title: The role of a proliferation-inducing ligand (APRIL) in the pathogenesis of rheumatoid arthritis.
abstract: OBJECTIVE
  To determine the differences in a proliferation-inducing ligand (APRIL) between seropositive and seronegative rheumatoid arthritis (RA) patients and further investigate the possible pathogenesis of the two subtypes of RA.
  
  
  METHODS
  Concentrations of APRIL in sera (18 seropositive RA patients, 16 seronegative RA patients, and 10 healthy controls) and synovial fluid (SF) (eight seropositive RA patients, two seronegative RA patients, and 10 controls) were detected by enzyme-linked immunosorbent assay (ELISA). Infiltration of plasma cells, macrophages, and APRIL-positive cells in the synovium [14 seropositives, eight seronegatives, and 10 osteoarthritis (OA) controls] was detected by immunohistochemistry. Correlations between serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), 28-joint Disease Activity Score (DAS28), and sera/SF levels of APRIL and synovial cell infiltration were analysed.
  
  
  RESULTS
  The mean serum APRIL level of seropositive RA patients was significantly higher than that of seronegative patients (26.1 ± 31.2 vs. 8.0 ± 10.2 ng/mL, p = 0.03). The level of APRIL in the SF of seropositive RA patients was comparable to that of seronegative patients [47.9 ± 54.4 vs. 32.82 (6.52-59.12) ng/mL, p > 0.05]. The SF APRIL level of RA patients was higher than that of patients with other inflammatory arthritis. Dramatically increased infiltration of APRIL-positive cells in the RA synovium was observed compared with the OA group (seropositive RA vs. OA, p < 0.001; seronegative RA vs. OA, p = 0.001). The infiltration of both plasma cells and macrophages was more in seropositive RA than in OA (p = 0.013 and p = 0.003, respectively).
  
  
  CONCLUSIONS
  The serum APRIL levels of seropositive RA patients are significantly higher than those of seronegative RA patients. APRIL may participate in the formation of seropositive RA.
authors.affiliation: Department of Rheumatology and Clinical Immunology, Peking University First Hospital , Beijing , China.
authors.forename: J
authors.initials: J
authors.lastname: Zhao
authors.forename: J
authors.initials: J
authors.lastname: Guo
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.forename: W
authors.initials: W
authors.lastname: Zhou
authors.forename: Z
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000209:etiology*; D005260:Female; D006801:Humans; D008264:Macrophages / Q000502:physiology; D008297:Male; D008875:Middle Aged; D010950:Plasma Cells / Q000502:physiology; D013582:Synovial Fluid / Q000737:chemistry; D013583:Synovial Membrane / Q000166:cytology; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000032:analysis / Q000097:blood / Q000502:physiology*
chemical_list: C114631:TNFSF13 protein, human; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13