Immunoglobulin M Concentrations Research Articles

Serum Immunoglobulin M Concentration Varies with Triglyceride Levels in an Adult Population: Tianjin Chronic Low-Grade Systemic Inflammation and Health (TCLSIHealth) Cohort Study.

Persistent low-grade inflammation is thought to underlie the pathogenesis of many chronic diseases, such as cardiovascular diseases and metabolic syndrome. Autoimmunity is correlated with increased levels of chronic low-grade inflammation, and immunoglobulin M (IgM) is reactive to autoantigens and believed to be important for autoimmunity. Triglyceride (TG) is fatty acid carrier and initiator of oxidative stress, and it has been hypothesized that TG stimulates B cells to secrete IgM. However, few studies have investigated the relationship between TG and IgM in human populations. We designed a cross-sectional and prospective cohort study to evaluate how serum TG levels are related to IgM concentration. Participants were recruited from Tianjin Medical University General Hospital-Health Management Centre. Both a baseline cross-sectional (n = 10,808) and a prospective assessment (n = 2,615) were performed. Analysis of covariance was used in the cross-sectional analysis. After multiple adjustments for confounding factors, serum IgM level in the highest quartile of TG in males was significantly higher than levels in lower quartiles (P <0.05). There was no significant difference between the four quartiles in females (P = 0.91). In follow-up analysis, a multiple linear regression model showed a significant and positive correlation between changes in IgM levels and changes of TG concentration in males (P = 0.04, standard β coefficient = 0.882). This cross-sectional and cohort study is the first to show that serum concentration of IgM varies with TG levels in adult male populations. Further research is needed to explore the mechanism by which TG leads to increased IgM concentration.

Waldenström macroglobulinemia: 2015 update on diagnosis, risk stratification, and management.

Waldenström macroglobulinemia (WM) is a lymphoplasmacytic lymphoma with immunoglobulin M (IgM) monoclonal protein. Clinical features include anemia, thrombocytopenia, hepatosplenomegaly, lymphadenopathy, and rarely hyperviscosity. Presence of IgM monoclonal protein associated with ≥10% clonal lymphoplasmacytic cells in bone marrow confirms the diagnosis. The L265P mutation in MYD88 is detectable in more than 90% of patients. Age, hemoglobin level, platelet count, β2 microglobulin, and monoclonal IgM concentrations are characteristics required for prognosis. Not all patients who fulfill WM criteria require therapy; these patients can be observed until symptoms develop. Rituximab-based therapy is used in virtually all US patients with WM and can be combined with alkylating agent or purine nucleoside analog (or both). The preferred Mayo Clinic nonstudy therapeutic induction is rituximab, cyclophosphamide, and dexamethasone. Future stem cell transplantation should be considered in induction therapy selection. Management of Refractory Disease: Bortezomib, thalidomide, everolimus, ibrutinib, carfilzomib, lenalidomide, and bendamustine have all been shown to have activity in WM. Given WM's natural history, reduction of complications will be a priority for future treatment trials.

Effect of moderate and vigorous physical exercises on serum immunoglobulins G and M of healthy male individuals in Anambra State

Background: Alterations in immunoglobulin levels have been implicated in physical exercises, of varying intensity and frequency. This has been largely attributed to decline in physical exercise thus predisposing many to various chronic ailments. The objective of this study was to determine and compare results of the effect of moderate and vigorous exercises on Immunoglobulin G (IgG) and Immunoglobulin M (IgM) before exercise, two weeks after exercise and four weeks after exercise. Methods: Serum concentration of IgG and IgM of both vigorous exercise group (50 male individuals who played football for 2 hours daily for 5 days/week) and moderate exercise group (50 male individuals who played football for 30 minutes daily for 3 days/week) were determined using Enzyme Linked Immunosorbent Assay (ELISA) method. All data were expressed as Mean ± Standard Deviation (SD) and analyzed with Analysis of Variance (ANOVA) while multiple comparisons were done using Post Hoc test. Pearson’s correlation coefficient was used for correlational analysis. Results: In the moderate exercise group, mean BMI was reduced while IgG was increased but not significantly at P<0.05 all through. Mean serum IgM was increased significantly at P<0.05 mostly 4 weeks after exercise as compared with the results before exercise. In the vigorous exercise group, mean BMI was decreased while mean serum IgG was increased but not significantly at P<0.05. Mean serum IgM was significantly increased all through at P<0.05. Conclusions: Vigorous physical exercise can substantially increase fitness, but, moderate physical exercise, when performed frequently and over an extended period, produces enhanced immune response.

