Sadayoshi Yoshinoya

IgG1 Antibodies to House Dust Mite (Dermatophagoides farinae) and Late Asthmatic Response

Thirteen asthmatic patients sensitive to mite were challenged by inhalation of an extract of mites (Dermatophagoides farinae). Seven showed dual bronchial reactions and 5 showed isolated immediate responses. No patient showed an isolated late reaction. Six of seven patients with dual reaction had higher IgG1 antibodies than the 5 patients with isolated immediate reaction when examined before the challenge. A similar result was obtained in terms of levels of immune complex. IgE, IgG4 and total IgG antibodies were not predictive for late reaction. These results suggest that there is a close correlation of the presence of high IgG1 antibodies with a propensity to develop late asthmatic responses. The meaning of this observation is discussed.

Detection of Fc-receptor on human renal glomerulus.

Abstract Six surgically removed normal human kidney specimens were examined by rosette formation techniques on tissue sections. Sheep red cells (SRC) sensitized with IgG hemolysin (IgG-EA) and those with IgM hemolysin and complement (IgM-EAC) exclusively stuck to renal glomeruli, while SRC sensitized with reduced and alkylated IgG hemolysin ( R A IgG-EA) and those with IgM hemolysin only (IgM-EA) or nonsensitized SRC (E) did not stick to renal specimens. The sticking of IgG-EA was significantly inhibited by aggregated human IgG, as well as by the sera from patients with active SLE. In the present study, the evidence that human renal glomeruli bear not only complement receptors but also Fc-receptors was presented. The possibility was discussed that circulating immune complexes may be trapped into renal glomeruli by these receptors and will result in the depositions as observed in immune complex nephritis such as lupus nephritis.

Annular erythema, dermatomyositis, and Sjögren's syndrome

In January 1989, a 26-year-old man first noted a fever of 39 to 40°C and swelling of the parotid glands bilaterally. Within 1 week, asymptomatic erythema developed on his upper eyelids and anterior chest. He denied photosensitivity, muscle weakness, and intake of drugs. With a diagnosis of viral toxic eruption the patient was given antibiotics with no effect. A high fever lasting for 2 weeks caused moderate dehydration. Laboratory examination showed hyponatremia of 117 mEq/L and hypoalbuminemia of 2.3 g/dL, in addition to severe leukopenia of 900 per IJL and a high CPK value of 6600 lU per L. An indirect immunofluorescent study revealed a speckled and cytoplasmic pattern, both at a titer of 1:160 on Hep-2 cells. A Jo-1, SS-A antibody and rheumatic factor were also detected, whereas an SS-B antibody test was negative. The HLA phenotype was A2, A24(9), B67, B52(5), Cw7, DR2, DR8. The patient was referred as an emergency to a Department of Internal Medicine in Tokyo University Hospital on February 27, 1989. A dusky erythematous eruption was observed on the brow, upper eyelid, and malar region that was characteristic of a skin lesion of dermatomyositis (Fig. IA). On the dorsum of hands, Gottrons papules developed (Fig. IB). We hesitated to do a skin and muscle biopsy because of his serious general condition. Steroid pulse therapy (hydrocortisone, 1500 mg per day) was started immediately, although the diagnosis of dermatomyositis/Sjogren syndrome was based on circumstantial evidence alone. After 5 days, the clinical findings and laboratory data had improved dramatically. During the next 6 weeks, the dosage of the corticosteroid was gradually reduced without a relapse and the patient left hospital on April 15, with 20 mg per day of prednisolone as a maintenance dose. After discharge, low dose prednisolone (5 to 15 mg per day) was continued and his general condition had been quite stable for almost 1 year. The erythema on the face and chest had disappeared, leaving only slight pigmentation; however, he has noted an asymptomatic annular erythema in front of the ears bilaterally since January 1990. In the following 4 months, this new rash spread in a centrifu-

Destruction of cultured vascular endothelial cells and red blood cells by immune-activated polymorphonuclear leukocytes

The cytotoxicity of human polymorphonuclear leukocytes (PMNs) against autologous red blood cells (RBC) and cultured vascular endothelial cells (EC) was investigated. PMNs were activated by phorbol myristate acetate (PMA) together with immune stimuli such as immune complexes and aggregated IgG. In the standard51Cr-release assay, in which PMA concentration was 5 ng/ml and effector versus target ratio was 5, 76.7% and 34.2% specific51Cr release was observed from RBC and EC, respectively. Significant levels of51Cr were released, albeit to a lesser degree, when PMNs were stimulated by immune stimuli. Further experiments which employed various scavengers of oxygen radicals suggested that hydrogen peroxide was the most potent mediator of this cytotoxicity; the implications of these in vitro observations with the pathogenesis of immune vasculitis are of clinical interest.

