Immunoglobulin Y (IgY) is an effective orally administered antibody used to protect against various intestinal pathogens, but which cannot tolerate the acidic gastric environment. In this study, IgY was microencapsulated by alginate (ALG) and coated with chitooligosaccharide (COS). A response surface methodology was used to optimize the formulation, and a simulated gastrointestinal (GI) digestion (SGID) system to evaluate the controlled release of microencapsulated IgY. The microcapsule formulation was optimized as an ALG concentration of 1.56% (15.6 g/L), COS level of 0.61% (6.1 g/L), and IgY/ALG ratio of 62.44% (mass ratio). The microcapsules prepared following this formulation had an encapsulation efficiency of 65.19%, a loading capacity of 33.75%, and an average particle size of 588.75 μm. Under this optimum formulation, the coating of COS provided a less porous and more continuous microstructure by filling the cracks on the surface, and thus the GI release rate of encapsulated IgY was significantly reduced. The release of encapsulated IgY during simulated gastric and intestinal digestion well fitted the zero-order and first-order kinetics functions, respectively. The microcapsule also allowed the IgY to retain 84.37% immune-activity after 4 h simulated GI digestion, significantly higher than that for unprotected IgY (5.33%). This approach could provide an efficient way to preserve IgY and improve its performance in the GI tract.
Alginic Acid/chemistry* ; Chitin/chemistry* ; Chitosan ; Delayed-Action Preparations ; Digestion ; Drug Compounding ; Drug Liberation ; Gastrointestinal Tract/metabolism* ; Immunoglobulins/metabolism* ; Oligosaccharides

A 61-year-old man presented with a 3-year history of erythematous firm nodules on the hands and feet. Histopathological findings of the lesional skin revealed perivascular and diffuse neutrophilic infiltrations on the upper and mid-dermis. Increased and dilated blood vessels were observed in the upper dermis. Fibrinoid necrosis of the vessel walls was unremarkable, but endothelial swelling and scant red blood cell (RBC) extravasation were noted. Fibrosis and sclerosis of collagen fibers were noted on the deep dermis. Results of laboratory examinations, including complete blood count (CBC), routine chemistry, c-reactive protein (CRP), syphilis and human immunodeficiency virus (HIV) tests, and serum immunoglobulin electrophoresis, were all negative or within normal limit. A diagnosis of erythema elevatum diutinum was made based on the clinical and histological findings. The patient was treated with prednisolone, dapsone, colchicine, and intralesional injection of triamcinolone and showed slight improvement after treatment for 8 months.
Blood Cell Count ; Blood Vessels ; C-Reactive Protein ; Chemistry ; Colchicine ; Collagen ; Dapsone ; Dermis ; Diagnosis ; Electrophoresis ; Erythema ; Erythrocytes ; Fibrosis ; Foot ; Hand ; HIV ; Humans ; Immunoglobulins ; Injections, Intralesional ; Middle Aged ; Necrosis ; Neutrophils ; Prednisolone ; Sclerosis ; Skin ; Syphilis ; Triamcinolone

OBJECTIVETo explore the influence of rosa roxburghii tratt preparation on immune function of arseniasis patients caused by burning coal.

METHODSAccording to the diagnosis standard for endemic arseniasis(WS/T 211-2001), 62 cases of arseniasis patients who resided in endemic arseniasis area in Guizhou province were selected and divided stratified randomly into two groups: rosa roxburghii tratt juice treatment group and superoxide dismutase(SOD)-enriched rosa roxburghii tratt juice treatment group, with 31 patients in each group.Each patient took 120 ml/d rosa roxburghii tratt preparation or SOD-enriched rosa roxburghii tratt orally for one month. Another 30 healthy residents from a neighbour township 12 km away where arsenic was not prevalent were selected as controls. A 2 ml blood and 50 ml urine samples were collected from individuals and the urine arsenic contents, peripheral blood T-lymphocyte subsets (CD3(+), CD4(+), CD8(+) T cell), serum immunoglobulin (IgG, IgM, IgA) and complement (C3, C4) were detected. The differences between more than two groups on above indicators were compared. The correlations between urinary arsenic and immune parameters were analyzed.

