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IgG Production (igg + production)
Selected AbstractsNatural killer T cells in families of patients with systemic lupus erythematosus: Their possible role in regulation of IGG productionARTHRITIS & RHEUMATISM, Issue 1 2007Matthew R. J. Green Objective To determine whether there is a link between the frequency of natural killer T (NKT) cells and high levels of IgG in patients with systemic lupus erythematosus (SLE) and their relatives. Methods Blood samples were obtained from patients with SLE, their first-degree relatives, patients with rheumatoid arthritis (RA), and healthy control subjects. The frequency of NKT cells (defined as CD56+ T cells) was expressed as a percentage of total blood lymphocytes. Plasma levels of total IgG and IgM, and IgG antibodies to double-stranded DNA (dsDNA) were determined. Results The frequency of NKT cells was lower in patients with SLE than in control subjects. No such decrease was observed in the relatives of patients with SLE or in patients with RA. High levels of IgG were observed in both patients with SLE and their relatives, while low levels of IgM were observed in these same groups. In relatives of patients with SLE, an inverse correlation between the frequency of NKT cells and IgG levels was observed. Moreover, raised levels of IgG in patients with SLE and their relatives and high levels of IgG anti-dsDNA in patients were associated with low frequencies of NKT cells. Conclusion These results suggest that NKT cells have an important role in the regulation of IgG production, although NKT cells with invariant T cell receptors may not necessarily be involved. NKT cells in the setting of SLE could lack the cytokine stimulus from NK or other cells that is needed to exert control on IgG production. Enhancement of NKT cell activity may provide a novel basis for therapy in SLE. [source] Expression of CD66a in multiple myelomaJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 2 2002Yukihiko Satoh Abstract CD66a is a member of the carcinoembryonic antigen family and has been suggested to function as an intercellular adhesion molecule and cell growth regulator. Expression of CD66a in myeloma cells was examined with mAb TS135 against CD66a transfectants of murine-transformed fibroblasts. The reactivity of mAb TS135 with CD66a, CD66c, and CD66e was revealed. CD66a in myeloma cells was considered to be detectable with this mAb, since CD66c and CD66e are not expressed in them. CD66a was detected in three myeloma cell lines and an IgM-producing B-cell line. In clinical bone marrow specimens, including 18 multiple myeloma, two primary macroglobulinemia, and a case of CLL-like chronic lymphoproliferation with monoclonal IgG production, CD66a and three conventional myeloma cell markers (PCA-1, CD38, and CD56) were examined by indirect immunofluorescence assay. The results showed that 18 out of 21 cases (86%) were CD66a+, and PCA-1 showed the highest correlation with CD66a among conventional markers. Primary macroglobulinemia and chronic lymphoproliferation were also CD66a+. Two-dimensional flow cytometry with mAbs TS135 and CD38 confirmed the reactivity of TS135 with myeloma cells in those bone marrow specimens. The findings suggest that CD66a is expressed in multiple myeloma with high frequency. J. Clin. Lab. Anal. 16:79,85, 2002. © 2002 Wiley-Liss, Inc. [source] Induction of immune responses and prevention of alveolar bone loss by intranasal administration of mice with Porphyromonas gingivalis fimbriae and recombinant cholera toxin B subunitMOLECULAR ORAL MICROBIOLOGY, Issue 6 2007Y. Takahashi Introduction:, Adult periodontitis is initiated by specific periodontal pathogens represented by Porphyromonas gingivalis; however, an effective measure for preventing the disease has not yet been established. In this study, the effectiveness of a vaccine composed of fimbriae of P. gingivalis and recombinant cholera toxin B subunit (rCTB) was evaluated using BALB/c mice. Methods:, Fimbriae and rCTB were co-administered intranasally to BALB/c mice on days 0, 14, 21, and 28. On day 35, mice were sacrificed to determine immunoglobulin levels in serum, saliva, and nasal and lung extracts by enzyme-linked immunosorbent assay. The prevention effect of the vaccine on P. gingivalis -induced periodontitis in mice was evaluated by measuring alveolar bone loss. Results:, The rCTB significantly increased serum immunoglobulin (Ig)A levels when mice were administered with a minimal amount (0.5 ,g) of the fimbrial antigen. The adjuvant effect