Total Immunoglobulin M Research Articles

Production of a monoclonal antibody specific to the IgM heavy chain of Asian seabass (Lates calcarifer Bloch, 1790) and its application in assessing health status following vaccination and challenges with Flavobacterium covae and Streptococcus iniae

Immunoglobulin M (IgM) shows potential as a significant immunological marker in Asian seabass (Lates calcarifer), accentuating the importance of developing specific monoclonal antibodies (mAbs) for immunological studies. In this study, we investigated the antigenicity of the IgM heavy chain (IgMH), particularly the Cμ3 region of IgMH (IgMHCμ3), and synthesized a peptide for anti-IgMHCμ3 mAb production. The synthesized peptide was used to generate a specific mAb in rabbits. The produced mAb demonstrated high specificity and affinity for Asian seabass IgMH, as confirmed through indirect ELISA, Western blot analysis, indirect immunofluorescence assay (IIFAT) and flow cytometry analysis. In addition, an indirect ELISA was developed and optimized to measure anti-Flavobacterium covae and anti-Streptococcus iniae antibody titers in Asian seabass serum. The monoclonal antibody (mAb) was subsequently used to assess the health status of Asian seabass post-vaccination and challenge with these pathogens, demonstrating its potential as a valuable tool for immunological studies and health assessments in Asian seabass. Vaccination and postchallenge fish exhibited a pronounced increase in specific antibodies and total serum IgM and IgM+ cell populations. Thus, this study establishes a foundational platform for using the anti-IgMHCμ3 mAb as an essential tool for evaluating and understanding the immune responses and health status of Asian seabass, especially in the context of bacterial infections and vaccinations, and paves the way for more studies in fish immunology.

Detectable Respiratory Viruses IgM and IgG Antibodies among Children with Acute Respiratory Tract Infections in Owo, Ondo State, Nigeria

Globally, in children, less than 5 years of age, acute respiratory tract infections (ARTIs) are a major cause of morbidity and mortality. Long-lasting immunity is not induced by respiratory infections as reinfection can occur throughout life. This study aimed to determine the seroprevalence of six respiratory viruses specific immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies in children with ARTIs in Owo, Ondo State. The sera samples of two hundred (200) subjects who consented to participate in the study were collected and tested using serum-specific Enzyme-Linked Immunosorbent Assay (ELISA) kits, anti-immunoglobulin M (IgM) and anti-immunoglobulin G (IgG) antibodies to the influenza A virus (FLU-A), respiratory syncytial virus (RSV), parainfluenza virus (PIV), coronavirus (CoV), rhinovirus (RV) and adenovirus (AdV) respectively (IgM and IgG ELISA Kits; Melsin Medical Co., China). The mean age of the subjects tested was 3.49±1.41. The total IgM seropositivity was detected in 83% of the children with the highest being AdV 91 (45.5%), followed by PIV 89 (44.5%), FLU-A and RV with 88 (44%) respectively, CoV 85 (42.5%), and RSV 80 (40%). The total IgG seropositivity was detected in 87.5% of the children with the highest being PIV 152 (76%), followed by RSV 135 (67.5%), RV 93 (46.5%), AdV 81 (40.5%), CoV and FLU A 76 (38%) respectively. The study revealed the presence of primary and secondary infection of respiratory viruses in Owo and the need for preventive and control measures against respiratory tract viruses are suggested.

