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Frontiers in Immunology 2022Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease that mainly affects women in their reproductive years. A complex interaction of environmental and... (Review)
Review
Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease that mainly affects women in their reproductive years. A complex interaction of environmental and genetic factors leads to the disruption of immune tolerance towards self, causing overt immune activation and production of autoantibodies that attack multiple organs. Kidney damage, termed lupus nephritis, is the leading cause of SLE-related morbidity and mortality. Autoantibodies are central to propagating lupus nephritis through forming immune complexes and triggering complements. Immunoglobulin G (IgG) potently activates complement; therefore, autoantibodies were mainly considered to be of the IgG isotype. However, studies revealed that over 50% of patients produce autoantibodies of the IgE isotype. IgE autoantibodies actively participate in disease pathogenesis as omalizumab treatment, a humanized anti-IgE monoclonal antibody, improved disease severity in an SLE clinical trial. IgE is a hallmark of T helper 2-associated immunity. Thus, T helper 2-associated immunity seems to play a pathogenic role in a subset of SLE patients. This review summarizes human and animal studies that illustrate type 2 immune responses involved during the pathology of SLE.
Topics: Animals; Autoantibodies; Complement System Proteins; Female; Humans; Immunoglobulin E; Immunoglobulin G; Lupus Erythematosus, Systemic; Lupus Nephritis; Male
PubMed: 35444658
DOI: 10.3389/fimmu.2022.866549 -
Proceedings of the Royal Society of... Sep 1969
Review
Topics: Allergens; Antibodies; Antigen-Antibody Reactions; Binding Sites; Histamine; Humans; Immunochemistry; Immunoglobulin E; Immunoglobulin G; Immunoglobulin M; Molecular Weight; gamma-Globulins
PubMed: 4186358
DOI: No ID Found -
PeerJ 2022To analyze the long-term dynamics of antibodies against SARS-CoV-2 and understand the impact of age, gender, and viral load on patients' immunological response.
OBJECTIVE
To analyze the long-term dynamics of antibodies against SARS-CoV-2 and understand the impact of age, gender, and viral load on patients' immunological response.
METHODS
Serum samples were obtained from 231 COVID-19 positive patients from Macaé, in Rio de Janeiro state, in Brazil, from June 2020 until January 2021. The production of IgA, IgM, IgG, and IgE against S glycoprotein was analyzed using the S-UFRJ assay, taking into account the age, gender, and viral load.
RESULTS
Analysis of antibody production over 7 months revealed that IgA positivity gradually decreased after the first month. Additionally, the highest percentage of IgM positivity occurred in the first month (97% of patients), and declined after this period, while IgG positivity remained homogeneous for all 7 months. The same analysis for IgE revealed that almost all samples were negative. The comparison of antibody production between genders showed no significant difference. Regarding the age factor and antibody production, patients aged ≥60 years produced almost twice more IgA than younger ones (17-39 years old). Finally, a relationship between viral load and antibody production was observed only for older patients.
CONCLUSIONS
Our work provides an overview of long-term production of antibodies against SARS-CoV-2, suggesting prolonged production of IgA and IgM antibodies for 3 months and continued IgG production for over 7 months. In addition, it identified a correlation between viral load and IgM titers in the older group and, finally, different IgA production between the age groups.
Topics: Humans; Female; Male; Adolescent; Young Adult; Adult; SARS-CoV-2; COVID-19; Antibodies, Viral; Immunoglobulin G; Brazil; Immunoglobulin M; Immunoglobulin A; Immunoglobulin E
PubMed: 36540807
DOI: 10.7717/peerj.14547 -
RMD Open Aug 2023The first biomarker associated with the rheumatoid arthritis is rheumatoid factor (RF) and since the earliest reports a role has been proposed in the diagnosis and in... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The first biomarker associated with the rheumatoid arthritis is rheumatoid factor (RF) and since the earliest reports a role has been proposed in the diagnosis and in the prediction of clinical features and outcome. The study of RF isotypes has further attempted to improve diagnostic accuracy and identify specific subgroups of patients. The main objective of this study is to provide an analysis of the literature on the role of RF isotypes in the diagnosis and prognosis of rheumatoid arthritis (RA).