on serum IgG production was indistinct because the minimal amount of the antigen still induced a large amount of IgG. In contrast to systemic responses, a fimbria-specific secretory IgA response was strongly induced by co-administration of rCTB and 0.5 ,g fimbriae; the same amount of the antigen alone scarcely induced a response. Histopathological examination revealed IgA-positive plasma cells in the nasal mucosal tissue but no observable mast cells in the area. In addition, nasal administration of the fimbrial vaccine significantly protected the mice from P. gingivalis -mediated alveolar bone loss. Conclusion:, Nasal vaccination with a combination of fimbriae and rCTB can be an effective means of preventing P. gingivalis -mediated periodontitis. [source] Antikörper-Nachweis bei invasiver AspergilloseMYCOSES, Issue 2004R. Kappe Aspergillus; aspergillosis; invasive infection; antibody detection Zusammenfassung Der Stellenwert von Aspergillus -Antikörpertesten zur Diagnostik der invasiven Aspergillose (IA) ist unklar. In zwei Studien wurden drei verschiedene Antikörperteste an Patienten mit gesicherter IA evaluiert: (i) kommerzieller Hämagglutinationstest (HAT), (ii) kommerzieller Enzymimmunoassay (EIA) IgG, IgM, IgA und (iii) ein experimenteller Mitogillin EIA IgG, IgM, IgA. In der ersten Studie wurden 99 Serumproben von 26 Patienten mit IA und 22 Serumproben von 22 Kontrollpatienten mit allen drei Tests untersucht. 10 von 26 Patienten (38%) waren in mindestens einem Antikörpertest positiv. Die höchste Sensitivität wies der IgG-Nachweis in beiden EIA-Tests auf (22 bzw. 21%), der HAT erreichte eine Sensitivität von 8%. IgM-Antikörper wurden nur bei zwei Patienten, IgA-Antikörper bei keinem Patienten nachgewiesen. Die Spezifität des HAT betrug 85%, des IgG-EIA 72%. Bei zwei Patienten mit gesicherter bzw. wahrscheinlicher IA war der Antikörpernachweis der einzig positive Labortest. In der zweiten Studie wurden retrospektiv die Ergebnisse von 60 Patienten mit gesicherter IA untersucht. 14 Patienten (23%) wiesen einen positiven Antikörpernachweis im EIA und/oder HAT auf. Die Untersuchung des zeitlichen Verlaufs der Antikörper zeigte, daß die IgG-Antikörperbildung bei immunsupprimierten Patienten durchschnittlich 10,8 Tage nach der Diagnosestellung der IA einsetzte. Schlußfolgerungen Aspergillus -Antikörper waren bei ca. 23% der Patienten mit invasiver Aspergillose nachweisbar. Die Antikörperbildung setzte bei erfolgreich therapierten immunsupprimierten Patienten durchschnittlich 10,8 Tage nach Beginn der Infektion ein. Insbesondere der IgG-Antikörpernachweis im EIA-Format kann hilfreich für die Diagnose-Sicherung und Verlaufskontrolle sein. Summary The clinical significance of Aspergillus antibody assays for the diagnosis of invasive aspergillosis (IA) is unclear. In two studies, three different antibody assays were evaluated with patients suffering from proven IA: (i) a commercial haemagglutination test (HAT), (ii) a commercial enzyme immunoassay (EIA) for IgG, IgM, and IgA, and (iii) an experimental mitogillin enzyme immunoassay for IgG, IgM, and IgA. In the first study, 99 serum samples from 26 patients with IA and 22 serum samples from 22 control patients were tested with all the three tests. Ten of the 26 patients (38%) reacted positively in at least one antibody assay. The highest sensitivity was generated by the detection of IgG using the EIA formats (22 and 21%, respectively), the HAT had a sensitivity of 8%. IgM type antibodies were detected in only two patients; no IgA type antibodies were detected. The specificities of the IgG EIA and the HAT were 72 and 85%, respectively. Antibody detection was the single positive laboratory test in two patients with proven and probable IA. In the second study, antibody test results of 60 patients with proven IA were retrospectively evaluated. Fourteen patients (23%) tested positive in the EIA and/or in the HAT. Investigations of the antibody levels in individual immunocompromised patients over time revealed that IgG production started after a mean of 10.8 days after diagnosis of IA. To conclude, antibodies against Aspergillus were detected in 23% of patients with IA. The antibody production started in successfully treated immunosuppressed patients after a mean of 10.8 days after the onset of infection. In particular, the detection of IgG-antibodies with an EIA can be useful for the confirmation of the diagnosis of IA and for the monitoring of the treatment of IA. [source] B-cell dysfunction and depletion using mycophenolate mofetil in a pediatric combined