In vitro complement activation by antinuclear antibodies in the epidermis from patients with systemic sclerosis

Abstract

Skin biopsies from twenty-one systemic sclerosis patients with significant serum fluorescent antinuclear antibody (FANA) titres (more than 1:40) were examined by direct immunofluorescence (DIF) and by in vitro immunofluorescent complement (C) activation (C + DIF). Eight patients showed epidermal nuclear ANA deposits by DIF. In vitro complement activation was achieved in epidermal nuclei from all eight patients. In addition, one patient with diffuse scleroderma revealed a dense speckled, and two patients with the CREST syndrome a discrete speckled, epidermal nuclear staining pattern by C + DIF. The latter two patients showed high titres of anticentromere antibody in their sera. We consider that the C + DIF findings of these two patients with the CREST syndrome reflect binding of serum anticentromere antibodies to their antigens in vivo.

Activation of the complement system in systemic sclerosis. Relationship to clinical severity

“…Circulating immune complexes and immunoglobulin deposits are capable of inciting tissue damage through activation of the complement cascade (24). However, although autoantibodies from the epidermis of patients with SSc have been shown to activate complement in vitro (25), studies to date have failed to demonstrate that complement activation occurs in vivo (7,8).…”

Relevance of complement fixing antinuclear antibodies

“…In the problem case, traces of IgG in epidermal nuclei 7 and a positive C + DIF test 5 directed our attention to a systemic CTD. The clinical findings of a facial eruption, photosensitivity, oral ulceration, arthritis, and pleuritis fulfill five of the revised American Rheumatism Association (ARA) criteria for SLE.…”

“…A skin biopsy from the right zygomatic arch of the latter case was placed in Michel’s transport medium for direct immunofluorescence (DIF) and tests by the C + DIF method of Reimer et al . 5 which entails the use of: (i) fresh normal serum as a source of C′ and (ii) fluorescein‐labeled antibodies to C′ complement C3.…”

“…Sera were obtained from eight cases of SCLE characterized by the criteria of Sontheimer et al 2 and from one case with an unidentified facial eruption. A skin biopsy from the right zygomatic arch of the latter case was placed in Michel's transport medium for direct immunofluorescence (DIF) and tests by the C ϩ DIF method of Reimer et al, 5 which entails the use of: (i) fresh normal serum as a source of CЈ;…”