Low IgM Levels Research Articles

The Effects Of Anti-Seizure Medications On Patients With Antibody Deficiency Syndrome

RationaleAntibody deficiency is associated with both primary and secondary immunodeficiency. Secondary immunodeficiency is often caused by medications including antiepileptic drugs (AEDs). It is unknown how AEDs affect ADS patients. This study examined whether ADS subjects treated with AEDs (test group) will reveal differences as compared to control ADS subjects.MethodsClinical features and laboratory findings in the test group (children N=8, adults N=5), were retrospectively reviewed in comparison with control ADS subjects (children N=18, adults N=5). In the test group, AEDs were mainly prescribed for seizure disorders (grand mal and/or partial complex seizures with variable etiology). Most of the test group subjects were prescribed multiple AEDs in the past and/or currently.ResultsChildren in the test group had lower levels of IgM /IgA than control ADS children (IgM 57.2 ± 32.2 vs 101.4 ± 48.6 mg/dL, IgA 37.7±25.4 vs 85.0 ± 50.9 mg/dL, respectively). However, there were no differences in total and isotype switched memory B cell numbers between the test and control groups irrespective of age. In cytokine production by peripheral blood mononuclear cells (PBMCs), the test group revealed lower IL-6, IL-12, and TNF-alpha production in response to TLR7/8 agonist (p<0.05) but IL-10 production in response to T cell mitogens was higher in the test group (p<0.05).ConclusionsLower IgM /IgA levels in the test group children may be associated with lower IL-6 production and higher IL-10 production by PBMCs in the test group, since IL-10 is a suppressive cytokine and IL-6 promotes B cell maturation. RationaleAntibody deficiency is associated with both primary and secondary immunodeficiency. Secondary immunodeficiency is often caused by medications including antiepileptic drugs (AEDs). It is unknown how AEDs affect ADS patients. This study examined whether ADS subjects treated with AEDs (test group) will reveal differences as compared to control ADS subjects. Antibody deficiency is associated with both primary and secondary immunodeficiency. Secondary immunodeficiency is often caused by medications including antiepileptic drugs (AEDs). It is unknown how AEDs affect ADS patients. This study examined whether ADS subjects treated with AEDs (test group) will reveal differences as compared to control ADS subjects. MethodsClinical features and laboratory findings in the test group (children N=8, adults N=5), were retrospectively reviewed in comparison with control ADS subjects (children N=18, adults N=5). In the test group, AEDs were mainly prescribed for seizure disorders (grand mal and/or partial complex seizures with variable etiology). Most of the test group subjects were prescribed multiple AEDs in the past and/or currently. Clinical features and laboratory findings in the test group (children N=8, adults N=5), were retrospectively reviewed in comparison with control ADS subjects (children N=18, adults N=5). In the test group, AEDs were mainly prescribed for seizure disorders (grand mal and/or partial complex seizures with variable etiology). Most of the test group subjects were prescribed multiple AEDs in the past and/or currently. ResultsChildren in the test group had lower levels of IgM /IgA than control ADS children (IgM 57.2 ± 32.2 vs 101.4 ± 48.6 mg/dL, IgA 37.7±25.4 vs 85.0 ± 50.9 mg/dL, respectively). However, there were no differences in total and isotype switched memory B cell numbers between the test and control groups irrespective of age. In cytokine production by peripheral blood mononuclear cells (PBMCs), the test group revealed lower IL-6, IL-12, and TNF-alpha production in response to TLR7/8 agonist (p<0.05) but IL-10 production in response to T cell mitogens was higher in the test group (p<0.05). Children in the test group had lower levels of IgM /IgA than control ADS children (IgM 57.2 ± 32.2 vs 101.4 ± 48.6 mg/dL, IgA 37.7±25.4 vs 85.0 ± 50.9 mg/dL, respectively). However, there were no differences in total and isotype switched memory B cell numbers between the test and control groups irrespective of age. In cytokine production by peripheral blood mononuclear cells (PBMCs), the test group revealed lower IL-6, IL-12, and TNF-alpha production in response to TLR7/8 agonist (p<0.05) but IL-10 production in response to T cell mitogens was higher in the test group (p<0.05). ConclusionsLower IgM /IgA levels in the test group children may be associated with lower IL-6 production and higher IL-10 production by PBMCs in the test group, since IL-10 is a suppressive cytokine and IL-6 promotes B cell maturation. Lower IgM /IgA levels in the test group children may be associated with lower IL-6 production and higher IL-10 production by PBMCs in the test group, since IL-10 is a suppressive cytokine and IL-6 promotes B cell maturation.