liver and kidney graft recipientPEDIATRIC TRANSPLANTATION, Issue 1 2001R. Ganschow Abstract: The use of mycophenolate mofetil (MMF) in combination with cyclosporin A (CsA) and steroids is well established after kidney transplantation (Tx) in children. A 9-yr-old girl with primary hyperoxaluria type 1 and systemic oxalosis underwent a combined kidney and liver Tx at our institution. The post-operative immunosuppression consisted of CsA, prednisolone, and MMF. Four weeks post-transplant the girl suffered from a severe urinary tract infection caused by Pseudomonas aeruginosa, when the serum immunoglobulin G (IgG) concentration was found to be critically low (< 1.53 g/L). Additionally, there was an isolated B-cell depletion (240/µL) at that time. In the following course, the B-cell count was significantly diminished until the MMF was stopped 13 weeks post-transplant. As a result of the very low serum IgG concentration, intravenous immunoglobulin (IVIG) substitution was necessary. There was no significant loss of immunoglobulins in the ascites and urine and no other medication with possible side-effects on B cells was given. We suggest that MMF can lead to suppressed IgG production by B cells and can cause a defective differentiation into mature B cells. In vitro studies demonstrated these effects of MMF on B cells, but no in vivo cases of this phenomenon have been reported. B-cell counts and serum IgG concentrations returned to normal values after discontinuing the MMF. As we can assume that the observed B-cell dysfunction and depletion were MMF related, we suggest that serum IgG concentrations should be monitored when MMF is used after solid-organ Tx. [source] Effect of intravenous immunoglobulins on in vitro immunoglobulin formation in patients with antibody immunodeficiencyAPMIS, Issue 3 2002Zuzana Krátká Seventeen patients with antibody immunodeficiency (9 subclass IgG immunodeficiencies, 8 common variable immunodeficiencies) and clinically unambiguous immunodeficiency symptomatology participated in the study with 14 healthy donors. The patients were given regular intravenous immunoglobulin (IVIG) infusions with Endobulin. Blood was collected before and 7 days after infusion of the usual IVIG dose. Mononuclear cells were isolated from peripheral blood (PBMC) of the patients by Ficoll-Paque gradient centrifugation. In order to monitor the ability to inhibit or activate polyclonal production of immunoglobulins in vitro, we stimulated PBMC with pokeweed mitogen (PWM) and with a mixture of pokeweed mitogen + concanavalin A (PWM+ConA). We found that an immunomodulatory effect of IVIG persists in vitro even one week after infusion. Polyclonally stimulated IgA and IgM production was suppressed by IVIG infusion mainly in patients with IgG subclass deficiency. The positive stimulatory effect of IVIG infusion on IgG production was confirmed. The IgG production increased in vitro after infusion in both groups of patients and was significantly higher than in healthy donors. Co-stimulation of PWM-stimulated cells with ConA caused an inhibition of immunoglobulin release in normal healthy donors. The infusion supported the capability of ConA to inhibit IgG production in vitro in patients with IgG subclass deficiency, whereas an increase in IgG production with PWM+ConA stimulation after infusion was found in CVID patients. We assume that lymphocytes activated by ConA produce suppressive factors, which can be affected by the IVIG infusion and which can have both an immunostimulatory and an immunosuppressive effect. [source] The critical role of kinase activity of interleukin-1 receptor,associated kinase 4 in animal models of joint inflammationARTHRITIS & RHEUMATISM, Issue 6 2009Magdalena Koziczak-Holbro Objective We have previously reported that the kinase activity of interleukin-1 receptor,associated kinase 4 (IRAK-4) is important for Toll-like receptor and interleukin-1 receptor signaling in vitro. Using mice devoid of IRAK-4 kinase activity (IRAK-4 KD mice), we undertook this study to determine the importance of IRAK-4 kinase function in complex disease models of joint inflammation. Methods IRAK-4 KD mice were subjected to serum transfer,induced (K/BxN) arthritis, and migration of transferred spleen lymphocytes into joints and cartilage and bone degradation were assessed. T cell response in vivo was tested in antigen-induced arthritis (AIA) by measuring the T cell,dependent antigen-specific IgG production and frequency of antigen-specific T cells in the spleen and lymph nodes. T cell allogeneic response was