Circadian type, chronic fatigue, and serum IgM in the shift workers of an industrial organization.

Background:Night shift workers are more vulnerable to immune-related diseases. Immunoglobulin M (IgM) is a potent activator of complement, and complement has a crucial role in defense against bacterial infections. Circadian type is known as an effective agent on vulnerability and adaptation with shift work due to non-compliance with shift stress. The objective of this study was to investigate the correlation of circadian type and chronic fatigue with the serum concentration of IgM in a group of shift workers.Materials and Methods:This cross-sectional study was performed in an industrial organization in Isfahan, Iran. The study population consisted of 221 male employees working at night shifts who were selected by random cluster sampling. The following questionnaires were used: composite morningness (Torsvall and Akerstedt), circadian type (Folkard), and chronic fatigue (Barton and colleagues). The serum concentration of IgM was measured by the nephelometric method. The data were analyzed with the Pearson coefficient correlation and the path analysis for finding the pattern of the structural equations to evaluate the direct and indirect relationships between variables, using the SPSS 15 and LISREL 8.5 statistical software.Results:Significant correlation was documented between morningness, flexibility, languidness, and chronic fatigue with the serum concentration of IgM (P < 0.01).Conclusion:The results showed that the shift workers with morningness and languidness experienced more problems during the working hours due to more tiredness, and had decreased serum concentration of IgM. Correct management of shift work may attenuate fatigue in workers and also improve many health issues experienced by the shift workers.

Relationship between the concentration of anti-polyethylene glycol (PEG) immunoglobulin M (IgM) and the intensity of the accelerated blood clearance (ABC) phenomenon against PEGylated liposomes in mice.

PEGylation, which is the surface modification of nanocarriers with polyethylene glycol (PEG), has increased the circulation time and reduced the immunogenic responses to nanocarriers. However, many reports have demonstrated that the intravenous injection of sterically stabilized PEGylated liposome (SL) causes an accelerated blood clearance (ABC) of subsequent doses via anti-PEG immunoglobulin M (IgM)-mediated complement activation. In the present study, the relationships between serum anti-PEG IgM concentration, the intensity of complement activation and the hepatic clearance of SL were quantitatively investigated for their role in the ABC phenomenon. Interestingly, with increasing serum anti-PEG IgM concentrations, the intensity of complement activation increased linearly, while the intensity of the hepatic clearance of SL was increased and then saturated. In addition, only 15-17% of anti-PEG IgM in blood circulation induced by SL at different doses was associated with a second dose SL. The present results indicate that it is the hepatic uptake of SL that is the limiting step in the ABC phenomenon, rather than the association of anti-PEG IgM to the SL and a subsequent complement activation.

Effects of High-Protein Diet and/or Resveratrol Supplementation on the Immune Response of Irradiated Rats.

We investigated the effects of a high-protein diet and resveratrol supplementation on immune cells changes induced by abdominal irradiation in rats. Female Wistar rats were divided into 5 groups: 1) control diet, 2) control diet with irradiation 3) 30% high-protein diet with irradiation, 4) normal diet with resveratrol supplementation and irradiation, and 5) 30% high-protein diet with resveratrol supplementation and irradiation. We measured blood protein and albumin concentrations, lipid profiles, white blood cell (WBC) counts, proinflammatory cytokine production, and splenocyte proliferation in rats that had been treated with a 17.5 Gy dose of radiation 30 days prior. A high-protein diet affected plasma total cholesterol and very low density lipoprotein-cholesterol levels, which were increased by the radiation treatment. In addition, the lymphocyte percentage and immunoglobulin M (IgM) concentration were increased, and the neutrophil percentage was decreased in rats fed a high-protein diet. Resveratrol supplementation decreased the triglyceride (TG) level, but increased the IgM concentration and splenocyte proliferation. Proinflammatory cytokine production was lower in rats fed a high-protein diet supplemented with resveratrol than in rats fed a control diet. The results of the present study indicate that high-protein diets, with or without resveratrol supplementation, might assist with recovery from radiation-induced inflammation by modulating immune cell percentages and cytokine production.