Comparative skin mucus and serum humoral defence mechanisms in the teleost gilthead seabream (Sparus aurata)

Mucosal surfaces of fish, including skin, gill and gut, contain numerous immune substances poorly studied that act as the first line of defence against a broad spectrum of pathogens. This study aimed to identify and characterize for the first time different constitutive humoral defence mechanisms of the skin mucus of gilthead seabream (Sparus aurata). To do this, the levels of total immunoglobulin M, several enzymes and proteins (peroxidase, lysozyme, alkaline phosphatase, esterases, proteases and antiproteases), as well as the bactericidal activity against opportunist fish pathogens (Vibrio harveyi, Vibrio angillarum, Photobacterium damselae) and non-pathogenic bacteria (Escherichia coli, Bacillus subtilis) were measured in the skin mucus and compared with those found in the serum. This study demonstrates that gilthead seabream skin mucus contains lower levels of IgM, similar levels of lysozyme, alkaline phosphatase and proteases, and higher esterase, peroxidase and antiprotease activities than serum. In addition, skin mucus revealed stronger bactericidal activity against tested fish pathogen bacteria compared to the serum activity, while human bacteria can even grow more in the presence of mucus. The results could be useful for better understanding the role of the skin mucus as a key component of the innate immune system with potential application for the aquaculture.

Development, Manufacturing and Characterization of a Highly Purified, Liquid Immunoglobulin G Preparation from Human Plasma

Background: The use of plasma-derived immunoglobulin G (IgG) is increasing, and the number of diseases, including immunodeficiencies, neurological diseases and autoimmune conditions, treated with intravenous IgG (IVIG) is expanding. Consequently, there is a great need for high-yield production processes for plasma-derived IgG. The aim of this work was to develop a high-yield process leading to a highly purified, liquid, ready-to-use IgG for intravenous use. Methods: Plasma from healthy, voluntary, non-remunerated donors was fractionated by ethanol precipitation. IgG was extracted from fraction II + III using a phosphate/acetate buffer, pH 4, and purified by chromatography. Results: Precipitation with 6% polyethylene glycol at pH 7 removed high molecular-weight contaminating proteins, aggregates and contaminating viruses. Ion exchange chromatography at pH 5.7 on serially connected anion and cation exchange columns allowed for elution of IgG from the cation exchange column in good yield and high purity. Further safety was achieved by solvent/detergent treatment and repeated ion exchange chromatography. The product consisted of essentially only IgG monomers and dimers, and had a high purity with very low levels of IgM and IgA. Conclusion: A process providing highly purified IVIG in good yield was developed.

Increased sialylation of anti-Thomsen-Friedenreich antigen (CD176) antibodies in patients with gastric cancer: a diagnostic and prognostic potential.

Aim. To study whether alterations in the sialylation of antibodies (Ab) specific to the Thomsen-Friedenreich (TF) glycotope have a diagnostic and prognostic potential in gastric cancer. Methods. Serum samples were taken from patients with gastric carcinoma (n = 142) and controls (n = 61). The level of TF-specific antibodies and their sialylation was detected using ELISA with synthetic TF-polyacrylamide conjugate as antigen and sialic acid-specific Sambucus nigra agglutinin (SNA). Results. The level of TF-specific IgM was significantly decreased in cancer compared with controls (P ≤ 0.001). Cancer patients showed a higher level of SNA binding to anti-TF IgM and IgA (P ≤ 0.001) irrespective of disease stage, tumor morphology, and gender. Changes in the SNA/Ab index demonstrated moderate sensitivity (66–71%) and specificity (60–73%) for stomach cancer. The best diagnostic accuracy (100%) was achieved in 29% patients with high SNA binding and low anti-TF IgM level. This subset of patients demonstrated the poorest survival. Conclusion. Our findings are the first evidence that the increased sialylation of TF-specific Abs combined with a low level of anti-TF IgM is strongly linked to gastric cancer and patients survival, which can be used as a novel biomarker for cancer detection and prognosis.

An unusual cause of recurrent pneumonia in adults.

Selective IgM deficiency is a rare primary immunodeficiency defined as isolated low levels of IgM. It presents with recurrent infections and has been described as first presenting in adulthood with recurrent respiratory tract infections. Unlike its better known counterpart of IgA deficiency, this particular immunodeficiency is often overlooked. We present a case of selective IgM deficiency who presented with recurrent respiratory infections.

