The oxidation induced by antimyeloperoxidase antibodies triggers fibrosis in microscopic polyangiitis.
Lung fibrosis is considered a severe manifestation of microscopic polyangiitis (MPA). Antimyeloperoxidase (anti-MPO) antibodies in MPA patients' sera can activate MPO and lead to the production of reactive oxygen species (ROS). While high levels of ROS are cytotoxic, low levels can induce fibroblast proliferation. Therefore, we hypothesised that the oxidative stress induced by anti-MPO antibodies could contribute to lung fibrosis. 24 MPA patients (45 sera) were enrolled in the study, including nine patients (22 sera) with lung fibrosis. Serum advanced oxidation protein products (AOPP), MPO-induced hypochlorous acid (HOCl) and serum-induced fibroblast proliferation were assayed. AOPP levels, MPO-induced HOCl production and serum-induced fibroblast proliferation were higher in patients than in healthy controls (p<0.0001, p=0.0001 and p=0.0005, respectively). Increased HOCl production was associated with active disease (p=0.002). Serum AOPP levels and serum-induced fibroblast proliferation were higher in patients with active MPA and lung fibrosis (p<0.0001). A significant linear relationship between fibroblast proliferation, AOPP levels and HOCl production was observed only in patients with lung fibrosis. Oxidative stress, in particular the production of HOCl through the interaction of MPO with anti-MPO antibodies, could trigger the fibrotic process observed in MPA.
Laboratoire d'Immunologie, EA, UPRES 1833, Pôle de Médecine Interne et CentreNational de Référence pour lesVascularites Nécrosantes et laSclérodermie Systémique, UniversitéParis Descartes, Faculté deMédecine, Pavillon Gustave Roussy, 4e étage, Hôpital Cochin, 8 rue Méchain, 75014, Paris, France.
P
P
Guilpain
C
C
Chéreau
C
C
Goulvestre
A
A
Servettaz
D
D
Montani
N
N
Tamas
C
C
Pagnoux
E
E
Hachulla
B
B
Weill
L
L
Guillevin
L
L
Mouthon
F
F
Batteux
D000328:Adult; D000368:Aged; D000906:Antibodies / Q000276:immunology*; D001798:Blood Proteins / Q000378:metabolism; D049109:Cell Proliferation; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D006997:Hypochlorous Acid / Q000097:blood; D008297:Male; D055953:Microscopic Polyangiitis / Q000201:enzymology / Q000276:immunology*; D008875:Middle Aged; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D009195:Peroxidase / Q000276:immunology* / Q000378:metabolism*; D011658:Pulmonary Fibrosis / Q000201:enzymology / Q000276:immunology*; D012720:Severity of Illness Index
D000906:Antibodies; D001798:Blood Proteins; D006997:Hypochlorous Acid; D009195:Peroxidase