Immunoglobulin M Response Research Articles

Mucosal immune responses of gut IgM in common carp (Cyprinus carpio) following infection with spring viremia of carp virus (SVCV)

Immunoglobulin M (IgM) specifically recognizes various antigens and can activate complement, mediate cytotoxicity, opsonize and agglutinate pathogens to induce phagocytosis, all of which play an important role in immunity. However, the IgM response of common carp (Cyprinus carpio) in the intestinal mucosa after viral infection has not been thoroughly. Therefore, we successfully produced an anti-carp IgM monoclonal antibody and developed a model of viral infection to study the kinetics of immune responses after viral infection. Our results showed that the expression of IL1-β and Igs were dramatically increased, implying that common carp exhibited a significant innate and adaptive immune response to viral infection. Furthermore, we found that the IgM responses varied between the two infection strategies. At 14 days post-infection (DPI), a significant population of IgM+ B cells were observed in the gut, accompanied by a sharp rise in IgM levels. The immune response to secondary infection started at 7 DPI, suggesting that the IgM response is faster in the gut after re-infection. Importantly, we also explored the variability of different gut compartments to viral infection, and result revealed a stronger immune response in the hindgut than in the foregut and midgut. Overall, our findings indicate that IgM plays an important role in the intestinal immune response following primary and secondary viral infection, in which the hindgut plays a major immune function.

Dimeric immunoglobulin A as a novel diagnostic marker of measles infection.

The world is facing a measles resurgence, and improved diagnostic tests for measles infection are an urgent World Health Organization research priority. Detection of measles-specific immunoglobulin M (IgM) as a standard diagnostic test has low positive predictive value in elimination settings, and there is a need for new biomarkers of measles infection to enable enhanced surveillance and response to outbreaks. We demonstrate the detection of measles-specific dimeric immunoglobulin A (dIgA) in patients with confirmed measles infections using a new indirect enzyme-linked immunosorbent assay protocol that selects for the dIgA fraction from total IgA in the blood. The magnitude of measles-specific dIgA responses showed a low correlation with IgM responses, and our results highlight the potential of dIgA for further development as an alternative and/or complementary biomarker to IgM for serological diagnosis of measles infection.

Chemotherapy-induced broadly reactive autoantibodies in the treatment of malignancies

The aim of the study was to evaluate the relationship between chemotherapy and autoimmune reactions in patients with metastatic colorectal cancer. Cancer and autoimmunity are known to be interrelated, but until now it has been unclear to what extent chemotherapy specifically contributes to autoimmune reactions. We studied immunoglobulin M (IgM) levels in response to the administration of various human tissues before and during adjuvant chemotherapy. Patients received seven cycles of chemotherapy with the FOLFIRI plus cetuximab regimen. IgM levels against the tested tissues increased already after the first cycle of chemotherapy and continued to increase during the second and third cycles. Autoimmune responses then began to decrease from the fourth to seventh cycles, but remained elevated from baseline for most of the study tissues. Our results suggest that chemotherapy can induce a wide range of autoimmune reactions. Monitoring self-reactive IgM responses during treatment may help prevent or alleviate side effects associated with autoimmunity.

Spike- and nucleocapsid-based gold colloid assay toward the development of an adhesive bandage for rapid SARS-CoV-2 immune response detection and screening

Immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies are important biomarkers used for the diagnosis and screening of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in both symptomatic and asymptomatic individuals. These antibodies are highly specific to the spike (S) and nucleocapsid (N) proteins of the SARS-CoV-2 virus. This paper outlines the development steps of a novel hybrid (vertical-lateral-vertical) flow assay in the form of a finger-stick point-of-care device, similar to an adhesive bandage, designed for the timely detection and screening of IgM and IgG immune responses to SARS-CoV-2 infections. The assay, comprising a vertically stacked plasma/serum separation membrane, conjugate pad, and detection (readout) zone, utilizes gold nanoparticles (AuNPs) conjugated with SARS-CoV-2 S and N proteins to effectively capture IgM and IgG antibodies from a pinprick (~15 µL) of blood in just one step and provides results of no immune IgM−/IgG−, early immune IgM+/IgG−, active immune IgM+/IgG+ or immune IgM−/IgG+ in a short amount of time (minutes). The adhesive bandage-like construction is an example of the design of rapid, low-cost, disposable, and easy-to-use tests for large-scale detection and screening in households. Furthermore, the bandage can be easily adjusted and optimized to detect different viral infections as they arise by simply selecting appropriate antigens related to pandemics and outbreaks.

