. In the current study, we activated the human Burkitt's lymphoma Ramos B cells with anti-IgM to mimic B cell hyperactivation observed in patients of autoimmune diseases. Consistent with other reported findings, anti-IgM led to the downregulation of proteins involved in B cell survival and proliferation, as well as the activation of caspase 3 activity and DNA damage, resulting in apoptotic cell death after 48-hour treatment. Although both IL-4 and IL-21 reversed anti-IgM-induced apoptosis and cell cycle arrest, they did so via different mechanisms: while IL-4 could directly suppress anti-IgM-induced caspase 3 activation and marker indicative of DNA damage, IL-21 could induce B cell proliferation in the presence of anti-IgM. Importantly, IL-21 also suppressed activation induced cell death in human primary B cells. Pre-treatment with clinically validated JAK inhibitors completely reversed the effects of IL-4 and IL-21 to rescue anti-IgM induced cell death and DNA damage. The results indicate the underlying mechanisms of how IL-4 and IL-21 differentially promote survival of hyperactivated B cells and provide hints to treat autoimmune diseases.
Assuntos
Doenças Autoimunes , Linfoma de Células B , Anticorpos Anti-Idiotípicos , Apoptose , Doenças Autoimunes/tratamento farmacológico , Caspase 3/metabolismo , Humanos , Imunoglobulina M , Interleucina-4/farmacologia , Interleucinas/farmacologiaRESUMO
Previous case reports have described patients with COVID-19-associated autoimmune hemolytic anemia (AIHA), and cold agglutinin disease (CAD) which is characterized by a positive direct antiglobulin (DAT) or "Coombs" test, yet the mechanism is not well understood. To investigate the significance of Coombs test reactivity among COVID-19 patients, we conducted a retrospective study on hospitalized COVID-19 patients treated at NMC Royal Hospital between 15 April and 30 May 2020. There were 27 (20%) patients in the Coombs-positive group and 108 (80%) in the Coombs-negative group. The cold agglutinin titer was examined in 22 patients due to symptoms suggestive of cold agglutinin disease, and all tested negative. We demonstrated a significant association with reactive Coombs test results in univariate analysis through clinical findings such as ICU admission rate, the severity of COVID-19, and several laboratory findings such as CRP, D-dimer, and hemoglobin levels lactate dehydrogenase, and RDW-CV. However, only hemoglobin levels and disease severity had a statistically significant association in multivariate analysis. A possible explanation of COVID-19-associated positive Coombs is cytokine storm-induced hyperinflammation, complement system activation, alterations of RBCs, binding of SARS-CoV-2 proteins to hemoglobin or its metabolites, and autoantibody production. Coombs-positive patients were tested for hemolysis using indirect bilirubin, consumed haptoglobin, and/or peripheral smear that ruled out any evidence of hemolysis. Understanding this etiology sheds new light on RBC involvement as a pathophysiological target for SARS-CoV-2 by interfering with their function; consequently, therapies capable of restoring RBC function, such as erythrocytapheresis, could be repurposed for the treatment of worsening severe and critical COVID-19.
Assuntos
Anemia Hemolítica Autoimune , COVID-19 , Anemia Hemolítica Autoimune/diagnóstico , Anemia Hemolítica Autoimune/tratamento farmacológico , Anticorpos Anti-Idiotípicos/uso terapêutico , Teste de Coombs/métodos , Hemoglobinas , Hemólise , Humanos , Estudos Retrospectivos , SARS-CoV-2RESUMO
Chronic spontaneous urticaria (CSU) considerably alters patients' quality of life, often for extended periods, due to pruriginous skin lesions, impaired sleep, unexpected development of angioedema, and failure of conventional treatments in properly controlling signs and symptoms. Recent research focused on the development of new therapeutic agents with higher efficacy. Although the production of specific immunoglobulin E (IgE) antibodies against certain allergens is not a characteristic of the disease, treatment with omalizumab, a monoclonal anti-IgE antibody, proved efficient and safe in patients with moderate to severe chronic spontaneous urticaria uncontrolled by H1-antihistamines. Ligelizumab, a high-affinity monoclonal anti-IgE antibody, may also efficiently relieve symptoms of unresponsive chronic urticaria to standard therapies. This comprehensive review aims to present recently acquired knowledge on managing chronic spontaneous urticaria with new anti-IgE antibodies. We conducted extensive research on the main databases (PubMed, Google Scholar, and Web of Science) with no restrictions on the years covered, using the search terms "anti-IgE antibodies", "omalizumab", "ligelizumab", and "chronic spontaneous urticaria". The inclusion criteria were English written articles, and the exclusion criteria were animal-related studies. ClinicalTrials.gov was also reviewed for recent relevant clinical trials related to CSU treatment. CSU is a challenging disease with a significant effect on patients' quality of life. Current therapies often fail to control signs and symptoms, and additional treatment is needed. New biologic therapies against IgE antibodies and FcεRIα receptors are currently under investigation in advanced clinical trials. We reviewed recently published data on CSU management using these novel treatments. The development of new and improved treatments for CSU will lead to a more personalized therapeutical approach for patients and provide guidance for physicians in better understanding disease mechanisms. However, some agents are still in clinical trials, and more research is needed to establish the safety and efficacy of these treatments.