Production of a monoclonal antibody against serum immunoglobulin M of South American camelids and assessment of its suitability in two immunoassays

A monoclonal antibody (mAb) was produced against immunoglobulin M (IgM) of South American camelids. A single radial immunodiffusion (SRID) assay and a competitive enzyme-linked immunosorbent assay (ELISA) were developed to measure IgM in serum samples. Isotype and specificity of the mAb were assessed. The performance of the SRID assay was preliminarily evaluated in terms of working range, plate stability over a 4-week period, and initial intra- and interassay variation. The concentration of IgM was determined in 55 samples by SRID assay and ELISA, and results were not significantly different by t-test (0.64 ± 0.19 mg/ml for the SRID assay, and 0.58 ± 0.24 mg/ml for ELISA; P = 0.1489). The mAb was shown to be stable over the 4-week evaluation period, and the SRID assay was reproducible when tested in triplicate for intra-assay variability and in quadruplicate for interassay variability, with a percentage coefficient of variation of less than or equal to 5%. Also, the SRID assay proved to be sensitive enough to measure IgM levels in undiluted serum samples, and had a good correlation with ELISA. The current study is intended to submit a preliminary report of a mAb against IgM of South American camelids, and suggest the future potential of the mAb developed for diagnostic application, including use in the SRID assay.

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.

Immunoglobulin M, C-Reactive Protein and Complement Activation in Rat Hepatic Ischemia-Reperfusion Injury

Background: Ischemia-reperfusion (I/R) models have shown that C-reactive protein (CRP) and immunoglobulin M (IgM) are involved in complement activation. Binding of CRP and IgM to damaged cell membranes initiates complement activation and aggravates I/R injury in various organs. However, the time course of CRP- and IgM-mediated complement activation and the relation to hepatocellular injury and inflammation in liver I/R are unknown. Aim: To evaluate the time course of IgM- and CRP-related complement activation and the relation to hepatocellular injury and inflammation in a hepatic I/R rat model. Methods: Male Wistar rats were allocated to (1) five groups of animals exposed to 60 min of partial ischemia (70%) induced via clamping of the left segmental portal triad, followed by 0, 3, 6, 12 or 24 h of reperfusion (n = 6 in each group); (2) five groups of sham-operated animals with corresponding reperfusion times (n = 5), and (3) a control group sacrificed before ischemia (n = 5). Hepatocellular injury, inflammatory response, rat plasma CRP and IgM levels and immunohistochemical depositions of CRP, IgM and C3 were assessed for each group. Results: Histopathological injury scores of hematoxylin and eosin sections of ischemic liver lobes demonstrated increasing values throughout the reperfusion time with a peak at 12 h. Plasma aminotransferases (alanine aminotransferase and aspartate aminotransferase) significantly increased after 3 h of reperfusion, peaking at 6 h (3,100 ± 800 U/l; p < 0.05). Hepatic neutrophil influx significantly increased from 3 to 6 h of reperfusion (p < 0.05) and demonstrated the highest value at 12 h (1.1 ± 0.2 U/mg of protein). Plasma IL-6 levels in the ischemia groups showed peak values after 6 h of reperfusion, decreasing significantly thereafter (p < 0.05). Plasma CRP values reached highest levels after 3 h of reperfusion (mean 91 ± 5% of control pool), decreasing significantly thereafter. Rat IgM concentrations in plasma did not significantly change throughout the reperfusion time. Immunohistochemical depositions of IgM, CRP and C3 in ischemic lobes demonstrated a similar pattern in time, reaching maximum values at 12 h of reperfusion. The percentages of depositions of CRP and IgM were significantly correlated [r(S) = 0.569; p < 0.001; Spearman test]. The time course of C3 and CRP depositions throughout reperfusion and C3 and IgM staining were significantly similar [r(S) = 0.797 and r(S) = 0.656, respectively; p < 0.0001; ANOVA]. Conclusions: CRP and IgM depositions demonstrate a parallel time course throughout the reperfusion to hepatocellular damage, inflammatory response and activated complement deposition in this rat hepatic I/R model. Furthermore, the time course of CRP and IgM depositions was significantly similar to that of activated complement depositions.

