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IgM Response (igm + response)
Selected AbstractsSpecific ICAM-3 grabbing nonintegrin-related 1 (SIGNR1) expressed by marginal zone macrophages is essential for defense against pulmonary Streptococcuspneumoniae infectionEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 10 2005Estella Abstract The dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN) homolog, SIGN-related 1 (SIGNR1) is a pathogen receptor expressed by splenic marginal zone and peritoneal macrophages, and is essential for clearance of Streptococcus pneumoniae by phagocytosis after intraperitoneal infection. Here, we identified an important in vivo function for SIGNR1 in S.pneumonia infection induced via its natural entrance route. Upon intranasal infection with S. pneumoniae, SIGNR1-deficient mice did not clear bacteria from lung and blood, and displayed severely enhanced inflammatory parameters compared to the wild-type mice. However, SIGNR1 is not expressed by alveolar macrophages, suggesting that another mechanism than a decrease in phagocytosis is responsible for this difference. Natural anti-phosphorylcholine IgM produced by marginal zone B cells is essential for protection against infection with S. pneumoniae. Strikingly, during infection, SIGNR1-deficient mice failed to produce a rapid anti-phosphorylcholine IgM response. Marginal zone macrophages have been suggested to capture antigens for presentation to marginal zone B cells. We demonstrate that marginal zone macrophages from SIGNR1-deficient mice in contrast to wild-type mice are not able to capture pneumococci from blood, suggesting that SIGNR1 on marginal zone macrophages captures S. pneumoniae for antigen presentation to and activation of marginal zone B cells, resulting in an anti-phosphorylcholine IgM response. [source] Serological response to hepatitis E virus genotype 3 infection: IgG quantitation, avidity, and IgM responseJOURNAL OF MEDICAL VIROLOGY, Issue 1 2008R. Bendall Abstract Sequential sera were collected from 18 acute cases of UK-acquired hepatitis E. The virus strains in all cases were of genotype 3. The IgM and IgG response to acute infection were documented over time using EIA kits based on a peptide antigen, pE2, which is derived from a genotype 1 strain of hepatitis E virus (HEV). Ninety-five percentage of acute sera were IgM positive; after 6 months or more only 12% remained positive. The kit was adapted to quantify the IgG response (in WHO U/ml) and to determine antibody avidity. Following acute infection, anti-HEV IgG concentrations rose between 6.9- and 90-fold. IgG avidity was low (<25%) in most acute sera. After 6 months IgG avidity was greater than 50% in all cases. One patient with a poor IgM response and high avidity antibody in acute sera may have had a second HEV infection. Taken together, these results confirm that the pE2-based EIA kits are suitable for diagnosing acute HEV genotype 3 infection. With simple modifications the IgG kit can measure anti-HEV concentration and avidity, which can be used to confirm acute infection. J. Med. Virol. 80:95,101, 2008. © 2007 Wiley-Liss, Inc. [source] Quantitative mouse model of implant-associated osteomyelitis and the kinetics of microbial growth, osteolysis, and humoral immunity,JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 1 2008Dan Li Abstract Although osteomyelitis (OM) remains a serious problem in orthopedics, progress has been limited by the absence of an in vivo model that can quantify the bacterial load, metabolic activity of the bacteria over time, immunity, and osteolysis. To overcome these obstacles, we developed a murine model of implant-associated OM in which a stainless steel pin is coated with Staphylococcus aureus and implanted transcortically through the tibial metaphysis. X-ray and micro-CT demonstrated concomitant osteolysis and reactive bone formation, which was evident by day 7. Histology confirmed all the hallmarks of implant-associated OM, namely: osteolysis, sequestrum formation, and involucrum of Gram-positive bacteria inside a biofilm within necrotic bone. Serology revealed that mice mount a protective humoral response that commences with an IgM response after 1 week, and converts to a specific IgG2b response against specific S. aureus proteins by day 11 postinfection. Real-time quantitative PCR (RTQ-PCR) for the S. aureus specific nuc gene determined that the peak bacterial load occurs 11 days postinfection. This coincidence of decreasing bacterial load with the generation of specific antibodies is suggestive of protective humoral immunity. Longitudinal in vivo bioluminescent imaging (BLI) of luxA-E transformed S. aureus (Xen29) combined with nuc RTQ-PCR demonstrated the exponential growth phase of the bacteria immediately following infection that peaks on day 4, and is followed by the biofilm growth phase at a significantly lower metabolic rate (p,<,0.05). Collectively, these studies demonstrate the first quantitative model of implant-associated OM that defines the kinetics of microbial growth, osteolysis, and humoral immunity following infection. