Drug-induced Lymphocyte Stimulation Tests Research Articles

リンパ球刺激試験（DLST）2回目測定の有用性

リンパ球刺激試験（DLST）2回目測定の有用性

Discrepancy Between Clinical Course and Drug-Induced Lymphocyte Stimulation Tests in a Case of Saireito-Induced Liver Injury Accompanied by Sjögren Syndrome

Saireito consists of components of shosaikoto and goreisan. There are several reports of liver injury caused by shosaikoto and saireito, whereas cases caused by goreisan are rarely seen. A 70-year-old woman suffered from sicca of the eyes and oral cavity that arose in 2003. In June 2004, we diagnosed her as having Sjögren syndrome on the basis of Schirmer's test, salivary scintigraphy, presence of anti-SS-A/Ro antibody, and subjective symptoms. Although a muscarinic agonist was commenced, her sicca symptoms did not improve. In February 2008, 7.5 g/day of shosaikoto extract granules (for ethical use, Tsumura & Co., Tokyo, Japan) was introduced. Her symptoms and laboratory data did not change. The next month, the treatment was replaced by 9.0 g/day of saireito extract granules (for ethical use, Tsumura & Co., Tokyo, Japan). After 10 weeks, elevation of liver enzymes was observed. On suspicion of drug-induced liver injury (DILI), saireito was withdrawn, and the patient's liver enzymes returned to normal the next month. Drug-induced lymphocyte stimulation tests (DLSTs) for saireito, shosaikoto, and goreisan were all positive. The clinical course suggested allergy to the goreisan component of saireito. It is important to be aware of the limitation of DLST as a diagnostic tool for DILI, especially for herbal medicines.

Severe hypoglycaemia in a person with insulin autoimmune syndrome accompanied by insulin receptor anomaly type B

A rare case of the insulin autoimmune syndrome (IAS) accompanied by insulin receptor anomaly is reported. Antibodies to insulin and insulin receptor were determined in the patient with severe hypoglycaemia before and after the treatment with prednisolone. Titers of antibody to insulin and insulin receptors were 73.0% and 41.5%, respectively. Drug-induced lymphocyte stimulation tests were all negative for the suspicious drugs. Her HLA-DR was DRB1*0403/04051. Following steroid therapy, the formation of antibodies was suppressed and alleviated her symptoms. Scatchard analysis yielded findings specific to polyclonal antibodies. The changes in autoantibodies resulted in alleviation of the hypoglycemic symptoms as a result of steroid therapy.

Different patterns of cytokines, ECP and immunoglobulin profiles at two adverse drug reactions in a patient

Drug-induced hypersensitivity syndrome (HS) is a rare but life-threatening disease. We experienced carbamazepine-induced HS in a 14-year-old boy, who had cefaclor-induced cutaneous eruptions 15 months later. To clarify the mechanisms of HS and the differences between two diseases we studied this case in detail. We investigated the associated viral agents by polymerase chain reaction and the specific antibodies. We also studied the mechanism of diseases by measuring chemical mediators including cytokines, ECP and immunoglobulins. The patient was diagnosed as having carbamazepine-induced HS associated with reactivation of human herpesvirus 6 based on the clinical course and laboratory data including drug-induced lymphocyte stimulation tests. Similarly, the diagnosis of cefaclor-induced eruption without any viral reactivation was made. Serum levels of IFN-gamma, IL-6, TNF-alpha, IL-5 and ECP were increased significantly at HS but mildly at cefaclor-induced eruptions. Furthermore, we detected transient hypogammaglobulinemia only at HS. This is the first report of anticonvulsant-induced HS followed by antibiotic-induced eruptions in a patient. In addition, we demonstrated difference in serum levels of inflammatory cytokines, immunoglobulins, activated eosinophils and viral reactivation between these diseases. This case would contribute to the understanding of the pathophysiology of adverse drug reactions including HS.

小柴胡湯のヒトリンパ球に対する免疫薬理作用 薬剤添加リンパ球刺激試験と白血球遊走阻止試験における小柴胡湯の抗原調製の検討

We performed drug-induced lymphocyte stimulation tests (DLST) and leukocyte migration inhibition tests (LMIT) in an analysis of a traditional Chinese medicine, Xiao-chai-hu-tang (Japanese name : Shosaiko-to) and seven kinds of the constituent herbs in healthy volunteers to study their immunopharmacological effects on the peripheral blood lymphocytes.The DLST findings were positive at concentrations of more than 0.01mg/mL for the heated suspension of Shosaiko-to and more than 0.1mg/mL for the centrifuged supernatant and the 0.22μm membrane-filtrate. On the other hand, the LMIT findings were positive at concentrations of more than 0.1mg/mL for three kinds of Shosaiko-to preparations. The activities of Shosaiko-to in DLST and LMIT decreased after removing insoluble materials using centrifugation and filtration and were higher in enriched T-cells than in unfractionated peripheral blood mononuclear cells. Scutellariae Radix, Glycyrrhizae Radix and Bupleuri Radix showed higher DLST and LMIT activities among the constituent herbs of Shosaiko-to.Our findings indicate that DLST should be performed at concentrations of less than 0.001mg/mL using the heated suspension of Shosaiko-to or less than 0.01mg/mL using the centrifuged supernatant and LMIT at less than 0.01mg/mL using either the heated suspension or the centrifuged supernatant to determine whether patients have hypersensitivity to Shosaiko-to, because high concentrations of Shosaiko-to cause in vitro polyclonal stimulation of the peripheral blood mononuclear cells isolated from healthy donors. Furthermore, our results also suggest that the above activities of Shosaiko-to may effect T-cells due to high molecular weight insoluble particles most likely contained in the Scutellariae Radix, Glycyrrhizae Radix and Bupleuri Radix.

THREE INFANTS WITH SIDE EFFECTS AFTER VACCINATION

Three infants had redness and swelling on their arms one or two days after gelatin component vaccine inoculation. Drug induced lymphocyte stimulation tests for vaccine and gelatin were positive in the cases. Lymphocyte stimulation tests for gelatin were positive in one of eight adult volunteers. The positive volunteer had a redness area of 11×13mm after 48hours following an intradermal test of measles vaccine. Gelatin component vaccine may cause side effects of delayed hypersensitivity.