Thyroid Peroxidase Antibody (TPO) as a Predictor of Radiation Induced Thyroid Dysfunction Among Nurses and Technicians Working in Mansoura Specialized Medical Hospital: Cross Sectional Study.

BACKGROUND: Thyroid gland is a probable goal tissue for radiation-related injury. Occupational exposure to ionizing radiation leads to thyroid dysfunction and exposure to high dose may lead to thyroid carcinoma. OBJECTIVE: Evaluation of the role of Thyroid peroxidase antibody as a predictor for thyroid dysfunction among nurses and technicians in the radiology department in Mansoura Specialized Medical hospital (MSMH). SUBJECTS AND METHODS: Subjects were Nurses and technicians who are working in (MSMH) with persistent daily duty in the last 3 years and fulfilling the inclusion and exclusion criteria. All subjects included in the study were recruited in one month and divided into two groups; Group 1: 50 subjects who were working in radiology, coronary angiography and ERCP unit, Radiation -exposed group. Group 2: 33 subjects who were working in In-patient departments and in out- patient clinics and not exposed to any type of radiation. Non fasting blood sample was taken from all enrolled subjects for measurement of TSH and Anti-TPO. RESULTS: TPO was positively and significantly correlated to age, TSH, duration of radiology/ y (r=0.388, 0.364, 0.342respectively) p value <0.05. Roc curve was done to detect the sensitivity and specificity of TSH in relation to TPO that revealed the cutoff value of TSH > 1.69 with Sensitivity and Specificity. PPV, NPV and accuracy at cutoff >1.69 were 70.6%, 51.5%, 42.8%, 77.3% and 58%. CONCLUSION: Working personnel with positive anti TPO and their TSH levels are more than 1.69 associated with symptoms of hypothyroidism, a trial of treatment is mandatory to relieve symptoms.

[Some features of immunological status in young peoples irradiated in utero or in age up to 4 years as result of Chernobyl accident].

Some characteristics of immune system, namely quantities of serum immunoglobulins A, G, M and activity of free and hidden autoantibodies to DNA, cardiolipin and microsomal thyroid antigen were studied in young people irradiated in utero or in age up to 4 years through Chernobyl accident. The hallmarker of observed immunological changes is low content of immunoglobulin A. Degree of reduction was in back proportion with level 137Cs contamination inhabit territory. A lowering of the content of IgA in persons irradiated in utero depends on period of pregnancy at a moment of the accident: the most reduction was observed in young people irradiated in the first trimester of gestation. It was shown elevation of activity autoantibodies to cardiolipin. Both deficit of IgA and elevation activity the autoantibodies were observed only in proportion of young people irradiated in utero or in early period of life.

Ultraviolet radiation intensity predicts the relative distribution of dermatomyositis and anti-Mi-2 autoantibodies in women.

OBJECTIVE: Because studies suggest that ultraviolet (UV) radiation modulates the myositis phenotype and Mi-2 autoantigen expression, we conducted a retrospective investigation to determine whether UV radiation may influence the relative prevalence of dermatomyositis and anti-Mi-2 autoantibodies in the US. METHODS: We assessed the relationship between surface UV radiation intensity in the state of residence at the time of onset with the relative prevalence of dermatomyositis and myositis autoantibodies in 380 patients with myositis from referral centers in the US. Myositis autoantibodies were detected by validated immunoprecipitation assays. Surface UV radiation intensity was estimated from UV Index data collected by the US National Weather Service. RESULTS: UV radiation intensity was associated with the relative proportion of patients with dermatomyositis (odds ratio [OR] 2.3, 95% confidence interval [95% CI] 0.9-5.8) and with the proportion of patients expressing anti-Mi-2 autoantibodies (OR 6.0, 95% CI 1.1-34.1). Modeling of these data showed that these associations were confined to women (OR 3.8, 95% CI 1.3-11.0 and OR 17.3, 95% CI 1.8-162.4, respectively) and suggests that sex influences the effects of UV radiation on autoimmune disorders. Significant associations were not observed in men, nor were UV radiation levels related to the presence of antisynthetase or anti-signal recognition particle autoantibodies. CONCLUSION: This first study of the distribution of myositis phenotypes and UV radiation exposure in the US showed that UV radiation may modulate the clinical and immunologic expression of autoimmune disease in women. Further investigation of the mechanisms by which these effects are produced may provide insights into pathogenesis and suggest therapeutic or preventative strategies.

Standard treatments induce antigen-specific immune responses in prostate cancer.

