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Anti-fibroblast antibodies from systemic sclerosis patients bind to α-enolase and are associated with interstitial lung disease
  1. Benjamin Terrier (bterrier{at}noos.fr)
  1. Hopital Cochin, France
    1. Mathieu C Tamby
    1. Hopital Cochin, France
      1. Luc Camoin
      1. Institut Cochin, France
        1. Philippe Guilpain
        1. Hopital Cochin, France
          1. Alice Bérézné
          1. Hopital Cochin, France
            1. Nicolas Tamas
            1. Hopital Cochin, France
              1. Cédric Broussard
              1. Institut Cochin, France
                1. Françoise Hotellier
                1. Institut Cochin, France
                  1. Marc Humbert
                  1. Hopital Antoine Beclere, France
                    1. Gérald Simonneau
                    1. Hopital Antoine Beclere, France
                      1. Loic Guillevin
                      1. Hopital Cochin, France
                        1. Luc Mouthon (luc.mouthon{at}cch.aphp.fr)
                        1. Hopital Cochin, France

                          Abstract

                          Objective: To identify target antigens of anti-fibroblasts antibodies (AFAs) in systemic sclerosis (SSc) patients.

                          Patients and methods: In the first part, sera from 24 SSc patients (12 with pulmonary arterial hypertension [PAH] and 12 without) and 36 idiopathic PAH (IPAH) patients, tested in pooled sera for groups of 3, were compared to a sera pool from 14 healthy controls (HCs). Serum IgG reactivity was analyzed by use of a 2-D electrophoresis and immunoblotting technique with normal human fibroblasts antigens. In the second part, serum IgG reactivity for 2 groups - 158 SSc, 67 IPAH and 100 HCs; and 35 SSc and 50 HCs - was tested against α-enolase from Saccharomyces cerevisiae (Sc) and human recombinant (rHu) α-enolase, respectively, on ELISA.

                          Results: In the first part, we identified α-enolase as a main target antigen of AFAs from SSc patients. In the second part, 37/158 (23%) SSc patients, 6/67 (9%) IPAH patients and 4/100 (4%) HCs (p<0.0001) had anti-Sc α-enolase antibodies; 12/35 (34%) SSc patients and 3/50 (6%) HCs had anti-rHu α-enolase antibodies (p=0.001). In SSc, the presence of anti-Sc α-enolase antibodies was associated with interstitial lung disease (ILD), decreased total lung capacity (73.2 vs. 89.7%, p=0.0001) and diffusion capacity for carbon monoxide (47.4 vs. 62.3%, p=0.0009)], and anti-topoisomerase 1 antibodies (46 vs. 21%, p=0.005) but not anti-centromere Abs (11 vs. 34%, p=0.006). Results were similar with rHu α-enolase testing.

                          Conclusion: In SSc, AFAs recognize α-enolase and are associated with ILD and anti-topoisomerase antibodies.

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