Changes In Immunoglobulin Levels Research Articles

Changes in immunoglobulin levels during clozapine treatment in schizophrenia

Background and hypothesisUse of clozapine in treatment-resistant schizophrenia is often limited due to risk of adverse effects. Cross-sectional associations between clozapine treatment and low immunoglobulin levels have been reported, however prospective studies are required to establish temporal relationships. We tested the hypothesis that reductions in immunoglobulin levels would occur over the first 6 months following initiation of clozapine treatment. Relationships between immunoglobulin levels and symptom severity over the course of clozapine treatment were also explored. DesignThis prospective observational study measured immunoglobulin (Ig) levels (A, M and G) in 56 patients with treatment-resistant schizophrenia at 6-, 12- and 24-weeks following initiation with clozapine. Clinical symptoms were also measured at 12 weeks using the positive and negative syndrome scale (PANSS). ResultsIgA, IgG and IgM all decreased during clozapine treatment. For IgA and IgG the reduction was significant at 24 weeks (IgA: β = –32.66, 95% CI = -62.38, −2.93, p = 0.03; IgG: β = -63.96, 95% CI = -118.00, −9.31, p = 0.02). For IgM the reduction was significant at 12 and 24 weeks (12 weeks: β = –23.48, 95% CI = -39.56, −7.42, p = 0.004; 24 weeks: β = –33.12, 95 %CI = -50.30, −15.94, p = <0.001). Reductions in IgA and IgG during clozapine treatment were correlated with reductions in PANSS-total over 12 weeks (n = 32, IgA r = 0.59, p = 0.005; IgG r = 0.48, p = 0.03). ConclusionsThe observed reductions in immunoglobulin levels over six months of clozapine treatment add further evidence linking clozapine to secondary antibody deficiency. Associations between Ig reduction and symptom improvement may however indicate that immune mechanisms contribute to both desirable and undesirable effects of clozapine.

Determination of Immunoglobulin's levels in cutaneous Leishmainasis patients

Human leishmaniasis is distributed worldwide, butmainly in the tropics and subtropics, with a prevalenceof 12 million cases and an approximate incidence of 0.5million cases of VL (visceral leishmaniasis) and 1.5 million cases of cutaneousleishmaniasis (CL) Leishmaniaspecies are intra‐cellularparasites invading monocytes, macrophages, and langerhans celland begin the differentiation process into amastigotes, the parasite form which persists in the host. Theirinfection in man induces both humoral andcellular immune responses, but the balanceof their expression varies with the type of the disease. To identify the profile of autoantibodies levels of patients with cutaneous leishmaniasis, this study showed that a significance changes of immunoglobulin levels as high level, especially in IgG and no significance value for elevation of IgM and IgA.

Hypogammaglobinemia in Patients Palliated with the Fontan Circulation: Implications for Cardiac Transplantation

<h3>Purpose</h3> Protein-losing enteropathy (PLE) is a complication after the Fontan operation believed to result from lymphatic dysfunction. As a consequence of protein loss, patients can develop hypogammaglobinemia (HGG). PLE typically resolves following heart transplant, but changes in immunoglobulin levels are not well-described. HGG can increase peri-transplant infection risk and may impair the accurate assessment of pre-transplant antibodies against potential donors. In our case series, we present the changes in immunoglobulin levels among patients palliated with the Fontan procedure that later underwent heart transplant. <h3>Methods</h3> Patients who underwent Fontan with subsequent heart or heart-liver transplant were included (n=10). Variables included are listed in Table 1. Post-transplant IgG levels were collected at a minimum of 3 months post-transplant to avoid interference from high-dose steroids and higher doses of immunomodulation used in the immediate post-transplant period. HGG was defined as IgG < 700 mg/dL pre-transplant. <h3>Results</h3> The mean age at transplant was 22.3 years; 90% of patients were male. Three (30%) patients had HGG. Two had complete resolution of HGG. The third was treated with subcutaneous immunoglobulin before transplant. PLE resolved post-transplant. One of the patients with HGG had a persistent de novo donor-specific antibody in the setting of immunosuppression non-adherence. <h3>Conclusion</h3> In this case series, we present HGG as a consideration in patients palliated with Fontan. Due to the risk of infection, HGG may lead clinicians to reduce immunosuppression in the peri-transplant period. HGG may also impact the ability to detect the degree of sensitization as the panel of reactive antibodies relies on sufficient immunoglobulin titers against human-leukocyte antigen to identify unacceptable donors. Lastly, if HGG resolves predictably post heart-transplant, that may have further implications on early risk for rejection in this patient population.

