Characterize and unravel the phenotype of plasma cells in primary Sjögren Syndrome

• Applicant: Dr. Tobit Steinmetz
• Subject Area: Clinical Immunology and Allergology ; Immunology
• Term: from 2020 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 456067883

• Final Report Year: 2023

Final Report Abstract

Antibodies are protective defense proteins of our body that shield us from viruses and bacteria. But antibodies can become harmful when directed against ourselves. Patients suffering from primary Sjögren’s Syndrome (pSS) have self-directed antibodies that might limit the ability to produce saliva and tears. All kinds of antibodies are made by special immune cells, called plasma cells. However, plasma cells are not well studied in Sjögren’s patients. To investigate potential contributions of plasma cells to pSS this project aimed to characterize plasma cells according to their survival, longevity and inflammatory properties in pSS. Another part of this project was to assess the potential existence of pro-survival structures for plasma cells in the salivary glands of pSS patients and to investigate effects of medication on plasma cells during a clinical trial. Using blood samples from pSS-affected and healthy individuals, plasma cells in pSS patients could be identified to be more abundant and to show increased maturity. Both aspects were either linked to markers of longer survival, a pro-inflammatory state or more severe disease parameters of the pSS patients. Studying pSS plasma cells in the context of COVID-19 vaccination revealed a robust induction of anti-COVID antibodies but no alteration of the specific adaptive immune cell fingerprint of pSS patients despite the vaccine-induced immune stimulus. In summary, the results of this project give indications that plasma cells have an altered phenotype in pSS that might be a stable disease characteristic but could also contribute to the disease severity or serve as a biomarker for it.

Publications

• Immunisation with Coronavirus-2 vaccines induces potent antibody responses and does not aggravate the lymphocyte compartment of primary Sjögren's syndrome patients. Clinical and Experimental Rheumatology.
  Steinmetz, Tobit D.; de Wolff, Liseth; Terpstra, Janneke H.; Visser, Annie; Bootsma, Hendrika; Kroese, Frans G.M. & Verstappen, Gwenny M.
  
• OP0010 A MORE MATURE PLASMA CELL AND PLASMABLAST COMPARTMENT IS ASSOCIATED WITH DISEASE MANIFESTATION IN PRIMARY SJÖGREN'S SYNDROME. Annals of the Rheumatic Diseases, 81, 6.
  Steinmetz, T.D.; Verstappen, G.M.; Bootsma, H. & Kroese, F.G.M.
  
• Association of Circulating Antibody‐Secreting Cell Maturity With Disease Features in Primary Sjögren's Syndrome. Arthritis & Rheumatology, 75(6), 973-983.
  Steinmetz, Tobit D.; Verstappen, Gwenny M.; Schulz, Sebastian R.; de Wolff, Liseth; Wilbrink, Rick; Visser, Annie; Terpstra, Janneke; Bootsma, Hendrika & Kroese, Frans G. M.
  
• Targeting plasma cells in systemic autoimmune rheumatic diseases – Promises and pitfalls. Immunology Letters, 260, 44-57.
  Steinmetz, Tobit D.; Verstappen, Gwenny M.; Suurmond, Jolien & Kroese, Frans G.M.