Association between haptoglobin and IgM levels and the clinical progression of caseous lymphadenitis in sheep

BackgroundSheep caseous lymphadenitis (CLA), caused by Corynebacterium pseudotuberculosis (Cp), is associated with direct economic losses and presents significant zoonotic potential. Despite the importance of the disease, a satisfactory vaccine model has not been developed. Thus, this study aimed to investigate the association between haptoglobin (Hp) and IgM levels and the clinical progression of CLA in primarily infected sheep and in sheep immunized with Cp- secreted antigens adjuvanted with Quillaja saponaria saponins. These animals were kept with CLA-positive sheep to simulate natural exposure that occurs in field conditions. During the experiment, the Hp and IgM levels were monitored for 21 days, and the development of internal CLA lesions was investigated through necropsies on day182 post-immunization.ResultsPrimarily infected sheep in Group 2 (inoculated with 2x105 Cp virulent strain) had higher Hp values between the first and ninth days post inoculation (PI) than sheep in Group 1 (control; P < 0.05). Immunized animals in Group 3 had significantly higher Hp values between the third and seventh days PI, compared with the control group (P < 0.01). Binary logistic regression (BLR) analysis of primarily infected sheep indicated an association between Hp concentration and CLA clinical progression: animals with high Hp values had 99.9% less risk of having CLA abscesses than animals with low Hp levels (Odds ratio = 0.001, P < 0.05). Both experimental groups had significantly higher IgM titers than the control group around the ninth and eleventh days PI (P < 0.05). The BLR analysis for immunized sheep indicated an association between IgM levels and clinical progression: sheep with high IgM titers had 100.0% less risk of having CLA abscesses than animals with low IgM levels (Odds ratio = 0.000, P < 0.05).ConclusionsResistance to C. pseudotuberculosis infection is supported by the early acute phase response, in which up-regulation of Hp and IgM were predictive of a lower risk of CLA lesion development. Because the immunogen used in this study induced a high production of both Hp and IgM, Q. saponaria saponin should be considered a promising candidate in vaccine formulations against sheep CLA.

Role of Fms‐like Tyrosine Kinase 3 Ligand as a Potential Biologic Marker of Lymphoma in Primary Sjögren's Syndrome

Patients with primary Sjögren's syndrome (SS) are at greater risk of developing lymphoma. This study was undertaken to evaluate whether the Fms-like tyrosine kinase 3 ligand (Flt-3L) might be associated with lymphoma in primary SS. Serum levels of Flt-3L were measured in 369 patients with primary SS from the French Assessment of Systemic Signs and Evolution of Sjögren's Syndrome study cohort and in 10 patients with primary SS at the time of lymphoma diagnosis in an Italian cohort. Associations between increased levels of Flt-3L and a history of lymphoma, history of previously diagnosed criteria related to a high risk of lymphoma, and greater extent of disease activity were evaluated. Among patients with primary SS, higher levels of Flt-3L were significantly associated with a history of lymphoma (P = 0.0001). Previous markers for risk of lymphoma development, such as presence of purpura, low levels of C4, presence of lymphocytopenia, low levels of IgM, high levels of β2 -microglobulin, and a higher primary SS disease activity score, were all associated with higher levels of Flt-3L. The levels of Flt-3L were also increased in serum obtained from patients with primary SS at the time of lymphoma diagnosis. Furthermore, the Flt-3L levels were elevated in the serum of 6 patients up to 94 months (mean 46 months) prior to the diagnosis of lymphoma. Receiver operating characteristic curve analysis showed that an Flt-3L level of 175 pg/ml was the ideal cutoff value for demonstrating an association with lymphoma (specificity 97.5%, sensitivity 44%, negative predictive value 97%). Flt-3L is associated with lymphoma in primary SS, and constitutes a good biologic marker. Higher levels of this cytokine are present several years before the diagnosis of lymphoma, and may be useful as a predictive marker of lymphoproliferative disorders in primary SS.