Short-term effect of low-dose rituximab on myasthenia gravis with muscle-specific tyrosine kinase antibody.

The study aims to investigate the short-term efficacy of low-dose rituximab and its effect on immunological biomarker levels in myasthenia gravis (MG) patients with antibodies against muscle-specific tyrosine kinase (MuSK-MG). Twelve MuSK-MG patients were enrolled in this prospective, open-label, self-controlled pilot study. Clinical severity was evaluated at baseline and 6mo after a single rituximab treatment (600 mg). B lymphocyte subtypes, MuSK antibody titers, together with levels of immunoglobulins, serum B-cell activating factor (BAFF), a proliferation-inducing ligand (APRIL), soluble CD40L, and four exosomal microRNAs were evaluated. A correlation matrix to reveal pairwise relationships among above variables was also generated. The single rituximab treatment significantly lowered the clinical severity scores and reduced daily dosage of prednisone (P=.032) at 6mo. MuSK antibody titers decreased (P=.035) without significant changes in immunoglobulin levels. Serum BAFF level increased (P=.010), which negatively correlated with the percentages of B cells in lymphocytes as well as clinical severity. Additionally, serum exosomal miR-151a-3p showed a reduction of 28.1% (P=.031). We confirmed the clinical efficacy of low-dose rituximab in MuSK-MG, accompanied by a decrease in MuSK antibody titers and an increase in serum BAFF. Serum BAFF levels negatively correlated with B-cell counts as well as clinical severity.

Immunomodulatory Effect of Sodium Saccharin and Potassium Acesulfame in BALB/C Mice in Short-Term Trials

Introduction: Sweeteners are molecules that give a sweet taste to a foodstuff. The question of the correct use of sweeteners is still being studied because the results of investigations are often contradictory.&#x0D; Objective: the current study aims at evaluating the risk of short-term immunotoxicity induced by sodium saccharin and potassium acesulfame in BALB/c mice.&#x0D; Methods: Animals are given low concentrations of sweeteners (0%, 0.5%, 1%, 2%) in drinking water for 90 days. During this period, a subcutaneous immunization is conducted. Blood is taken from the retro-orbital sinus and the animals are sacrificed by cervical dislocation. Weight measurements and histological studies have involved spleen, thymus, bladder and lungs. Levels of immunoglobulins are measured by reversed single radial immunodiffusion.&#x0D; Results: A significant rise in the consumption of sweeteners is found in the groups receiving doses of 1% and 2% (p&lt;0.05). Organ weight is not affected in both sexes (p&gt;0.05). Histology shows no tissue abnormality of thymus and lungs in groups consuming sweeteners. However, histological disturbances of the spleen are observed in mice that have received the dose of 2%. Histological study of bladder has revealed hyperplasia in the groups receiving 1% and 2% of sweeteners. Immunodiffusion assay shows no change in immunoglobulin levels in the groups consuming sweeteners (p&gt;0.05).&#x0D; Conclusion: Sweeteners have adverse effects on the immune system in BALB/c mice and induce histological abnormalities in the spleen and bladder.&#x0D; Keywords: Sweeteners, Saccharin, Potassium Acesulfame, Immunotoxicity, Immunoglobulins, Reversed single Radial Immunodiffusion.

Low immunoglobulin G4 subclass level is associated with recurrent wheezing in young children.

