{
  "abstract": "Introduction Pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc) is associated with anti-centromere antibodies (ACA) directed against the CENP-B antigen. Both these assays are usually performed semi-quantitatively. We have developed a quantitative anti-CENP-B assay to investigate whether anti-CENP-B levels would impact the risk of PAH development and the time between SSc and PAH diagnosis.Material and Methods This study encompasses 212 consecutive ACA-positive SSc patients fulfilling the 2013 classification criteria followed at our tertiary referral center during a 25-year time period. PAH was diagnosed by right heart catheterization, and ACA positivity historically determined with indirect immunofluorescence. Serum samples were collected at regular intervals starting at SSc diagnosis. Concentration of anti-CENP-B was assessed using addressable laser bead immunoassay (FIDIS, Biosynex, Croissy Beaubourg, France). This semi-quantitative assay was equipped with a standard curve to yield quantitative anti-CENP-B levels, and the cutoff representing the 98th percentile among 200 healthy blood donors was set to 1 arbitrary unit (AU)/ml. Samples were analysed at the time of PAH diagnosis or after similar SSc disease duration in PAH negative subjects. In 7 patients with and without PAH respectively, anti-CENP-B concentrations were assessed over a 10+ year time period preceding PAH-diagnosis.Results In this ACA positive cohort, PAH developed in 44/212 patients. The median (IQR) age at SSc diagnosis was 58 (50-68) years; highest among patients developing PAH (median 67 vs. 56 years; p=0.0004). Anti-CENP-B antibody concentration varied almost 100 times, from 0.46-45 AU/ml, with higher levels in patients with PAH compared to patients without PAH (median 15.3 vs. 5.7 au/ml p=2.4*10-5 ( figure 1A). Dichotomozing the cohort at the most discriminatory cutoff, 12.3 AU/ml, the odds ratio for having PAH was 6.2 (95% CI 3.0-12.6) for patients with high levels.Among the 44 PAH+ patients, the median (range) time between SSc and PAH diagnosis was 4.2 (-0.44 – 21.8) years, and this time correlated negatively with anti-CENP-B levels (Spearman’s rho -0.37, p=0.014). For the four patients with highest anti-CENP-B levels, PAH was diagnosed in parallel to SSc diagnosis (n=3) or earlier (n=1).ACA levels remained relatively stable over a 10-year time period from time of SSc diagnosis and onward in both patients with and without PAH (figure 1B).Conclusions We conclude that high anti-CENP-B levels confer the highest risk for PAH, especially early after SSc diagnosis. We suggest quantitative assessment of anti-CENP-B as a non-invasive approach to identify SSc subjects with the highest risk for PAH.Abstract P.136 Figure 1",
  "authors": [
    {
      "affiliations": [
        "Lund University, Department of Rheumatology, Lund, Sweden"
      ],
      "name": "Kristofer Andréasson"
    },
    {
      "affiliations": [
        "Lund University, Department of Rheumatology, Lund, Sweden"
      ],
      "name": "Maria Frida Bengtsson"
    },
    {
      "affiliations": [
        "Lund University, Department of Rheumatology, Lund, Sweden"
      ],
      "name": "Marie Wildt"
    },
    {
      "affiliations": [
        "Uppsala University, Department of Immunology, Genetics and Pathology, Uppsala, Sweden"
      ],
      "name": "Christine AM Möller Westerberg"
    },
    {
      "affiliations": [
        "Uppsala University, Department of Immunology, Genetics and Pathology, Uppsala, Sweden"
      ],
      "name": "Anna Katherina Svanqvist"
    },
    {
      "affiliations": [
        "Uppsala University, Department of Immunology, Genetics and Pathology, Uppsala, Sweden"
      ],
      "name": "Johan Kristian Rönnelid"
    }
  ],
  "title": "P.136 Concentration of anti-centromere-antibodies associates with and may predict development of pulmonary arterial hypertension",
  "uid": "47d9b0db-a1c1-5f44-8a88-8efc466fa489"
}