To Determine the Clinical Profile and Manifestations of Scrub Typhus among People

Introduction: In developing countries acute febrile illness (AFI) is the most common presenting complaint in emergency and outpatients department. Usually in the rainy season and post rainy season Outbreaks of AFI occur in India. Outbreaks like Dengue, Malaria, Typhoid, Scrub typhus and several viral infections have been classically responsible. Orientia tsutsugamushi is an obligate intracellular gram negative bacteria which cause Scrub typhus. Scrub typhus is the infection caused by the bite of infected chiggers. The clinical manifestation is characterised by the presence of fever, body pain, headache and rarely can cause rashes. Scrub typhus is mite borne rickettsiosis and is an endaemic infection in area unique to Asia, with an estimated one billion people. In recent years, many parts of India scrub typhus have rapidly remerged to become the major cause of AFI during monsoon seasons. In India, of the 29 states, 23 have reported the presence of scrub typhus.
 Aim: The main aim of this study is to determine the clinical profile and manifestation of scrub typhus infection among people. Material and method: Total 72 patients with conform cases of scrub typhus fever were included in this study. The evaluation of fevers were undergone clinically initially serological test and Weil–Felix test followed by immunoglobulin M (IgM) scrub typhus and positive cases were included in this study. Consideration was taken of their clinical appearance and investigations.
 Results: Total 72 positive cases were included in this study. Among the total IgM positive for scrub typhus were analyzed with their age and sex variation. From each and every patient different clinical manifestations and complications were analyzed and recorded. The common symptoms were fever; myalgia, breathlessness, rash, and abdominal pain were recorded as 100%, 66.7%, 8.3%, 13.9% and 36.1% respectively. Renal failure was the most common complications followed by pneumonia as 19.4% and 9.7% respectively. In laboratory findings high C-reacting protein and leukocytosis are also found in 81.9% and 33.3% respectively. 
 Conclusion: Scrub typhus is a widespread tropical infection and often occurs as pyrexia of unknown origin. However sometime it is under diagnosed due to low indication of suspicion and due to non-specific clinical manifestation and also in most of clinical settings due to lack of diagnostic procedures. If there was early diagnosed then treatment will be easy and cost effective due to good response of antibiotics.

Decrease in Serum Anti-MAG Autoantibodies Is Associated With Therapy Response in Patients With Anti-MAG Neuropathy: Retrospective Study.

Background and ObjectivesThe objective of the retrospective analysis was to test the hypothesis that changes in serum anti-myelin-associated glycoprotein (MAG) autoantibodies are associated with clinical response to immunotherapy in patients with anti-MAG neuropathy.MethodsAs of January 29, 2020, we used anti-myelin-associated glycoprotein-related search strings in the Medline database to identify studies that provided information on anti-MAG immunoglobulin M (IgM) autoantibodies and clinical outcomes during immunotherapies. The relative change in anti-MAG IgM titers, paraprotein levels, or total IgM was determined before, during, or posttreatment, and the patients were assigned to “responder,” “nonresponder,”’ or “acute deteriorating” category depending on their clinical response to treatment. The studies were qualified as “supportive” or “not supportive” depending on the percentage of patients exhibiting an association between relative change of anti-MAG antibody titers or levels and change in clinical outcomes.ResultsFifty studies with 410 patients with anti-MAG neuropathy were included in the analysis. Forty studies with 303 patients supported the hypothesis that a “responder” patient had a relative reduction of anti-MAG antibody titers or levels that is associated with clinical improvements and “nonresponder” patients exhibited no significant change in anti-MAG IgM antibodies. Six studies with 93 patients partly supported, and 4 studies with 26 patients did not support the hypothesis.DiscussionThe retrospective analysis confirmed the hypothesis that a relative reduction in serum anti-MAG IgM antibodies is associated with a clinical response to immunotherapies; a sustained reduction of at least 50% compared with pretreatment titers or levels could be a valuable indicator for therapeutic response.

Surface Plasmon Resonance-Based Immunosensor for Igm Detection with Gold Nanoparticles.

