Identification of novel autoantibodies in Sjögren’s disease
IntroductionThe diagnosis of Sjögren’s disease (SjD) in patients without autoantibodies against Ro/SSA is a major challenge. We aimed to identify novel autoantibodies in SjD that may facilitate the diagnostic procedure for Ro/SSA negative SjD.MethodsIgG and IgA autoantibody reactivity of 94 potentia...
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Frontiers Media S.A.
2025-02-01
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| author | Fiona Engelke Petra Budde Salvatore De Vita Thomas Dörner Diana Ernst Jan Gras Harald Heidecke Annika Loredana Kilian Katja Kniesch Ann-Sophie Lindemann Luca Quartuccio Jacob Ritter Kai Schulze-Forster Benjamin Seeliger Hans-Dieter Zucht Torsten Witte |
| author_facet | Fiona Engelke Petra Budde Salvatore De Vita Thomas Dörner Diana Ernst Jan Gras Harald Heidecke Annika Loredana Kilian Katja Kniesch Ann-Sophie Lindemann Luca Quartuccio Jacob Ritter Kai Schulze-Forster Benjamin Seeliger Hans-Dieter Zucht Torsten Witte |
| author_sort | Fiona Engelke |
| collection | DOAJ |
| description | IntroductionThe diagnosis of Sjögren’s disease (SjD) in patients without autoantibodies against Ro/SSA is a major challenge. We aimed to identify novel autoantibodies in SjD that may facilitate the diagnostic procedure for Ro/SSA negative SjD.MethodsIgG and IgA autoantibody reactivity of 94 potential candidate autoantigens for SjD, selected from a discovery screen of 1,629 human antigens coupled to Luminex beads and prior knowledge about potential biological relevance, were examined in serum of SjD patients (n=347) using Luminex and ELISA technology. Healthy (HC, n=118) and non-Sjögren’s sicca syndrome (NSS, n=44) individuals served as controls. To assess disease specificity, the novel autoantibodies were also measured in serum of patients with Rheumatoid Arthritis (RA, n=50), Systemic Lupus Erythematosus (SLE, n=49), and Systemic Sclerosis (SSc, n=37). Results45 novel autoantibodies were significantly (p ≤ 0.05) more prevalent in SjD than in HC and were detected in up to 19% of the SjD cohort. The most common autoantibodies were against CCL4, M5, TMPO and OAS3. Some of the novel autoantibodies were associated with extraglandular disease manifestations, such as anti-TONSL or anti-IL6 with pulmonary involvement. We have developed a three and five marker panel for the detection of Ro/SSA negative patients, consisting of anti-FNBP4, anti-SNRPC, anti-CCL4, anti-M3 and anti-KDM6B, which had a sensitivity of up to 46% with a specificity of 95% (SjD vs. HC). Both panels discriminate these patients from HC, whereas the three-marker more effectively differentiates between Ro/SSA negative patients and NSS.DiscussionNovel autoantibodies will facilitate the diagnosis of Ro/SSA negative patients with SjD, in particular our predictive panel will be useful in the diagnosis and differentiation of these patients from healthy and NSS individuals in a clinical context. In addition, the autoantibodies may also be useful for risk stratification of extraglandular manifestations. |
| format | Article |
| id | doaj-art-13c16124b1b149398759621863bda9fa |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-13c16124b1b149398759621863bda9fa2025-02-03T06:33:28ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-02-011610.3389/fimmu.2025.15249401524940Identification of novel autoantibodies in Sjögren’s diseaseFiona Engelke0Petra Budde1Salvatore De Vita2Thomas Dörner3Diana Ernst4Jan Gras5Harald Heidecke6Annika Loredana Kilian7Katja Kniesch8Ann-Sophie Lindemann9Luca Quartuccio10Jacob Ritter11Kai Schulze-Forster12Benjamin Seeliger13Hans-Dieter Zucht14Torsten Witte15Department of Rheumatology and Clinical Immunology, Hannover Medical School, Hanover, GermanyOncimmune Germany GmbH, Dortmund, GermanyDepartment of Medicine, University of Udine, Udine, ItalyRheumatology and Clinical Immunology, Charité – Universitätsmedizin Berlin, Berlin, GermanyDepartment of Rheumatology and Clinical Immunology, Hannover Medical School, Hanover, GermanyDepartment