BackgroundThe most important infectious trigger of asthma is the virus and patients with immunoglobulin deficiencies are prone to recurrent respiratory infections.ObjectiveWe investigated the relationship between immunoglobulin G subclass and recurrent respiratory symptom exacerbation and explored possible therapeutic effects of intravenous immunoglobulin administration.MethodsTwenty-eight infants less than 24 months old with 2 or more recurrent wheezing episodes (infantile wheezer group) and 29 asthmatic children aged 24 months to 15 years (bronchial asthma [B-asthma] group) visited our hospital from October 2010 to January 2018. Serum immunoglobulin G, A, M, E, G1, G2, G3, and G4 were measured in each group and compared. In both groups, serum immunoglobulin and symptoms were compared before and after intravenous immunoglobulin administration.ResultsThe 2 study groups exhibited several statistically significant differences when comparing respiratory virus infection rate (p < 0.001), coinfection rate (p < 0.0001), most commonly found viral infection (human bocavirus vs. human rhinovirus), and immunoglobulin A (p < 0.001), E (p = 0.008), G2 (p < 0.001), and G4 (p = 0.011) levels. In the infantile wheezer group, there was an inverse correlation between immunoglobulin G4 levels and wheezing numbers (R = -0.5538, P = 0.0022). Both groups showed significant changes in immunoglobulin levels and respiratory symptom exacerbations (recurrent wheezing, shortness of breath, chest tightness, cough, and fever) over 1 year after intravenous immunoglobulin administration.ConclusionThere was an association between recurrent wheezing and specific immunoglobulin G deficiencies. We suggest that intravenous immunoglobulin therapy significantly elevates specific immunoglobulin G levels though it lasts only for short term and might be associated with decreased respiratory symptoms. Therefore, low IgG4 levels among infants with recurrent wheezing may be indicative for intravenous immunoglobulin therapy.

Oral administration of yeast β-glucan ameliorates inflammation and intestinal barrier in dextran sodium sulfate-induced acute colitis

Ulcerative colitis is a chronic inflammatory disease that is characterized by relapsing inflammation and dysfunction within the gastrointestinal tract. The purpose of this study was to investigate the protective effects of yeast β-glucan on regulating inflammation and disruption of the epithelial barrier in colitis caused by dextran sulfate sodium (DSS). Oral administration of yeast β-glucan reduced clinical symptoms, inflammatory infiltrates and cell apoptosis in the colon epithelium, ameliorated intestinal permeability and the structural integrity of tight junctions. Moreover, treatment with yeast β-glucan not only decreased myeloperoxidase, eosinophil peroxidase and N-acetyl-β-d-glucosaminidase levels, but also modified the immune status characterized by the change in immunoglobulin levels in DSS-treated mice. These results suggest that yeast β-glucan improves DSS-induced changes in mucosal inflammatory lesions and the intestinal barrier by inhibiting the expression of inflammatory mediators and enhancing the expression of tight junction proteins associated with intestinal permeability.

FRI0326 Efficacy and Safety of Tabalumab, an Anti-B Cell Activating Factor Monoclonal Antibody, in Patients with Rheumatoid Arthritis Who HAD an Inadequate Response to Methotrexate Therapy: Results from A Phase 3 Multicenter, Randomized, Double-Blind Study

BackgroundTabalumab is a monoclonal antibody that neutralizes membrane-bound and soluble B cell activating factor (BAFF).ObjectivesEvaluate efficacy and safety of tabalumab, in RA pts who had an inadequate response to methotrexate...

AB0438 Efficacy and Safety of Tabalumab, an Anti-B Cell Activating Factor Monoclonal Antibody, in Patients with Rheumatoid Arthritis WHO HAD an Inadequate Response to Tnf-Alpha Inhibitors: Results from A Phase 3 Multicenter, Randomized, Double-Blind Study

BackgroundTabalumab is a monoclonal antibody that neutralizes membrane-bound and soluble B cell activating factor (BAFF).ObjectivesEvaluate efficacy and safety of tabalumab, in RA pts who had an inadequate response to ≥1...

Serum immunoglobulin levels and risk factors for hypogammaglobulinaemia during long-term maintenance therapy with rituximab in patients with granulomatosis with polyangiitis.