RESULTSAmong the rosa roxburghii tratt juice group, SOD-enriched rosa roxburghii tratt juice before intervention group and the control group, the levels of urine arsenic were (76.55 ± 23.02) , (72.60 ± 25.91) and (26.33 ± 11.30) µg/g Cr respectively and IgG were (11.31 ± 1.68), (11.35 ± 1.94) and (9.23 ± 1.75) g/L respectively. The differences were statistically significant(F values were 82.01, 13.82, both P values < 0.05). After intervention with rosa roxburghii tratt preparation, the levels of urine arsenic were (53.21 ± 16.51) and (51.72 ± 17.70)µg/g Cr, both decreased than before intervention (t values were 5.80 and 3.78, both P values < 0.05). The levels of CD3(+) were (44.47 ± 7.14)%, (43.44 ± 6.61)% and (70.78 ± 5.26)%, CD4(+) were (29.87 ± 5.67)%, (29.42 ± 5.87)% and (46.08 ± 5.87)%, CD4(+)/CD8(+) were(1.25 ± 0.42), (1.22 ± 0.39) and (1.79 ± 0.26) and C4 were (0.13 ± 0.08), (0.13 ± 0.09) and (0.20 ± 0.11) g/L respectively among the two treatment group before intervention and the control group. The differences were significant (F values were 178.04, 76.71, 23.13 and 5.26, all P values < 0.05). After intervention, the levels of CD3(+) were (59.73 ± 7.38)% and (66.31 ± 7.57)%, CD4(+) were (34.00 ± 7.97)% and (39.11 ± 5.81)%, CD4(+)/CD8(+) were (1.41 ± 0.37) and(1.58 ± 0.26), all increased than before intervention(t values were 12.47, 25.18, 5.41, 10.47, 3.22 and 5.05, all P values < 0.05). The levels of urine arsenic and CD3(+), CD4(+), CD4(+)/CD8(+), C4 were inversely correlated correlation, while positive correlation existed between the level of urine arsenic and IgG(r values were -0.68, -0.56, -0.51, -0.43 and 0.36, all P values < 0.01).

CONCLUSIONSThe level of urinary arsenic level is closely related to immune function suppression in arseniasis patients caused by burning coal, rosa roxburghii tratt preparation can effectively improve immune function of arseniasis patients.

Adult ; Arsenic ; urine ; Arsenic Poisoning ; etiology ; immunology ; China ; Coal ; Complement System Proteins ; immunology ; Female ; Humans ; Immunoglobulins ; immunology ; Male ; Middle Aged ; Plant Extracts ; pharmacology ; Rosa ; chemistry ; Superoxide Dismutase ; pharmacology ; T-Lymphocyte Subsets ; immunology

Leukocyte immunoglobulin-like receptors (LILRs), also called CD85s, ILTs, or LIRs, are important mediators of immune activation and tolerance that contain tandem immunoglobulin (Ig)-like folds. There are 11 (in addition to two pseudogenes) LILRs in total, two with two Ig-like domains (D1D2) and the remaining nine with four Ig-like domains (D1D2D3D4). Thus far, the structural features of the D1D2 domains of LILR proteins are well defined, but no structures for the D3D4 domains have been reported. This is a very important field to be studied as it relates to the unknown functions of the D3D4 domains, as well as their relative orientation to the D1D2 domains on the cell surface. Here, we report the crystal structures of the D3D4 domains of both LILRB1 and LILRB2. The two Ig-like domains of both LILRB1-D3D4 and LILRB2-D3D4 are arranged at an acute angle (∼60°) to form a bent structure, resembling the structures of natural killer inhibitory receptors. Based on these two D3D4 domain structures and previously reported D1D2/HLA I complex structures, two alternative models of full-length (four Ig-like domains) LILR molecules bound to HLA I are proposed.
Amino Acid Sequence ; Antigens, CD ; chemistry ; Crystallography, X-Ray ; Histocompatibility Antigens Class I ; chemistry ; Humans ; Immunoglobulins ; chemistry ; Leukocyte Immunoglobulin-like Receptor B1 ; Membrane Glycoproteins ; chemistry ; Models, Molecular ; Peptides ; chemistry ; metabolism ; Protein Binding ; Protein Structure, Tertiary ; Receptors, Immunologic ; chemistry ; Signal Transduction

Ig superfamily (IgSF) constitutes the largest superfamily in human genome. In particular, Ig-like domains are the most abundant structural module within cell surface receptors, functioning in nervous as well as immune system. Here I describe some key sequence signature of an I-set Ig-like domain from known structures of IgSF members. These signature residues define the I-set Ig-like domain, which should aid structural and functional studies of cell surface receptors.
Amino Acid Sequence ; Humans ; Hydrogen Bonding ; Immunoglobulins ; chemistry ; metabolism ; Molecular Sequence Data ; Protein Folding ; Protein Structure, Tertiary