of Respiratory Medicine, Hannover Medical School, Hanover, GermanyCellTrend GmbH, Luckenwalde, GermanyOncimmune Germany GmbH, Dortmund, GermanyDepartment of Rheumatology and Clinical Immunology, Hannover Medical School, Hanover, GermanyOncimmune Germany GmbH, Dortmund, GermanyDepartment of Medicine, University of Udine, Udine, ItalyRheumatology and Clinical Immunology, Charité – Universitätsmedizin Berlin, Berlin, GermanyCellTrend GmbH, Luckenwalde, GermanyDepartment of Respiratory Medicine, Hannover Medical School, Hanover, GermanyOncimmune Germany GmbH, Dortmund, GermanyDepartment of Rheumatology and Clinical Immunology, Hannover Medical School, Hanover, GermanyIntroductionThe diagnosis of Sjögren’s disease (SjD) in patients without autoantibodies against Ro/SSA is a major challenge. We aimed to identify novel autoantibodies in SjD that may facilitate the diagnostic procedure for Ro/SSA negative SjD.MethodsIgG and IgA autoantibody reactivity of 94 potential candidate autoantigens for SjD, selected from a discovery screen of 1,629 human antigens coupled to Luminex beads and prior knowledge about potential biological relevance, were examined in serum of SjD patients (n=347) using Luminex and ELISA technology. Healthy (HC, n=118) and non-Sjögren’s sicca syndrome (NSS, n=44) individuals served as controls. To assess disease specificity, the novel autoantibodies were also measured in serum of patients with Rheumatoid Arthritis (RA, n=50), Systemic Lupus Erythematosus (SLE, n=49), and Systemic Sclerosis (SSc, n=37). Results45 novel autoantibodies were significantly (p ≤ 0.05) more prevalent in SjD than in HC and were detected in up to 19% of the SjD cohort. The most common autoantibodies were against CCL4, M5, TMPO and OAS3. Some of the novel autoantibodies were associated with extraglandular disease manifestations, such as anti-TONSL or anti-IL6 with pulmonary involvement. We have developed a three and five marker panel for the detection of Ro/SSA negative patients, consisting of anti-FNBP4, anti-SNRPC, anti-CCL4, anti-M3 and anti-KDM6B, which had a sensitivity of up to 46% with a specificity of 95% (SjD vs. HC). Both panels discriminate these patients from HC, whereas the three-marker more effectively differentiates between Ro/SSA negative patients and NSS.DiscussionNovel autoantibodies will facilitate the diagnosis of Ro/SSA negative patients with SjD, in particular our predictive panel will be useful in the diagnosis and differentiation of these patients from healthy and NSS individuals in a clinical context. In addition, the autoantibodies may also be useful for risk stratification of extraglandular manifestations.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1524940/fullautoantibodiesbiomarkersconnective tissue diseasesextraglandular manifestationsseronegative patientssicca syndrome |
| spellingShingle | Fiona Engelke Petra Budde Salvatore De Vita Thomas Dörner Diana Ernst Jan Gras Harald Heidecke Annika Loredana Kilian Katja Kniesch Ann-Sophie Lindemann Luca Quartuccio Jacob Ritter Kai Schulze-Forster Benjamin Seeliger Hans-Dieter Zucht Torsten Witte Identification of novel autoantibodies in Sjögren’s disease Frontiers in Immunology autoantibodies biomarkers connective tissue diseases extraglandular manifestations seronegative patients sicca syndrome |
| title | Identification of novel autoantibodies in Sjögren’s disease |
| title_full | Identification of novel autoantibodies in Sjögren’s disease |
| title_fullStr | Identification of novel autoantibodies in Sjögren’s disease |
| title_full_unstemmed | Identification of novel autoantibodies in Sjögren’s disease |
| title_short | Identification of novel autoantibodies in Sjögren’s disease |
| title_sort | identification of novel autoantibodies in sjogren s disease |
| topic | autoantibodies biomarkers connective tissue diseases extraglandular manifestations seronegative patients sicca syndrome |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1524940/full |
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