Alternative pathway activation due to low level of complement factor H in primary antiphospholipid syndrome.

Introduction: Although complement activation has been proposed as a possible thrombophilic mechanism in antiphospholipid syndrome (APS), the origin of complement activation in APS remains unclear. Here, we focused on complement regulatory factors (CRF), which control the complement system to prevent damage to host tissue. We evaluated the function of two major CRF, membrane cofactor protein (MCP) and factor H (FH), in APS patients.

Studies of innate immune systems against human cells.

Background: Pigs are frequently used as animal models for experiments in the surgical field, including allo- and xeno-transplantation. Regeneration studies, including studies dealing with human- and monkey-induced pluripotent stem cells (iPSC), have gradually progressed, with pigs sometimes being used as the scaffold. However, the immunological response of pigs against humans, especially innate immunities, remain unclear.

Serial change of C1 inhibitor in patients with sepsis--a preliminary report.

Objective: C1 inhibitor (C1INH) regulates not only the complement system but also the plasma kallikrein-kinin, fibrinolytic, and coagulation systems. The biologic activities of C1INH can be divided into the regulation of vascular permeability and anti-inflammatory functions. The objective was to clarify the serial change of C1INH in patients with sepsis.

A case of fibrillary glomerulonephritis associated with thrombotic microangiopathy and anti-glomerular basement membrane antibody.

We present the first report of a case of fibrillary glomerulonephritis (FGN) associated with thrombotic microangiopathy (TMA) and anti-glomerular basement membrane antibody (anti-GBM antibody). A 54-year-old man was admitted to our hospital for high fever and anuria. On the first hospital day, we initiated hemodialysis for renal dysfunction.

A case of infantile systemic lupus erythematosus with severe lupus nephritis and EBV infection.

Infantile systemic lupus erythematosus (iSLE) is extremely rare. Patients with iSLE usually become severely unwell and have poor prognosis. Epstein-Barr virus (EBV) infection has been implicated in the development of SLE in both adults and children.

The identification of a novel splicing mutation in C1qB in a Japanese family with C1q deficiency: a case report.

C1q deficiency is a rare disease that is associated with a high probability of developing systemic lupus erythematosus. We report a 4-year-old Japanese girl who presented with fever, facial erythema, joint pain, and oral ulceration. Complement deficiencies were suspected because of her persistent hypocomplementemia and normal levels of the complement proteins C3 and C4.

Thomsen-Friedenreich antigen exposure as a cause of Streptococcus pyogenes-associated hemolytic-uremic syndrome.

Infection with Streptococcus pyogenes, a Group A beta-hemolytic streptococcus (GAS), is a rare cause of hemolyticuremic syndrome (HUS). Invasive infections with Streptococcus pneumoniae that produce neuraminidase are a well-recognized cause of HUS without diarrhea. The Thomsen- Friedenreich antigen (T antigen) plays a role in the pathophysiology of pneumococcal HUS.

Successful pregnancy in a patient suffering from recurrent mid-trimester miscarriage with C9 deficiency after receiving cervical cerclage followed by clindamycin and progesterone: a case report.

Complement component 9 (C9) deficiency is relatively common, especially in Japan. Here we present the case of a 27-year-old Japanese woman whose obstetric history involved three mid-trimester miscarriages (at 22 weeks', 18 weeks' and 21 weeks' gestation) and one early spontaneous miscarriage. Her fifth pregnancy was successfully managed by cervical cerclage at 13 weeks' gestation, followed by clindamycin administration (600 mg/day for 7 days) and progesterone injections (250 mg/week).

Etanercept is safely used for treating psoriatic arthritis in a patient complicated with type 1 hereditary angioedema.

Hereditary angioedema (HAE) is a life-threatening disorder caused by deficiency or dysfunction of the C1 inhibitor protein. Patients with HAE are restricted in various medical treatments, which can induce an HAE attack. We herein report the first case of psoriatic arthritis (PSA) with type 1 HAE successfully treated with 25 mg of etanercept without HAE attack.

A case of dense deposit disease associated with a group A streptococcal infection without the involvement of C3NeF or complement factor H deficiency.

A 14-year-old girl presented with acute glomerulonephritis. Tests revealed hypocomplementemia and elevated Antistreptolysin-O titers, and renal biopsy revealed endocapillary and mesangial proliferative glomerulonephritis with double contours of the glomerular basement membrane (GBM). Despite methylprednisolone pulse therapy and the administration of oral prednisolone, overt proteinuria and hypocomplementemia persisted.