Waldenström macroglobulinemia: 2013 update on diagnosis, risk stratification, and management

Waldenström macroglobulinemia (WM) is a lymphoplasmacytic lymphoma with immunoglobulin M (IgM) monoclonal protein. Clinical features include anemia, thrombocytopenia, hepatosplenomegaly, and lymphadenopathy. The presence of IgM monoclonal protein associated with ≥10% clonal lymphoplasmacytic cells in bone marrow confirms the diagnosis. Age, hemoglobin level, platelet count, β2 microglobulin, and monoclonal IgM concentrations are characteristics required for prognosis. Not all patients who fulfill WM criteria require therapy; these patients can be observed until symptoms develop. Rituximab-based therapy is used in virtually all US patients with WM and can be combined with alkylating agent or purine nucleoside analog (or both). The preferred Mayo Clinic nonstudy therapeutic induction is rituximab, cyclophosphamide, and dexamethasone. Future stem cell transplantation should be considered in induction therapy selection. Bortezomib, thalidomide, everolimus, lenalidomide, and bendamustine have all been shown to have activity in WM. Given WM's natural history, reduction of complications will be a priority for future treatment trials.

Intestinal IgA+ Cell Numbers as well as IgA, IgG, and IgM Contents Correlate with Mucosal Humoral Immunity of Broilers During Supplementation with High Fluorine in the Diets

Fluoride (F), a well-recognized harmful substance, is easily absorbed by the intestinal mucosa. The intestinal mucosal immune system is equipped with unique innate and adaptive defense mechanisms that provide a first line of protection against infectious agents. Meanwhile, immunoglobulins are the major secretory products of the adaptive immune system and their levels can be a strong indicator of a disease or condition. In this study, therefore, we investigated the effects of high dietary fluorine on the numbers of immunoglobulin A-positive (IgA(+)) cells in the lamina propria of intestines (duodenum, jejunum and ileum) by immunohistochemistry as well as on the contents of immunoglobulin A (IgA), immunoglobulin G (IgG), and immunoglobulin M (IgM) in the mucosa of intestines (duodenum, jejunum, and ileum) by enzyme-linked immunosorbent assay (ELISA). A total of 280 1-day-old healthy avian broilers were randomly divided into four groups and fed on a corn-soybean basal diet as control diet (fluorine 22.6 mg/kg) or the same basal diet supplemented with 400, 800, and 1,200 mg/kg fluorine (high fluorine groups I, II, and III) in the form of sodium fluoride (NaF) for 42 days. The experimental data showed that the numbers of IgA(+) cells as well as the IgA, IgG, and IgM contents were significantly decreased (P < 0.01 or P < 0.05) in the high fluorine groups II and III when compared with those of the control group. It was concluded that dietary fluorine in the range of 800-1,200 mg/kg significantly reduced the numbers of the IgA(+) cells and the contents of aforementioned immunoglobulins in the intestines (duodenum, jejunum, and ileum) of broilers, which could finally impact the mucosal humoral immune function in the intestines by a way that reduces the lymphocyte population and/or lymphocyte activation.

Decreased IgA+ B Cells Population and IgA, IgG, IgM Contents of the Cecal Tonsil Induced by Dietary High Fluorine in Broilers