Assuntos
Antialérgicos , Urticária Crônica , Urticária , Animais , Antialérgicos/uso terapêutico , Anticorpos Anti-Idiotípicos , Doença Crônica , Urticária Crônica/tratamento farmacológico , Humanos , Imunoglobulina E , Omalizumab/uso terapêutico , Qualidade de Vida , Urticária/tratamento farmacológicoRESUMO
Near-infrared photoimmunotherapy (NIR-PIT) is a novel cancer treatment modality that utilizes antibody-photoabsorber conjugates (APCs) and selectively kills target cells after irradiation with NIR light. Originally, NIR-PIT was targeted against cancer cell surface antigens, but as it became clear that NIR-PIT induced a strong immune response, an effort was made to target selected immune cell populations in the tumor microenvironment to encourage an even stronger immune response. Thus, CD25-targeted NIR-PIT and cytotoxic T-lymphocyte associated protein 4 (CTLA4)-targeted NIR-PIT were developed to kill regulatory T cells (Tregs) in conjunction with cancer-cell-targeted NIR-PIT, in order to amplify the host immune response. It was found that CD25-targeted NIR-PIT, using an antibody with the Fc portion removed, led to better results than the unmodified anti-CD25 antibody-directed NIR-PIT presumably because of a negative effect on activated T cells. The aim of this study was to compare the efficacy of an antibody fragment [anti-CTLA4-F(ab')2] and a whole antibody (anti-CTLA4-IgG) for NIR-PIT. There was no significant difference in NIR-PIT-induced Treg killing between the anti-CTLA4-F(ab')2 and anti-CTLA4-IgG antibodies. Although both the antibody and the antibody fragment resulted in significant tumor growth inhibition, the antibody induced more robust CD8+ T cell activation in ipsilateral lymph nodes and was more effective compared to the antibody fragment. The slower clearance of the anti-CTLA4-IgG APC enhanced antitumor immunity by promoting T cell priming in lymph nodes. In conclusion, unlike the results with CD25 where modified antibodies produced superior results to unmodified antibodies, anti-CTLA4-IgG antibody-based NIR-PIT proved more effective in reducing tumor growth than anti-CTLA4-F(ab')2 antibody-based NIR-PIT.
Assuntos
Imunoconjugados , Fragmentos de Imunoglobulinas , Anticorpos Anti-Idiotípicos , Linhagem Celular Tumoral , Imunoglobulina G , Imunoterapia/métodos , Fármacos Fotossensibilizantes , Fototerapia/métodos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Current evidence on the association between allergic diseases and bone metabolism indicates asthma may be a potential risk factor for bone health. Using anti-IgE has been proven effective in allergic asthma treatment with a good safety profile; however, its effects on bone health are unknown. Thus, we aimed to investigate whether: (i) chronic allergic asthma (CAA) causes any meaningful changes in bone, and if any, (ii) anti-IgE therapy prevents any CAA-induced adverse alteration. A murine model was used to study CAA. Thirty-two BALB/c male-mice were assigned into four groups (eight-mice/group): Control, CAA (treated with saline), CAA + 100 µg of anti-IgE (CAA + 100AIgE), and CAA + 200 µg of anti-IgE (CAA + 200AIgE) groups. After immunization, saline or anti-IgE was performed intraperitoneally for 8-weeks (in five-sessions at 15-days interval). Three-point bending test was used for the mechanical analysis. Bone calcium (Ca2+) and phosphorus (P3-) as well as Ca/P ratio were evaluated using inductively-coupled plasma-mass-spectrometer (ICP-MS). Compared to control, reductions observed in yield and ultimate moments, rigidity, energy-to-failure, yield and ultimate stresses, elastic modulus, toughness, and post-yield toughness parameters of the CAA group were found significant (P < 0.05). Similar declines were also detected regarding bone Ca2+, P3- and Ca/P ratio (P < 0.05). Compared to control, we observed that 200 µg administration of anti-IgE in CAA + 200AIgE group hindered CAA-related impairments in mineral and mechanical characteristics of bone, while 100 µg in CAA + 100AIgE failed to do so. Our results showed CAA may cause bone loss, leading to a decrease in bone strength, and anti-IgE administration may dose-dependently inhibit these impairments in bone.