Immunobiology and Host Response to HEV.

Hepatitis E virus (HEV) usually causes acute self-limiting hepatitis but sometimes leads to chronic infection in immunocompromised persons. HEV is not directly cytopathic. Immunologically mediated events after HEV infection are believed to play important roles in the pathogenesis and clearance of infection. The anti-HEV antibody responses have been largely clarified since the determination of major antigenic determinant of HEV, which is located in the C-terminal portion of ORF2. This major antigenic determinant also forms the conformational neutralization epitopes. Robust anti-HEV immunoglobulin M (IgM) and IgG responses usually develop 3-4weeks after infection in experimentally infected nonhuman primates. In humans, potent specific IgM and IgG responses occur in the very early phase of the disease and are critical in eliminating the virus, in concert with the innate and adaptive T-cell immune responses. Testing anti-HEV IgM is valuable in the diagnosis of acute hepatitis E. The long-term persistence and protection of anti-HEV IgG provide the basis for estimating the prevalence of HEV infection and for the development of a hepatitis E vaccine. Although human HEV has four genotypes, all the viral strains are considered to belong to a single serotype. It is becoming increasingly clear that the innate and adaptive T-cell immune responses play critical roles in the clearance of the virus. Potent and multispecific CD4+ and CD8+ T cell responses to the ORF2 protein occur in patients with acute hepatitis E, and weaker HEV-specific CD4+ and CD8+ T cell responses appear to be associated with chronic hepatitis E in immunocompromised individuals.

Comparative analysis of SARS-CoV-2 detection methods using stool, blood, and nasopharyngeal swab samples.

as a public health policy, the ongoing global coronavirus disease 2019 vaccination drives require continuous tracking, tracing, and testing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Diagnostic testing is important in virus detection and understanding its spread for timely intervention. This is especially important for low-income settings where the majority of the population remains untested. This is well supported by the fact that of about 9% of the Kenyan population had been tested for the virus. this was a cross-sectional study conducted at the Kisumu and Siaya Referral Hospitals in Kenya. Here we report on the sensitivity and specificity of the rapid antigen detection test (Ag-RDT) of SARS-CoV-2 compared with the quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) using stool and nasopharyngeal swab samples. Further, the mean Immunoglobulin M (IgM) and Immunoglobulin G (IgG) antibody levels among symptomatic and asymptomatic individuals in western Kenya were evaluated. the sensitivity and specificity of Ag-RDT were 76.3% (95% CI, 59.8-88.6%) and 96.3% (95% CI, 87.3-99.5%) with a negative and positive predictive value of 85% (95% CI, 73.8%-93.0%) and 93% (95% CI, 78.6%-99.2%) respectively. There was substantial agreement of 88% (Kappa value of 0.75, 95% CI, 0.74-0.77) between Ag-RDT and nasopharyngeal swab RT-qPCR, and between stool and nasopharyngeal swab RT-qPCR results (83.7% agreement, Kapa value 0.62, 95% CI 0.45-0.80). The mean IgM and IgG antibody response to SARS-CoV-2 were not different in asymptomatic individuals, 1.11 (95% CI, 0.78-1.44) and 0.88 (95% CI, 0.65-1.11) compared to symptomatic individuals 4.30 (95% CI 3.30-5.31) and 4.16 (95% CI 3.32 -5.00). the choice of an appropriate SARS-CoV-2 diagnostic, screening, and surveillance test should be guided by the specific study needs and a rational approach for optimal results.

A One Health Clinic for People Experiencing Homelessness and Their Animals: Treating the Human-Animal Unit.