In this work, a surface plasmon resonance (SPR) based immunosensor was prepared by the immobilization of the amine-functionalized gold nanoparticles (N-AuNPs) on the sensing surface to sense immunoglobulin M (IgM) antibodies in the aqueous solution and artificial plasma. The characterization studies of SPR based immunosensor for IgM detection were performed with scanning electron microscope (SEM), contact angle measurements, and ellipsometry. Kinetic studies for the IgM immunosensor were carried out in the range of 1.0 to 200 ng/mL IgM concentrations in an aqueous solution. The total IgM analysis time including adsorption, desorption, and regeneration cycles was nearly 10 min for the prepared immunosensor. The limit of detection (LOD) and limit of quantification (LOQ) were found as 0.08 and 0.26 ng/mL, respectively. The reusability of the proposed immunosensor was tested with 6 consecutive adsorption-desorption, and regeneration cycles. Also, enzyme-linked immunosorbent assay (ELISA) method was utilized in the validation of the immunosensor.

Effects of Hydrolysable Tannins as Zinc Oxide Substitutes on Antioxidant Status, Immune Function, Intestinal Morphology, and Digestive Enzyme Activities in Weaned Piglets.

Simple SummaryZinc oxide (ZnO) is generally used to control diarrhea and improve gut health in weaned piglets. To protect weaned pigs from intestinal injuries and to decrease environmental zinc load, it is essential to find an alternative to ZnO. In the present study, hydrolysable tannins (HT) showed decreased diarrhea rate and improving gut health via multiple pathways. Herein we demonstrate that HT supplementation may be a potential alternative of ZnO in weaned piglets.Zinc oxide (ZnO) has negative environmental effects and bioavailability in weaned piglets. Thus, finding safe and effective ZnO substitutes to improve intestinal health and to prevent diarrhea of weaned piglets is urgently required. Therefore, this experiment was conducted to evaluate the effects of hydrolysable tannins (HT), ZnO and HT versus ZnO on growth performance, antioxidant status, serum immunity, intestinal morphology, and digestive enzyme activities in weaned pigs. A total of 144 piglets (28 d-old, initial body weight 7.81 ± 0.99 kg) were assigned to 4 treatments with 6 replicates of 6 piglets each. The experiment lasted 28 d (d 1 to 14 as for phase 1 and d 15 to 28 as for phase 2). The dietary treatments include a corn-soybean meal basal diet (CON); ZnO diet (CON + 2000 mg/kg ZnO in phase 1 and 137.5 mg/kg ZnO in phase 2); HT diet (CON + 1000 mg/kg HT in the overall period (d 1 to 28); HT + ZnO diet (CON + 2000 mg/kg ZnO + 1000 mg/kg HT in phase 1, and 137.5 mg/kg ZnO + 1000 mg/kg HT in phase 2). In phase 1, the incidence of diarrhea was lower (p < 0.05) in the HT + ZnO group than CON. Serum catalase (CAT) and glutathione peroxidase (GSH-Px) were increased (p < 0.01) and malondialdehyde (MDA) was decreased (p < 0.01) in the HT + ZnO group than CON. Compared with CON, immunoglobulin M (IgM), immunoglobulin A (IgA) were increased (p < 0.05) in the HT + ZnO group. In phase 2, both HT and HT + ZnO had a trend to improve (p < 0.10) daily gain. The concentration of total antioxidant capacity (T-AOC) and IgM in serum was higher (p < 0.01) in HT compared with CON. Supplementation of HT improved (p < 0.01) GSH-Px activities in ileum mucosa than the ZnO group. Compared with CON, trypsin, lipase activities, and villus height of jejunum were improved (p < 0.05) in HT and HT + ZnO. The ratio of villus height to crypt depth in the jejunum was improved (p < 0.05) in the HT + ZnO group and which also was increased (p < 0.05) in ileum in the HT group compared with CON. Propionic acid, butyric acid, and acetic acid concentrations in the colon were increased (p < 0.05) in the HT group than CON. Overall, HT + ZnO treatments could be used to replace ZnO for reducing diarrhea and improving antioxidant capacity, immunity, and digestive enzyme activities in weaned piglets.

Evaluation of the frequency of CD5+ B cells as natural immunoglobulin M producers and circulating soluble CD5 in patients with bladder cancer.