Assuntos
Asma , Imunoglobulina E , Animais , Anticorpos Anti-Idiotípicos , Anticorpos Monoclonais , Asma/tratamento farmacológico , Imunoglobulina E/metabolismo , Masculino , CamundongosRESUMO
OBJECTIVES: To assess associations between ophthalmological features and the main systemic biomarkers of primary Sjögren's Syndrome (pSS), and to identify systemic biomarkers associated with severe keratoconjunctivitis sicca (KCS) in pSS patients. METHODS: In this cross-sectional study, data was retrospectively extracted from the monocentric cohort of the French reference centre for pSS. We analysed data from the initial visit of patients admitted for suspicion of pSS and included patients validating pSS ACR/EULAR classification criteria. Ophthalmological assessment included Schirmer's test, tear break-up time, ocular staining score (OSS), and visual analogue scale (DED-VAS) for dry eye disease (DED) symptoms. Results of minor salivary gland biopsy, unstimulated whole salivary flow rate, anti-SSA/Ro antibodies, anti-SSB/La antibodies, and rheumatoid factor (RF) were collected. RESULTS: A total of 253 patients (245 females) with confirmed pSS, aged 56.6±13.0 years, were included, among which 37% had severe KCS. Multivariate analysis showed that the presence of anti-SSA/Ro antibodies, anti-SSB/La antibodies and RF were associated with conjunctival OSS (odds ratio-OR-=1.25 per OSS unit increase; confidence interval-CI-95%=1.05-1.49; P=0.01; OR=1.31 per OSS unit increase; CI95%=1.09-1.58, P=0.002, and OR=1.34 per OSS unit increase; CI95%=1.12-1.59; P=0.001, respectively). Both anti-SSB/La antibodies and DED-VAS ≥ 5 were significantly associated with severe KCS (OR=2.03; CI95%=1.03-4.00; P<0.05 and OR=2.52, CI95%=1.31-4.90; P<0.01, respectively). CONCLUSION: Association between conjunctival OSS and systemic biomarkers of pSS indicate the crucial importance of conjunctival staining when pSS is suspected as a cause of DED. Conversely, patients with anti-SSB and DED-VAS ≥ 5 features should be prioritized for extensive evaluation by an ophthalmologist due to their association with severe KCS.
Assuntos
Síndrome de Sjogren , Anticorpos Anti-Idiotípicos , Biomarcadores , Estudos Transversais , Feminino , Humanos , Estudos Retrospectivos , Fator Reumatoide , Síndrome de Sjogren/diagnósticoRESUMO
Rare immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a life-threatening disease resulting from a severe autoantibody-mediated ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 motifs, member 13) deficiency. Acute iTTP episodes are medical emergencies, but when treated appropriately &gt;95% of patients survive. However, at least half of survivors will eventually experience a relapse. How remission of an initial episode is achieved and factors contributing to reemergence of anti-ADAMTS13 Abs and a relapsing course are poorly understood. In acquired hemophilia and systemic lupus erythematosus, anti-idiotypic Abs counteracting and neutralizing pathogenic autoantibodies contribute to remission. We selected and amplified the splenic anti-idiotypic IgG<sub>1</sub> Fab κ/λ repertoire of two relapsing iTTP patients on previously generated monoclonal inhibitory anti-ADAMTS13 Fabs by phage display to explore whether anti-idiotypic Abs have a role in iTTP. We obtained 27 single anti-idiotypic Fab clones, half of which had unique sequences, although both patients shared four H chain V region genes (V<sub>H</sub>1-69*01, V<sub>H</sub>3-15*01, V<sub>H</sub>3-23*01, and V<sub>H</sub>3-49*03). Anti-idiotypic Fab pools of both patients fully neutralized the inhibitor capacity of the monoclonal anti-ADAMTS13 Abs used for their selection. Preincubation of plasma samples of 22 unrelated iTTP patients stratified according to functional ADAMTS13 inhibitor titers (&gt;2 Bethesda units/ml, or 1-2 Bethesda units/ml), with anti-idiotypic Fab pools neutralized functional ADAMTS13 inhibitors and restored ADAMTS13 activity in 18-45% of those cases. Taken together, we present evidence for the presence of an anti-idiotypic immune response in iTTP patients. The interindividual generalizability of this response is limited despite relatively uniform pathogenic anti-ADAMTS13 Abs recognizing a dominant epitope in the ADAMTS13 spacer domain.