<b><i>Objective:</i></b> To characterize an acquired, symmetric, demyelinating neuropathic variant with distal sensory or sensorimotor features. <b><i>Background:</i></b> Classic chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) patients have prominent proximal and distal weakness. However, chronic demyelinating neuropathies may present with different phenotypes. An approach that distinguishes these disorders primarily according to the pattern of weakness may be useful to the clinician. <b><i>Methods:</i></b> A total of 53 patients with acquired symmetric demyelinating polyneuropathies were classified primarily according to the pattern of the neuropathy and secondarily according to the presence and type of monoclonal protein (M-protein) in this retrospective review. The authors distinguished between patients with distal sensory or sensorimotor involvement, designated as distal acquired demyelinating symmetric (DADS) neuropathy, from those with proximal and distal weakness, who were designated as CIDP. <b><i>Results:</i></b> M-proteins were present in 22% of patients with CIDP. There were no features that distinguished clearly between CIDP patients with or without an M-protein, and nearly all of these patients responded to immunomodulating therapy. In contrast, nearly two-thirds of the patients with DADS neuropathy had immunoglobulin M (IgM) kappa monoclonal gammopathies, and this specific combination predicted a poor response to immunomodulating therapy. Antimyelin-associated glycoprotein (anti-MAG) antibodies were present in 67% of these patients. <b><i>Conclusion:</i></b> Distinguishing acquired demyelinating neuropathies by phenotype can often predict the presence of IgM kappa M-proteins, anti-MAG antibodies, and responses to immunomodulating therapy.

The Immunoglobulin M Response to Pneumococcal Polysaccharide Vaccine Is Sufficient for Conferring Immunity.

In mice, pneumococcal polysaccharide (PPS) vaccines generate antigen-specific immunoglobulin M (IgM) and immunoglobulins G1, G2, and G3. Antibody and complement-dependent opsonophagocytosis correlates with the protection induced by PPS vaccines in vivo. Since IgM is a very efficient immunoglobulin isotype in activating the complement system, we evaluated whether anti-PPS IgM alone is sufficient to confer protective immunity to Streptococcus pneumoniae. We found that immunization of wild-type and activation-induced cytidine deaminase-deficient mice capable of producing only IgM with Pneumovax 23 generated comparable anti-PPS IgM and resistance to lethal systemic challenge with S pneumoniae. These data suggest that an IgM response to PPS vaccines is sufficient for conferring immunity.

Polyglycerol and Poly(ethylene glycol) exhibit different effects on pharmacokinetics and antibody generation when grafted to nanoparticle surfaces

Poly(ethylene glycol) (PEG) is widely employed for passivating nanoparticle (NP) surfaces to prolong blood circulation and enhance localization of NPs to target tissue. However, the immune response of PEGylated NPs—including anti-PEG antibody generation, accelerated blood clearance (ABC), and loss of delivery efficacy—is of some concern, especially for treatments that require repeat administrations. Although polyglycerol (PG), which has the same ethylene oxide backbone as PEG, has received attention as an alternative to PEG for NP coatings, the pharmacokinetic and immunogenic impact of PG has not been studied systematically. Here, linear PG, hyperbranched PG (hPG), and PEG-coated polylactide (PLA) NPs with varying surface densities were studied in parallel to determine the pharmacokinetics and immunogenicity of PG and hPG grafting, in comparison with PEG. We found that linear PG imparted the NPs a stealth property comparable to PEG, while hPG-grafted NPs needed a higher surface density to achieve the same pharmacokinetic impact. While linear PG-grafted NPs induced anti-PEG antibody production in mice, they exhibited minimal accelerated blood clearance (ABC) effects due to the poor interaction with anti-PEG immunoglobulin M (IgM). Further, we observed no anti-polymer IgM responses or ABC effects for hPG-grafted NPs.