Bladder cancer is the most common malignancy of the genitourinary tract. It is the fourth most common malignancy in men and the fifth most common malignancy in the general population, with a high recurrence rate. CD5+ B lymphocytes are a subset of B lymphocytes, which contribute to innate immune responses. These cells are involved in the spontaneous production of self-reactive natural antibodies. On the other hand, natural antibodies can recognize tumor-associated antigens, including proteins or carbohydrates, and eliminate these cells in a complement-dependent manner or via induction of apoptosis. Besides surface CD5, the soluble form of this molecule is involved in the regulation of immune system. Considering the role of CD5+ B cells in the production of natural immunoglobulin M (IgM) and role of these antibodies in antitumor responses, in this study, we aimed to investigate the frequency of CD5 in B cells and to evaluate the diagnostic potential of these cells and also soluble CD5 (sCD5) in patients with bladder cancer. Blood specimens were collected from 40 patients with bladder cancer, who were referred to Sina Hospital in Tehran, IRAN. The levels of CD5+ and CD5- B lymphocytes were measured in the peripheral blood via flow cytometry, and the levels of sCD5 and total IgM were investigated in the serum by ELISA and nephlometry techniques, respectively. The frequency of CD5+ and CD5- B cells was significantly lower in patients, compared with the healthy controls. Detectable levels of sCD5 were found in two patients (5%), while total IgM showed no significant difference between the patient and control groups. The present results suggest that B cell subsets may be affected by malignancy. Therefore, further research is needed to identify B cells and their soluble markers for diagnosis of patients with bladder cancer.

Spectral-domain optical coherence tomography of retinal vessels in Waldenström's macroglobulinemia.

To image retinal blood vessels in patients with Waldenström's macroglobulinemia using optical coherence tomography (OCT). Retrospective case series examining fundus photographs and OCT scans of 16 eyes in eight patients with Waldenström's macroglobulinemia. Analyses included intravascular OCT reflectivity profiles and vessel diameters, and their relation to total immunoglobulin M (IgM) levels. In six out of eight patients, cross-sectional OCT scans of larger retinal vessels (diameter>100μm) showed normal intravascular reflectivity and retrovascular shadowing. In two patients with the highest total IgM>60g/l, altered intravascular reflectivity, distinct anterior and posterior vessel wall reflexes, and retrovascular hyposhadowing were seen. Normalization of the OCT reflectivity in these patients occurred after reduction of total IgM to<17g/l and was accompanied by decreasing venous tortuosity and disappearance of retinal haemorrhages and cotton wool spots. This study found that Waldenström's macroglobulinemia and total IgM>60g/l were associated with abnormal intravascular reflectivity and retrovascular shadowing on OCT. Awareness of these signs of hyperviscosity could potentially enable earlier detection of critical conditions in patients with Waldenström's macroglobulinemia and improve the assessment of severity and treatment effect.

Development and characterization of a Zaire Ebola (ZEBOV) specific IgM ELISA

Immunoglobulin M (IgM) is the first antibody induced after the onset of an adaptive immune response against a pathogen or vaccine. Serological assays play a central role in evaluating these adaptive immunological responses. Such assays are not only crucial for the assessment of vaccine immunogenicity, but also inform on exposure to pathogens and cross-reactivity with other viruses. To date, there is no ELISA-based assay available that measures IgM responses against Zaire Ebola virus (ZEBOV). To address this critical need, our laboratory has developed a novel immunoassay capable of detecting total IgM against ZEBOV glycoprotein in serum samples from individuals exposed to the antigen through infection or vaccination. Here, we describe a sensitive, high-throughput, and inexpensive assay that can be performed in any laboratory. The performance criteria of the newly developed ZEBOV glycoprotein-based IgM ELISA were assessed using antisera collected from human patients immunized with the rVSVΔG-ZEBOV-GP vaccine being tested in a phase 1 clinical trial. This assay demonstrates high specificity and sensitivity and will also be a valuable tool in the mission to find immune correlates of protection for a successful Ebola vaccine.