The Variable in Common Variable Immunodeficiency: A Disease of Complex Phenotypes

Common variable immunodeficiency (CVID) is the most common and clinically most important severe primary antibody deficiency and is characterized by low levels of IgG, IgA, and/or IgM, with a failure to produce specific antibodies. This diagnostic category represents a heterogeneous group of disorders, which present not only with acute and chronic infections but also with a range of inflammatory and autoimmune disorders as well as an increased incidence of lymphoma and other malignancies. Patients can now be categorized into distinct clinical phenotypes based on analysis of large cohort studies and be further stratified by immunologic laboratory testing. The biologic importance of this categorization is made clear by the 11-fold increase in mortality if even one of these phenotypes (cytopenias, lymphoproliferation, or enteropathy) is present. Limited progress in defining the underlying molecular causes has been made with known causative single gene defects accounting for only 3% of cases, and, for this and the reasons mentioned above, CVID remains resolute in its variability. This review provides a practical approach to risk stratification of these complex phenotypes by using current clinical categories and laboratory biomarkers. The effects of infection as well as inflammatory and autoimmune complications on different organ systems are discussed alongside strategies to reduce diagnostic delay. Recent developments in diagnostics and therapy are also explored.

PROSPECTS OF THE USE "STIMFORTE" IN CHRONIC HEPATITIS B

Despite the fact that over the last few years downward trend in the incidence of acute forms of viral hepatitis B continues, the incidence of chronic hepatitis B (CHV) has increased by 2.5 times since 1998. To date, there are a sufficient number of antiviral drugs, but their use is associated with a set of contraindications, as well as the development of resistance. In this study there was performed an evaluation of a new national drug " Stimforte " in patients with chronic viral hepatitis B (CVHB - DNA positive, HBsAg - positive) at the stage of exacerbation. In the study there were included 28 patients with chronic hepatitis B (HBsAg positive), at different grades of activity, at a stage of viral replication. The diagnosis of chronic hepatitis B was made on the presence in a history acute viral hepatitis for more than 1 year, complaints, hepatolienal, astenovegetative, cytolytic syndromes, the presence of DNA-HBV, anti-HBcore IgM, HBsAg. After 1 course of treatment with " Stimforte " the well-being of patients has improved: in 30% of patients asthenic- vegetative syndrome had disappeared, weakness, fatigue and dyspeptic symptoms were decreased. The use of "Stimforte" in chronic hepatitis B with positive HBsAg at the stage of exacerbation contributed to a more rapid normalization of such indices as ALT, AST, compared with those in the control group. Long-term biochemical and virological remission was achieved in 40 %. It is established that during the treatment the viral load was reduced progressively until the undetectable or low level of HBV DNA and anti-HBc IgM disappeared. In only one case an allergic reaction was observed, which has not hindered to perform a complete course of treatment. No other side effects were detected. The inclusion of the drug "Stimforte" in the complex therapy of patients with exacerbation of chronic hepatitis B reduces the time of recovery of immune status and functional activity of IFN system and contributes to reduction of the viral load or elimination of the virus.

Familial pyoderma gangrenosum in association with common variable immunodeficiency

Funding sources: none. Conflicts of interest: none declared. Dear Editor, Pyoderma gangrenosum (PG) is a rare skin disease characterized by noninfective, painful, necrotizing ulcerations. PG is extremely rare in the paediatric population; 4% of patients are infants and children.1 The occurrence of PG in a familial pattern is extremely rare. As far as we could ascertain, only three reports of familial predisposition in PG have been published previously in the English literature.2 3 4 The aetiopathogenesis of PG is still unclear. Its association with a variety of immunological disorders suggests an underlying defective immune system.5 6 However, to date, no cases of PG have been described in the context of common variable immunodeficiency (CVID). We report familial PG in two siblings with CVID, which we believe to be the first documentation of this kind. Patient 1, a 9‐year‐old boy born to nonconsanguineous parents, presented with painful ulcers that had appeared 2 months before. He had a history of recurrent episodes of lower respiratory tract infection since the age of 3 years leading to bronchiectasis. On clinical examination, the child was febrile, underweight and had multiple ulcers with undermined, violaceous margins and indurated bases on his neck, scalp, upper and lower extremities, groin and buttocks. The oral mucosa was particularly affected, presenting pustular exophytic lesions with an erythematous halo and friable membrane that easily disintegrated leading to exulcerated and vegetating lesions of the labial mucosa (Fig. 1). The rest of the clinical examination was unremarkable. Laboratory investigations revealed an elevated level of inflammatory markers. Cultures for bacteria and fungi from skin lesions and blood were repeatedly negative. A skin biopsy specimen revealed an ulcerated epidermis with a massive neutrophilic infiltrate in the upper and lower dermis. Based on the clinical and histological features, the diagnosis of PG was made and the patient was treated with oral prednisone 1 mg kg−1 daily, which induced a great improvement in his lesions and complete resolution in 4 weeks. The steroids were slowly tapered with no recurrence 1 year after the diagnosis. CVID was diagnosed when screening investigations revealed low IgG and IgM levels (IgG 5 g L−1, normal range 6·13–15·12; IgM 0·4 g L−1, normal range 0·7–2·84), absent response to polysaccharide and protein antigens, a reverse CD4:CD8 ratio, with normal complement levels and nitroblue tetrazolium test functional assays. The percentage of total B cells was within the lower normal range (5% of circulating lymphocytes) but with a reduced number of memory B cells identified by the surface marker CD27 (2% of B cells, normal range 6·5–29·2%).