Longitudinal measurement of human immune responses to SARS-CoV-2 vaccines through serum immunoglobulins

Abstract Introduction The novel SARS-CoV-2 (COVID-19) vaccines generate antibodies to the viral spike protein. The mRNA vaccines Moderna Inc. and Pfizer-BioNTech and adenovirus vaccine Johnson &amp; Johnson (J&amp;J) work through generation of humoral immune responses, particularly immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies. We assessed IgG and IgM response in vaccinated patients longitudinally. Methods Blood was drawn from 106 subjects over the course of five time points ranging from pre-to post-vaccine inoculation of Moderna, Pfizer, or J&amp;J. Blood was collected into serum separating tubes (SST). SSTs were spun at 1200rcf for 15 minutes; the serum was isolated and used for testing. Levels of IgG and IgM were measured in geometric mean titers, then analyzed through multiple t-tests across vaccines and demographics. Results Moderna vaccine recipients had a significantly higher IgG titer following vaccine inoculation (p &amp;lt; 0.0005 for Time Point 1, 2, 3, 4). No significant difference was observed across various demographics (age/gender) within vaccine types (p &amp;gt; 0.05). There was a steady decline in IgG and IgM levels after full inoculations, which were trending towards baseline levels. J&amp;J recipients had little change in IgG and IgM after receiving the vaccine; however, significantly lower IgG than the Moderna (p = 0.0006) and Pfizer (p =0.0071). Conclusion With the use of IgG and IgM as immune response indicator, our data shows Moderna outperforming Pfizer at all Time Points following baseline testing, which suggests greater, longer-lasting immunity against COVID-19. With a low sample size for J&amp;J (n = 5), it is unclear what implications the poor IgG response observed in this study indicates about the adenovirus vaccine.

Role of Programmed Cell Death Protein-1 and Lymphocyte Specific Protein Tyrosine Kinase in the Aryl Hydrocarbon Receptor- Mediated Impairment of the IgM Response in Human CD5+ Innate-Like B Cells.

Innate-like B cells (ILBs) are a heterogeneous population B cells which participate in innate and adaptive immune responses. This diverse subset of B cells is characterized by the expression of CD5 and has been shown to secrete high levels of immunoglobulin M (IgM) in the absence of infection or vaccination. Further, CD5+ ILBs have been shown to express high basal levels of lymphocyte specific protein tyrosine kinase (LCK) and programmed cell death protein-1 (PD-1), which are particularly sensitive to stimulation by interferon gamma (IFNγ). Previous studies have demonstrated that activation of the aryl hydrocarbon receptor (AHR), a cytosolic ligand-activated transcription factor, results in suppressed IgM responses and is dependent on LCK. A recent study showed that CD5+ ILBs are particularly sensitive to AHR activation as evidenced by a significant suppression of the IgM response compared to CD5- B cells, which were refractory. Therefore, the objective of this study was to further investigate the role of LCK and PD-1 signaling in AHR-mediated suppression of CD5+ ILBs. In addition, studies were conducted to establish whether IFNγ alters the levels of LCK and PD-1 in CD5+ ILBs. We found that AHR activation led to a significant upregulation of total LCK and PD-1 proteins in CD5+ ILBs, which correlated with suppression of IgM. Interestingly, treatment with recombinant IFNγ reduced LCK protein levels and reversed AHR-mediated IgM suppression in CD5+ ILBs in a similar manner as LCK inhibitors. Collectively, these results support a critical role for LCK and PD-1 in AHR-mediated suppression of the IgM response in human CD5+ ILBs.

Unique B-1 cells specific for both N-pyrrolated proteins and DNA evolve with apolipoprotein E deficiency

