Inorganic or organic zinc and MUC-2, IgA,IL-17, TGF-β4 gene expression and sIgA secretion in broiler chickens

The study compared the effect of dietary supplementation with an inorganic or organic source of zinc (Zn) on mucin 2 (MUC-2) and IgA gene expression, the cytokines IL-17 and TGF-β4 and the secretory IgA content (sIgA) in broiler jejunum. One-day-old chickens were fed an unsupplemented basal diet (BD) or the same BD supplemented with 30 or 70?mg/kg of added Zn from ZnSO₄·H₂O or Zn chelate of glycine hydrate for 40 days. The highly expressed MUC-2 and IgA genes were observed in both groups supplemented with the low-dose Zn sources (30?mg/kg). A higher sIgA concentration was observed in both the ZnSO₄ groups and the glycine-zinc/30?mg group. Our data indicate that the organic Zn chelate has better availability than the inorganic Zn source, and the low-dose Zn diets proved to be more beneficial to the maintenance of intestinal immune homeostasis.     

New insights in the pathogenesis of immunoglobulin A vasculitis (Henoch-Schönlein purpura)

Immunoglobulin A vasculitis (IgAV), also referred to as Henoch-Schönlein purpura, is the most common form of childhood vasculitis. The pathogenesis of IgAV is still largely unknown. The disease is characterized by IgA1-immune deposits, complement factors and neutrophil infiltration, which is accompanied with vascular inflammation. Incidence of IgAV is twice as high during fall and winter, suggesting an environmental trigger associated to climate. Symptoms can resolve without intervention, but some patients develop glomerulonephritis with features similar to IgA nephropathy that include hematuria, proteinuria and IgA deposition in the glomerulus. Ultimately, this can lead to end-stage renal disease. In IgA nephropathy immune complexes containing galactose-deficient (Gd-)IgA1 are found and thought to play a role in pathogenesis. Although Gd-IgA1 complexes are also present in patients with IgAV with nephritis, their role in IgAV is disputed. Alternatively, it has been proposed that in IgAV IgA1 antibodies are generated against endothelial cells. We anticipate that such IgA complexes can activate neutrophils via the IgA Fc receptor FcαRI (CD89), thereby inducing neutrophil migration and activation, which ultimately causes tissue damage in IgAV. In this Review, we discuss the putative role of IgA, IgA receptors, neutrophils and other factors such as infections, genetics and the complement system in the pathogenesis of IgA vasculitis.     

Enhanced differentiation of intraepithelial lymphocytes in the intestine of polymeric immunoglobulin receptor‐deficient mice

To clarify the effect of secretory IgA (sIgA) deficiency on gut homeostasis, we examined intraepithelial lymphocytes (IELs) in the small intestine (SI) of polymeric immunoglobulin receptor-deficient (pIgR^−/−) mice. The pIgR^−/− mice exhibited the accumulation of CD8αβ⁺ T-cell receptor (TCR)-αβ⁺ IELs (CD8αβ⁺αβ-IELs) after weaning, but no increase of CD8αβ⁺γδ-IELs was detected in pIgR^−/− TCR-β^−/− mice compared with pIgR^+/+ TCR-β^−/− mice. When 5-bromo-2′-deoxyuridine (BrdU) was given for 14 days, the proportion of BrdU-labelled cells in SI-IELs was not different between pIgR^+/+ mice and pIgR^−/− mice. However, the proportion of BrdU-labelled CD8αβ⁺-IELs became higher in pIgR^−/− mice than pIgR^+/+ mice 10 days after discontinuing BrdU-labelling. Intravenously transferred splenic T cells migrated into the intraepithelial compartments of pIgR^+/+ TCR-β^−/− mice and pIgR^−/− TCR-β^−/− mice to a similar extent. In contrast, in the case of injection of immature bone marrow cells, CD8αβ⁺αβ-IELs increased much more in the SI of pIgR^−/− TCR-β^−/− mice than pIgR^+/+ TCR-β^−/− mice 8 weeks after the transfer. αβ-IELs from pIgR^−/− mice could produce more interferon-γ and interleukin-17 than those of pIgR^+/+ mice, and intestinal permeability tended to increase in the SI of pIgR^−/− mice with aging. Taken together, these results indicate that activated CD8αβ⁺αβ-IELs preferentially accumulate in pIgR^−/− mice through the enhanced differentiation of immature haematopoietic precursor cells, which may subsequently result in the disruption of epithelial integrity.     