Low Levels of Antibodies Against Oxidized but not Nonoxidized Cardiolipin and Phosphatidylserine Are Associated with Atherosclerotic Plaques in Systemic Lupus Erythematosus

We have reported that the prevalence of atherosclerotic plaques and their echolucency was increased in systemic lupus erythematosus (SLE). We here study antibodies against oxidized cardiolipin (anti-OxCL) and phosphatidylserine (anti-OxPS) in SLE and in relation to atherosclerosis measures. Patients with SLE (n = 114) were compared with age- and sex-matched population-based controls (n = 122). Common carotid intima-media thickness and plaque occurrence were determined by B-mode ultrasonography. Plaques were graded according to echogenicity as 1-4, with 1 being echolucent. Antibodies were determined by ELISA. In the SLE group, the prevalence of low IgM anti-OxPS and low total IgM levels (below 33rd percentile) was increased compared to controls (p = 0.045 and p = 0.0079, respectively). Among SLE patients with atherosclerotic plaques, the prevalence of low IgM anti-OxPS (p = 0.0019) and anti-OxCL (p = 0.031) was increased. Only IgM anti-OxPS remained significant (p = 0.019) after adjusting for other significant factors. Echolucent plaques (total, or left side) were more prevalent among SLE patients with low IgM anti-OxCL and anti-OxPS when controlled for other significant factors (p < 0.05). Low total IgM was independently associated with echolucent plaque on left side (p < 0.05), but not other atherosclerosis measures. IgM anticardiolipin antibodies (aCL) and antiphosphatidylserine antibodies (anti-PS) were higher among SLE patients with cardiopulmonary disease, including arterial, valvular, and venous disease (p < 0.05). There were no associations between antibodies and other disease manifestations or activity. Both anti-OxCL and anti-OxPS, in contrast to aCL, and anti-PS, were cofactor-β2-glycoprotein I (β2-GPI)-independent. The prevalence of low levels of IgM anti-OxCL and anti-OxPS (both cofactor-β2-GPI-independent) is associated with the presence of plaques and echolucent plaques in SLE.

Low levels of a natural IgM antibody are associated with vein graft stenosis and failure

All humans have natural, protective antibodies directed against phosphorylcholine (PC) epitopes, a common inflammatory danger signal appearing at sites of cell injury, oxidative stress, and on bacterial capsules. In large human cohorts, low levels of anti-PC IgM were associated with a significantly increased risk of stroke or myocardial infarction. However, it is not known if these antibodies protect against the premature closure of arterial reconstructions. A prospective, observational study of patients undergoing elective, infrainguinal, autogenous vein bypasses for atherosclerotic occlusive disease of the legs was conducted. Clinical data were recorded prospectively, and preoperative levels of anti-PC IgM measured with the CVDefine kit from Athera Biotechnologies (Solna, Sweden). The principal clinical end point was the loss of primary patency (loss of graft flow, or any intervention for stenosis). Patients were followed regularly by duplex ultrasound at 1, 3, 6, 12, 18 months, and yearly thereafter. Fifty-six patients were studied, for an average of 1.3 years. Indications for surgery were claudication (33.9%), ischemic rest pain (17.9%), and ischemia with ulceration or gangrene (48.2%). Seventeen (30.4%) patients experienced loss of primary patency (10 graft occlusions, seven surgical or endovascular revisions of graft stenoses). Kaplan-Meier survival analysis showed that the quartile of patients with the lowest anti-PC IgM levels had significantly worse primary graft patency (log-rank test, P = .0085). Uni- and multivariate Cox proportional hazards analysis revealed that the preoperative anti-PC IgM level was an important predictor of graft failure. Patients with IgM values in the lowest quartile had a 3.6-fold increased risk of graft failure (95% confidence interval: 1.1-12.1), even after accounting for other significant clinical or technical factors such as indication for surgery, site of distal anastomosis, or vein graft diameter. A naturally occurring IgM antibody directed against the proinflammatory epitope PC may be protective against vein graft stenosis and failure, through anti-inflammatory mechanisms. Measurement of this antibody may be a useful prognostic indicator, although larger studies of more diverse populations will be needed to confirm these results. The biological actions of anti-PC IgM suggest it may be useful in developing immunotherapies to improve bypass longevity.

