Delayed hypersensitivity reaction resulting in maculopapular-type eruption due to entecavir in the treatment of chronic hepatitis B

Several clinical trials have demonstrated the potent antiviral efficacy of entecavir (ETV), and this relatively new nucleoside analogue drug has rapidly become a frequently prescribed therapy for chronic hepatitis B (CHB) worldwide. While the studies have also shown a good overall safety profile for ETV, adverse drug reactions (ADRs) in patients with advanced cirrhosis have been reported and represent a broad spectrum of drug-induced injuries, including lactic acidosis, myalgia, neuropathy, azotemia, hypophosphatemia, muscular weakness, and pancreatitis, as well as immune-mediated responses (i.e., allergic reactions). Cutaneous ADRs associated with ETV are very rare, with only two case reports in the publicly available literature; both of these cases were classified as unspecified hypersensitivity allergic (type I) ADR, but neither were reported as pathologically proven or as evaluated by cytokine release analysis. Here, we report the case of a 45-year-old woman who presented with a generalized maculopapular rash after one week of ETV treatment for lamivudine-resistant CHB. The patient reported having experienced a similar skin eruption during a previous three-month regimen of ETV, for which she had self-discontinued the medication. Histopathological analysis of a skin biopsy showed acanthotic epidermis with focal parakeratosis and a perivascular lymphocytic infiltrate admixed with interstitial eosinophils in the papillary and reticular dermis, consistent with a diagnosis of drug sensitivity. A lymphocyte stimulation test showed significantly enhanced IL-4, indicating a classification of type IVb delayed hypersensitivity. The patient was switched to an adefovir-lamivudine combination regimen and the skin eruption resolved two weeks after the ETV withdrawal. This case represents the first pathologically and immunologically evidenced ETV-induced delayed type hypersensitivity skin reaction reported to date. Physicians should be aware of the potential, although rare, for cutaneous ADRs associated with ETV treatment.

Effects of Tremella Polysaccharide on Immune Function of Physically-Stressed Mice

An immunosuppressive animal model induced by physical stress that forced mice to swim in cold water(14±1℃)and the restorative effect of Tremella polysac charide(TP)on the suppressed immune function by stress were studied in mice.It was found that the spleen plaque forming cell(PFC)response to sheep red blood cells,delayed cuta- neous hypersensitivity(DCH)induced by dinitrochlorobenzene and the lymphocyte prolifer- ation stimulated by concanavalin A(Con A)were significantly decreased in stressed mice. In addition.the maximal decrease of PFC was reached in 9-12 days after stress.A- drenolectomy could not affect the decrease of PFC in stressed mice.TP(200.400mg/kg) ig for 8-14 days significantly restored the PFC.DCH and lymphocyte proliferation to nor- mal level in stressed mice.

Immunosuppressive Activities of Fucoidan from Laminaria japonica

Effects of fucoidan from Laminaria japonica on 2,4 dinitrochlorobenzene induced delayed type hypersensitivity (DTH) reaction and the serum levels of IgG, IgM, complement C3 and C4 were investigated in the present study. Results showed that oral administration of fucoidan at dose of 150 and 300 mg/(kg·d) for 9 days before the hapten challenge significantly inhibited 2,4 dinitrochlorobenzene induced delayed type hypersensitivity reaction; and also inhibited the humoral immunity. Serum C3 and C4 levels were markedly reduced by fucoidan at dose of 150 and 300 mg/kg; and serum IgG and IgM levels were reduced by fucoidan at dose of 300 mg/kg. The inhibitory effects of fucoidan on delayed type hypersensitivity suggested that it may be potential medication for chronic inflammatory diseases in the future.

Reduced capacity of dendritic cells from trauma-hemorrhage mice in initiating delayed-type hypersensitivity to fluorescein isothiocyanate

Objective： To study the role of dendritic cells （DCs） in initiating delayed-type hypersensitivity （DTH） to fluores- cein isothiocyanate （FITC） after trauma-hemorrhage in mice. Methods： Inbred BALB/c mice （6-8 weeks old, male） were epicutaneously sensitized with FITC 12 hours, 1 day, 2 days, 4 days and 7 days after closed bilateral femur fractures combined with hemorrhage. And 5 days after sensitization, DTH was evaluated by ear swelling after a challenge of FITC. Draining lymph node cells were examined for the percentages of FITC-positive cells, cluster of differentiation （CD）11c positive cells and major histocom- patibility complex II （MHC II）-positive cells by means of flow cytometry. In vitro proliferative responses of syngeneic lymphocytes and in vivo passive transfer of DTH to naive recipients induced by isolated DCs from the draining lymph nodes were determined. Results： The time of DTH to FITC decreased more significantly in the mice with trauma-hemorrhage （12 hours to 4 days） than in the mice with sham injury. After sensitization, the relative percentages of FITC^＋ cells, FITC^＋/ CD 11c^＋ cells and FITC^＋/CD 11c^＋/MHC II^＋ cells from the draining lymph nodes were all significantly reduced following injury. And the capacity of DCs from the draining lymph nodes in stimulating proliferative responses of lymphocytes and transferring DTH to naive recipients were also inhibited after injury. Conclusions： Trauma-hemorrhage induces repressive DTH in mice, which may be attributed, at least partially, to the reduced trafficking of DCs into the draining lymph nodes and insufficient maturation during DC migration.

