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Circulating forms of l -selectin were found to be elevated in several autoimmune diseases. ICAM-1 has been suggested a predictor of the onset of GO. The aim of the study was an estimation of serum l -selectin and ICAM-1 in patients with Graves’ disease with ophthalmopathy during treatment with corticosteroids to assess their potential as a guideline of immunosuppressive therapy. We detected serum l -selectin and ICAM-1 in three groups of subjects: 20 patients with Graves’ disease without ophtamopathy (Gd), 17 patients with clinical symptoms of ophthalmopathy (CAS≥3, anamnesis of GO≥1 year) and 24 healthy volunteers. Corticosteroid therapy consisted of intravenous infusions of metyloprednisolone (MP) and subsequent treatment with oral prednisone (P). The serum samples were collected 24 h before MP, 24 h after MP, 12±2 days of treatment with prednisone and after the end of the corticosteroid therapy. The levels of soluble l -selectin and ICAM-1 in the serum were determined by the ELISA method. The statistical significance was estimated by the Mann-Whitney U-test. Serum l -selectin and ICAM-1 were significantly increased in patients with GO (respectively 1182±222 and 438±68 ng/ml) and in patients with Graves’ disease without ophthalmopathy (respectively: 1168±130 and 343±109) in relation to the controls. After MP treatment in corticosteroid-responsive patients (improvement in CAS ≤1) serum concentration of l -selectin and ICAM-1 decreased significantly and gradually increased during subsequent treatment with prednisone. In corticosteroid-responsive patients serum l -selectin was significantly higher before MP administration and after P treatment in relation to corticosteroid-resistant subjects. Conclusions: 1. Serum l -selectin and ICAM-1 were elevated in patients with active GO 2. Metyloprednizolone decreased levels of the studied adhesion molecules in corticosteroid-responsive patients with GO 3. Lack of clinical results in corticosteroid therapy in patients with a low starting l -selectin level would suggest the possibility of serum l -selectin estimation as a prognostic for immunotherapy efficacy.

There have been some studies published recently which have suggested that L-selectin and/or other adhesion molecules could be the new markers for diabetes type 1 risk development in humans and animal models of the disease. The alterations of soluble L-selectin have been found not only in overt but also in the preclinical stage of disease development and were independent from the presence of ICA — a marker of ongoing autoimmunity, but associated with HLA related genetic predisposition to insulin-dependent diabetes mellitus (IDDM). The aim of our study was to evaluate the frequency of the L-selectin gene T668C mutation (from thymine to cytosine at position 668) resulted in F206L an amino acid substitution in patients with overt diabetes and their unaffected first degree relatives in comparison to the unselected control population. In the unaffected siblings of IDDM subjects we have observed a significantly higher frequency of the L-selectin gene T668C mutation in comparison to their relatives with type 1 diabetes and healthy controls. It was also shown that there is an association between T668C mutation and low HLA related risk of IDDM development, the highest frequency of F206L mutation in the EGF domain of L-selectin was observed in relatives with ‘protective’ HLA DQB1*0602 allele and nonDRB1*03-nonDRB1*04 haplotype, while in subjects with highest risk of IDDM haplotype the frequency of T668C mutation was similar to the controls. We would like to hypothesise that the T668C L-selectin gene mutation could have a (protective?) role in the development of IDDM, but further studies concerning their role in type 1 diabetes are needed.

There is increasing evidence that CD3 + cells bearing gammadelta T-cell receptor (represent the minor subpopulation of the T-cells in the peripheral blood in humans) are involved in autoimmunity development. Gammadelta T-cell receptor (TCR)+ /CD8+ T-cells have been recently found to play a critical role in the pathogenesis and prevention of autoimmune diabetes in the animal model. The aim of the present study was the estimation the gammadelta T-cell subpopulation levels in the peripheral blood of subjects with preclinical and overt type 1 diabetes and their possible associations with the humoral immunity, metabolic parameters and pancreatic B-cells function. The study was carried out in three groups of subjects: 26 first degree relatives of type 1 diabetes patients (prediabetics) with the combinations of autoantibodies against pancreatic B-cells (ICA, GADA, IA-2A, IAA), 22 patients with a recent onset of type 1 diabetes and age and sex-matched 24 healthy volunteers (control group). A decrease was observed in the absolute numbers and percentages of gammadelta+ /CD8+ and gammadelta+ /CD8- T-cell subpopulations in peripheral blood in the prediabetics with the impaired first phase of insulin secretion in comparison to relatives with autoantibodies but still with normal B-cells function, patients with clinical diabetes and healthy controls. In conclusion, the study suggests that the gammadelta T-cells play an important role in the development of insulin-dependent diabetes mellitus (IDDM). It is possible that their levels in the peripheral blood could be an additional marker of preclinical detection of the disease, but further prospective studies in high risk of IDDM subjects are needed.

A pair of correspondent adhesion molecules: LFA-1 (CD11aCD18) and ICAM-1 (CD54) was shown to be involved in autoimmune insulitis in animal models. Anti-LFA-1 or anti-ICAM-1 monoclonal antibodies administered in vivo had a very strong preventive effect on the development of spontaneous diabetes with a marked reduction of insulitis. On the other hand elevated levels of the soluble form of ICAM-1 (sICAM-1) were documented in subjects at risk for type 1 diabetes. Recently sICAM-1 was shown to play an immunoregulatory role as an inhibitor of islet insulitis. The aim of the present study was to evaluate CD11a+mononuclear cells (lymphocytes and monocytes) and soluble sICAM-1 levels in the peripheral blood of subjects with preclinical and overt type 1 diabetes to assess their role in the development of the autoimmune process and their possible associations with the humoral autoimmune markers. The study was carried out in three groups of subjects: 26 first degree relatives of type 1 diabetes patients (prediabetics) with the combinations of autoantibodies against pancreatic B cells (ICA, GADA, IA-2A, IAA), 22 patients with a recent onset of type 1 diabetes and age and sex-matched 24 healthy volunteers (control group). We observed an increased fluorescence intensity of CD11a on mononuclear cells in overt diabetes subjects and a positive correlation between CD11a fluorescence intensity on monocytes and ICA titre. The highest sICAM-1 levels we obtained in the peripheral blood in the prediabetics in comparison to patients with clinical diabetes and the healthy controls. We found a positive correlation between sICAM-1 and values of ICA, GADA and a total number of antibodies present. In conclusion our study suggests that LFA-1 and sCAM-1 play an important role in the pathogenesis of type 1 diabetes. The assessment of the CD11a bearing monocytes and sICAM-1 levels are potential markers of the preclinical stage of the autoimmune diabetes, but further prospective studies in high risk diabetes type 1 subjects are needed.