Homophilic interaction of the L1 family of cell adhesion molecules plays a pivotal role in regulating neurite outgrowth and neural cell networking in vivo. Functional defects in L1 family members are associated with neurological disorders such as X-linked mental retardation, multiple sclerosis, low-IQ syndrome, developmental delay, and schizophrenia. Various human tumors with poor prognosis also implicate the role of L1, a representative member of the L1 family of cell adhesion molecules, and ectopic expression of L1 in fibroblastic cells induces metastasis-associated gene expression. Previous studies on L1 homologs indicated that four N-terminal immunoglobulin-like domains form a horseshoe-like structure that mediates homophilic interactions. Various models including the zipper, domain-swap, and symmetry-related models are proposed to be involved in structural mechanism of homophilic interaction of the L1 family members. Recently, cryo-electron tomography of L1 and crystal structure studies of neurofascin, an L1 family protein, have been performed. This review focuses on recent discoveries of different models and describes the possible structural mechanisms of homophilic interactions of L1 family members. Understanding structural mechanisms of homophilic interactions in various cell adhesion proteins should aid the development of therapeutic strategies for L1 family cell adhesion molecule-associated diseases.
Cell Adhesion ; Crystallography, X-Ray ; Escherichia coli ; Humans ; Immunoglobulins/chemistry ; Neural Cell Adhesion Molecule L1/*chemistry/*metabolism ; *Neurites/chemistry/metabolism ; Protein Conformation ; *Protein Interaction Domains and Motifs

Using directed mutagenesis and phage display on a soluble fragment of the human immunoglobulin super-family receptor ILT2 (synonyms: LIR1, MIR7, CD85j), we have selected a range of mutants with binding affinities enhanced by up to 168,000-fold towards the conserved region of major histocompatibility complex (MHC) class I molecules. Produced in a dimeric form, either by chemical cross-linking with bivalent polyethylene glycol (PEG) derivatives or as a genetic fusion with human IgG Fc-fragment, the mutants exhibited a further increase in ligand-binding strength due to the avidity effect, with resident half-times (t(1/2)) on the surface of MHC I-positive cells of many hours. The novel compounds antagonized the interaction of CD8 co-receptor with MHC I in vitro without affecting the peptide-specific binding of T-cell receptors (TCRs). In both cytokine-release assays and cell-killing experiments the engineered receptors inhibited the activation of CD8(+) cytotoxic T lymphocytes (CTLs) in the presence of their target cells, with subnanomolar potency and in a dose-dependent manner. As a selective inhibitor of CD8(+) CTL responses, the engineered high affinity ILT2 receptor presents a new tool for studying the activation mechanism of different subsets of CTLs and could have potential for the development of novel autoimmunity therapies.
Amino Acid Sequence ; Antigens, CD ; chemistry ; genetics ; pharmacology ; Autoimmunity ; Biological Assay ; Cell Line ; Cytotoxicity, Immunologic ; genetics ; immunology ; Dose-Response Relationship, Immunologic ; Humans ; Immunoglobulins ; immunology ; metabolism ; Immunologic Factors ; chemistry ; genetics ; pharmacology ; Kinetics ; Leukocyte Immunoglobulin-like Receptor B1 ; Lymphocyte Activation ; genetics ; immunology ; Major Histocompatibility Complex ; genetics ; immunology ; Molecular Sequence Data ; Molecular Targeted Therapy ; Mutagenesis, Site-Directed ; Peptide Library ; Polyethylene Glycols ; Protein Binding ; genetics ; immunology ; Receptors, Immunologic ; chemistry ; genetics ; Recombinant Fusion Proteins ; genetics ; metabolism ; T-Lymphocytes, Cytotoxic ; immunology ; metabolism

OBJECTIVETo investigate the effect and mechanisms of Compound Astragalus Recipe (CAR) for regulating cellular immune in patients with myasthenia gravis (MG).

METHODSSixty MG patients were equally assigned to two groups randomly, the test group administered with CAR and the control group with prednisone for 3 months. Changes of patients' symptoms and adverse reactions were observed. The peripheral lymphocyte subsets distribution was examined by flow cytometry, and the levels of immunoglobulins and complements in the peripheral blood were measured by immuno-turbidimetry before and after treatment.