Rituximab (RTX) is a B cell depleting agent used to induce and maintain remission in patients with granulomatosis with polyangiitis (GPA). As the development of hypogammaglobulinaemia in GPA patients on long-term RTX has not been addressed, the aim of this study was to investigate changes in immunoglobulin levels and risk factors for hypogammaglobulinaemia during long-term RTX maintenance therapy in GPA. We used a single-centre cohort study of 29 GPA patients who received a median total cumulative dose of CYC of 17 g and were treated with 2 g RTX followed by re-treatment with either 2 g once annually, 1 g biannually or a combination of both. Ig levels were measured before each RTX re-treatment and hypogammaglobulinaemia was defined as levels of total immunoglobulin <6 g/l. During a median follow-up of 4 years, patients received a cumulative dose of 9 g RTX. While serum Ig levels decreased during RTX maintenance, the largest decrease occurred after the first infusion. Baseline Ig levels and the CYC cumulative dose predicted Ig levels, whereas the RTX cumulative dose did not. Eight patients (28%) discontinued RTX due to hypogammaglobulinaemia. Male gender [hazard ratio (HR) = 8.7, P = 0.044], kidney involvement (HR = 6.5, P = 0.083) and the 1 g biannual regimen (HR = 8.0, P = 0.024) increased the risk to discontinue RTX due to hypogammaglobulinaemia, whereas orbital-subglottic involvement (HR = 0.23, P = 0.080) decreased it. Hypogammaglobulinaemia occurred in one-quarter of GPA patients during RTX maintenance, independent of the RTX cumulative dose. Male gender, kidney involvement and the 1 g biannual RTX regimen constitute risk factors for severe hypogammaglobulinaemia necessitating withdrawal of RTX.

Bench-to-bedside review: Immunoglobulin therapy for sepsis - biological plausibility from a critical care perspective

Sepsis represents a dysregulated host response to infection, the extent of which determines the severity of organ dysfunction and subsequent outcome. All trialled immunomodulatory strategies to date have resulted in either outright failure or inconsistent degrees of success. Intravenous immunoglobulin (IVIg) therapy falls into the latter category with opinion still divided as to its utility. This article provides a narrative review of the biological rationale for using IVIg in sepsis. A literature search was conducted using the PubMed database (1966 to February 2011). The strategy included the following text terms and combinations of these: IVIg, intravenous immune globulin, intravenous immunoglobulin, immunoglobulin, immunoglobulin therapy, pentaglobin, sepsis, inflammation, immune modulation, apoptosis. Preclinical and extrapolated clinical data of IVIg therapy in sepsis suggests improved bacterial clearance, inhibitory effects upon upstream mediators of the host response (for example, the nuclear factor kappa B (NF-κB) transcription factor), scavenging of downstream inflammatory mediators (for example, cytokines), direct anti-inflammatory effects mediated via Fcγ receptors, and a potential ability to attenuate lymphocyte apoptosis and thus sepsis-related immunosuppression. Characterizing the trajectory of change in immunoglobulin levels during sepsis, understanding mechanisms contributing to these changes, and undertaking IVIg dose-finding studies should be performed prior to further large-scale interventional trials to enhance the likelihood of a successful outcome.

Serum immunoglobulin G, M and IgG:IgM ratio as predictors for outcome of childhood nephrotic syndrome

Nephrotic syndrome is an immune mediated disorder of the kidney associated with T cell dysfunction and secondary disturbance of B cell with changes in levels of immunoglobulin and IgG:IgM ratio. These changes in immunoglobulin levels can be used as a proxy marker to understand the clinical variety and prognosis of nephrotic syndrome. We studied 43 children with nephrotic syndrome during January 2003 to January 2005 in the Pediatric Nephrology Unit, Department of Pediatrics, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh. Blood samples were collected from the 43 patients, and serum levels of IgG, IgM and IgG:IgM were measured by liquid phase immunoprecipitation assay. Another 20 healthy children attending the laboratory for blood grouping and hepatitis B screening test were enrolled as controls. In the 43 children with nephrotic syndrome, 24 had steroid sensitive nephrotic syndrome (SSNS) and 19 steroid resistant nephrotic syndrome (SRNS). Compared with healthy children, the IgG level was low, IgM level was high, and IgG:IgM ratio was low (P<0.05). The serum IgG level and IgG:IgM ratio were significantly lower in children with SRNS and in children with frequent relapse (FRNS) combined with steroid dependent nephrotic syndrome (SDNS) than in those with infrequent relapse nephrotic syndrome (IFRNS) (P<0.05, respectively). Management of different nephrotic syndromes is based on the levels of immunoglobulins along with clinical and biochemical parameters. The decrease of IgG level as a predictive marker for unfavorable prognosis of nephrotic syndrome in children needs further evaluation in larger scale studies.