Enhanced Endothelial Cell Proliferation in Acute Kawasaki Disease (Muco-Cutaneous Lymph Node Syndrome)

Abstract: Paired sera from 30 patients with mucocutaneous lymph node syndrome (Kawasaki disease) were studied for possible effects on human vascular endothelial cells growth in vitro. The majority of sera from acute phase muco-cutaneous lymph node syndrome patients significantly enhanced endothelial cell proliferation more than those from convalescent phase patients, infectious diseases patients, and age-matched normal controls. This stimulation was considered to be specific for EC since muco-cutaneous lymph node syndrome sera did not enhance fibroblast growth more than normal sera. Fractionation of the serum with gel filtration failed to clearly detect the molecular properties of this effect, although both heavy and light material possessed this activity. Extensive search for circulating immune complex in muco-cutaneous lymph node syndrome sera were negative, suggesting that the enhanced endothelial cell proliferation was due to serum components other than immune complexes.

Endothelial Cell Destruction by Polymorphonuclear Leukocytes Incubated with Sera from Patients with Systemic Lupus Erythematosus (SLE)

When normal polymorphonuclear leukocytes (PMN) were incubated with sera from patients with active systemic lupus erythematosus (SLE), a significantly increased cytotoxicity against human cultured vascular endothelial cells (EC), compared with normal control sera, was demonstrated by the standard 51Cr release method. The degree of this cytotoxicity was correlated with the immune complex level in each serum. The cytotoxicity did not correlate with the presence of anti-EC antibody. An absorption study with C1q-Sepharose 4B further suggested that the immune complexes are the factor which induce cytotoxicity. A gel fractionation study, however, indicated the heterogenity of the cytotoxic activity, and suggested the possible contribution of other substances including anti-EC, at least in some of the patients. This type of cytotoxicity may initiate the inflammatory process including vascular damage of the disease.

Accessory Cell Function of Human Vascular Endothelial Cells in Pokeweed-Mitogen-Stimulated Immunoglobulin Production by Peripheral Blood Lymphocytes

The possibility that human vascular endothelial cells (EC) can function as accessory cells for pokeweed mitogen (PWM)-induced immunoglobulin synthesis by peripheral blood lymphocytes was examined. Adherent cells (AC) were vigorously depleted from peripheral blood mononuclear cells (PBMC) and PBMC were cocultured with or without various numbers of EC or AC in the presence of PWM. EC which had been treated with interferon-gamma (IFN-gamma) expressed HLA class II antigens on the surface and promoted both IgM and IgG production by lymphocytes as effectively as monocytes did. Nontreated EC also enhanced immunoglobulin synthesis, but less effectively. Pretreatment of EC with monoclonal anti-HLA class II antigen antibody suppressed the accessory cell function of EC. These results indicate that EC have the ability to function as sufficient accessory cells in the mitogen-induced in vitro immunoglobulin synthesis, and that this ability was closely related to the expression of HLA class II antigen. Under the circumstance of an inflammatory response where IFN-gamma would exist, the accessory cell function of EC would be enhanced and would modify the immune response of immunocompetent cells.

Extracorporeal hydrophobic amino acid adsorbent therapy in rheumatoid arthritis.

SummaryWe developed a new adsorbent utilizing hydrophobic amino acids in order to treat severe rheumatoid arthritis patients with extracorporeal adsorption therapy. In in vitro experiment, the new adsorbent selectively removed immune complexes and rheumatoid factors from RA plasma presumably due to hydrophobic adsorption. Six out of elevent patients markedly improved in clinical as well as laboratory parameters of disease activities, particularly in their extra-articular manifestations. We recommend preferential use of this treatment since it can spare the replacement protein solution and is expected to give similar efficacy to simple plasma exchange therapy.

Circulating immune complexes in patients with house-dust-mite-sensitive bronchial asthma

Sera from forty patients with house‐dust‐mite‐sensitive bronchial asthma were examined for the presence of circulating immune complexes (CIC) by the sensitive and quantitative CIq solid‐phase radioimmunoassay (Clq‐SP) and a monoclonal rheumatoid factor solid‐phase radioimmunoassay (mRF‐SP). Compared to fifteen normal individuals, the asthmatic patients showed significantly higher mean values of Clq‐reactive materials; however, there was no difference between the results from the patients treated by immunotherapy using Dermatophagoides farinae extract and those not so treated. Moreover, immune complexes in eight patients before and after immunotherapy showed that the amount of the complexes tend to decrease during immunotherapy. Furthermore, the presence of complexes had no relationship with the amounts of mite‐specific IgG antibody. Similar results were also obtained in tests using mRF‐SP. These data suggest that complexes in the sera of the house‐dust‐mite‐sensitive asthmatic patients are not necessarily associated either with immunotherapy or with the mite‐specific IgG antibodies.

Clinical trial with ciclosporin (CYA) in rheumatoid arthritis(RA).

CYA is an immunosuppressant, which is preferentialy used for organ transplantation. Recently, there has been frequent reports that CYA is effective for immunological disorders, such as RA, nephrotic syndrome etc.A clinical trial was carried out in order to investigate the efficacy of CYA on thirty three patients with RA. The initial daily dosage of CYA was 3 mg/kg and later adjusted based on individual informations from clinical symptoms and adverse effects.Statistically significant improvements were acknowledged in the number of swollen joints, grip strength, activities of daily living and serum concentration of CRP.The main adverse effects were hypertrichosis, renal dysfunction and stomach pain. It was concluded that CYA was beneficial in management of RA patients.