A new mouse anti-mouse complement receptor type 2 and 1 (CR2/CR1) monoclonal antibody as a tool to study receptor involvement in chronic models of immune responses and disease

Although reagents are available to block mouse complement receptor type 2 and/or type 1 (CR2/CR1, CD21/CD35) function in acute or short term models of human disease, a mouse anti-rat antibody response limits their use in chronic models. We have addressed this problem by generating in Cr2−/− mice a mouse monoclonal antibody (mAb 4B2) to mouse CR2/CR1. The binding of murine mAb 4B2 to CR2/CR1 directly blocked C3dg (C3d) ligand binding. In vivo injection of mAb 4B2 induced substantial down regulation of CR2 and CR1 from the B cell surface, an effect that lasted six weeks after a single injection of 2 mg of mAb. The 4B2 mAb was studied in vivo for the capability to affect immunological responses to model antigens. Pre-injection of mAb 4B2 before immunization of C57BL/6 mice reduced the IgG1 antibody response to the T-dependent antigen sheep red blood cells (SRBC) to a level comparable to that found in Cr2−/− mice. We also used the collagen-induced arthritis (CIA) model, a CR2/CR1-dependent autoimmune disease model, and found that mice pre-injected with mAb 4B2 demonstrated substantially reduced levels of pathogenic IgG2a antibodies to both the bovine type II collagen (CII) used to induce arthritis and to endogenous mouse CII. Consistent with this result, mice pre-injected with mAb 4B2 demonstrated only very mild arthritis. This reduction in disease, together with published data in CII-immunized Cr2−/− mice, confirm both that the arthritis development depends on CR2/CR1 receptors and that mAb 4B2 can be used to induce biologically relevant receptor blockade. Thus mAb 4B2 is an excellent candidate for use in chronic murine models to determine how receptor blockage at different points modifies disease activity and autoantibody responses.     

单克隆抗体反向间接血凝诊断血吸虫病的现场应用研究

在现场条件下,用双盲法对单克隆抗体反向间接血凝试验(McAb—RIHA)诊断血吸虫病的效果进行了观察。结果显示,McAb—RIHA 与 Kato 法粪检总的样本检测符合率达80.0%,与粪检阳证样本的符合率(校正)达83.9%,对粪检阳性,McAb-RIHA 阴性的样本复查排除37.5%(3/8)的粪检假阳性,对粪检阴性,McAb—RIHA 阳性的样本Kato 法复查一次(3张涂片)检出24.6%的样本阳性(14/57),是总样本粪阳率6.79%(34/501)的2.62倍,与单克隆抗体斑点酶联免疫吸附试验(McAb—Dot—ELISA)的检测结果比较,两法无显著性差异。实验结果表明,McAb-RIHA 在现场用于诊断血吸虫病具有较为理想的准确性,且其操作简便、诊断快速,具有较高的现场实用性。     

Successful treatment with rituximab for autoimmune hemolytic anemia concomitant with proliferation of Epstein-Barr virus and monoclonal gammopathy in a post-nonmyeloablative stem cell transplant patient

A 30-year-old Japanese woman who underwent nonmyeloablative stem cell transplantation from her HLA-matched sister developed autoimmune hemolytic anemia (AIHA). There was proliferation of EBV-DNA in her peripheral blood and monoclonal gammopathy, both predictive factors of post-transplant lymphoproliferative disorder (PTLD). As conventional immunosuppressive therapy for AIHA could lead to overt PTLD, we decided to give her rituximab 375 mg/m² once weekly for a total of four doses. After this therapy, both her AIHA and monoclonal gammopathy were resolved and EBV-DNA became undetectable. Rituximab therapy deserves consideration for treatment of post-allogeneic stem cell transplant patients with AIHA, especially for patients who cannot be given immunosuppressive therapy.     