Fluoride is an environmental and industrial pollutant that affects various organs in humans and animals. The cecal tonsil is an important component of the mucosal immune system and performs important and unique immune functions. In the present study, we investigated the effects of dietary high fluorine on the quantities of IgA+ B cells in the cecal tonsil by immunohistochemistry, and the immunoglobulin A (IgA), immunoglobulin G (IgG) and immunoglobulin M (IgM) contents in the cecal tonsil by ELISA. A total of 280 one-day-old avian broilers were divided into four groups and fed on a corn-soybean basal diet as control diet (fluorine 22.6 mg/kg) or the same diet supplemented with 400, 800 and 1,200 mg/kg fluorine (high fluorine groups I, II and III) in the form of sodium fluoride, respectively, throughout a 42-day experimental period. The results showed that the quantities of IgA+ B cells were lower (p < 0.05 or p < 0.01) and the IgA, IgG, and IgM contents were decreased (p < 0.05 or p < 0.01) in high fluorine groups II and III in comparison with those of control group. It was concluded that dietary fluorine, in the 800–1,200 mg/kg range, could reduce the numbers of the IgA+ B cells and immunoglobulin contents in the cecal tonsil, implying the local mucosal immune function was ultimately impacted in broilers.

Waldenström Macroglobulinemia: 2012 update on diagnosis, risk stratification, and management

Waldenström macroglobulinemia (WM) is a lymphoplasmacytic lymphoma with immunoglobulin M (IgM) monoclonal protein. Clinical features include anemia, thrombocytopenia, hepatosplenomegaly, and lymphadenopathy. Presence of IgM monoclonal protein associated with ≥10% clonal lymphoplasmacytic cells in bone marrow confirms the diagnosis. Age, hemoglobin level, platelet count, β(2) microglobulin, and monoclonal IgM concentrations are characteristics required for prognosis. Not all patients who fulfill WM criteria require therapy; these patients can be observed until symptoms develop. Rituximab-based therapy is used in virtually all US patients with WM and can be combined with alkylating agent or purine nucleoside analog (or both). The preferred Mayo Clinic nonstudy therapeutic induction is rituximab, cyclophosphamide, and dexamethasone. Future stem-cell transplantation should be considered in induction therapy selection. Bortezomib, thalidomide, lenalidomide, and bendamustine have all been shown to have activity in WM. Given WM's natural history, reduction of complications will be a priority for future treatment trials.

Levels of Immunoglobulin Classes Are Not Associated with Severity of HIV Infection in Nigerian Patients

The serum concentrations of immunoglobulin G (IgG), immunoglobulin A (IgA), immunoglobulin M (IgM), total protein and albumin were measured in 35 Human Immunodeficiency Virus—positive, HAART (highly active antiretroviral therapy) na?ve subjects attending the PEPFAR (President's Emergency Plan for AIDS relief) clinic, University College Hospital, Ibadan and in 30 apparently healthy control subjects to assess the relationship between serum protein, immunoglobulin concentrations and laboratory indices of HIV disease (CD4 cell counts and viral load). Serum IgG (1008.6 ± 530.7 mg/dl), IgA (170.4 ± 69 mg/dl) and total protein (9.9 ± 1.7 g/dl) levels were higher among HIV positive subjects compared with mean values in healthy subjects (549.8 ± 193.8 mg/dl, 106.8 ± 26.4 mg/dl and 7.8 ± 0.5 g/dl respectively). The median serum IgM concentration (131mg/dl) was significantly higher in HIV positive subjects compared with 35 mg/dl in healthy controls (p 200 cells/μL. There was also no statistically significant correlation observed between viral load and serum immunoglobulin levels.

Isolation and characterization of immunoglobulin M of Asian sea bass, Lates calcarifer and its level in serum

Asian sea bass immunoglobulin M (IgM) was purified from the sera of Lates calcarifer by affinity chromatography. Analysis of the purified IgM on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) under reducing and non-reducing conditions revealed that the sea bass IgM was a tetrameric protein with a molecular weight of 896 kDa; it contained an equimolar heavy chain and light chain with molecular weight of 83 kDa and 27 kDa respectively. However, besides the covalently linked tetrameric IgM, noncovalently linked tetramer dissociated into dimeric and monomeric forms also demonstrated by non-reducing SDS-PAGE. Carbohydrate moieties were found to be linked with both heavy and light chains. A polyclonal rabbit anti-Asian sea bass IgM was prepared which showed a specific reaction of anti-fish IgM antibody with IgM of sea bass. Sea bass IgM concentration was determined in the serum by indirect ELISA. The average IgM concentration in the sera of the healthy sea bass was 5.4±1.8 mg ml−1; it amounted to 16.7% of the total serum protein.