METHODS
We performed a systematic literature review and meta-analysis on the role of RF isotypes in RA (only in English, from PubMed, search terms: "rheumatoid factor isotypes", "diagnosis", "prognosis" and "rheumatoid arthritis", last search 31 July 2022, two independent assessment of quality and biases, results included in tables and in the meta-analysis).
RESULTS
Thirty-six articles were examined (7517 patients). Testing all RF isotypes with latex test or nephelometry allows for the highest sensitivity (68.6%, 95% CI 66.2% to 71.0%); nonetheless, the determination of IgA isotype provides the highest specificity (91.4%, 95% CI 90.8% to 92.0%) and the highest positive likelihood ratio (7.7, 95% CI 5.7 to 10.4). When testing IgM isotype the highest diagnostic OR (21.7, 95% CI 16.1 to 29.3) is reached. When analysing anti-citrullinated protein antibodies, RF isotype determination increases diagnostic accuracy. On the other hand, these do not provide relevant prognostic information, as results are conflicting.
CONCLUSIONS
Testing RF allows the highest sensitivity, while IgA isotype the highest specificity and positive likelihood ratio for RA diagnosis. On the other hand, determination of RF isotypes dose not allow prognostic information, as data are limited and heterogeneous.
Topics: Humans; Rheumatoid Factor; Arthritis, Rheumatoid; Immunoglobulin Isotypes; Anti-Citrullinated Protein Antibodies; Immunoglobulin A
PubMed: 37541740
DOI: 10.1136/rmdopen-2022-002817 -
Journal of Medical Virology Nov 2022With the global prevalence of COVID-19 and the constant emergence of viral variants, boosters for COVID-19 vaccines to enhance antibody titers in human bodies will...
With the global prevalence of COVID-19 and the constant emergence of viral variants, boosters for COVID-19 vaccines to enhance antibody titers in human bodies will become an inevitable trend. However, there is a lack of data on antibody levels and the protective effects of booster injections. This study monitored and analyzed the antibody potency and the antibody responses induced by the booster injection in the subjects who received three vaccine doses. The study was conducted in a multicenter collaboration and recruited 360 healthy adults aged 20-74. Participants received the first, second, and booster doses of inactivated Sinopharm/BBIBP COVID-19 vaccine at 0, 1, and 7 months. Vaccine-induced virus-specific antibody levels (SARS-COV-2-IgA/IgM/IgG) were monitored at multiple time points, surrogate virus neutralization test (sVNT), and the spatial distribution and proportion of immune cells and markers were analyzed using the CyTOF method before vaccination and a month after the second dose. The titers of SARS-CoV-2-IgA/IgM/IgG and neutralizing antibodies increased to a high level in the first month after receiving the second dose of vaccine and declined slowly after that. The antibody levels of SARS-CoV-2-IgG and sVNT were significantly increased at 0.5 months after the induction of the booster (p < 0.05). Despite a downward trend, the antibody levels were still high in the following 6 months. The B cell concentration (in humoral sample) a month after the second injection was significantly reduced compared to that before the vaccine injection (p < 0.05). The proportion of the C01 cell cluster was significantly decreased compared with that before vaccine injection (p < 0.05). Individual cell surface markers showed distinctions in spatial distribution but were not significantly different. This study has shown that serum antibody titer levels will decrease with time by monitoring and analyzing the antibody efficacy and the antibody reaction caused by the booster injection of healthy people who received the whole vaccination (completed three injections). Still, the significant peak of the antibody titer levels after booster highlights the recall immune response. It can maintain a high concentration of antibody levels for a long time, which signifies that the protection ability has been enhanced following the injection of booster immunization. Additionally, CyTOF data shows the active production of antibodies and the change in the immunity environment.
Topics: Adult; Antibodies, Neutralizing; Antibodies, Viral; COVID-19; COVID-19 Vaccines; Humans; Immunoassay; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; SARS-CoV-2; Vaccines
PubMed: 35801663
DOI: 10.1002/jmv.27983 -
Clinical and Experimental Immunology Jul 2022Increasing evidence has linked the humoral immune response with the development of various cancers. Therefore, there is growing interest in investigating the predictive...