Investigation into the Mechanism(s) That Leads to Platelet Decreases in Cynomolgus Monkeys During Administration of ISIS 104838, a 2'-MOE-Modified Antisense Oligonucleotide.

ISIS 104838, a 2'-O-methoxyethyl (2'-MOE)-modified antisense oligonucleotide (ASO), causes a moderate, reproducible, dose-dependent, but selflimiting decrease in platelet (PLT) counts in monkeys and humans. To determine the etiology of PLT decrease in cynomolgus monkeys, a 12-week repeat dose toxicology study in 5 cynomolgus monkeys given subcutaneous injections of ISIS 104838 (30-60 mg/kg/week). Monkeys were also injected intravenously with 111Indium(In)-oxine-labeled PLTs to investigate PLT sequestration. In response to continued dosing, PLT counts were decreased by 50%-90% by day 30 in all monkeys. PLT decreases were accompanied by 2- to 4.5-fold increases in immunoglobulin M(IgM), which were typified by a 2- to 5-fold increase in antiplatelet factor 4 (antiPF4) IgM and antiPLT IgM, respectively. Monocyte chemotactic protein 1 increased upon dosing of ISIS 104838, concomitant with a 2- to 6-fold increase in monocyte-derived extracellular vesicles (EVs), indicating monocyte activation but not PLT activation. Despite a 2- to 3-fold increase in von Willebrand factor antigen in all monkeys following ASO administration, only 2 monkeys showed a 2- to 4-fold increase in endothelial EVs. Additionally, a ∼60 - 80%% increase in PLT sequestration in liver and spleen was also observed. Collectively, these results suggest the overall increase in total IgM, antiPLT IgM and/or antiPF4 IgM, in concert with monocyte activation contributed to increased PLT sequestration in spleen and liver, leading to decreased PLTs in peripheral blood.

Infectious Mononucleosis Triggers Generation of IgG Auto-Antibodies against Native Myelin Oligodendrocyte Glycoprotein.

A history of infectious mononucleosis (IM), symptomatic primary infection with the Epstein Barr virus, is associated with the development of autoimmune diseases and increases the risk to develop multiple sclerosis. Here, we hypothesized that immune activation during IM triggers autoreactive immune responses. Antibody responses towards cellular antigens using a HEp-2 based indirect immunofluorescence assay and native myelin oligodendrocyte glycoprotein (MOG) using a flow cytometry-based assay were determined in 35 patients with IM and in 23 control subjects. We detected frequent immunoglobulin M (IgM) reactivity to vimentin, a major constituent of the intermediate filament family of proteins, in IM patients (27/35; 77%) but rarely in control subjects (2/23; 9%). IgG autoantibodies binding to HEp-2 cells were absent in both groups. In contrast, IgG responses to native MOG, present in up to 40% of children with inflammatory demyelinating diseases of the central nervous system (CNS), were detectable in 7/35 (20%) patients with IM but not in control subjects. Normalization of anti-vimentin IgM levels to increased total IgM concentrations during IM resulted in loss of significant differences for anti-vimentin IgM titers. Anti-MOG specific IgG responses were still detectable in a subset of three out of 35 patients with IM (9%), even after normalization to increased total IgG levels. Vimentin-specific IgM and MOG-specific IgG responses decreased following clinical resolution of acute IM symptoms. We conclude from our data that MOG-specific memory B cells are activated in subset of patients with IM.

Seroprevalence of Hepatitis A and E Virus Infections Among Healthy Population in Shiraz, Southern Iran.