Waldenström macroglobulinemia: 2011 update on diagnosis, risk stratification, and management

Waldenström macroglobulinemia (WM) is a lymphoplasmacytic lymphoma with immunoglobulin M (IgM) monoclonal protein. Clinical features include anemia, thrombocytopenia, hepatosplenomegaly, and lymphadenopathy. Presence of IgM monoclonal protein associated with 10% clonal lymphoplasmacytic cells in bone marrow confirms the diagnosis. Age, hemoglobin level, platelet count, b2-microglobulin, and monoclonal IgM concentrations are characteristics required for prognosis. Not all patients who fulfill WM criteria require therapy; these patients can be observed until symptoms develop. Rituximab-based therapy is used in virtually all US patients with WM and can be combined with alkylating agent or purine nucleoside analogue, or both. The preferred Mayo Clinic nonstudy therapeutic induction is rituximab, cyclophosphamide, and dexamethasone. Future stem cell transplantation should be considered in induction therapy selection. Bortezomib, thalidomide, lenalidomide, and bendamustine have all been shown to have activity in WM. Given WM’s natural history, reduction of complications will be a priority for future treatment trials.

Isolation and characterization of immunoglobulin M of Asian sea bass, Lates calcarifer and its level in serum

Abstract Asian sea bass immunoglobulin M (IgM) was purified from the sera of Lates calcarifer by affinity chromatography. Analysis of the purified IgM on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) under reducing and non-reducing conditions revealed that the sea bass IgM was a tetrameric protein with a molecular weight of 896 kDa; it contained an equimolar heavy chain and light chain with molecular weight of 83 kDa and 27 kDa respectively. However, besides the covalently linked tetrameric IgM, noncovalently linked tetramer dissociated into dimeric and monomeric forms also demonstrated by non-reducing SDS-PAGE. Carbohydrate moieties were found to be linked with both heavy and light chains. A polyclonal rabbit anti-Asian sea bass IgM was prepared which showed a specific reaction of anti-fish IgM antibody with IgM of sea bass. Sea bass IgM concentration was determined in the serum by indirect ELISA. The average IgM concentration in the sera of the healthy sea bass was 5.4±1.8 mg ml−1; it amounted to 16.7% of the total serum protein.

Restoration of the antibody response upon rabies vaccination in HIV-infected patients treated with HAART

Rabies vaccine was used as a T-cell-dependent neoantigen to investigate several aspects of the primary and booster immune response in vivo in HIV-infected individuals receiving antiretroviral treatment. Study participants received rabies vaccination twice, within a 3-month interval. Serum samples were taken before and 1, 2 and 4 weeks after both vaccinations and 1 and 5 years after the primary vaccination. Antirabies antibodies [immunoglobulin G (IgG), IgG subclasses, immunoglobulin A (IgA) and immunoglobulin M (IgM)] were determined; antibody avidity was measured after both vaccinations. T-cell subsets were characterized by flow cytometry. Eighteen healthy controls and 30 HIV-infected adults, treated with HAART for almost 4 years, with a median CD4(+) T-cell count of 537 cells/microl, were immunized. The postvaccination concentrations of antirabies IgG and IgM were significantly lower in HIV-infected individuals as compared with controls. Three T-cell-dependent processes, a true booster response, a class switch from IgM to IgG and avidity maturation were present in both healthy controls and HIV-infected individuals. Higher age was associated with lower postvaccination antirabies IgG and IgM titers. Five years after the primary vaccination, 63% of the HIV-infected individuals still had antibody titers above the protection threshold. Immune restoration in HIV-infected individuals treated with HAART, resulting in a CD4(+) T-cell count greater than 500 cells/microl, is incomplete. However, the majority of HIV-infected individuals are capable of mounting a long-lasting immune response, including several pivotal T-cell-dependent processes, upon vaccination with a neoantigen such as the rabies vaccine.