Increasing evidence has linked the humoral immune response with the development of various cancers. Therefore, there is growing interest in investigating the predictive value of antibodies to assess overall and tissue site-specific cancer risk. Given the large amount of antibody types and the broad scope of the search (i.e. cancer risk), the primary aim of this systematic review was to present an overview of the most researched antibodies (i.e. immunoglobulin (Ig) isotypes (IgG, IgM, IgA, and IgE), tumour and self-antigen-reactive antibodies, infection-related antibodies) in relation to overall and site-specific cancer risk. We identified various antibody types that have been associated with the risk of cancer. While no significant associations were found for IgM serum levels, studies found an inconsistent association among IgE, IgA, and IgG serum levels in relation to cancer risk. When evaluating antibodies against infectious agents, most studies reported a positive link with specific cancers known to be associated with the specific agent recognized by serum antibodies (i.e. helicobacter pylori and gastric cancer, hepatitis B virus and hepatocellular carcinoma, and human papillomavirus and cervical cancer). Several reports identified autoantibodies, as single biomarkers (e.g. anti-p53, anti-MUC1, and anti-CA125) but especially in panels of multiple autoantibodies, to have potential as diagnostic biomarkers for specific cancer types. Overall, there is emerging evidence associating certain antibodies to cancer risk, especially immunoglobulin isotypes, tumour-associated antigen-specific, and self-reactive antibodies. Further experimental studies are necessary to assess the efficacy of specific antibodies as markers for the early diagnosis of cancer.
Topics: Autoantibodies; Biomarkers; Enzyme-Linked Immunosorbent Assay; Humans; Immunoglobulin A; Immunoglobulin E; Immunoglobulin G; Immunoglobulin M; Neoplasms
PubMed: 35380164
DOI: 10.1093/cei/uxac030 -
Cell Reports Jun 2023Continued evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is eroding antibody responses elicited by prior vaccination and infection. The...
Continued evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is eroding antibody responses elicited by prior vaccination and infection. The SARS-CoV-2 receptor-binding domain (RBD) E406W mutation abrogates neutralization mediated by the REGEN-COV therapeutic monoclonal antibody (mAb) COVID-19 cocktail and the AZD1061 (COV2-2130) mAb. Here, we show that this mutation remodels the receptor-binding site allosterically, thereby altering the epitopes recognized by these three mAbs and vaccine-elicited neutralizing antibodies while remaining functional. Our results demonstrate the spectacular structural and functional plasticity of the SARS-CoV-2 RBD, which is continuously evolving in emerging SARS-CoV-2 variants, including currently circulating strains that are accumulating mutations in the antigenic sites remodeled by the E406W substitution.
Topics: Humans; SARS-CoV-2; Combined Antibody Therapeutics; COVID-19; Antibodies, Viral; Antibodies, Neutralizing; Antibodies, Monoclonal; Spike Glycoprotein, Coronavirus; Neutralization Tests
PubMed: 37300832
DOI: 10.1016/j.celrep.2023.112621 -
Oncology (Williston Park, N.Y.) Aug 2013Immunoglobulin D multiple myeloma (IgD MM) accounts for almost 2% of all myeloma cases. It is associated with an increased frequency of undetectable or small monoclonal... (Review)
Review
Immunoglobulin D multiple myeloma (IgD MM) accounts for almost 2% of all myeloma cases. It is associated with an increased frequency of undetectable or small monoclonal (M)-protein levels on electrophoresis; osteolytic lesions; extramedullary involvement; amyloidosis; a lambda (lambda) light chain predilection; renal failure; hypercalcemia; and, often, advanced disease at diagnosis. Immunoglobulin E (IgE) MM is rare, with fewer than 50 cases reported in the literature. IgE MM presents with features similar to those of IgD MM, along with a higher incidence of plasma cell leukemia. The hallmark of IgE MM is t(11;14) (q13;q32). IgD and IgE levels are generally very low and hence may escape detection; thus, it is important that, when myeloma is suspected, patients be screened for the presence of IgD and IgE if they have an apparently free monoclonal immunoglobulin light chain in the serum. Although survival of patients with IgD MM or IgE MM is shorter in comparison to those with immunoglobulin G (IgG) MM or immunoglobulin A (IgA) MM, the outcome for patients with IgD and IgE subtypes is improving with the use of novel agents and autologous transplantation.
Topics: Humans; Immunoglobulin D; Immunoglobulin E; Immunoglobulin Light Chains; Immunoglobulin lambda-Chains; Multiple Myeloma
PubMed: 24133829
DOI: No ID Found -
Analytical Chemistry Sep 2022Current design of serological tests utilizes conservative immunoassay approaches and is focused on fast and convenient assay development, throughput, straightforward...