Background:Enterically-transmitted acute viral hepatitis is caused predominantly by hepatitis A virus (HAV) and hepatitis E virus (HEV). The prevalence of HEV and HAV infections varies in different geographical regions.Objectives:This study was conducted to determine the prevalence of HEV and HAV infections among Iranian healthy individuals in southern Iran.Patients and Methods:Totally, 1030 samples were collected from healthy subjects in schools, those referred to tertiary outpatient clinics and health centers in Shiraz between November 2011 and May 2012. Their ages ranged between six months and 95 years. The presence of total anti-HAV and anti-HEV immunoglobulin M (IgM) in plasma was assessed by ELISA.Results:The results showed that 66.2% and 0.6% of the general population in this area were positive for total anti-HAV and IgM antibodies by ELISA, respectively. As seen, 13.4% and 0.9% were positive for total anti-HEV and IgM antibodies, respectively. The difference in total anti-HAV and anti-HEV antibodies was significant among the age groups (P < 0.001).Conclusions:This study showed that the prevalence rates of HAV and HEV antibodies were positively correlated with age. The results demonstrated that the infection with these two viruses in the region was high and some high-risk individuals including females at child-bearing age were more susceptible. HAV vaccination could be recommended for antibody-negative adults.

The effects of fructooligosaccharide on the immune response, antioxidant capability and HSP70 and HSP90 expressions in blunt snout bream (Megalobrama amblycephala Yih) under high heat stress

This study evaluated the effects of fructooligosaccharide (FOS) on the immune response, antioxidant capability and HSP70 and HSP90 mRNA expressions in blunt snout bream ( Megalobrama amblycephala ) under high heat stress. A total of 360 fish were randomly distributed into three groups (each with four replicates) and fed with three levels of FOS (0, 0.4% and 0.8%) for 8 weeks. After the feeding trial, 20 fish per tank were exposed to high heat stress at 34 °C (ambient temperature + 8 °C). At 3 and 6 h after stress, both the plasma cortisol and glucose levels of fish fed with 0.4% FOS were significantly lower than those of fish fed with the control diets. This also held true for the lactate levels of fish fed with 0.4% FOS, except that a significant difference was only observed at 3 h. Plasma lysozyme, acid phosphatase (ACP) and alternative complement (ACH50) activities, as well as total protein, immunoglobulin M (IgM) and nitrogen monoxide (NO) contents, increased significantly, with maximum levels attained at 6 h for all parameters except for the ACP activity. Thereafter, these parameters all decreased significantly. In addition, fish fed with 0.4% or 0.8% FOS obtained significantly higher lysozyme, ACP and ACH50 activities as well as total protein, IgM and NO contents at 3 and/or 6 h after stress. The liver superoxide dismutase and catalase activities of fish fed with 0.4% FOS were both significantly higher than those of the control group before and after stress, while the opposite was true for the malondialdehyde content. After stress, the HSP70 and HSP90 expressions of fish fed with 0.4% FOS were both significantly higher than those of fish fed with the control diets at 3, 6 and 12 h (except the HSP90 at 12 h). Similar results were also observed in fish fed with 0.8% FOS except that the differences in HSP70 expression were only significant at 3 and 12 h. The results indicated that the supplementation of 0.4% FOS could increase the non-specific immunity, antioxidant capacity and HSP70 and HSP90 expressions of blunt snout bream and enhance its resistance to high heat stress. • Non-specific immunity decreased under high heat stress. • Antioxidant capacity also decreased under high heat stress. • HSP70 and HSP90 mRNA expression levels were induced under high heat stress. • FOS relieved the adverse effects of high heat stress.

Low total IgM values and high cytomegalovirus loads in the blood of newborns with symptomatic congenital cytomegalovirus infection.

