Dataset Information

The TFIID complex is a new autoantibody target in systemic sclerosis.

ABSTRACT: Systemic sclerosis (SSc) is characterized by systemic fibrosis, vascular dysfunction, and the presence of antinuclear autoantibodies. In up to 10% of persons with SSc, the target antigens of the antinuclear autoantibodies are unknown. Using IP-MS, we here describe another new target antigen in SSc. We examined a database of IP-MS identifications of 106 persons with SSc from two Belgian academic hospitals [Ghent University Hospital (n=59) and University Hospitals Leuven (n=47)] without autoantibody specificity as tested by commercial assays.TATA-binding protein (TBP)-associated factors (TAFs) were precipitated by sera of four persons (two from Ghent, two from Leuven). Together with TBP, TAFs form the three-lobed transcription factor IID complex (TFIID) (figure 1B). The TFIID complex recognizes core promoter sequences on DNA. The binding of TFIID is the first step of the assembly of the preinitiation complex, which is needed to position RNA polymerase II onto the correct DNA sequence to start transcription. To identify additional cases, we tested samples from individuals with SSc with unidentified autoantibodies from 3 extra hospitals [Cliniques Universitaires Saint-Luc (Belgium) (n=45), Chris Hani Baragwanath Hospital (South Africa) (n=28) and Centre Hospitalier Universitaire d’Angers (France) (n=13)] by IP-MS. Two additional cases precipitating TFIID subunits were identified. In order to confirm the specificity of anti-TIFIID antibodies for SSc, IP-MS was performed in healthy individuals (n=34) and in patients with idiopathic inflammatory myopathy (IIM, n=12), Sjögren’s disease (SjD, n=12), systemic lupus erythematosus (SLE, n=36) and anti-topoisomerase-I-, anti-centromere- or anti-RNA polymerase III-positive SSc (n=28). TAF9, TAF9B and TAF10 were often precipitated in these control samples. In conclusion, we describe TFIID as a new target of autoantibodies in SSc, thereby expanding the spectrum of SSc-associated autoantigens related to transcription.

INSTRUMENT(S): Xevo G3 QTof, LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Serum

SUBMITTER: Birthe Michiels