CD11a expression and soluble ICAM-1 levels in peripheral blood in high-risk and overt type 1 diabetes subjects

A pair of correspondent adhesion molecules: LFA-1 (CD11aCD18) and ICAM-1 (C D54) was shown to be involved in autoimmune insulitis in animal models. Ant i-LFA-1 or anti-ICAM-1 monoclonal antibodies administered in vivo had a ver y strong preventive effect on the development of spontaneous diabetes with a marked reduction of insulitis. On the other hand elevated levels of the s oluble form of ICAM-1 (sICAM-1) were documented in subjects at risk for typ e 1 diabetes. Recently sICAM-1 was shown to play an immunoregulatory role a s an inhibitor of islet insulitis. The aim of the present study was to eval uate CD11a + mononuclear cells (lymphocytes and monocytes) and soluble sICA M-1 levels in the peripheral blood of subjects with preclinical and overt t ype 1 diabetes to assess their role in the development of the autoimmune pr ocess and their possible associations with the humoral autoimmune markers. The study was carried out in three groups of subjects: 26 first degree rela tives of type 1 diabetes patients (prediabetics) with the combinations of a utoantibodies against pancreatic B cells (ICA, GADA, IA-2A, IAA), 22 patien ts with a recent onset of type 1 diabetes and age and sex-matched 24 health y volunteers (control group). We observed an increased fluorescence intensi ty 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 pre diabetics 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 su ggests 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 dia betes, but further prospective studies in high risk diabetes type 1 subject s are needed. (C) 1999 Published by Elsevier Science B.V. All rights reserv ed.