Current design of serological tests utilizes conservative immunoassay approaches and is focused on fast and convenient assay development, throughput, straightforward measurements, and affordability. Limitations of common serological assays include semiquantitative measurements, cross-reactivity, lack of reference standards, and no differentiation between human immunoglobulin subclasses. In this study, we suggested that a combination of immunoaffinity enrichments with targeted proteomics would enable rational design and development of serological assays of infectious diseases, such as COVID-19. Immunoprecipitation-targeted proteomic assays allowed for sensitive and specific measurements of NCAP_SARS2 protein with a limit of detection of 313 pg/mL in serum and enabled differential quantification of anti-SARS-CoV-2 antibody isotypes (IgG, IgA, IgM, IgD, and IgE) and individual subclasses (IgG1-4 and IgA1-2) in plasma and saliva. Simultaneous evaluation of the numerous antigen-antibody subclass combinations revealed a receptor-binding domain (RBD)-IgG1 as a combination with the highest diagnostic performance. Further validation revealed that anti-RBD IgG1, IgG3, IgM, and IgA1 levels were significantly elevated in convalescent plasma, while IgG2, IgG4, and IgA2 were not informative. Anti-RBD IgG1 levels in convalescent (2138 ng/mL) vs negative (95 ng/mL) plasma revealed 385 ng/mL as a cutoff to detect COVID-19 convalescent plasma. Immunoprecipitation-targeted proteomic assays will facilitate improvement and standardization of the existing serological tests, enable rational design of novel tests, and offer tools for the comprehensive investigation of immunoglobulin subclass cooperation in immune response.
Topics: Antibodies, Viral; COVID-19; COVID-19 Testing; Humans; Immunization, Passive; Immunoglobulin A; Immunoglobulin D; Immunoglobulin E; Immunoglobulin G; Immunoglobulin M; Immunoprecipitation; Proteomics; SARS-CoV-2; COVID-19 Serotherapy
PubMed: 36095284
DOI: 10.1021/acs.analchem.2c01325 -
Journal of Translational Medicine Apr 2022Antibody response to SARS-CoV-2 is a valuable biomarker for the assessment of the spread of the virus in a population and evaluation of the vaccine candidates. Recent...
BACKGROUND
Antibody response to SARS-CoV-2 is a valuable biomarker for the assessment of the spread of the virus in a population and evaluation of the vaccine candidates. Recent data suggest that antibody levels also may have a prognostic significance in COVID-19. Most of the serological studies so far rely on testing antibodies against spike (S) or nucleocapsid (N) protein, however antibodies can be directed against other structural and nonstructural proteins of the virus, whereas their frequency, biological and clinical significance is unknown.
METHODS
A novel antigen array comprising 30 SARS-CoV-2 antigens or their fragments was developed and used to examine IgG, IgA, IgE and IgM responses to SARS-CoV-2 in sera from 103 patients with COVID-19 including 34 patients for whom sequential samples were available, and 20 pre-pandemic healthy controls.
RESULTS
Antibody responses to various antigens are highly correlated and the frequencies and peak levels of antibodies are higher in patients with severe/moderate disease than in those with mild disease. This finding supports the idea that antibodies against SARS-CoV-2 may exacerbate the severity of the disease via antibody-dependent enhancement. Moreover, early IgG and IgA responses to full length S protein may be used as an additional biomarker for the identification of patients who are at risk of developing severe disease. Importantly, this is the first study reporting that SARS-CoV-2 elicits IgE responses and their serum levels positively correlate with the severity of the disease thus suggesting a link between high levels of antibodies and mast cell activation.
CONCLUSIONS
This is the first study assessing the prevalence and dynamics IgG, IgA, IgE and IgM responses to multiple SARS-CoV-2 antigens simultaneously. Results provide important insights into the pathogenesis of COVID-19 and have implications in planning and interpreting antibody-based epidemiological studies.
Topics: Antibodies, Viral; Antibody Formation; Biomarkers; COVID-19; Humans; Immunoglobulin A; Immunoglobulin E; Immunoglobulin G; Immunoglobulin M; SARS-CoV-2; Severity of Illness Index
PubMed: 35428263
DOI: 10.1186/s12967-022-03382-y