PURPOSE: Prostate tumors express antigens that are recognized by the immune system in a significant proportion of patients; however, little is known about the effect of standard treatments on tumor-specific immunity. Radiation therapy induces expression of inflammatory and immune-stimulatory molecules, and neoadjuvant hormone therapy causes prominent T-cell infiltration of prostate tumors. We therefore hypothesized that radiation therapy and hormone therapy may initiate tumor-specific immune responses. EXPERIMENTAL DESIGN: Pretreatment and posttreatment serum samples from 73 men with nonmetastatic prostate cancer and 50 cancer-free controls were evaluated by Western blotting and SEREX (serological identification of antigens by recombinant cDNA expression cloning) antigen arrays to examine whether autoantibody responses to tumor proteins arose during the course of standard treatment. RESULTS: Western blotting revealed the development of treatment-associated autoantibody responses in patients undergoing neoadjuvant hormone therapy (7 of 24, 29.2%), external beam radiation therapy (4 of 29, 13.8%), and brachytherapy (5 of 20, 25%), compared with 0 of 14 patients undergoing radical prostatectomy and 2 of 36 (5.6%) controls. Responses were seen within 4 to 9 months of initiation of treatment and were equally prevalent across different disease risk groups. Similarly, in the murine Shionogi tumor model, hormone therapy induced tumor-associated autoantibody responses in 5 of 10 animals. In four patients, SEREX immunoscreening of a prostate cancer cDNA expression library identified several antigens recognized by treatment-associated autoantibodies, including PARP1, ZNF707 + PTMA, CEP78, SDCCAG1, and ODF2. CONCLUSION: We show for the first time that standard treatments induce antigen-specific immune responses in prostate cancer patients. Thus, immunologic mechanisms may contribute to clinical outcomes after hormone and radiation therapy, an effect that could potentially be exploited as a practical, personalized form of immunotherapy.

Ultraviolet light and cutaneous lupus.

Exposure to ultraviolet (UV) light is one of the major factors known to trigger cutaneous disease activity in (systemic) lupus erythematosus patients. UV light, UVB in particular, is a potent inducer of apoptosis. Currently, disturbed clearance of apoptotic cells is one of the concepts explaining the development of inflammation in lupus patients. We review the role of apoptotic cells and autoantibodies in the pathogenesis of UVB induced skin lesions.

Global surface ultraviolet radiation intensity may modulate the clinical and immunologic expression of autoimmune muscle disease.

OBJECTIVE: To determine if geoclimatic factors may influence the nature and frequency of dermatomyositis (DM), polymyositis, and associated autoantibodies around the world. METHODS: We assessed, in the first global evaluation of these conditions, the relationship between 13 geoclimatic variables that may modulate disease and the relative proportion of DM and its associated autoantibody anti-Mi-2, directed against an SNF2-superfamily helicase associated with the nucleosome remodeling and histone acetylation and deacetylation complex, in a global myositis population. Altogether, 919 consecutive patients from populations at 15 locations were studied. RESULTS: Univariate and multivariate analyses demonstrated that of the variables evaluated, surface ultraviolet (UV) radiation intensity (irradiance) most strongly contributed to the relative proportion of DM and was strongly related to the proportion of anti-Mi-2 autoantibodies (weighted r = 0.939, P < 4 x 10(-7) and weighted r = 0.69, P = 0.02, respectively). Published ethnogeographic immunogenetic allele frequencies imply that the striking differences in the proportion of DM- and DM-specific autoantibodies observed around the world are not the result of inherent global variations in known genetic risk factors. CONCLUSION: These data suggest that UV radiation exposure may modulate the clinical and immunologic expression of an autoimmune disease in different populations around the world.

[The functional status of the thyroid system in those irradiated as a consequence of the accident at the Chernobyl Atomic Electric Power Station (based on screening study data)]. / Funktsional'nyi stan tyreoïdnoï systemy u oprominenykh vnaslidok avariï na ChAES (za danymy skryninhovoho doslidzhennia).