Lysine N-pyrrolation, a posttranslational modification, which converts lysine residues to Nε-pyrrole-L-lysine, imparts electronegative properties to proteins, causing them to mimic DNA. Apolipoprotein E (apoE) has been identified as a soluble receptor for pyrrolated proteins (pyrP), and accelerated lysine N-pyrrolation has been observed in apoE-deficient (apoE−/−) hyperlipidemic mice. However, the impact of pyrP accumulation consequent to apoE deficiency on the innate immune response remains unclear. Here, we investigated B-1a cells known to produce germline-encoded immunoglobulin M (IgM) from mice deficient in apoE and identified a particular cell population that specifically produces IgM antibodies against pyrP and DNA. We demonstrated an expansion of B-1a cells involved in IgM production in the peritoneal cavity of apoE−/− mice compared with wild-type mice, consistent with a progressive increase of IgM response in the mouse sera. We found that pyrP exhibited preferential binding to B-1a cells and facilitated the production of IgM. B cell receptor analysis of pyrP-specific B-1a cells showed restricted usage of gene segments selected from the germline gene set; most sequences contained high levels of non-templated-nucleotide additions (N-additions) that could contribute to junctional diversity of B cell receptors. Finally, we report that a subset of monoclonal IgM antibodies against pyrP/DNA established from the apoE−/− mice also contained abundant N-additions. These results suggest that the accumulation of pyrP due to apoE deficiency may influence clonal diversity in the pyrP-specific B cell repertoire. The discovery of these unique B-1a cells for pyrP/DNA provides a key link connecting covalent protein modification, lipoprotein metabolism, and innate immunity.

Systematic Review : Immunoglobulin Concentration in Breast Milk as a Body Defense against Sars-Cov-2

The largest cases of pneumonia occurred in Wuhan City, Hubei Province of China in December 2019, which resembles SARS-CoV as a cause of SARS (Severe Acute Respiratory Syndrome) virus infection. The number of cases reaches 3.2 million people worldwide, and among them are breastfeeding mothers. Although virus transmission occurs through direct contact with infected patients, the number of infants or young children who were infected with COVID-19 during breastfeeding was only 10%. There is no scientific evidence for vertical transmission from mother to her baby during pregnancy and breastfeeding. The content of immunoglobulin A (IgA), immunoglobulin M (IgM), and immunoglobulin G (IgG) has a positive impact on the infant’s body. The objective of the study was to determine the immunoglobulin concentration in breast milk against SARS CoV2. The method used a systematic review approach with the design of Preferred Reporting Items For Systematic Reviews &amp; Meta-Analyses (PRISMA). The result showed laboratory clinical trials, the IgA, IgG, and IgM responses showed good results in the spread of the coronavirus into the baby's body. IgA reactivity has a higher concentration than other cells. In conclusion, Covid-19 pandemic made the public worried about their health, including breastfeeding mothers. The role of health workers is needed to provide information related to breastfeeding exclusively to their babies so that they will receive protection against virus entered their bodies. Suggestion: It is necessary to develop studies regarding the typical responses that come up from IgA, IgM, IgG and are able to protect infants from Covid-19 and vertical transmission between mother and her baby during pregnancy to breastfeeding.

Broad auto-reactive IgM responses are common in critically ill patients, including those with COVID-19

SummaryThe pathogenesis of severe coronavirus disease 2019 (COVID-19) remains poorly understood. While several studies suggest that immune dysregulation plays a central role, the key mediators of this process are yet to be defined. Here, we demonstrate that plasma from a high proportion (93%) of critically ill COVID-19 patients, but not healthy controls, contains broadly auto-reactive immunoglobulin M (IgM) and less frequently auto-reactive IgG or IgA. Importantly, these auto-IgMs preferentially recognize primary human lung cells in vitro, including pulmonary endothelial and epithelial cells. By using a combination of flow cytometry, analytical proteome microarray technology, and lactose dehydrogenase (LDH)-release cytotoxicity assays, we identify high-affinity, complement-fixing, auto-reactive IgM directed against 260 candidate autoantigens, including numerous molecules preferentially expressed on the cellular membranes of pulmonary, vascular, gastrointestinal, and renal tissues. These findings suggest that broad IgM-mediated autoimmune reactivity may be involved in the pathogenesis of severe COVID-19, thereby identifying a potential target for therapeutic interventions.

IgG Antibody Responses Are Preferential Compared With IgM for Use as Serological Markers for Detecting Recent Exposure to Plasmodium vivax Infection.

