Session Type: Abstract Submissions (ACR)
Systemic sclerosis (SSc) is a complex fibrosing disease of unknown etiology. The past decade clear indications for an aberrant immune system have been revealed. SSc is classified either as limited (lSSc) or diffuse cutaneous (dSSc), of which the latter is more severe with excessive involvement of the skin. Although the pathogenesis of SSc is largely unknown, the past few years it has been appreciated that a substantial part of the SSc patients display an Interferon (IFN) type I signature. In this study we assessed the prevalence of such an IFN type I signature in monocytes in a cohort of SSc patients from two clinics in the Netherlands and correlated the IFN type I signature with disease manifestations.
41 patients with SSc were included and 25 healthy controls (HC). Patients were stratified as having lSSc (n=25) or dSSc (n=16), and further divided into patients with late (> 3 years) or early disease (<3 years). Expression levels of 11 IFN type I inducible genes, which were previously detected by us in CD14+ monocytes from Sjögren patients, were assessed using real time quantitative PCR. Expression levels were next submitted to a principal component analysis to identify correlated groups of genes. Results of factor analysis showed that 4 genes (IFI44L, IFITM1, IFIT1 and MX1) explained 95% of the total variance of the 11 genes, and we therefore adopted overexpression of these 4 genes as our operational definition of positivity for an IFN type I signature. Expression levels of these 4 genes were used to calculate IFN type I scores for each subject. SSc patients positive for the IFN type I signature (IFN score≥10) and patients negative for the signature (IFN score< 10) were then compared for clinical disease manifestations.
IFN type I signature was present in 29% of SSc patients compared with 0% of HC. Stratifying the patients in lSSc and dSSc, we found the IFN type I signature to be present in 24% of lSSc patients and 38% of dSSc. Further dividing the patients into early and late SSc, we observed a statistically significant increase in IFN scores in the early diffuse SSc group compared with HC (P<0.001). SSc patients positive for the IFN type I signature were also significantly younger compared with the patients negative for the signature (p=0.008). Moreover SSc patients with the presence of anti-RNP had significantly higher IFN scores compared to patients without anti-RNP antibodies (P=0.003). In contrast to the presence of anti-RNP antibodies, SSc patients positive for anticentromere antibodies (9 out of 38 patients) were all negative for the IFN type I signature. Studying anti-topoisomerase and anti-SSA antibodies, we observed a trend of higher IFN scores in the patients with these autoantibodies, however no significant differences were detected. When stratifying patients according to the presence of digital ulcers, lung fibrosis, pulmonary hypertension or Raynauds’s phenomenon, no differences in IFN scores were observed.
The monocyte IFN type I signature is present in about 1/3 of SSc patients and mainly in the early diffuse SSc group with anti-RNP autoantibodies. Such patients might benefit from treatment blocking the IFN type I production or activity.
L. van Bon,
C. G. van Helden-Meeuwsen,
M. C. Vonk,
W. van den Berg,
P. L. Van Daele,
V. A. Dalm,
M. A. Versnel,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-interferon-type-i-signature-is-increased-in-monocytes-from-systemic-sclerosis-patients/