Immunospecific immunoglobulins and IL‐10 as markers for Trypanosoma brucei rhodesiense late stage disease in experimentally infected vervet monkeys

To determine the usefulness of IL-10 and immunoglobulin M (IgM) as biomarkers for staging HAT in vervet monkeys, a useful pathogenesis model for humans. Vervet monkeys were infected with Trypanosoma brucei rhodesiense and subsequently given sub-curative and curative treatment 28 and 140 days post-infection (dpi) respectively. Matched serum and CSF samples were obtained at regular intervals and immunospecific IgM, immunoglobulin G (IgG) and IL-10 were quantified by ELISA. There was no detectable immunospecific IgM and IgG in the CSF before 49 dpi. CSF IgM and IgG and serum IgM were significantly elevated with peak levels coinciding with meningoencephalitis 98 dpi. The serum IL-10 was upregulated in both early and late disease stage, coinciding with primary and relapse parasitaemia respectively. CSF white cell counts (CSF WCC) were elevated progressively till curative treatment was given. After curative treatment, there was rapid and significant drop in serum IgM and IL-10 concentration as well as CSF WCC. However, the CSF IgM and IgG remained detectable to the end of the study. Serum and CSF concentrations of immunospecific IgM and CSF IgG changes followed a pattern that mimics the progression of the disease and may present reliable and useful biomarkers of the disease stage. Due to rapid decline, serum IgM and IL-10 are, additionally, potential biomarkers of the success of chemotherapy.

Improvement of the thermal amplitude after rituximab treatment for cold agglutinin disease with Waldenström’s macroglobulinemia

Dear Editor, Cold agglutinin disease (CAD) is an uncommon autoimmune hemolytic anemia characterized by the production of cold agglutinins (CA) [1]. CA exhibits the strongest affinity for the antigen at 0–4°C but binding may occur at temperatures approaching the normal body temperature of mammals, depending on the thermal amplitude of the antibody. Rituximab has been demonstrated to be useful in treating CAD that is refractory to conventional therapies [2]. However, CA titers did not concur with the observed clinical and hematologic responses, and it has become apparent that the CA titer is not an important index for the clinical features of CAD. The detailed effect(s) of rituximab on CAD have not been reported. We present a case of a 68-year-old man who was diagnosed with Waldenstrom’s macroglobulinemia with CAD in 1999, in whom the thermal amplitude was improved after rituximab treatment. His Hb level was 4.9 g/dL, and an immunoglobulin M (IgM) kappa monoclonal protein was evident at diagnosis (IgM, 58.2 g/L). His bone marrow was diffusely infiltrated with CD20+ lymphoplasmacytoid lymphocytes. The direct antiglobulin test was positive for complement (C3d). CAwas positive with a titer of 8,192 at 4°C. He underwent six courses of cyclophosphamide, adriamycin, vinctistine, and prednisolone and low-dose prednisolone up to July 2007. Due to worsening anemia with acrocyanosis, he was treated with rituximab alone at 375 mg/m four times every 8 weeks. Although the CAD-related symptoms were improved, the high-CA titers at 4°C remained. He relapsed 42 weeks after the initial treatment, and the duration to response was 10 months. After informed consent was obtained, we determined the agglutination titer and tested the thermal amplitude of the patient’s plasma and serum, as described previously [3]. As shown in Table 1, 4 weeks after the initial injection of rituximab, increases of hemoglobin and improvement of the thermal amplitude of the antibody were observed simultaneously. Up to 24 weeks later, the improvement of the thermal amplitude remained. Hemoglobin increased progressively up to 28 weeks. Based on the changes of the thermal range in reactivity of the antibody, the clinical sign(s), such as acrocyanosis, improved along with amelioration of the symptoms related to anemia. Temperatures of 30°C and lower normally occur in the superficial skin vessels of the parts of the body exposed to cold air or water. The thermal range of the antibody is more important than the agglutination titer for clinical symptoms [4]. The present findings suggested that both elevation of hemoglobin and resolution of clinical sign(s) are closely associated with improvement of thermal amplitude of the CA after rituximab treatment. The present case suggested that hemoglobin was elevated as a consequence of the improvement of thermal amplitude after rituximab treatment. Schoellkopf et al. observed a significant and persistent reduction of serum IgM concentration after rituximab Ann Hematol (2010) 89:103–104 DOI 10.1007/s00277-009-0773-z