Assuntos
Púrpura Trombocitopênica Trombótica , Humanos , Proteína ADAMTS13 , Autoanticorpos , Epitopos , Recidiva , Anticorpos Anti-IdiotípicosRESUMO
Staphylococcus aureus is a common food-borne pathogenic microorganism that poses a serious threat to food quality and safety, and can do harm to human health. In the past, researchers relied on antibiotics to control Staphylococcus aureus, though very effective, yet it was also worrying in the aspect of bio-safety. In fact, anti-idiotypic antibody (Anti-Id) shows its potential to mimic some of the structural and biological functions of antigens. Therefore, in this study, based on Anti-Id theory and technology, we expect to obtain the vancomycin Anti-Id which can mimic vancomycin against Staphylococcus aureus from a human phage display domain antibody library. After four rounds of bio-panning, a total of 18 positive Anti-Ids were obtained. Among them, two Anti-Ids named Anti-Id-2C12 and Anti-Id-1F5 were identified as "ß" type Anti-Ids, and afterwards they were selected for gene cloning and protein expression in prokaryotic expression system. As a result, a concentration of purified proteins with 568.6 µg/mL (Anti-Id-2C12) and 602.3 µg/mL (Anti-Id-1F5) were successfully obtained, and their minimum inhibitory concentration (MIC) values for Staphylococcus aureus were 125 and 200 µg/mL, respectively. As they are human heavy-chain domain antibodies, which were theoretically harmless to humans, they have the potential application value as preservatives in food and edible agricultural products.
Assuntos
Bacteriófagos , Infecções Estafilocócicas , Anticorpos Anti-Idiotípicos , Bacteriófagos/genética , Humanos , Cadeias Pesadas de Imunoglobulinas/genética , Biblioteca de Peptídeos , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus , Vancomicina/farmacologiaRESUMO
Ulcerative colitis is a relapsing and remitting inflammatory bowel disease of the large intestine. Risk factors include recent Salmonella or Campylobacter infection and a family history of ulcerative colitis. Diagnosis is suspected based on symptoms of urgency, tenesmus, and hematochezia and is confirmed with endoscopic findings of continuous inflammation from the rectum to more proximal colon, depending on the extent of disease. Fecal calprotectin may be used to assess disease activity and relapse. Medications available to treat the inflammation include 5-aminosalicylic acid, corticosteroids, tumor necrosis factor-alpha antibodies, anti-integrin antibodies, anti-interleukin-12 and -23 antibodies, and Janus kinase inhibitors. Choice of medication and method of delivery depend on the location and severity of mucosal inflammation. Other treatments such as fecal microbiota transplantation are considered experimental, and complementary therapies such as probiotics and curcumin have mixed data. Surgical treatment may be needed for fulminant or refractory disease. Increased risk of colorectal cancer and use of immunosuppressive therapies affect the preventive care needs for these patients.
Assuntos
Colite Ulcerativa , Anticorpos Anti-Idiotípicos , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/terapia , Transplante de Microbiota Fecal , Humanos , Inflamação , Complexo Antígeno L1 LeucocitárioRESUMO
Among the myositis-specific antibodies (MSA), anti-transcriptional intermediary factor 1 (TIF1)-γ and anti-nuclear matrix protein 2 (NXP2) antibodies are reportedly associated with cancer-associated myositis (CAM). We aimed to investigate patient characteristics of CAM and the clinical role of cancer-associated MSA (caMSA) in a retrospective cohort from a city hospital. All patients visiting our department between April 2014 and October 2021 with newly diagnosed dermatomyositis, polymyositis, and clinically amyopathic dermatomyositis were included. Anti-TIF1-γ and anti-NXP2 antibodies were collectively considered as caMSA. First, we compared clinical characteristics in CAM, defined as cases showing onset or recurrence of malignancy within 5 years, versus non-CAM. Second, we investigated independent risk factors for CAM. Third, we compared clinical characteristics with and without caMSA within CAM. Finally, we investigated whether caMSA was predictive of poor prognosis. The cohort of 39 patients included 12 (30.7%) CAM cases. Compared with non-CAM, CAM had significantly more dermatomyositis and higher frequencies of dysphagia, anti-TIF1-γ antibody, and caMSA. Using logistic regression analysis, caMSA was an independent risk factor for CAM. In a comparison between caMSA and non-caMSA within CAM, caMSA was associated with higher frequencies of stage ≥ II. However, caMSA did not necessarily indicate a poor prognosis. Only caMSA represented an independent risk factor for CAM and showed a significant association with advanced cancer. Key Points ⢠Cancer-associated MSA was an independent risk factor for cancer-associated myositis. ⢠Cancer-associated MSA was associated with advanced cancer.