To achieve malaria elimination, new tools are required to explicitly target Plasmodium vivax. Recently, a novel panel of P. vivax proteins were identified and validated as serological markers for detecting recent exposure to P. vivax within the last 9 months. In order to improve the sensitivity and specificity of these markers, immunoglobulin M (IgM) in addition to immunoglobulin G (IgG) antibody responses were compared with a down-selected panel of 20 P. vivax proteins. IgM was tested using archival plasma samples from observational cohort studies conducted in malaria-endemic regions of Thailand and Brazil. IgM responses to these proteins generally had poorer classification performance than IgG.

Identification of a Sensitive Human Immunological Target of Aryl Hydrocarbon Receptor Activation: CD5+ Innate-Like B Cells.

Xenobiotic-mediated activation of the aryl hydrocarbon receptor (AHR) is immunotoxic in a number of immune cell types, with the B cell being a well-established sensitive target. Recent advances have provided evidence that the B cell repertoire is a heterogeneous population, with subpopulations exhibiting vastly different cellular and functional phenotypes. Recent work from our laboratory identified the T cell specific kinase lck as being differentially regulated by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), which is a potent activator of AHR. While LCK is primarily expressed in T cells, a subset of CD5+ B cells also express LCK. CD5 positivity describes a broad class of B lymphocytes termed innate-like B cells (ILBs) that are critical mediators of innate immunity through constitutive secretion of polyvalent natural immunoglobulin M (IgM). We hypothesized that CD5+ ILBs may be sensitive to AHR-mediated immunotoxicity. Indeed, when CD5+ B cells were isolated from the CD19+ pool and treated with TCDD, they showed increased suppression of the CD40 ligand-induced IgM response compared to CD5- B cells. Further, characterization of the CD5+ population indicated increased basal expression of AHR, AHR repressor (AHRR), and cytochrome p450 family 1 member a1 (CYP1A1). Indeed the levels of AHR-mediated suppression of the IgM response from individual donors strongly correlated with the percentage of the B cell pool that was CD5+, suggesting that CD5+ B cells are more sensitive to AHR-mediated impairment. Together these data highlight the sensitive nature of CD5+ ILBs to AHR activation and provide insight into mechanisms associated with AHR activation in human B cells.

LB01 Maternal antibody response and placental antibody transfer following asymptomatic and symptomatic SARS-CoV-2 infection

Objective: This prospective cohort study characterized the immune response to the SARS-CoV-2 virus during pregnancy. Study Design: Paired maternal and cord blood samples were collected at the time of delivery from women who tested positive for SARS-CoV-2 RNA at any point during pregnancy. Difference in transmission of immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies across the placenta were analyzed according to symptomatic vs asymptomatic infection and latency from time of infection to delivery. Sera was tested for the presence of anti-SARS-CoV-2 IgG and IgM antibodies using an enzyme-linked immunosorbent assay (ELISA) developed against the receptor binding domain (RBD) of the SARS-CoV-2 spike protein (Suthar et al, 2020). Result(s): A total of 23 paired maternal-infant dyads were included in the study. The mean gestational age at diagnosis was 37.7 weeks' (+/- 1.2, range 31.0 - 40) and the mean gestational age at delivery was 38.4 (+/- 0.3, range 34.4 - 40.1). All maternal delivery serum samples had detectable SARS-CoV-2 IgG antibody (n=23) and 91% had detectable SARS-CoV-2 IgM (n = 21). Among cord blood samples, 87% had detectable SARS-CoV-2 IgG (n= 20), while 13% had detectable SARS-CoV-2 IgM antibody (n=3). In stratifying the study sample based on latency from initial SARS-COV-2 test positive to delivery, there were no significant differences in the end point titers of maternal or cord blood IgG or IgM levels (Figure 1). Similarly, no significant differences were found based on indication for testing (asymptomatic testing vs symptomatic/person under investigation - Figure 2). All three cord blood samples with detectable SARS-CoV-2 IgM antibodies were from symptomatic women (Figure 2). Conclusion(s): These data demonstrate that pregnant women in this cohort almost uniformly mounted an IgG and IgM response to SARS-CoV-2, even if asymptomatic at the time of diagnosis;almost all samples showed robust transfer of IgG antibodies into the cord blood. These results form a promising foundation for further investigation into the maternal humoral response to SARS-CoV-2 infection in pregnancy. [Formula presented] [Formula presented]Copyright © 2020