A screening study was made of functional indices for the status of the thyroid system in 1097 persons who took part in the elimination of the effects of the Chernobyl accident (PChAEE) during the "iodine" and "non-iodine" periods of irradiation. In 94.6% of the "iodine" period PChAEE, the basal levels of the thyroid-stimulating hormone (TSH) were in the normal range, 4.79% displayed a rise in the parameter. 90.06% of the "non-iodine" period had normal range TSH, 8.77% exhibited augmented levels. 94.68% of the "iodine" period PChAEE showed normal range for the basal levels of free thyroxin, in 3.72% there was a rise, in 1.6% a decrease in the values. Among the examinees of the "non-iodine" period, the levels of free thyroxin were within normal range in 92%, above norm in 5%, decreased in 3%. The level of antibodies to thyroglobulin in 86.38% of the "iodine" period examinees was in the normal range, in 90.99% of the "non-iodine" period it was also normal. There were no statistically significant differences suggesting effects of radiation factors of the "iodine" period of irradiation on the functional indices for the hypophysis-thyroid system during the first 7 years following irradiation.

Ultraviolet light-induced keratinocyte apoptosis: a potential mechanism for the induction of skin lesions and autoantibody production in LE.

Systemic lupus erythematosus (SLE) is a prototype systemic autoimmune disease which is characterized clinically by pleiotropy and periodicity. The immune features which accompany the characteristic flares of the disease have strongly suggested that the autoimmune response is driven by self antigen, and is T cell-dependent. These features have prompted the search for potential initiating process(es) which induce the release of self-antigens in a form which causes T cell tolerance to those self molecules to be broken. We review here several recent observations which implicate apoptotic cells as an important potential source of clustered and concentrated autoantigens in SLE, and present our current model whereby the novel autoantigen fragments generated in apoptotic surface blebs initiate and drive the autoimmune response in this disease.

[A comparative evaluation of the content of T-lymphocyte subpopulations, alpha 1-thymosin and autoantibodies to epithelial thymic cells in the personnel in the 30-kilometer control zone of the accident at the Chernobyl Atomic Electric Power Station]. / Sravnitel'naia otsenka soderzhaniia subpopuliatsii T-limfotsitov, al'fa 1-timozina i autoantitel k épitelial'nym kletkam timusa u personala 30-kilometrovoi zony kontrolia avarii na Chernobyl'skoi AES.

A significant decrease in mean number of CD5+, CD8(+)-lymphocytes in persons, who worked in 30-km zone of Chernobyl nuclear power station was revealed. A significant increase in percent of CD5+, CD4(+)-cell percents was observed in workers, who worked for 1,2-2,5 years in zone, but absolute number, were decreased comparing a control and data received in people, who have just arrived to work in 30-km zone. The positive correlation exists between the percent of lymphocytes and years of service in 30-km zone. The lower level of alpha 1-thymosine was revealed in serum of the persons, who worked in zone for 4.5-5 years than data received in people, who worked for 0.5 year. Increase level of serum autoantibodies reacting with thymic epithelial cell was detected in men, who worked in zone for 3-3.5 years. In persons, who worked more 5 years and have just arrived in zone identical data were received.

[The role of immunological changes in diseases in regions contaminated by radionuclides after the accident at the Chernobyl Atomic Electric Power Station]. / O roli immunologicheskikh izmenenii pri nekotorykh zabolevaniiakh v raionakh, zagriaznennykh radionuklidami posle avarii na ChAES.

Autoimmune deviations, both humoral and cellular, related to antigens of thyroid gland, microsomes and thyroglobulin, were observed in residents of controlled districts of Bryansk and Tula regions of Russia. The importance of these deviations at hyperplasia of thyroid gland was demonstrated. In formation of cataracts under chronic influence of low doses of ionizing radiation the humoral autoimmune mechanisms are active but not the cellular ones. The increased content of antibodies against the antigens of crystalline lens found in the residents of the controlled regions shows the possibility to develop initial manifestations of cataract under the effect of low radiation doses.

Ultraviolet-A1 irradiation decreases clinical disease activity and autoantibodies in patients with systemic lupus erythematosus.

In this study we assess the effect of ultraviolet radiation, exclusively within the UV-A1 (340-400 nm) range, on disease activity in SLE. Ten SLE patients were irradiated for 15 days, four of them then continuing treatment for 8 months, with low doses (60 kJ/m2/d) of UV-A1 irradiation. They were assessed clinically and serologically before, after 3 weeks, and after 8 months of therapy. Clinical indices of disease decreased in the 10 patients after 3 weeks by 39%; they decreased in the four patients irradiated for 8 months by 70%. Antibodies to Sjögren's syndrome A (anti-SSA) or antinuclear antibodies (ANA) decreased or disappeared in most patients. There were no side effects. In this uncontrolled study, UV-A1 irradiation appears to have been an effective and seemingly innocuous therapeutic modality for patients with SLE, decreasing signs and symptoms of disease, diminishing levels of autoantibodies and increasing in effectiveness with time.