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J. Orthop Res 26:96,105, 2008 [source] Phase II trial of weekly bortezomib in combination with rituximab in untreated patients with Waldenström MacroglobulinemiaAMERICAN JOURNAL OF HEMATOLOGY, Issue 9 2010Irene M. Ghobrial This study aimed to determine the activity and safety of weekly bortezomib and rituximab in patients with untreated Waldenström Macroglobulinemia (WM). Patients with no prior therapy and symptomatic disease were eligible. Patients received bortezomib IV weekly at 1.6 mg/m2 on days 1, 8, 15, q 28 days × 6 cycles, and rituximab 375 mg/m2 weekly on cycles 1 and 4. Primary endpoint was the percent of patients with at least a minor response (MR). Twenty-six patients were treated. At least MR was observed in 23/26 patients (88%) (95% CI: 70,98%) with 1 complete response (4%), 1 near-complete response (4%), 15 partial remission (58%), and 6 MR (23%). Using IgM response evaluated by nephlometry, all 26 patients (100%) achieved at least MR or better. The median time to progression has not been reached, with an estimated 1-year event free rate of 79% (95% CI: 53, 91%). Common grade 3 and 4 therapy related adverse events included reversible neutropenia in 12%, anemia in 8%, and thrombocytopenia in 8%. No grade 3 or 4 neuropathy occurred. The combination of weekly bortezomib and rituximab exhibited significant activity and minimal neurological toxicity in patients with untreated WM. Am. J. Hematol., 2010. © 2010 Wiley-Liss, Inc. [source] Effects of anti-CD154 treatment on B cells in murine systemic lupus erythematosusARTHRITIS & RHEUMATISM, Issue 2 2003Xiaobo Wang Objective To determine the immunologic effects of anti-CD154 (CD40L) therapy in the (NZB × NZW)F1 mouse model of systemic lupus erythematosus. Methods Twenty-week-old and 26-week-old (NZB × NZW)F1 mice were treated with continuous anti-CD154 therapy. Mice were followed up clinically, and their spleens were studied at intervals for B and T cell numbers and subsets and frequency of anti,double-stranded DNA (anti-dsDNA),producing B cells. T cell,dependent immunity was assessed by studying the humoral response to the hapten oxazolone. Results IgG anti-dsDNA antibodies decreased during therapy and disease onset was delayed, but immune tolerance did not occur. During treatment, there was marked depletion of CD19+ cells in the spleen; however, autoreactive IgM-producing B cells could still be detected by enzyme-linked immunospot assay. In contrast, few IgG- and IgG anti-dsDNA,secreting B cells were detected. Eight weeks after treatment cessation, the frequency of B cells producing IgG anti-dsDNA antibodies was still decreased in 50% of the mice, and activation and transition of T cells from the naive to the memory compartment were blocked. Anti-CD154 treatment blocked both class switching and somatic mutation and induced a variable period of relative unresponsiveness of IgG anti-dsDNA,producing B cells, as shown by decreased expression of the CD69 marker and failure to generate spontaneous IgG anti-dsDNA,producing hybridomas. Treated mice mounted an attenuated IgM response to the hapten oxazolone and produced no IgG antioxazolone antibodies. Conclusion Anti-CD154 is a B cell,depleting therapy that affects multiple B cell subsets. Activation of both B and T cells is prevented during therapy. After treatment cessation, autoreactive B cells progress through a series of activation steps before they become fully competent antibody-producing cells. The general immunosuppression induced during treatment will need to be taken into account when using B cell,depleting regimens in humans. [source] HHV-6 A- or B-specific P41 antigens do not reveal virus variant-specific IgG or IgM responses in human serumJOURNAL OF MEDICAL VIROLOGY, Issue 3 2002Yunhe Xu Abstract The etiology of multiple sclerosis (MS) remains unknown, but there are indications of a role of human herpesvirus 6 (HHV-6), especially variant A, in the pathogenesis. Higher serum antibody reactivity against an HHV-6 early protein, p41, has been found in MS cases than in controls. The antigen, however, was purified from infected cells with a monoclonal antibody also reactive with a protein (p38) likely to be of cellular origin. To avoid serological crossreactivity with the