Studies of monkey complement: measurement of cynomolgus monkey CH50, ACH50, C4, C2 and C3.

Background: The cynomolgus monkey is commonly used as the recipient in transplantation experiments. However, study of the complement system of cynomolgus monkeys is lacking. In the present study, the complement system of cynomolgus monkeys was compared with that of humans, by checking hemolytic titers.

Effect of tandem forms of DAF(CD55) on complement-mediated xenogeneic cell lysis.

Background: It is difficult to produce a transgenic animal with high expression of decay-accelerating factor (CD55: DAF) or other molecules. The purpose of this study was to assess the effect of tandem forms of DAF on a xenogeneic cell membrane against human complement.

Methods: cDNAs of the delta-Short Consensus Repeat (SCR) 1-DAF, the double-DAF, the triple-DAF, and the tetra-DAF with a FLAG-tag were established.

Interaction of poly(styrene sulfonic acid) with the classical pathway of the serum complement system.

Bioartificial pancreas, in which the islets of Langerhans (islets) are enclosed in artificial membrane to be protected from the host immune system, is expected to be a promising medical device to treat patients who suffer from insulin-dependent diabetes. Our strategy for the preparation of a bioartificial pancreas involves utilizing a membrane including polymeric materials that can inhibit the complement. When we examined a membrane containing poly(styrene sulfonic acid), long survival of islets enclosed in the membrane was observed in recipients carrying antibodies against islet cells.

Interaction of poly(styrene sulfonic acid) with the alternative pathway of the serum complement system.

Bioartificial pancreas, in which the islets of Langerhans are enclosed in artificial membrane to be protected from the host immune system, is expected to be a promising medical device to treat patients who suffer from insulin-dependent diabetes. Our strategy for preparation of a bioartificial pancreas involves utilizing a membrane including polymeric materials that can inhibit the complement reaction. In this study, we examined the effects of poly(styrene sulfonic acid) (PSSa) on the alternative pathway of the serum complement system to identify the mechanism(s) involved.

A study of the xenoantigenicity of adult pig islets cells.

Background: The pig pancreas is considered to be the most suitable source of islets for xenotransplantation into patients with type I diabetes. The purpose of this study was to assess the antigenicity of pig islets, including the Galalpha1-3Galbeta1-4GlcNAc-R (the alpha-Gal) and Hanganutziu-Deicher (H-D) antigens, and the pathway involved in human complement activation.

Methods: The expression of alpha-Gal on islets from adult pigs was investigated by immunohistochemical staining and flowcytometric analysis.

Effect of adsorbent of Riposorber, a cellulose microparticle with immobilized dextran sulfate, on the serum complement system.

Abstract-Apheresis. using columns of cellulose microparticles with immobilized dextran sulfate, Riposorber, has been applied to treatment of patients with various diseases, such as hypercholesterolemia and systemic lupus erythematosus. Unfortunately, it has been reported that the apheresis activates the complement system.

Dextran sulfate as a material for the preparation of a membrane for immunoisolation.

Bioartificial pancreas, in which the islets of Langerhans (islets) are enclosed in an artificial membrane to be protected from the host immune system, is expected to be a promising medical device to treat patients who suffer from insulin-dependent diabetes. Our strategy for preparation of a bioartificial pancreas involves utilizing a membrane including polymeric materials that can inhibit the complement. In our series of studies, we have examined interactions of various polyanions with the complement system to search for potential complement inhibitors.

Deposition of complement protein C3b on mixed self-assembled monolayers carrying surface hydroxyl and methyl groups studied by surface plasmon resonance.

Since complement activation is recognized as a common response of the host defense system when an artificial medical device is applied to a patient, great effort has been devoted to studies on the interaction of the complement system with artificial materials. However, some uncertainties remain, partially because of the lack of well characterized surfaces and suitable analytic methods for study of the surface phenomena that occur on artificial materials under physiologic conditions. In this study, we employed self-assembled monolayers (SAMs) and the surface plasmon resonance (SPR) technique to study interactions of the serum complement with well characterized surfaces.

Development of a novel cytomedical treatment that can protect entrapped cells from host humoral immunity.

Cell therapy is expected to relieve the shortage of donors needed for organ transplantation. When patients are treated with allogeneic or xenogeneic cells, it is necessary to develop a means by which to isolate administered cells from an immune attack by the host. We have developed "cytomedicine," which consists of functional cells entrapped in semipermeable polymer, and previously reported that alginate-poly-L-lysine-alginate microcapsules and agarose microbeads could protect the entrapped cells from injury by cellular immunity.