tested in vitro by mixed lymphocyte reaction (MLR). Results Lipopolysaccharide-induced local neutrophil influx into subcutaneous air pouches was impaired in IRAK-4 KD mice. These mice were also protected from inflammation in the K/BxN and AIA models, as shown by reduced swelling of joints. Histologic analysis of joints of K/BxN serum,injected mice revealed that bone erosion, osteoclast formation, and cartilage matrix proteoglycan loss were reduced in IRAK-4 KD mice. Assessment of T cell response by MLR, by frequency of antigen-specific clones, and by production of antigen-specific IgG did not reveal substantial differences between IRAK-4 KD and wild-type mice. Conclusion These results demonstrate that IRAK-4 is a key component for the development of proarthritis inflammation, but that it is not crucial for T cell activation. Therefore, the kinase function of IRAK-4 appears to be an attractive therapeutic target in chronic inflammation. [source] Natural killer T cells in families of patients with systemic lupus erythematosus: Their possible role in regulation of IGG productionARTHRITIS & RHEUMATISM, Issue 1 2007Matthew R. J. Green Objective To determine whether there is a link between the frequency of natural killer T (NKT) cells and high levels of IgG in patients with systemic lupus erythematosus (SLE) and their relatives. Methods Blood samples were obtained from patients with SLE, their first-degree relatives, patients with rheumatoid arthritis (RA), and healthy control subjects. The frequency of NKT cells (defined as CD56+ T cells) was expressed as a percentage of total blood lymphocytes. Plasma levels of total IgG and IgM, and IgG antibodies to double-stranded DNA (dsDNA) were determined. Results The frequency of NKT cells was lower in patients with SLE than in control subjects. No such decrease was observed in the relatives of patients with SLE or in patients with RA. High levels of IgG were observed in both patients with SLE and their relatives, while low levels of IgM were observed in these same groups. In relatives of patients with SLE, an inverse correlation between the frequency of NKT cells and IgG levels was observed. Moreover, raised levels of IgG in patients with SLE and their relatives and high levels of IgG anti-dsDNA in patients were associated with low frequencies of NKT cells. Conclusion These results suggest that NKT cells have an important role in the regulation of IgG production, although NKT cells with invariant T cell receptors may not necessarily be involved. NKT cells in the setting of SLE could lack the cytokine stimulus from NK or other cells that is needed to exert control on IgG production. Enhancement of NKT cell activity may provide a novel basis for therapy in SLE. [source] Production and Molecular Characterization of Clinical Phase I Anti-Melanoma Mouse IgG3 Monoclonal Antibody R24BIOTECHNOLOGY PROGRESS, Issue 5 2001Sven E. Kemminer R24 is a mouse IgG3 monoclonal antibody (mab) that reacts with the ganglioside GD3 expressed by cells of neuroectodermal origin. The anti-tumor activity of R24 has been demonstrated in initial phase I and pilot trials in patients suffering from metastatic melanoma. The purpose of this study was to investigate the biotechnological production and particularly the glycosylation of this clinically important antibody. Growth, metabolism, and IgG production of R24 secreting hybridoma cells were analyzed on 1 L bioreactor bench scale using repeated-batch mode. The amount of 57 mg of pure mab was obtained from 1.6 L crude supernatant by protein A chromatography. Western blot binding assays with sugar-specific lectins revealed glycosylation of the heavy chains, whereas no carbohydrates were detectable on the light chains. Because glycosylation is essential for antibody effector functions in vivo (such as complement fixation or binding to macrophage Fc receptors), mab R24 was subjected to both enzymatic deglycosylation using PNGase F and chemical deglycosylation by hydrazinolysis. Released glycans were structurally characterized by high pH anion exchange chromatography with pulsed amperometric detection (HPAEC-PAD), matrix assisted laser desorption ionization time-of-flight (MALDI-TOF), and electrospray ionization quadrupole time-of-flight (ESI-QTOF) mass spectrometry. Six major biantennary chains of the complex glycosylation phenotype were found with variations in galactosylation and core fucosylation. The predominant N-linked structure, indicating the high degree of agalactosyl glycoforms, was the agalacto biantennary chain with a relative