Pattern of Antibody Response to Trypanosoma evansi Infection: A step for production of high affinity antibodies

TThe aim of this study is to determine the pattern of immune response during Trypanosoma evansi infection as a preliminary step for production of high affinity antibodies for use in immunoassays. Antibody response to Typanosoma evansi infection in mice was monitored during a short and a long immunization protocols. Both protocols yielded immunoglobulin M (IgM) and immunoglobulin G (IgG) responses. Observed initial antibody response was of an IgM type and later replaced by an IgG response. The IgM response was similar in both immunization protocols. It first detected on day 4, reached a peak level on day 6 and declined thereafter until it disappeared on day 37-post infection. The IgG response in the short protocol was first detected on day 17-post infection, reached a peak level on day 23 and maintained a high level up to the end of the experiment on day 45 post-infection. The IgG response in the long protocol was first detected on day 10-post infection, reached a peak level on day 42 and maintained this level to the end of the experiment. The current study suggests for the first time the pattern of immune response during Trypanosoma evansi infection as a preliminary step for production of high affinity antibodies.

The variability of the serological response to SARS-corona virus-2: Potential resolution of ambiguity through determination of avidity (functional affinity).

Data on the serological response toward severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) in 16 recent reports were analyzed and a high degree of variability was shown. Immunoglobulin M (IgM) responses were either found earlier than IgG, or together with IgG, later than IgG, or were missing. Therefore, clear distinctions between early, intermediate, and past infections are obviously not possible merely on the basis of IgM and IgG determinations. A review of publications on the serology of other virus groups shows that variable IgM responses can be found as well and therefore are not unique for SARS‐CoV‐2 infections. A model to explain this variability is proposed. The inclusion of avidity determination into regular diagnostic procedures has allowed to resolve such “atypical” serological constellations. The potential use of avidity determination for the diagnosis of COVID‐19, for risk assessment, epidemiological studies, analysis of cross reactions, as well as for the control of vaccination programs is suggested and discussed.

Magnitude and Kinetics of Anti-Severe Acute Respiratory Syndrome Coronavirus 2 Antibody Responses and Their Relationship to Disease Severity.

BackgroundSARS-CoV-2 infection can be detected indirectly by measuring the host immune response. For some viruses, antibody concentrations correlate with host protection and viral neutralization, but in rare cases, anti-viral antibodies can promote disease progression. Elucidation of the kinetics and magnitude of the SARS-CoV-2 antibody response is essential to understand the pathogenesis of COVID-19 and identify potential therapeutic targets.MethodsSera (n=533) from patients with RT-PCR confirmed COVID-19 (n=94 with acute infections and n=59 convalescent patients) were tested using a high-throughput quantitative IgM and IgG assay that detects antibodies to the spike protein receptor binding domain and nucleocapsid protein. Individual and serial samples covered the time of initial diagnosis, during the disease course, and following recovery. We evaluated antibody kinetics and correlation between magnitude of the response and disease severity.ResultsPatterns of SARS-CoV-2 antibody production varied considerably. Among 52 patients with 3 or more serial specimens, 44 (84.6%) and 42 (80.8%) had observed IgM and IgG seroconversion at a median of 8 and 10 days, respectively. Compared to those with milder disease, peak measurements were significantly higher for patients admitted to the intensive care unit for all time intervals between 6 and 20 days for IgM, and all intervals after 5 days for IgG.ConclusionsHigh sensitivity assays with a robust dynamic range provide a comprehensive picture of host antibody response to SARS-CoV-2. IgM and IgG responses were significantly higher in patients with severe than mild disease. These differences may affect strategies for seroprevalence studies, therapeutics and vaccine development.