Factors Associated with Fluctuations in IgA and IgG Levels at the Cervix during the Menstrual Cycle

The objective of this analysis was to describe patterns and determinants of cervical immunoglobulin A (IgA) and G (IgG) levels during the menstrual cycle. A total of 154 women who attended 3 visits coinciding with the follicular, periovulatory, and luteal phases of their menstrual cycle were studied. Cervical secretions were collected at each visit for determination of total IgA and IgG levels. Questionnaires administered at each visit inquired about demographic characteristics and behavioral practices. Total IgA and IgG levels were higher among oral contraceptive (OC) users than among naturally cycling women (hereafter, "non-OC users"). IgA and IgG levels decreased at midcycle, particularly among non-OC users. After adjustment for phase of the current cycle, specimen weight, and detection of blood in the sample, report of a recent illness was associated with lower IgA and IgG levels and increased age with higher IgA and IgG levels among OC users and non-OC users. Increased lifetime number of pregnancies was associated with a higher IgA level among non-OC users and a higher IgG level among OC users. Change in immunoglobulin levels between visits was associated with sample weight and the presence of blood for both OC users and non-OC users. Phase of the current menstrual cycle and OC use were significant determinants of cervical IgA and IgG levels. The impacts of endogenous and exogenous hormones on cervical immunoglobulin levels should be further investigated.

Alterations In Immunity After Total vs Partial Tonsillectomy

Problem Palatine tonsils are secondary lymphoid organs active in sampling antigens entering the upper respiratory tract and in producing immunoglobulin (Ig) both locally and distally through migrating tonsillar B cells. Their size has been found to be directly proportional to the number of B and T cells. The aim of this study is to compare the change in serum and saliva Ig levels after total and partial tonsillectomy. Methods Children with obstructive tonsils and/or adenoid undergoing total or partial tonsillectomy were recruited in a pilot study. Patients with history of recurrent infections or immunodeficiency were excluded. Blood and saliva samples were obtained immediately preoperatively and at the 1st follow-up visit. Serum Ig's (G,M&amp;A) concentrations were determined using radial immunodiffusion. Saliva secretory IgA was measured using an Enzyme Immuoassay (EIA). Results Twenty five patients (13 partial and 12 total) were included. There were no statistically significant changes in serum Ig's levels after total or partial tonsillectomy, except for IgM which increased (1.317 to 1.632 g/L) after partial tonsillectomy, more significantly in males, in those aged 5 years and older, and when the postoperative samples were taken within a 2 month-period. Moreover, there was statistically non-significant decrease in secretory IgA level after both total and partial tonsillectomy. Conclusion The effect of partial or total tonsillectomy on immunoglobulin level seems reassuring. The increase in IgM and the non-significant decrease in SIgA may represent a kind of immunological readjustment after tonsillar surgery. Significance This is the first study (to our knowledge) that compares the changes in immunoglobulin levels (in serum &amp; saliva) after partial vs. total tonsillectomy. The obtained results are preliminary and are reassuring to the parents and physicians who have concerns regarding the immunological sequalae of tonsillectomy in children. A longer follow up will be done in a larger future study. Support This study was supported by Medtronic.

Effects of low-level radio-frequency (3 kHz to 300 GHz) energy on human cardiovascular, reproductive, immune, and other systems: A review of the recent literature

Objectives Occupational or residential exposures to radio-frequency energy (RFE), including microwaves, have been alleged to result in health problems. A review of recent epidemiological studies and studies of humans as subjects in laboratory investigations would be useful. Methods This paper is a narrative review of the recent medical and scientific literature (from mid-1998 through early 2006) dealing with possible effects of RFE on humans, relating to topics other than cancer, tumors, and central nervous system effects (areas covered in a previous review). Subject areas in this review include effects on cardiovascular, reproductive, and immune systems. Results A large number of studies were related to exposures from cellular telephones. Although both positive and negative findings were reported in some studies, in a majority of instances no significant health effects were found. Most studies had some methodological limitations. Although some cardiovascular effects due to RFE were reported in epidemiological studies (e.g., lower 24-h heart rate, blunted circadian rhythm of heart rate), there were no major effects on a large number of cardiovascular parameters in laboratory studies of volunteers during exposure to cell-phone RFE. In population-based studies of a wide range of RFE frequencies, findings were equivocal for effects on birth defects, fertility, neuroblastoma in offspring, and reproductive hormones. Some changes in immunoglobulin levels and in peripheral blood lymphocytes were reported in different studies of radar and radio/television-transmission workers. Due to variations in results and difficulties in comparing presumably exposed subjects with controls, however, it is difficult to propose a unifying hypothesis of immune-system effects. Although subjective symptoms may be produced in some sensitive individuals exposed to RFE, there were no straightforward differences in such symptoms between exposed and control subjects in most epidemiological and laboratory studies. Consistent, strong associations were not found for RFE exposure and adverse health effects. The majority of changes relating to each of the diseases or conditions were small and not significant. Conclusions On the basis of previous reviews of older literature and the current review of recent literature, there is only weak evidence for a relationship between RFE and any endpoint studied (related to the topics above), thus providing at present no sufficient foundation for establishing RFE as a health hazard.

