Treatment of inflammatory diseases with inhibitors of C5a activity
The present invention relates to inhibitors of C5a activity and their use in the treatment of cutaneous, neutrophilic, inflammatory diseases in a subject.
1. A method of inhibiting C5a-induced upregulation of neutrophil-expressed CD11b in a subject having hidradenitis suppurativa (HS) or an HS-related disorder; the method comprising: administering to a subject in need thereof an effective amount of monoclonal antibody 7H110 or S5/1, or an antigen binding fragment thereof, which specifically binds to the C5a receptor and blocks the binding of C5a to the C5a receptor, thereby inhibiting C5a-induced upregulation of neutrophil-expressed CD11b in the subject having HS or an HS-related disorder; wherein the HS-related disorder is selected from Pyoderma gangrenosum (PG); PAPA (pyogenic arthritis, PG and acne); PASH (PG, acne and hidradenitis suppurativa); PAPASH (pyogenic arthritis, acne, PG and hidradenitis suppurativa), Sweet syndrome (SS); or subcorneal pustular dermatosis (SPD).
2. The method of claim 1 , wherein the C5a receptor is one or both of C5aR and C5L2.
3. The method of claim 1 , wherein the monoclonal antibody 7H110 or S5/1, or an antigen binding fragment thereof, is a chimeric antibody.
4. The method of claim 1 , wherein the monoclonal antibody 7H110 or S5/1, or an antigen binding fragment thereof, is a humanized antibody.
5. A method of treating hidradenitis suppurativa (HS) or an HS-related disorder in a subject; the method comprising: administering to a subject in need thereof an effective amount of monoclonal antibody 7H110 or S5/1, or an antigen binding fragment thereof, which specifically binds to the C5a receptor and blocks the binding of C5a to the C5a receptor, thereby treating HS or an HS-related disorder; wherein the HS-related disorder is selected from Pyoderma gangrenosum (PG); PAPA (pyogenic arthritis, PG and acne); PASH (PG, acne and hidradenitis suppurativa); or PAPASH (pyogenic arthritis, acne, PG and hidradenitis suppurativa), Sweet syndrome (SS); or subcorneal pustular dermatosis (SPD).
6. The method of claim 5 , wherein the C5a receptor is one or both of C5aR and C5L2.
7. The method of claim 5 , wherein the monoclonal antibody 7H110 or S5/1, or an antigen binding fragment thereof, is a chimeric antibody.
8. The method of claim 5 , wherein the monoclonal antibody is 7H110, or an antigen binding fragment thereof, is a humanized antibody.