FRI0222 Prevalence of low immunoglobulin levels and associations with rheumatoid arthritis factors

BackgroundLittle is known about the prevalence and the clinically associated factors of low IgG and IgM levels in patients (pts) with RA.ObjectivesTo estimate the prevalence of low IgG and IgM...

SAT0085 Levels of CD19+ cells and IGM as predictors of an early and maintained response to rituximab in rheumatoid arthritis patients

BackgroundIdentifying predictors of response to biological agents is important for both the individual patient and health economics. There is data about several predictors of rituximab response, like a positive anti-CCP...

Anti-nuclear IgM antibodies protect against lymphoma/lymphocytic leukemia (P2219)

Abstract Our previous work showed that AID-deficient MRL/lpr (AID-/-) mice which had high levels of autoreactive IgM experienced a longer lifespan than muS-/-AID-/-MRL/lpr (muS-/-) mice whose B cells did not secrete any antibodies. Histology results indicated that these mice died of Lymphoma/lymphocytic leukemia (LLL). Further studies showed that at 6 months of age, all muS-/- mice developed LLL, while only 24% AID-/- mice had LLL. At 12 months of age, eventually all the mice from both strains developed LLL, but the LLL grade of muS-/- mice was higher than that of AID-/- mice (P = 0.004). When bone marrow cells from AID-/- mice were transferred to muS-/- mice, the mice with successful reconstitution of IgM-secreting B cells (showing high levels of IgM) displayed a lower grade of LLL than both the mice with poor reconstitution of IgM-secreting B cells (showing low levels of IgM) and PBS control mice. In vitro experiments demonstrated that autoreactive IgM-rich serum from AID-/- mice induced apoptosis of lymphoma cell line TK-1 cells, while antibody-absent serum from muS-/- mice did not had the effect. This led to the finding that some anti-nuclear monoclonal IgM antibodies also induced the apoptosis of TK-1 cells. Treatment of p53-/-mice with the mAb reduced the lymphoma grade compared to control mice (P = 0.021). These data demonstrate that anti-nuclear IgM antibodies can protect against LLL, probably through induction of tumor cell apoptosis. (CJ and MZ are equal contributors)

Comparative Response Assessment by Serum Immunoglobulin M M-Protein and Total Serum Immunoglobulin M After Treatment of Patients With Waldenström Macroglobulinemia

Serum immunoglobulin (Ig) M monoclonal protein determined by electrophoresis (sIgM-MP) and total serum IgM (sIgM) by nephelometry are widely used for response assessment in Waldenström macroglobulinemia (WM), although have not been compared for predicting changes in underlying disease burden. We, therefore, compared these serum markers with changes in bone marrow (BM) and extramedullary disease for 73 patients who were rituximab naive and treated with a rituximab-containing regimen. By linear regression analysis, reductions in sIgM-MP and sIgM showed moderate correlation with BM disease involvement (r = 0.4051 and r = 0.4490, respectively), and did not differ from one another as estimators of BM disease response (P = .3745). Neither sIgM-MP nor sIgM showed a strong correlation with BM disease response in patients with low (<1000 mg/dL) or high (>5000 mg/dL) IgM levels and extramedullary disease response. sIgM-MP and sIgM, therefore, are comparable response markers in WM. Development of newer, more accurate surrogate response markers are needed to better delineate treatment outcomes in patients with WM and with low or high IgM levels, and extramedullary disease.