NK cell abnormality and its treatment in women with reproductive failures such as recurrent pregnancy loss,implantation failures,preeclampsia, and pelvic endometriosis

The regulation of uterine and peripheral blood natural killer (NK) cells has been associated with problems related to reproductive immunology such as recurrent pregnancy loss (RPL), implantation failure or preeclampsia. NKp46, one of the natural cytotoxicity receptors (NCRs), is a unique marker that functions in NK cell cytotoxicity and cytokine production. Expression of NKp46 on NK cells is lower in women with recurrent pregnancy loss and pregnancy‐induced hypertension. Moreover, expression of NKp46 on peritoneal fluid NK cells is lower in women with pelvic endometriosis. Therefore, evaluation of NKp46 on peripheral blood NK cells may provide a means of screening for reproductive abnormalities. Recently, a new type of NK cell, the NK22 cell, has been reported. This cell may be a regulator not only of the mucosal barrier but also of reproduction. For women with RPL showing abnormal uterine and/or peripheral blood NK cells, both intravenous immunoglobulin treatment and intralipid treatment have been reported. The effects of these treatments are still controversial, and further studies are needed in order to clarify their true impact. The present review examines variations in the expression of NCRs on NK cells, the participation of NK22 cells in reproduction, and the possible use of intravenous immunoglobulin or intralipid treatment for women with recurrent pregnancy loss and NK cell abnormality.     

Immunoglobulin (Ig)G purified from human sera mirrors intravenous Ig human leucocyte antigen (HLA) reactivity and recognizes one's own HLA types,but may be masked by Fab complementarity‐determining region peptide in the native sera

Intravenous immunoglobulin (IVIg) reacted with a wide array of human leucocyte antigen (HLA) alleles, in contrast to normal sera, due possibly to the purification of IgG from the pooled plasma. The reactivity of IgG purified from normal sera was compared with that of native sera to determine whether any serum factors mask the HLA reactivity of anti‐HLA IgG and whether IgG purified from sera can recognize the HLA types of the corresponding donors. The purified IgG, unlike native sera, mirrored IVIg reactivity to a wide array of HLA‐I/‐II alleles, indicating that anti‐HLA IgG may be masked in normal sera – either by peptides derived from soluble HLA or by those from antibodies. A < 3 kDa peptide from the complementarity‐determining region (CDR) of the Fab region of IgG (but not the HLA peptides) masked HLA recognition by the purified IgG. Most importantly, some of the anti‐HLA IgG purified from normal sera – and serum IgG from a few donors – indeed recognized the HLA types of the corresponding donors, confirming the presence of auto‐HLA antibodies. Comparison of HLA types with the profile of HLA antibodies showed auto‐HLA IgG to the donors' HLA antigens in this order of frequency: DPA (80%), DQA (71%), DRB345 (67%), DQB (57%), Cw (50%), DBP (43%), DRB1 (21%), A (14%) and B (7%). The auto‐HLA antibodies, when unmasked in vivo, may perform immunoregulatory functions similar to those of therapeutic preparations of IVIg.     

Current treatment options with immunoglobulin G for the individualization of care in patients with primary immunodeficiency disease

Primary antibody deficiencies require lifelong replacement therapy with immunoglobulin (Ig)G to reduce the incidence and severity of infections. Both subcutaneous and intravenous routes of administering IgG can be effective and well tolerated. Treatment regimens can be individualized to provide optimal medical and quality‐of‐life outcomes in infants, children, adults and elderly people. Frequency, dose, route of administration, home or infusion‐centre administration, and the use of self‐ or health‐professional‐administered infusion can be tailored to suit individual patient needs and circumstances. Patient education is needed to understand the disease and the importance of continuous therapy. Both the subcutaneous and intravenous routes have advantages and disadvantages, which should be considered in selecting each patient's treatment regimen. The subcutaneous route is attractive to many patients because of a reduced incidence of systemic adverse events, flexibility in scheduling and its comparative ease of administration, at home or in a clinic. Self‐infusion regimens, however, require independence and self‐reliance, good compliance on the part of the patient/parent and the confidence of the physician and the nurse. Intravenous administration in a clinic setting may be more appropriate in patients with reduced manual dexterity, reluctance to self‐administer or a lack of self‐reliance, and intravenous administration at home for those with good venous access who prefer less frequent treatments. Both therapy approaches have been demonstrated to provide protection from infections and improve health‐related quality of life. Data supporting current options in IgG replacement are presented, and considerations in choosing between the two routes of therapy are discussed.