Levels of cytokines and thyroid autoantibodies in Omani patients with Graves' disease.

An altered balance of pro- and anti-inflammatory cytokines is thought to play an important role in the pathogenesis of autoimmune thyroiditis. The aim of the present study is to assess the cytokine and autoantibody profiles in Omani patients with Graves' disease (GD). Cytokines and autoantibodies including interleukin (IL)-2, IL-4, tumour necrosis factor (TNF)alpha, interferon (IFN)gamma, thyroid stimulating hormone receptor antibody (TRA) and thyroid peroxidase antibody (TPO) are measured in GD patients (n=59) before treatment (n=23) and after treatment (n=36) with 131I-labelled iodine, and compared with normal controls (n=20). Patients with GD showed comparable serum levels of IL-2 but significantly higher levels of IL-4, TNFalpha, IFNgamma, TRA and TPO, compared with the normal controls. There was also a significant increase in serum levels of IL-4 and TNFalpha, and a decrease in TRA in the treated group, compared to the untreated group. IL-4, TNFalpha, IFNgamma, TRA and TPO showed a high prevalence in Omani patients with GD. Thus, cytokines and autoantibodies may prove useful in the diagnosis of GD and in assessing prognosis.

Prevalence of autoantibodies in patients with hepatitis C virus infection in Oman.

BACKGROUND: HCV genotype patterns and HLA types in the Omani population may be unique. SUBJECTS AND METHODS: Tests for 12 different autoantibodies were carried out on 50 HCV-infected patients and on 27 HCV-seronegative controls. An immunoassay for the detection of anti-HCV antibodies was performed on patient and control sera. HCV PCR was carried out on those sera which were positive for HCV antibodies. RESULTS: All patients sera were positive for HCV antibodies and all control sera were negative. Sixty-six percent of patients were positive for at least one autoantibody. In contrast, only 33% of the controls showed positivity for one or more autoantibodies. CONCLUSION: This study found a significant difference in the prevalence of autoantibodies between patients and controls, and between organ- and non-organ specific autoantibodies among the patients. A comparison with autoantibody patterns reported for HCV-infected patients in other parts of the world suggest that patterns in HCV-infected individuals in the Omani population are unique.

Accessory cell damage and loss of overall white cell viability inhibit lymphocyte responses after ultraviolet-B irradiation but without evidence of in vitro suppression.

The effect of different doses of ultraviolet B irradiation (UVR) on the proliferative responses of Balb/c spleen cells has been tested. In 72-hour cultures, there was dose-dependent suppression of proliferation in response to phytohemagglutinin (PHA). Cell viability after UVR was found to be reduced in a dose- and time-dependent manner. Proliferation increased by greater than 100 percent after low-dose (20 J/m2) UVR when either normal or gamma-irradiated peritoneal cells were added to the cultures, but not at higher doses. Delaying UVR until 24 hours after stimulation of cultures with PHA did not substantially increase [3H]-thymidine uptake. Stimulation of mixtures of UV-irradiated and control cells or incorporation of medium conditioned with UV-irradiated cells provided no evidence of suppression of proliferation. The accessory cell population is an important target for UVR, but cells are physically damaged to the extent that, at higher doses, the response to PHA stimulation cannot be restored.

Studies of allogeneic bone marrow and spleen cell transplantation in a murine model using ultraviolet-B light.

Ultraviolet irradiation inhibits alloreactive and mitogen-induced responses and might reduce both graft-versus-host and host-versus-graft reactions after bone marrow transplantation (BMT). We have studied proliferative responses to mitogens and reactivity in mixed lymphocyte culture after irradiation with ultraviolet (UV)-B light using splenocytes from Balb/c (H-2d) and CBA (H-2k) mice. Response to mitogens and in MLC was strongly inhibited by 20 J/m2 and abolished at 50 J/m2. Clonogenic cell recovery (CFU-GM; CFU-S) after UV-B irradiation was also reduced. When bone marrow and spleen cells were transplanted from parent (Balb/c) animals into F1 hybrid (Balb/c X CBA) recipients, all animals died with features indicative of graft-versus-host disease (GVHD) in 34 days. If the grafts were first irradiated with 100 J/m2 of UV-B at a mean wavelength of 310 nm, then 76% survived to day 80 when they were killed and shown to have normal marrow cellularity. The remainder died in marrow aplasia or of GVHD. H-2 typing in a group of surviving recipients showed either donor hematopoiesis only (8 of 15), mixed allogeneic chimerism (5 of 15), or recipient type hematopoiesis (2 of 15). Higher doses (200 to 300 J/m2) were detrimental to survival with 88% of recipients dying in marrow aplasia. Syngeneic BMT in Balb/c mice showed slower hematopoietic reconstitution when the grafts were first irradiated with 100 J/m2. After BMT from Balb/c to CBA mice all recipients of unirradiated grafts died within 54 days. By contrast, after graft irradiation with 100 J/m2 survival of recipient animals to day 80 was 59%. If these grafts were treated with 50 J/m2 survival was only 26% with an increase in deaths due to GVHD. Hematopoiesis at day 80 in a group of survivors studied by Ig heavy chain allotyping indicated donor type hematopoiesis in 6 of 10 (50 J/m2) and 2 of 9 (100 J/m2). These data indicate that UV-B irradiation inhibits lymphocyte reactivity and can prevent GVHD. However, there is clear in vitro and in vivo evidence of stem cell damage, such that autologous marrow recovery was demonstrated in a proportion of recipients. In parent----F1 UV-irradiated transplants, sustained hematopoietic recovery was effected in the majority by donor stem cells.

Immunomodulation by ultraviolet light: clinical studies and biological effects.

The interest of immunologists in ultraviolet (UV) irradiation stems from observations made in vitro and in vivo. In vitro, UV irradiation inhibits mitogen and mixed lymphocyte culture (MLC) responses and in vivo, it can induce cutaneous anergy, apparently via suppressor cells and serum factors. At present much interest is focused on the possible use of UV irradiation to permit transfusion without allosensitization and transplantation without either rejection or graft-versus-host disease (GVHD). Here, Derwood Pamphilon and colleagues discuss the current uses and potential of UV irradiation in transfusion and transplantation and relate these to experimental evidence on its effects at the cellular level.