Assuntos
Dermatomiosite , Miosite , Neoplasias , Polimiosite , Anticorpos Anti-Idiotípicos , Autoanticorpos , Dermatomiosite/complicações , Hospitais Comunitários , Humanos , Japão , Análise de Mediação , Neoplasias/complicações , Polimiosite/complicações , Estudos RetrospectivosRESUMO
Maternal IgG antibodies directed against fetal red cells can cause hemolytic disease in fetus and newborn manifesting as anemia and jaundice. Sometimes, these antibodies are so strong that they encapsulate the antigens on neonatal red blood cells and result in erroneous laboratory findings when tested. A requisition for double volume exchange transfusion was received for a term,3.1 kg female baby with neonatal jaundice at day 2 of life, born to a multiparous woman. The neonate was typed as AB RhD negative and the mother as A Rh D negative. The maternal sample tested positive for Indirect antiglobulin testing showing presence of Anti-D with IgG titer of 128. The direct antiglobulin testing for baby was strongly (4 +) positive. The strong DAT result with negative RhD typing for the neonate indicated towards the Blocking-D phenomenon. We attempted to resolve the Blocked-D case using acid elution, which revealed the presence of D antigen on the eluted neonate's red cells. The report emphasizes the importance of appropriate blood typing for neonates to provide prompt adequate care as a team by the departments of Neonatology and Transfusion Medicine.
Assuntos
Eritroblastose Fetal , Recém-Nascido , Feminino , Humanos , Imunoglobulina rho(D) , Tipagem e Reações Cruzadas Sanguíneas , Anticorpos Anti-IdiotípicosRESUMO
INTRODUCTION: Use of fully automated solutions to perform analysis of immunohematology tests is highly desirable as it delivers an improved level of safety and security of results. However, full automation may not be feasible financially and practically in all circumstances. A solution that addresses most of the process step hazards of manual testing can assist in achieving a higher level of confidence in and safety of test results. METHODS: The study utilized a column agglutination technology (ORTHO BioVue ® System) to test a variety of samples on the ORTHO VISION ® Analyzer and compare to the reader capability of the ORTHO OPTIX™ Reader. Both direct agglutination and direct/indirect antiglobulin test methods were evaluated. The data was analysed for per cent agreement and for concordance at the lower bound 95% confidence interval. The acceptance criteria for concordance for direct agglutination was ≥ 99.4% and for indirect agglutination was ≥ 98.0% at a lower bound 95% confidence interval. RESULTS: There were 13,805 columns producing 5174 interpreted tests for direct agglutination and 5998 columns producing 2958 interpreted direct/indirect antiglobulin tests evaluated. Testing demonstrated that direct agglutination and direct/indirect antiglobulin testing generated greater than 99% concordance between the fully automated instrument system and the reader. CONCLUSIONS: The reader exceeded the approval criteria set for the study which demonstrates the capability to address the desire for a solution that moves manual testing to an enhanced level which achieves improved safety and security in immunohematology testing.
Assuntos
Anticorpos Anti-Idiotípicos , Humanos , Teste de Coombs , AutomaçãoRESUMO
ABO antibodies occur naturally and usually exist as alloantibodies. They are the most clinically significant in cases of transfusions. However, there are very few reports on auto-anti-A or B. A 58-year-old man visited our hospital for evaluation of an inguinal mass. Blood typing was performed, while preparing the patient for an excisional biopsy. Forward and reverse typing showed a typical AB and A pattern. Results of the direct antiglobulin and unexpected antibody screening tests were negative. The serum did not react with AB3 cells. The biopsy revealed a diffuse large B-cell lymphoma. After completing four cycles of R-CHOP chemotherapy, the patient achieved complete remission. There were no anti-B antibodies found on repeat ABO typing. This report shares our experience on unexpected anti-B antibody findings in a patient with an A1B blood type. To the best of our knowledge, this is the first report of anti-B antibodies in a patient with an A1B blood type in Korea.