Abstract
ObjectiveThe present study aimed to investigate progranulin autoantibodies in systemic sclerosis and autoimmune connective tissue disorders. Progranulin is a physiologic tumor necrosis factor (TNF) antagonist. Progranulin antibodies decrease progranulin levels.MethodsSerum samples of 123 patients with systemic sclerosis and various autoimmune connective tissue disorders (Sjoegren's syndrome [SjS], mixed connective tissue disorder, polymyositis [PM] and dermatomyositis [DM], antiphospholipid syndrome [APLS], and undifferentiated connective tissue disease [UCTD]) were tested for progranulin antibodies using enzyme‐linked immunosorbent assay.ResultsProgranulin antibodies were found in 34 of 123 (27.6%) patients at least once during their disease. In detail, 2 of 8 (25%) patients with limited cutaneous systemic sclerosis, 10 of 31 (32.3%) patients with diffuse cutaneous systemic sclerosis, 9 of 22 (40.9%) patients with SjS, 1 of 3 (33.33%) patients with mixed connective tissue disease, 4 of 33 (12.1%) patients with DM or PM, 6 of 15 (40%) patients with APLS, and 2 of 11 (18.2%) patients with UCTD were positive for progranulin antibodies during the course of disease.ConclusionsProgranulin antibodies are frequently present in patients with systemic sclerosis and other autoimmune connective tissue disorders. Despite the lack of specificity for a given autoimmune disease, progranulin antibodies might not only indicate a potential subtype but also play a pathogenic role in patients with autoimmune connective disorders. Given the important role of TNF‐α in inflammatory processes in autoimmune connective tissue disorders, progranulin antibodies might support the proinflammatory environment by neutralizing the TNF blocker progranulin.
Highlights
We identified progranulin autoantibodies (PGRN‐Abs) by a protein‐array screening of sera from patients with several primary systemic vasculitides
Two of eight (25%) patients with limited cutaneous systemic sclerosis, 10 of 31 (32.3%) patients with diffuse cutaneous systemic sclerosis, 9 of 22 (40.9%) patients with Sjoegren’s syndrome (SjS), 1 of 3 (33.33%) patients with mixed connective tissue disease, 4 of 33 (12.1%) patients with dermatomyositis or polymyositis, 6 of 15 (40.0%) patients with antiphospholipid syndrome, and 2 of 11 (18.2%) patients with undifferentiated connective tissue disease were positive for progranulin antibodies (Figure 1)
This study revealed the frequent occurrence of PGRN‐ Abs in the sera of patients with systemic sclerosis and other autoimmune connective tissue disorders, in addition to the previously described frequent occurrence of such antibodies in systemic lupus erythematosus (SLE)
Summary
We identified progranulin autoantibodies (PGRN‐Abs) by a protein‐array screening of sera from patients with several primary systemic vasculitides. This finding was confirmed by enzyme‐linked immunosorbent assay (ELISA) using recombinant C‐terminally FLAG‐tagged and in HEK293 cells expressed human progranulin as bait. PGRN‐ Abs restricts progranulin function but the cause for autoimmunity to progranulin itself limits progranulin function
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