[Antibodies to the thyroid microsomal antigen in children and adolescents subjected to radiation exposure as a result of the accident at the Chernobyl Atomic Electric Power Station]. / Antitela k mikrosomal'nomu antigenu shchitovidnoi zhelezy u detei i podrostkov, podvergshikhsia radiatsionnomu vozdeistviiu v rezul'tate avarii na Chernobyl'skoi AES.

For evaluation of the possibility of the appearance of autoimmune thyroiditis in children and juveniles lived in the areas of Kaluga Province [correction of region] suffered from the Chernobyl accident the content of antibodies to human thyroid microsomal antigen was investigated. Percentage of positive sera varied from 4.8% to 1.2% during 6 years. There is significant difference in the frequency of the antibody appearance between persons suffered from radioactive iodine and unsuffered ones. Correlation between levels of antimicrosomal antibodies and radiation dose obtained from incorporated radioactive iodine was not estimated.

Autoantibodies and immunoglobulins among atomic bomb survivors.

The purpose of this study was to determine if exposure to atomic bomb radiation affects immune responsiveness, such as the occurrence of autoantibodies and levels of immunoglobulins. Rheumatoid factor, antinuclear antibody, antithyroglobulin antibody, anti-thyroid-microsomal antibody and immunoglobulin levels (IgG, IgM, IgA and IgE) were measured among 2,061 individuals exposed to atomic bomb radiation in Hiroshima and Nagasaki whose estimated doses ranged from 0 to 5.6 Gy. The prevalence and titers of rheumatoid factor were found to be increased in the individuals exposed to higher radiation doses. The IgA level in females and the IgM level in both sexes increased as radiation dose increased, although the effects of radiation exposure were not large. No effect of radiation was found on the prevalence of antinuclear antibody, antithyroglobulin antibody and anti-thyroid-microsomal antibody or on the levels of IgG and IgE.

[Dynamics in changes of a1-thymosin level under irradiation of mice thymus in vivo and in vitro: relation to the antibody-antigen production of epithelial thymus reticulum]. / Dinamika izmenenii urovnia a1-timozina pri obluchenii timusa myshei in vivo i in vitro: sviaz s produktsiei autoantitel k antigenam épitelialnogo retikuluma timusa.

In 3- and 9-month experiments with mice, a study was made of the effect of radiation on serum alpha 1-thymosine concentration after whole-body irradiation and local exposure of the thymus at doses of 1-20 Gy. The effect of 137Cs-gamma-rays on the in vitro cultured thymus stroma cells, with respect to alpha 1-thymosine secretion, and the influence of local irradiation of the thymus of production of autoantibodies that react with epithelial thymus cells were studied. Both whole-body irradiation and local exposure of the thymus were shown to cause changes in the alpha 1-thymosine content of the blood plasma. The direction and dynamics of the changes observed are different with whole-body and local exposure. Irradiation of cultured thymus cells of mice causes alterations in alpha 1-thymosine secretion, that is, stimulation at a dose of 1 Gy and inhibition at higher doses. With respect to dose- and time-response, these changes are closer to those observed in alpha 1-thymosine concentration in mouse serum after whole-body irradiation than after local exposure of the thymus in vivo. At remote times after local irradiation of the thymus with doses of 1-10 Gy, autoantibodies are found in mouse serum that react with epithelial cells of the thymus stroma. Autoantibodies are absent at doses of 15 and 20 Gy.

Effect of ultraviolet irradiation on selected host cell proteins including Ro/SS-A and Epstein-Barr virus in cultured lymphoblastoid cell lines.

Although systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS) are distinct collagen vascular illnesses, they share certain features. Both have clinical manifestations involving skin and mucous membranes and characteristically have high titers of circulating autoantibodies to the cellular components Ro/SS-A, calreticulin/Ro, 52 kDa Ro and La/SS-B. Viruses have been postulated to be involved in the pathogenesis of both diseases. Sensitivity to sun is a cardinal feature of SLE, and UV light may be involved in its pathogenesis. Using human B-lymphoblastoid cell lines, the effect of the resident Epstein-Barr virus on the expression of the above cellular components was investigated by flow cytometry. Sublethal irradiation with ultraviolet B light appeared to diminish EBV antigen expression (gp350/220) during the first 48 to 72 hours in culture, whereas there was no change in the expression of MHC class I or immunoglobulin host cell proteins, and an apparent increase in the expression of host cell autoantigens. The virus appeared to be more sensitive to UVB-induced damage yet did appear to be able to undergo repair. No direct correlation could be made between the presence of the virus and the increase in autoantigen expression. La/SS-B and/or 52 kDa Ro antigen(s) were found to be present in the cytoplasm of the B lymphoblastoid cells at a higher base level in EBV-infected cell lines than in the EBV-negative cell lines.