RESULTSThe total effective rate in the test group after 12-week treatment reached 80% (24/30), while that of the control group reached 83.3% (25/30), difference between them showed no statistical significance (P > 0.05). CD4+ and CD4+/CD8+ ratio were lowered significantly in both groups, but the decrement of CD4+/CD8+ ratio in the test group was more significant than that in the control group, showing significance between groups (P < 0.05). While CD8+ in the test group after treatment was significantly increased as compared with that before treatment (P < 0.05), but with no significant difference in comparing with that in the control group (P > 0.05). Serum levels of IgM and IgA in MG patients were significantly higher than normal range (P < 0.01). Levels of C3 and C4 were significantly increased in both groups after treatment (P < 0.05). Moderate high level of ALT and AST revealed transiently at the 2nd week in 5 patients of the control group, while no adverse reaction was found in the test group.

CONCLUSIONOne of the mechanisms for CAR in playing its immuno-modulate effect may be its regulation on lymphocyte subsets distribution and humoral immune function.

Adolescent ; Adult ; Aged ; Astragalus membranaceus ; chemistry ; Child ; Complement System Proteins ; metabolism ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Immunoglobulins ; blood ; Lymphocyte Subsets ; drug effects ; Male ; Middle Aged ; Myasthenia Gravis ; drug therapy ; immunology ; Phytotherapy ; Young Adult

Intravenous immunoglobulin (IVIG) and/or plasmapheresis (PP) are effective in preventing antibody-mediated rejection (AMR) of kidney allografts, but AMR is still a problem. This study reports our experience in living donor renal transplantation in highly sensitized patients. Ten patients with positive crossmatch tests or high levels of panel-reactive antibody (PRA) were included. Eight patients were desensitized with pretransplant PP and low dose IVIG, and two were additionally treated with rituximab. Allograft function, number of acute rejection (AR) episodes, protocol biopsy findings, and the presence of donor-specific antibody (DSA) were evaluated. With PP/IVIG, six out of eight patients showed good graft function without AR episodes. Protocol biopsies revealed no evidence of tissue injury or C4d deposits. Of two patients with AR, one was successfully treated with PP/IVIG, but the other lost graft function due to de novo production of DSA. Thereafter, rituximab was added to PP/IVIG in two cases. Rituximab gradually decreased PRA levels and the percentage of peripheral CD20+ cells. DSA was undetectable and protocol biopsy showed no C4d deposits. The graft function was stable and there were no AR episodes. Conclusively, desensitization using PP/IVIG with or without rituximab increases the likelihood of successful living donor renal transplantation in sensitized recipients.
Adult ; Antibodies, Monoclonal/therapeutic use ; Antigens, CD20/biosynthesis ; Female ; Humans ; Immunoglobulins/metabolism ; Immunophenotyping ; Immunosuppressive Agents/therapeutic use ; Isoantibodies/chemistry ; Kidney Failure, Chronic/therapy ; Kidney Transplantation/*methods ; Lymphocytes/metabolism ; Male ; Middle Aged ; Retrospective Studies

A successful transplantation, across a positive crossmatch barrier, is one of the most persistent long- standing problems in the field of kidney transplant medicine. The aim of this study was to describe seven consecutive living renal transplantations in recipients with positive crossmatch for donors or positive for donor specific antibodies (DSAs). A preconditioning regimen including plasmapheresis and intravenous immunoglobulin was delivered three times a week until the crossmatch and/ or DSAs became negative. Mycophenolate mofetil and tacrolimus were started two days before the plasmapheresis. The protocol was modified to include administration of anti-CD 20 antibody (rituximab, 375 mg/m(2)) from the patient number 3 through the patient number 7. All seven patients achieved negative conversion of the crossmatch or DSAs, and the kidney transplantations were successfully performed in all cases. Acute cellular rejection occurred in two patients, which were subclinical and controlled with high dose steroid treatment. Antibody-mediated rejection occurred in one patient, which was easily reversed with plasmapheresis. All recipients attained normal graft function during the 7-24 months of follow up. Our study suggests that sensitized patients can be transplanted successfully with desensitization pretreatment.
Adult ; Antibodies, Monoclonal/pharmacology ; Antigens, CD20/biosynthesis ; Biopsy ; Female ; Graft Rejection ; Graft Survival ; Histocompatibility Testing/methods ; Humans ; Immunoglobulins/chemistry ; Kidney Transplantation/*methods ; Male ; Middle Aged ; Plasmapheresis ; Transplantation Conditioning