Demographic, clinical and antibody characteristics of patients with digital ulcers in systemic sclerosis: data from the DUO Registry

OBJECTIVES: The Digital Ulcers Outcome (DUO) Registry was designed to describe the clinical and antibody characteristics, disease course and outcomes of patients with digital ulcers associated with systemic sclerosis (SSc). METHODS: The DUO Registry is a European, prospective, multicentre, observational, registry of SSc patients with ongoing digital ulcer disease, irrespective of treatment regimen. Data collected included demographics, SSc duration, SSc subset, internal organ manifestations, autoantibodies, previous and ongoing interventions and complications related to digital ulcers. RESULTS: Up to 19 November 2010 a total of 2439 patients had enrolled into the registry. Most were classified as either limited cutaneous SSc (lcSSc; 52.2%) or diffuse cutaneous SSc (dcSSc; 36.9%). Digital ulcers developed earlier in patients with dcSSc compared with lcSSc. Almost all patients (95.7%) tested positive for antinuclear antibodies, 45.2% for anti-scleroderma-70 and 43.6% for anticentromere antibodies (ACA). The first digital ulcer in the anti-scleroderma-70-positive patient cohort occurred approximately 5 years earlier than the ACA-positive patient group. CONCLUSIONS: This study provides data from a large cohort of SSc patients with a history of digital ulcers. The early occurrence and high frequency of digital ulcer complications are especially seen in patients with dcSSc and/or anti-scleroderma-70 antibodies

Alteration of the Immune-response During Cancer Development and Prevention By Administration of a Mycobacterial Antigen

It has been shown previously that A60, an antigen complex of Mycobacterium bovis BCG, triggers humoral and cellular immune reactions in vivo and lymphocyte-dependent macrophage activation in vitro. In the present work, the ability of A60 to prevent murine tumour development, in conjunction of not with irradiated isologous cancer cells, was explored with Taper liver tumour (TLT), a mammary-derived neoplasm (EMT6), and Lewis lung carcinoma (3LL). Repeated injections of A60 prior to challenge reduced the incidence of EMT6 and 3LL solid tumours and increased life span. This effect was enhanced by simultaneous administration of gamma-irradiated cancer cells (80-100% suppression of EMT6 and 3LL tumour growth). In mice developing or rejecting tumours, the status of humoral and cellular immunity was evaluated by A60-based immunoassays. Tumor development was accompanied by a rapid decrease of both anti-A60 IgG titre in blood and A60-triggered delayed hypersensitivity reactions. Moreover, A60-induced T lymphocyte proliferation and macrophage-dependent autologous cancer cell cytolysis declined progressively during the course of tumour growth. In case of successful immunotherapy, a pattern similar to that of unchallenged controls was observed. Our results suggest that A60 promotes cancer rejection via tumour infiltration by lymphocytes and macrophages activated by A60-specific T lymphocytes. An increased processing of tumour-specific antigens and activation of tumour-infiltrating lymphocytes is induced by administration of irradiated cancer cells in conjunction with A60