IS GASTROESOPHAGEAL REFLUX DISEASE MORE PREVALENT IN PATIENTS WITH MONOCLONAL GAMMOPATHY OF UNDETERMINED SIGNIFICANCE?

Background The prevalence of clinically significant gastroesophageal reflux (GERD) in the general population varies between 3 and 6%. We observed GERD to be one of the major complaints of our patient population with monoclonal gammopathy of unknown significance (MGUS). There is no literature available on the incidence of GERD in MGUS. Moreover, there have been conflicting reports on the prevalence of Helicobacter pylori and MGUS. Objective To study the incidence and relationship of GERD, H. pylori, and MGUS. Methods We identified 394 patients with MGUS at Veterans Affairs Medical Center, Kansas City, diagnosed over the last 20 years. The control group consisted of patients with chronic lymphocytic leukemia (CLL) followed over the same period (20 years) at the same institution. Charts on these patients were reviewed for endoscopic findings, pathologic biopsies, and H. pylori staining on histology. Results Forty-one percent (162/394) of patients with MGUS were noted to have moderate to severe symptoms of GERD compared with 10% (47/460) in the control group. The median age of the patients was similar in both groups. Sixty percent (97/162) of MGUS patients with GERD underwent endoscopies compared with 25% (12/47) of patients in the control group. Histology was positively stained for H. pylori in 27.8% patients (27/97) in MGUS and 25% (3/12) of the control group. We found no correlation between H. pylori positivity and type or level of monoclonal protein in MGUS. In addition, we observed no change in immunoglobulin levels following treatment and eradication of H. pylori in MGUS patients. Conclusion At our institution, patients with MGUS have a higher prevalence of GERD. Our findings need to be confirmed and verified in further prospective studies. No correlation was seen between H. pylori infection and MGUS.

GERD, Helicobacter pylori and MGUS-Is There a Relationtionship?.

Background: The prevalence of clinically significant gastro esophageal reflux (GERD) in the general population varies between 3–6%. We have observed GERD to be one of the major complaints of our patient population with monoclonal gammopathy of unknown significance (MGUS). There is no literature available on the incidence of GERD in MGUS. However, there have been conflicting reports on the prevalence of helicobacter pylori (H. pylori) and MGUS.Objective: To study the incidence and relationship of GERD, H. pylori and MGUS.Methods: We identified all patients diagnosed with MGUS at the Kansas City VA Medical Center over the last 20 years. Out of the 417 patients identified with MGUS, 394 patients fulfilled the inclusion criteria. All patients with GERD were evaluated by gastroenterologists at our institution who determined their diagnostic and therapeutic management. Charts on these patients were then reviewed for endoscopic findings, pathological biopsies, H. pylori staining on histology, serum protein electrophoresis with immunofixation (SPEP/IFE), immunoglobulin levels, and bone marrow biopsies.Results: In this study, 41% patients with MGUS were noted to have moderate to severe symptoms of GERD (162/394). The median age of patients with and without GERD was similar (72 versus 71 years). Endoscopies were performed on 60% of the patients with GERD (97 of 162). Histology was positively stained for H. pylori in 27.8% patients (27/97). We did not find any correlation between H. pylori positivity and the type or level of monoclonal protein. In addition, we observed no change in immunoglobulin levels following treatment and eradication of H. pylori.Conclusion: The incidence of GERD is significantly higher in patients with MGUS than in the general population. In our study, no correlation was seen between H. pylori infection and MGUS.