In vivo and in vitro studies into the immunological changes following iodine 131 therapy for Graves' disease.

Radio-iodine therapy for Graves' disease is followed by immunological changes in addition to effects on thyroid hormone production. The present study examined these changes and the mechanisms responsible for them. Of the 15 patients enrolled in the study, 10 became hypothyroid in the first year after iodine 131 therapy. Patients who became hypothyroid had a tendency to show a rise in serum thyrotropin receptor antibody levels (30 +/- 14 to 40 +/- 9 units; NS) and a significant rise in immunoglobulin production (324 +/- 153 to 740 +/- 200 ng/ml; P less than 0.0005) from mitogen-stimulated peripheral blood lymphocytes (a measure of B-cell activity) 2 months after iodine 131 therapy. The increases were not seen in the patients who remained euthyroid at 1 year. In vitro studies suggested that the rise in B-cell activity is due to a fall in suppressor T cell numbers, a change shown to occur following iodine 131 therapy in previous studies. Our results indicate that immunological changes do arise after iodine 131 therapy for Graves' disease but appear to be confined to patients who subsequently became hypothyroid. It is not possible from this study to determine whether the immunological changes appear as a consequence of thyroidal destruction leading to hypothyroidism or whether they contribute directly to it.

Antibody-dependent cellular cytotoxicity and skin disease.

Antibody dependent cellular cytotoxicity (ADCC) is a recently described mechanism of immunologic lysis in which cellular targets sensitized by specific antibodies are efficiently and selectively lysed by Fc receptor (FcR) bearing nonspecific effectors. Immunoglobulins of various classes (IgG, IgM, IgA, IgE) and various cellular effectors (large granular lymphocytes, monocyte/macrophages, T lymphocytes, neutrophils, and eosinophils) can induce ADCC in vitro, and the importance of ADCC in vivo is being tested experimentally in resistance to viral, bacterial, and parasitic infection, in tumor surveillance, in allograft rejection, and in inflammatory diseases. There is much indirect evidence that ADCC may be the mechanism of damage of different cellular targets in skin diseases, but the best direct evidence concerns immunologic keratinocyte damage, especially in cutaneous lupus erythematosus (LE). We have shown that keratinocytes of several species are highly susceptible to lymphocyte and monocyte-mediated ADCC, but not to neutrophil or eosinophil ADCC in vitro using two different cytotoxicity assays. In contrast, complement was a relatively ineffective mediator of lysis of metabolically intact keratinocyte targets. Patients with certain cutaneous lupus syndromes have serum antibodies capable of inducing monocyte and lymphocyte ADCC of targets coated with extractable nuclear antigens. We have shown that these antigens apparently move to the cell membrane of keratinocytes in vitro following ultraviolet irradiation. In an animal model, we have shown that antibodies to SSA/Ro bind to human keratinocytes in vivo, especially after ultraviolet irradiation. This antigen/antibody system is highly associated with 3 different photosensitive LE syndromes. The experimental linkage of UV radiation to autoantibody binding to keratinocytes and the demonstration of mononuclear cell-mediated ADCC causing keratinocyte lysis support our hypothesis that the keratinocyte damage and mononuclear cell infiltrate seen histologically in cutaneous LE are part of an ADCC process.

Experimental erythrocyte autoimmunity. IV. Differential susceptibility to irradiation of suppressor cells for anti-rat RBC antibodies and suppressor cells for mouse RBC autoantibodies.

Mice injected with rat erythrocytes (RBC) produce RBC autoantibodies and antibodies against rat RBC. Transfer of spleen cells from autoantibody-producing mice to syngeneic recipients before the series of rat RBC injections causes a significant delay in autoantibody production although the response against rat RBC is elevated. Here it is shown that antibodies against rat RBC are markedly increased in recipients exposed to 350 rad of whole-body irradiation before transfer of spleen cells and the injections of rat RBC. In contrast, autoantibody production remained significantly suppressed. This shows that the anti-rat RBC response is regulated, at least in part, by cells in normal mice that are abrogated by 350 rad of whole-body irradiation.