Figure 4.

Many patients with RA have higher titers of autoantibodies recognizing citrullinated Env protein compared to unmodified Env. (A) Titers in patients with RA (n = 40) against HERV-K Env treated with buffer alone (PAD–) or with PAD4 for 1 hour at 37 °C (PAD+). Each individual patient is connected with a line between the 2 data points. (B) Titers in healthy subjects (n = 7) against HERV-K Env treated with buffer alone (PAD–) or with PAD4 for 1 hour at 37 °C (PAD+). Each individual subject is connected with a line between the 2 data points. (C) Relation between autoantibodies against unmodified (X-axis) and citrullinated (Y-axis) Env in each patient with RA. (D) Segregation by seronegativity (n = 5) vs seropositivity (n = 24) of autoantibodies against unmodified (PAD–) or citrullinated (PAD+) Env. The horizontal line in the graphs represents the median of each dataset. (E) Titers in patients with JIA (n = 32) against Env treated with buffer alone (PAD–) or with PAD4 (PAD+). (F) ELISA with detection by the patient-derived monoclonal ACPA 1325:04C03 of wells coated with Env, or only blocked, and treated with PAD4 (black bars) or citrullination buffer alone (gray bars). Statistical significance was calculated with the Wilcoxon matched-pairs signed-rank test ([A] and [B]), Spearman correlation test (C), and Mann-Whitney U test (D). ACPA: anticitrullinated protein antibodies; Anti-cit-Env: anticitrullinated Env; Env: envelope; HC: healthy controls; HERV-K: human endogenous retrovirus K; JIA: juvenile idiopathic arthritis; PAD: protein arginine deiminase; RA: rheumatoid arthritis; SU: surface; TM: transmembrane.