Peripheral T lymphocytes from patients with early systemic sclerosis co-cultured with autologous fibroblasts undergo an oligoclonal expansion similar to that occurring in the skin.

In recent years several reports have suggested that T cells may have a role in systemic sclerosis (SSc). The aim of our study was to investigate the dynamics of T cell repertoire in early SSc disease analysing a target organ, the skin, and the peripheral blood. To date, indeed, it is not clear if T cell expansions found in SSc reflect a general activation or result from specific antigen stimulation in the target organs. This is an important point to assess in order to characterize the role of T cells in the development of SSc. To address these questions we studied T cell repertoire by CDR3 length analysis in skin biopsies and peripheral blood obtained from patients affected by SSc and we found that a skewed T cell repertoire was present only in the biopsies. In order to characterize more effectively the meaning of these data, we performed co-cultures using fibroblasts and peripheral blood mononuclear cells (PBMCs) obtained from SSc patients. These experiments showed that same T cell expansions were detectable in the skin of SSc patients and in the cultures of PBMCs and autologous fibroblasts of the patients but not in their peripheral blood. Taken together, these data suggest that fibroblasts trigger specific T cell expansions in the early phase of SSc.

Central diabetes insipidus and autoimmunity: relationship between the occurrence of antibodies to arginine vasopressin-secreting cells and clinical, immunological, and radiological features in a large cohort of patients with central diabetes insipidus of known and unknown etiology.

Central diabetes insipidus (CDI) is a rare hypothalamus-pituitary disease due to the deficiency of arginine vasopressin (AVP) synthesis from the hypothalamus and/or secretion from the neurohypophysis. The etiology of CDI is unknown in over one third of cases, classified as idiopathic CDI. The aim of this study was 2-fold: 1) to evaluate the occurrence of circulating autoantibodies to AVP-secreting cells (AVPcAb), and 2) to correlate it to clinical (sex, age of disease onset, disease duration, and degree), immunological (clinical history of autoimmune diseases and presence of related organ-specific autoantibodies), and radiological features (neurohypophyseal bright spot, pituitary stalk thickening, and empty sella) in a large cohort of patients with apparently idiopathic CDI or CDI of known etiology. To this purpose, 150 patients with CDI were studied: 64 idiopathic, 6 familial, 12 associated to granulomatous diseases, and 68 secondary to cranial trauma, tumor, or surgery. AVPcAb were measured by an indirect immunofluorescence method. AVPcAb were found in 23.3% of CDI patients: 21 idiopathic (32.8%) and 14 nonidiopathic (16.3%; chi(2) = 13.1; P < 0.001). AVPcAb were independently associated with age less than 30 yr at disease onset (P = 0.001) in patients with idiopathic CDI and with history of autoimmune diseases (P = 0.006 and P = 0.02, respectively) and radiological evidence of pituitary stalk thickening (P = 0.02 and P = 0.003, respectively) in both idiopathic and nonidiopathic CDI. The likelihood of autoimmunity in one patient with apparently idiopathic CDI with age of disease onset less than 30 yr was 53%, it increased to 91% when history of autoimmune diseases was associated and to 99% when pituitary stalk thickening was further associated. In conclusion, autoimmunity is associated with one third of patients with apparently idiopathic CDI, which should therefore be classified as autoimmune CDI. Autoimmune CDI is highly likely in young patients with a clinical history of autoimmune diseases and radiological evidence of pituitary stalk thickening. Conversely, autoimmunity probably represents an epiphenomenon in patients with nonidiopathic CDI.