Neurological outcomes differ considerably between symptomatic and asymptomatic infants with congenital cytomegalovirus (CMV) infection. Our objective was to characterize laboratory markers in symptomatic newborns in comparison with asymptomatic newborns with congenital CMV infection. Ten newborns with symptomatic and 13 newborns with asymptomatic congenital CMV infection were included in this 3-year prospective cohort study. Total immunoglobulin M (IgM), CMV-IgM, CMV antigenemia, and CMV-DNA in blood and urine were measured and their positive rates and quantitative values compared between the symptomatic and asymptomatic groups. Fifty percent of newborns in the symptomatic group were positive based on total IgM; this was significantly lower than in the asymptomatic group (100%). Quantitative total IgM values were significantly lower, and there were significantly more copies of CMV-DNA in the blood of symptomatic newborns than in asymptomatic newborns (median values for total IgM: 14 vs. 43 mg/dL and blood CMV-DNA: 3.2×102 vs. 3.5×101 copies/106 white blood cells). CMV-IgM, CMV antigenemia, and urine CMV-DNA did not differ significantly between groups. Low total IgM values and high blood CMV loads were associated with the presence of symptoms in newborns with congenital CMV infection.

Design and evaluation of a tandemly arranged outer membrane protein U (OmpU) multi-epitope as a potential vaccine antigen against Vibrio mimicus in grass carps (Ctenopharyngodon idella)

Vibrio mimicus (V. mimicus) is an extracellular pathogen that causes ascites disease in aquatic animals. In our previous studies, the outer membrane protein U (OmpU) of V. mimicus has been proven to be a protective antigen, and several mimotopes of the protein were identified. Here, a tandemly arranged multi-epitope peptide (named 6EPIS) was designed with six mimotopes and heterologously expressed. Then, the immunoprotection efficacy of recombinant 6EPIS (r6EPIS) was evaluated in grass carps (Ctenopharyngodon idella) by determining relative percentage survival (RPS), specific immunoglobulin M (IgM) antibody titer, and transcriptional levels of immune-related genes of inoculated grass carps. Fish vaccinated with r6EPIS via intraperitoneal injection exhibited 85.71% RPS over the control, when challenged with V. mimicus. The enzyme-linked immunosorbent assay titer of specific IgM antibodies against r6EPIS reached 1:12,800 on Day 28 post the primary immunization. After 28 days post immunization, the transcriptional level of total IgM mRNA was significantly higher in the r6EPIS-vaccinated fish than in those vaccinated with recombinant OmpU, inactivated bacterin and rHis tag peptide (p<0.05). In addition, the transcription levels of interleukin-1β and tumor necrosis factor-α genes in the spleen and head kidney of r6EPIS-vaccinated fish were significantly increased during the period of immunization and early phase of infection, while the transcription level of interleukin-10 gene was significantly increased from Day 3 to 7 post challenge, compared to the control level. These results show that r6EPIS was highly immunogenic and could elicit strong protective immune responses. It may be an attractive vaccine candidate against V. mimicus infection.

Beneficial role of endogenous immunoglobulin subclasses and isotypes in septic shock

PurposeThere is increasing evidence on the relationship between endogenously produced immunoglobulins and the clinical outcome in septic shock (SS). Materials and methodsLevels of immunoglobulin G (IgG) subclasses, immunoglobulin A (IgA), immunoglobulin M (IgM), and immunoglobulin E were measured in plasma from 42 patients with SS and in 36 patients with systemic inflammatory response syndrome at diagnosis. Association of immunoglobulins levels with disease severity and outcome was evaluated. ResultsEighteen patients with SS finally died. Both patients with systemic inflammatory response syndrome and SS showed subnormal levels of total IgG, IgG2, and IgM. Patients with SS who died showed the lowest levels of total IgG and IgG1. Total IgG, IgG1, IgG2, IgG3, IgG4, and IgA correlated inversely with Acute Physiology and Chronic Health Evaluation II score in SS. Univariate Cox regression analysis showed that levels of IgG1, IgG2, IgG3, IgM, IgA, and total IgG were inversely associated to the probability of death at 28 days. Multivariate analysis showed that IgG1, total IgG, IgM, and IgA behaved as independent protective factors against mortality (hazard ratio, P): 0.23, 0.026; 0.16, 0.028; 0.11, 0.042; 0.05, 0.010, respectively, whereas IgG3 showed a protective trend also. ConclusionsOur study evidenced that, in addition to IgG1, other major endogenous immunoglobulins isotypes and subclasses seem to play a beneficial role in SS.