CCR5 gene expression in fulminant hepatitis and DTH in mice

IMS To isolate mouse CCR5 cDNA (muCCR5) and study its expression in vivo.METHODS Marathon PCR was used to isolate muCCR5 cDNA and two animal models were designed to investigate the gene expression in vivo, one was mouse fulminant hepatitis induced by Propionibacterium acnes (P.acnes) and the other was that with delayed type hypersensitivity reaction (DTH). A specific GSTNH2terminus of muCCR5 fusion protein antibody F(ab′)2 was prepared and clarified. RTPCR and immunohistochemical analysis were used to observe the expression level of CCR5 gene in mice.RESULTS A positive reaction of mouse macrophage was found in DTH but not expressed in P.acnes induced fulminant hepatitis by RTPCR and immunohistochemical analysis.CONCLUSION This muCCR5 expression may be involved in an allergic process mediated by cellular immunity but not acute inflammatory reaction induced by P.acnes..

Immunological Effects of Total Flavones from Leaves of Choerospondias axillaris on Mice

ObjectiveTo investigate the effect of total flavones from the leaves of Choerospondias axillaris (TFLCA) on the immune function of normal mice and to provide the experimental basis for the reasonable application of C. axillaris.MethodsThe carbon clearance method, cutaneous delayed hypersensitivity reaction method, serum hemolysin method, and index of immune organs were used to study the effect of TFLCA on the immune function of mice.ResultsTFLCA could enhance the phagocytic function of mononuclear macrophage and the cutaneous delayed hypersensitivity reaction of mice, and increase the content of hemolysin antibody and the thymus index in mice.ConclusionTFLCA could improve the celiac macrophage activity and specific immunity of mice, and TFLCA, consisting with the total flavones of Choerospondiatis Fructus (TFCF), has the effect on the immune function of mice. So both TFLCA and TFCF have the regulatory effects on the immune function of mice.

pcDNAL1 genetic immunization can induce specific cell-mediated immune responses in C57BL/6 mice

OBJECTIVE: To investigate the specific cell-mediated immune efficacy of the an HPV16 prophylactic vaccine. METHODS: C57BL/6 mice were randomly divided into 3 groups: experimental group I (treated with pcDNA L1), control group II (treated with pcDNA3.1) and control group III (treated with PBS buffer). The mice were immunized three times during a three-week interval. Ten to fourteen days after the third inoculation, a footpad swelling test was used to detect delayed-type hypersensitivity (DTH) responses. Antigen-specific splenocyte proliferation assay and quantitation of IFN-gamma cells in splenocytes were performed by FACS assay. RESULTS: In the experimental group, splenocytes actively proliferated after stimulation with HPV16 VLP, and had developed a markedly larger amount of CD8(+) IFN-gamma(+) cells, which is an index for special CTL. Also, the footpad was significantly thickened upon inoculation with HPV16 VLP. CONCLUSION: Naked DNA vaccine of HPV16 L1 can induce specific cell-mediated immune responses in mice, which should be considered for evaluation of HPV16 DNA vaccine feasibility.

Monoclonal anti-idiotype antibody bearing the internal image of nasopharyngeal carcinoma associated antigen

Objective To generate and characterize anti-idiotypic monoclonal antibody (Ab2) that bears the internal image of nasopharyngeal carcinoma (NPC) associated antigen. Methods Using NPC monoclonal antibody (Ab1) as immunogen, hybridoma cells were obtained by fusion of SP2/0 myeloma cells with immunized murine spleen cells. Positive clones were screened by Sandwich ELISA and a binding inhibition test. To determine whether Ab2 possess the internal image of the original antigen or not, mice were immunized with Ab2. ELISA and the competitive inhibition assay tested anti-anti-idiotypic antibodies (Ab3) in anti-sera. Cell-mediated immunity to tumors induced by Ab2 was investigated by a delayed-type hypersensitivity response and the mouse T-cell proliferation assay. Results Anti-idiotypic monoclonal antibodies against the monoclonal anti-NPC antibodies FC2 and HNL5 were generated that recognize NPC associated antigens. These Ab2, which were designated 2H4 and 5D3, could inhibit the binding of FC2 or HNL5 to NPC cell lines. Anti-sera from the immunized mice, which contained Ab3, could compete with FC2 or HNL5 for binding with NPC cell by a competitive inhibition assay. Mice immunized with 2H4 or 5D3 coupled with keyhole limpet hemocyanin (KLH), showed a positive and specific delayed-type hypersensitivity (DTH) reaction after stimulation by NPC cells. The mouse T cell proliferative assay indicated that there was a significantly higher proliferative response of the splenocytes in the experimental groups than that in control groups. Conclusions Anti-idiotypic antibodies 2H4 and 5D3 are Ab2 beta bearing the internal image of the epitope of NPC associated antigen. Either 2H4 or 5D3 expressing three-dimensional shapes that resemble the structure of natural antigens could induce humoral and cellular immune response.

Non-ischemic complications of dermal fillers

Dermal fillers have been commonly used for the filling of facial rhytids.As the use of dermal fillers has grown,so has the incidence of non-ischemic complications.These complications range from edema,bruising,and erythema to more complex conditions such as delayed hypersensitivity nodules and biofilms.This article sought to review the causes of various non-ischemic complications,discuss their risk factors,and review management techniques.Certain predisposing factors to delayed hypersensitivity nodules,such as Vycross technology,a history of viral illness,or coronavirus disease 19(COVID-19)infections,are discussed in detail in this review.Prevention techniques such as patient counseling,elucidating certain patient history(viral illness,dental procedures),the use of aseptic technique,and procedural factors are also discussed.Understanding appropriate management for these complications can also help in treatment.Imaging,such as ultrasound,computed tomography(CT)and magnetic resonance imaging(MRI),has taken on a larger role in the management of non-ischemic complications.