cellular protein, recombinant p41 proteins from HHV-6A strain GS and HHV-6B strain Z29 were expressed as glutathione-S-transferase fusion proteins (p41-GST), and used as antigens in an enzyme-linked immunosorbent assay (ELISA). p41 variant specific monoclonal antibodies reacted strongly with the respective recombinant proteins. Serum IgM and IgG reactivities with the recombinant p41 antigens were analysed in patients with manifest MS, patients with optic neuritis, patients with other neurological diseases, and in one group of healthy controls. All sera were HHV-6 IgG seropositive by immunofluorescence. The serum IgM or IgG reactivities against the recombinant p41 antigens did not differ significantly between the groups, and the reactivities against the variant A and B antigens were identical. In many samples, the reactivity was very low. The results indicate that p41 is not an optimal target for HHV-6 serology studies, and that the data obtained with the p41 antigen prepared from infected cells (possibly including also p38) should be interpreted with caution. J. Med. Virol. 66:394-399, 2002. © 2002 Wiley-Liss, Inc. [source] Detection of IgM and IgG antibodies to Cryptococcus neoformans proteins in blood donors and HIV patients with active cryptococcosisMYCOSES, Issue 2 2009H. C. Chai Summary The serological responses to Cryptococcus neoformans proteins of blood donors and HIV patients with active cryptococcosis from a tropical region were investigated in this study. Exposure to C. neoformans, an organism ubiquitous in the environment, contributes to the antibody responses observed in the blood donors. IgG responses to cryptococcal proteins were stronger than IgM responses in most sera tested in this study. A 53-kDa cryptococcal protein fragment was identified as the most immunoreactive protein on the IgM immunoblots of both blood donors and patients. Overall, there was no obvious difference in IgG responses of patients when compared with blood donors. Some immunogenic protein fragments (27.5, 76, 78 and 91.5 kDa) were detected at least two times more frequently on IgM immunoblots of patients compared with those of blood donors. It is yet to be investigated whether the proteins identified in this study may have any potential to be used as biomarker for cryptococcosis. [source] Immunological response to cytomegalovirus in congenitally infected neonatesCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2007J. Hassan Summary Cytomegalovirus (CMV) is the most common cause of congenital infection worldwide and occurs as a result of transplacental transmission of the virus. The human neonate is highly susceptible to infection due to a combination of immaturity of the immune system and antigenic inexperience. This study uses the in vivo model of congenital CMV to examine both the humoral and cell-mediated immune responses in vertically infected neonates and their mothers. Ten pairs of matched neonates and their mothers were evaluated for specific IgM responses to three immunodominant CMV antigens: pp38 (pUL80a), pp52 (pUL44) and pp150 (pUL32). In contrast to conventional enzyme immunoassay (EIA) testing for CMV-specific IgM, which found five of the mothers and four of the neonates to be positive, Western immunoblotting showed all 10 adults and nine newborns to be positive. Eight mothers and nine newborns had serological evidence of primary infection. All neonates showed a response to pp38, an assembly protein, nine responded to the pp52 immediate early antigen but only four had reactivity to the pp150 tegument associated protein. Of the mothers, eight had pp38 reactivity, 10 showed a response to the pp52 antigen and seven to the pp150 antigen. T cell-mediated immunity was assessed by measuring cytokines using a multiplex microarray assay. Levels of interferon (IFN)-, were high in both groups [mean ± standard error of the mean (s.e.m.): neonates = 657 ± 238 pg/ml, mothers = 1072 ± 677 pg/ml, pNS]; however, neonates had significantly higher levels of interleukin (IL)-8 (316 ± 136 pg/ml versus 48 ± 28 pg/ml, P < 0·005). Similar levels of IL-2, IL-7, IL-10 and IL-12 were measured in both groups, but levels of IL-1,, IL-1,, IL-4, IL-6 and tumour necrosis factor (TNF)-, were either absent or low. In response to CMV, neonates and adults mount a predominant T helper 1 (Th1) response, as evidenced by the presence of IL-2, IL-8, IL-12 and IFN-, with concomitant lack of IL-4. These findings suggest that the neonate, when presented with infection in utero, is capable of mounting an individual response; however, the lower IFN-, and higher IL-8 levels suggest reduced immune responsiveness when compared to their adult counterparts. [source] | |||||||||||||