A role for interleukin‐5 in promoting increased immunoglobulin M at the site of disease in leprosy

Leprosy is an infectious disease in which the clinical manifestations correlate with the type of immune response mounted to the pathogen, Mycobacterium leprae. To investigate which biological pathways or gene sets are over-represented in lepromatous (L-Lep) versus tuberculoid (T-Lep) patients that might be relevant in disease pathogenesis, we compared the gene expression profiles of L-lep versus T-lep skin lesions using knowledge-guided bioinformatic analysis, incorporating data on likely biological functions, including gene ontology information and regulatory data. Analysis of probe sets comparatively increased in expression in L-lep versus T-lep revealed multiple pathways and functional groups involving B-cell genes (P values all < 0.005) relevant to the dataset. Further pathways analysis of B-cell genes comparatively increased in expression in L-lep versus T-lep lesions revealed a potential network linking the expression of immunoglobulin M (IgM) and interleukin-5 (IL-5). Analysis of the leprosy lesions by immunohistology indicated that there was approximately 8% more IgM-positive cells in L-lep lesions than in T-lep lesions. Furthermore, IL-5 synergized in vitro with M. leprae to enhance total IgM secretion from peripheral blood mononuclear cells. This pathways analysis of leprosy in combination with our in vitro studies implicates a role for IL-5 in the increased IgM at the site of disease in leprosy.

Report Refuting Value of Immune Complexes To Diagnose Lyme Disease Is Invalid

Report Refuting Value of Immune Complexes To Diagnose Lyme Disease Is Invalid

Rituximab treatment of an IgM monoclonal autonomic and sensory neuropathy

Rituximab, a monoclonal antibody against B-cell membrane marker CD-20, is an effective treatment for immunoglobulin M (IgM) monoclonal anti-myelin-associated glycoprotein (MAG) neuropathies. We report a patient with an autonomic and painful sensory neuropathy associated with an IgM lambda monoclonal gammopathy, responsive to rituximab. Treatment resulted in a decline in total IgM and improvement in the patient's painful neuropathy and dysautonomia. Rituximab may be an effective and tolerable treatment for autonomic and sensory neuropathy associated with IgM monoclonal gammopathy.

Monocytosis and accelerated activation of lymphocytes in C1q-deficient autoimmune-prone mice.

C1q deficiency has been shown to accelerate spontaneous autoimmunity in mice. We studied the time course of activation of monocytes and lymphocytes in autoimmune and non-autoimmune mice in the presence or absence of C1q as a disease accelerator. Autoimmune MRL\Mp.C1qa-\- and non-autoimmune C57BL\6.C1qa-\- mice were analysed at various time points between 6 and 33 weeks of age and compared to strain- and age-matched C1q-sufficient controls. Splenic and peritoneal leucocytes were analysed by flow cytometry and plasma levels of immunoglobulin M (IgM), total IgG, IgG subclasses and IgM autoantibodies were measured. Both C1q-deficient strains had significantly more splenic monocytes than their controls at all time points analysed. In addition, MRL\Mp.C1qa-\- but not C57BL/6.C1qa-\- mice developed splenic hypercellularity starting at about 12-17 weeks old, had signs of accelerated CD4+ T-cell activation and showed a marked increase in splenic plasma cells and total serum IgM levels from about 22 weeks of age. The accelerated CD4+ T-cell activation was not due to a direct inhibitory effect of C1q on T cells. These data show that C1q deficiency causes splenic monocytosis together with accelerated T-cell activation in an autoimmune-prone mouse strain.