percentage of 57% (51% core-fucosylated, 6% nonfucosylated). The second most abundant oligosaccharide was the monogalacto biantennary chain amounting to 30% (26% core- and 4% nonfucosylated). The antibody contained 0.46 ,g sialic acid per mg protein, which splits into 0.243 ,g Neu5Gc and 0.217 ,g Neu5Ac, corresponding to a Neu5Ac:Neu5Gc ratio of 1:1.06. Furthermore, the antigen specificity of R24 was determined by immunodetection of GD3 on thin-layer chromatograms, and real time GD3-antibody binding interactions were measured with an optical biosensor (BIAcore). From the structural data obtained in this study it is concluded that glycosylation of the antibody may be important in the clinical outcome of targeted anti-cancer immunotherapy. [source] A mouse model of pemphigus vulgaris by adoptive transfer of naive splenocytes from desmoglein 3 knockout miceBRITISH JOURNAL OF DERMATOLOGY, Issue 2 2004M. Aoki-Ota Summary Background, Pemphigus vulgaris (PV) is an autoimmune blistering disease caused by antidesmoglein3 (anti-Dsg3) IgG autoantibodies. Recently, we developed a PV mouse model by adoptive transfer of splenocytes from recombinant Dsg3-immunized Dsg3,/, mice to Rag2,/, immunodeficient mice that expressed Dsg3. Objectives, We determined whether the adoptive transfer of naive splenocytes from nonimmunized Dsg3,/, mice induces the anti-Dsg3 IgG production and the PV phenoytpe in recipient mice. Methods, We adoptively transferred naive Dsg3,/, splenocytes into Rag2,/, mice and compared their PV phenoytpe with those mice receiving immunized Dsg3,/, splenocytes. The numbers of splenocytes and their subpopulations required for anti-Dsg3 IgG production were examined. Results, Mice that received naive Dsg3,/, splenocytes produced anti-Dsg3 IgG, which bound to keratinocyte cell surfaces in vivo, and developed the PV phenotype, including oral erosions with suprabasilar acantholysis. Antibody production and the appearance of the PV phenotype were delayed by approximately 2 weeks in mice that received naive splenocytes compared with mice that received immunized splenocytes. However, once the PV phenotypes developed, there were no apparent differences in disease severity between the two models. Interestingly, the anti-Dsg3 IgG titres were significantly lower in mice that received naive splenocytes than in mice that received immunized splenocytes, suggesting that the former antibodies were more potent than the latter. The frequency of anti-Dsg3 IgG production depended on the number of transferred naive splenocytes. Both CD4+ T cells and B220+ B cells from naive Dsg3,/, mice were essential for the production of anti-Dsg3 IgG antibodies. Conclusions, Dsg3-specific naive lymphocytes in Dsg3,/, mice can be primed and activated by the endogenous Dsg3 in recipient mice to produce pathogenic anti-Dsg3 IgG without active immunization. This approach using naive lymphocytes provides a unique model to dissect immunological mechanisms of tolerance against peripheral autoimmune targets. [source] Increased cerebrospinal fluid chitotriosidase index in patients with multiple sclerosisACTA NEUROLOGICA SCANDINAVICA, Issue 5 2010M. M. Verbeek Verbeek MM, Notting EA, Faas B, Claessens-Linskens R, Jongen PJH. Increased cerebrospinal fluid chitotriosidase index in patients with multiple sclerosis. Acta Neurol Scand: 2010: 121: 309,314. © 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objective,,, To investigate chitotriosidase (CTTS) activity in serum and cerebrospinal fluid (CSF) in multiple sclerosis (MS) patients in relation to disease course and CSF markers for immune activation or inflammation. Materials and methods,,, We studied 80 patients with relapsing,remitting MS (RRMS), 24 with secondary progressive MS (SPMS), 20 with primary progressive MS (PPMS) and 29 patients with other neurological disorders (OND). We measured CTTS activity and studied the correlation with CSF mononuclear cell count (MNC) and intrathecal IgG production. Results,,, CTTS activity was significantly higher in CSF, but not in serum, from the total MS group compared with OND and controls. In RRMS and SPMS CTTS, index was increased compared with controls (RRMS, 0.10 ± 0.21; SPMS, 0.10 ± 0.15; controls, 0.021 ± 0.020), but not in PPMS (0.061 ± 0.052). CTTS index was higher in MS patients with elevated MNC or CSF-restricted oligoclonal IgG bands than in MS patients without these CSF findings. Conclusions,,, CTTS index is elevated in RRMS and SPMS. The CTTS index is related to CSF markers of inflammation or immune activation. [source] | ||||||||||