An international, open label, randomised controlled trial comparing rituximab with azathioprine as maintenance therapy in relapsing ANCA-associated vasculitis (RITAZAREM)

© 2015 Elsevier Masson to achieve long-term B cells depletion. Patients were closely monitored during 46.5 (2–88) months follow-up with clinical and serological surveillance. They received a RTX cumulative dose of 8 g (2–13). Results.– Median serum Ig levels declined continuously – but not gradually – after each RTX re-treatment. The biggest decline in Ig took place after the first RTX round. IgM and IgG levels were below normal in respectively 22 (65%) and 16 (47%) patients – 15 patients (44%) with combined low levels of IgM and IgG – already after the first round. Eleven patients (29%) had a cumulative CYC dose of 50 g or more and they had lower levels of total Ig after the first 3 RTX rounds and lower levels during RTX maintenance. However the 12 patients (32%) receiving CYC in combination with RTX at induction had bigger overall decline in IgG (3.6 vs 2.2 g/L P = 0.028), IgA (0.78 vs 0.32 g/L P = 0.028), IgM (0.53 vs 0.26 g/L) and total Ig (4.9 vs 2.9 g/L P = 0.030) at last visit compared to those receiving RTX without CYC. Conclusion.– Ig decrease the most after the first RTX round under RTX maintenance. While a high cumulative CYC dose (> 50 g) decreases Ig levels at all time during RTX maintenance, the combination of CYC-RTX at initiation has a synergistic effect with bigger decline of Ig at last visit.

Hypogammaglobulinemia in sepsis is not correlated to high circulating angiopoietin-2 levels

Hypogammaglobulinemia has been frequently found in adult patients with severe sepsis and septic shock. Furthermore, it seems that at least a low serum level of IgM is correlated with higher mortality in sepsis. The mechanisms of hypogammaglobulinemia in septic shock have not yet been explained. It has been hypothesized that outflow of immunoglobulins into the extravascular space due to increased capillary permeability could reduce immunoglobulin serum concentrations. Angiopoietin-2, which directly disrupts the endothelial barrier, is markedly elevated in sepsis and other inflammatory states and its serum level has been correlated with microvascular leakage, end-organ dysfunction and death in sepsis.

Humoral immune response of the small-spotted catshark, Scyliorhinus canicula

Cartilaginous fishes are the oldest group in which an adaptive immune system based on immunoglobulin-superfamily members is found. This manuscript compares humoral immune function in small-spotted catshark (Scyliorhinus canicula) with that described for spiny dogfish (Squalus acanthias), another member of the Squalomorphi superorder, and nurse shark, the model for humoral immunity in elasmobranchs and a member of the Galeomorphi superorder. Although small-spotted catshark and nurse shark are separated by over 200 million years we found that immunoglobulin isoforms are well conserved between the two species. However, the plasma protein profile of small-spotted catshark was most similar to that of spiny dogfish, with low levels of pentameric IgM, and IgNAR present as a multimer in plasma rather than a monomer. We show that an antigen-specific monomeric IgM response, with a profile similar to that described previously for nurse sharks, can be raised in small-spotted catshark. Lacking polyclonal or monoclonal antibody reagents for detecting catshark IgNAR we investigated phage-display and recombinant Fc-fusion protein expression as alternative methods to look for an antigen-specific response for this isotype. However, we could find no evidence of an antigen-specific IgNAR in the animals tested using either of these techniques. Thus, unlike nurse sharks where antigen-specific monomeric IgM and IgNAR appear together, it seems there may be a temporal or complete ‘uncoupling’ of these isotypes during a humoral response in the small-spotted catshark.

Systemic Atopy and Immunoglobulin Deficiency in Turkish Patients with Vernal Keratoconjunctivitis

Purpose: To determine the prevalence of systemic atopy and immunoglobulin (Ig) deficiencies in vernal keratoconjunctivitis (VKC).Methods: Sixty-seven VKC subjects (79.1% boys) with a mean age of 11.3 ± 4.3 years were included. Serum Ig levels and specific IgE levels were measured using the nephelometric method and reversed enzyme immunoassay with sandwich ELISA technique, respectively. The patients underwent epidermal skin tests with commercial extracts.Results: Family history of atopy and associated systemic allergies were detected in 32.8 and 40.3% of the subjects, respectively. Blood eosinophilia, elevated total, and specific IgE and positive skin tests were detected in 33.8, 42.2, 50, and 35% of the subjects, respectively. Out of 62 subjects, low levels of IgA, IgG, IgM, and IgG3 were detected in 12.9, 8, 6.5, and 1.6% of the patients, respectively.Conclusion: IgE-mediated mechanisms are involved in approximately 40% of VKC patients. A new finding was the higher incidence of Ig deficiency.