Effects of parental effort on blood stress protein HSP60 and immunoglobulins in female blue tits: a brood size manipulation experiment

1. Physiological stress in animals may impose a limit for investment in current reproduction in the wild. A brood manipulation experiment was conducted in a population of blue tits Cyanistes caeruleus to study the effect of parental effort on changes in two types of proteins related with stress: the blood stress protein HSP60 and the plasma immunoglobulins. 2. Levels of HSP60 were reduced across the experiment for females attending reduced broods, and females attending enlarged broods experienced a reduction of immunoglobulin levels. Moreover, the overall changes in the levels of both proteins were positively related. 3. By controlling for the change in immunoglobulin levels we found an increase in HSP60 for females in the enlarged treatment, presumably to offset deleterious effects derived from increased effort. 4. Maternal effort was able to partially compensate for the effect of treatment as nestlings did not differ in mass and levels of immunoglobulins and HSP60 among treatments. 5. Physiological stress as reflected in stress and immunoglobulin proteins may limit maternal effort in breeding blue tits.

The efficacy and safety of B-cell depletion with anti-CD20 monoclonal antibody in adults with chronic immune thrombocytopenic purpura.

Because of its B-cell depleting effect, rituximab has entered clinical trials in several autoimmune conditions. This study assesses the efficacy and safety of rituximab in 57 adults with chronic immune thrombocytopenic purpura (ITP). All patients had platelet counts < 30 x 10(9)/l, all had received two or more previous ITP treatments and 31 had undergone splenectomy. Patients received rituximab 375 mg/m(2) weekly for 4 weeks. Thirty-one patients (54%) responded, achieving a platelet count >50 x 10(9)/l: 18 achieved a complete response (CR: platelet count >150 x 10(9)/l) and 13 a partial response (PR: platelet count 50-150 x 10(9)/l). Twenty-nine responses occurred within 8 weeks of the first infusion. Sixteen of 18 CR patients (28% overall), including eight who had failed splenectomy, continued in CR after a median of 72.5 weeks; 15 of 16 are >1 year from the first infusion. Only two of 13 maintained a PR. Thirty-three patients experienced grade 1-2 adverse events and one a grade 3 event, but they all completed treatment. Circulating B cells fell to < 0.03 x 10(9)/l. No changes in immunoglobulin levels or infectious complications were seen. In summary, rituximab was well tolerated with no immediate complications and induced a lasting, substantial response in 32% of adults with chronic ITP.

Immunoglobulin Levels and Lymphocyte Subsets Following Cardiac Operations: Further Evidence for a T-Helper Cell Shifting

Recent data indicate that cardiac surgery with cardiopulmonary bypass (CPB) results in an imbalance of T-helper cell subsets towards the anti-inflammatory pathway mediating humoral immune response. However, little is known about immunoglobulin levels as an important part of humoral immune response after CPB. Therefore, the objectives of this study were 1) to elucidate the effects of CPB on perioperative immunoglobulin levels, and 2) to find out if alterations in lymphocyte subsets are related to these findings. Blood samples from 83 patients undergoing elective cardiac operation were taken preoperatively (d0), on the first (d1), third (d3), and fifth day (d5) after operation. Levels of immunoglobulin (Ig) E, IgM, and IgG, including the subclasses IgG 1 - 4, were measured. IgG2/IgE-ratio was used as indicator for TH1/TH2 shifting, and production of tetanus antibodies (AB) was investigated as an in vivo parameter of humoral immune reaction. The number and percentage of T- and B-lymphocyte subsets were assessed in a subgroup of 50 patients to answer the second question. Clinically, no mortality or major morbidity were observed. IgE levels did not change until d3 and increased significantly on d5. In contrast, both IgG and IgM levels decreased significantly on d1. While IgM returned to baseline (BL) on d5, IgG levels remained below BL until d5. IgG2/IgE-ratio decreased significantly on d1, reached its nadir on d3 and remained depressed until d5. The number of T-lymphocytes decreased on d1 as well as the number of B-cells. T-cells returned to BL on d5, B-cells on d3. However, while the percentage of T-cells decreased on d1, the percentage of B-cells increased. The percentage of T-cells returned to BL on d3, and B-cell percentage returned to BL on d5. Tetanus AB production did not change until d5 when it increased significantly. 1) Increase of IgE and tetanus AB production indicate that humoral immune response is not affected by CPB, but possibly even enhanced. The relative increase of B-cells is in line with this hypothesis. 2) Postoperative changes in immunoglobulin levels provide further evidence for a TH1/TH2-shifting. 3) The transient deficit in IgM-and IgG levels did not result in clinically adverse events. Thus, therapeutic intervention appears not to be required.