HDL apoprotein immunization induces T cell-mediated venulitis and inflammation in aorta

The hypothesis that atherosclerotic processes are mostly caused by immune (autoimmune) mechanisms has recently been gaining attraction. At the same time, the autoimmune hypothesis of atherogenesis has not become generally accepted and requires additional evidence. Previously, we were able to induce changes in the aortic wall similar to those observed in the early stages of human atherosclerosis, and also to produce visceral obesity in normocholesterolaemic Wistar rats by a single immunization with human native high- or low-density lipoproteins. We also found that the immune response to native human HDL causes atherosclerosis-like lesions in the rabbit aorta, such as adipocyte and chondrocyte metaplasia, proteoglycan deposits, and leukocyte infiltration. Atherosclerosis-like lesions developed in the aorta of hnHDL-immunized rabbits against a background of normal blood LDL-cholesterol level. Thus, an immune response against HDL or LDL may be an independent cause of atherogenesis. The aim of this study was to test whether immunization with human HDL apoproteins (apoA1 and apoE proteins) would induce atherosclerosis-like lesions in the aorta of normocholesterolemic Wistar rats. HDL apoproteins were isolated from human or rat plasma. Wistar rats (n = 5) aged 2 months were used for immunization with human HDL apoproteins. HDL apoproteins were administered as a single intradermal injection of 100 mg per rat in incomplete Freund’s adjuvant. Control rats were injected subcutaneously with incomplete Freund’s adjuvant (n = 5). Rats were dissected 25 weeks after immunization. Rat aorta sections were stained with hematoxylin and eosin for light microscopy. T lymphocytes infiltration was determined by immunohistochemical staining with FITC-labeled antibodies specific to rat CD3. CD3+T lymphocytes were detected using an Olympus BX53 fluorescent microscope. The level of antibodies to human and rat HDL apoproteins was determined by indirect enzyme-linked immunosorbent assay. Immunization with HDL apoproteins induced a T cell mediated immune response without production of autoantibodies to HDL apoproteins. The aortic intima and adventitia were infiltrated with T lymphocytes in rats immunized with HDL apoproteins. Pronounced T lymphocytic infiltration was found in all layers of the vein wall in rats immunized with human HDL apoproteins. Thus, immunization with HDL apoproteins causes T cell mediated inflammation of the aorta and venulitis

A144

Existing methods for the preoperative detection of metastases in thyroid cancer have low efficiency and highly invasive. Therefore, the searches for laboratory markers that will indicate the presence of metastases including hidden with high reliability in cancer of the thyroid gland are relevant. Immune system is one of the key mechanisms for regulation of tissue proliferation. Autoreactive lymphocytes restrict the growth and proliferation of tissues. In turn autoreactive lymphocytes are controlled by idiotypic lymphocytes. Abnormalities in the regulation system can be the cause of tumor growth, such as excess activity of anti-idiotypic lymphocytes. Previously we conducted a comparative analysis of the level of autoantibodies to various antigens (thyroglobulin, thyroid stimulating hormone receptor, native DNA, anionic proteins vascular endothelium), as well as anti-idiotypic antibodies to thyroglobulin in thyroid cancer patients with metastases and without metastases. Significant differences between investigated groups were found in the level of anti-idiotypic antibodies against antibodies to thyroglobulin. Therefore, the aim of this study was to analyze the feasibility of using anti-idiotypic antibodies against antibodies to thyroglobulin as a marker of metastatic thyroid cancer. All studied patients with thyroid cancer were hospitalized at Primushko Regional Clinical Oncology Center of the Ministry of Health of the Udmurt Republic, Izhevsk. Blood was taken from patients before surgery. The level of anti-idiotype antibodies (AIAT) against autoantibodies to thyroglobulin (Tg) and the level of autoantibodies (AUAT) to thyroglobulin were determined in the blood plasma using the test system manufacturing MRC ”Immunkulus”. To determine the AIAT against AUAT to Tg, we used the principle of competitive inhibition of the binding reaction with antibodies to thyroglobulin in the presence of analyzed serum. As a source of antibodies to thyroglobulin, we used serum from patients with autoimmune thyroiditis in effective dilutions for competition. Analyzed samples were previously depleted by antibodies to thyroglobulin. The level of the test antibodies was expressed in conventional unit (CU) - optical density of the reaction of antibody binding to the antigen. We found that AIAT against AUAT to Tg were not defined in 43% of thyroid cancer patients with metastases (group I), 57% revealed a relatively high level of AIAT against AUAT to Tg – 0.343 ± 0.027 CU (Group II). In patients with thyroid cancer without metastases, the level of AIAT against AUAT to Tg (0.185 ± 0.083 CU) was lower than that of cancer patients with metastases. Metastatic cancer cannot be differentiated from cancer without metastases in 23% of studied cases. The level of AUAT to Tg in patients with thyroid cancer in the group I was 0.997 ± 0.084 CU and in the group II was 1.087 ± 0.174 CU. The level of AUAT to TG in cancer patients without metastasis was 0.794 ± 0.038 CU. It was found that when the level of AIAT against AUAT to Tg does not allow to distinguish metastatic thyroid cancer from cancer without metastases, it is possible to differentiate status data of thyroid cancer by using the level of autoantibodies to Tg. Moreover, the high level of AIAT against AUAT to Tg in patients with cancer without detectable metastases may be a marker of poor prognosis. So in one of the studied patients diagnosed with papillary cancer without metastasis, the level of AIAT against AUAT to Tg was equal to 0.37 CU, thus indicating the presence of metastases. Indeed, metastases were found in this patient 4 months later. Thus, the level of anti-idiotypic antibodies against autoantibodies to thyroglobulin may be used as a marker for metastases in the differential diagnosis of thyroid cancer