Impaired phagocytosis and reactive oxygen species production in phagocytes is associated with systemic vasculitis.
BACKGROUND
Anti-neutrophil cytoplasmic antibodies associated vasculitides (AAV) is a group of autoimmune diseases, characterized by small vessel inflammation. Phagocytes such as neutrophils and monocytes are the main effector cells found around the inflamed vessel wall. Therefore, we wanted to investigate aspects of function and activation of these cells in patients with AAV.


METHODS
Flow cytometry was used to evaluate: the expression of activation markers (CD11c, CD62L, CD177 and C5aR); the number of recently released neutrophils from bone marrow, defined as CD10(-)D16(low) cells in peripheral blood; and the capacity of peripheral blood monocytes and polymorphonuclear leukocytes (PMN) to produce reactive oxygen species and to phagocytose opsonized bacteria.


RESULTS
AAV patients (n = 104) showed an increase of CD10(-)CD16(low) neutrophils and total PMN in peripheral blood, suggesting a combination of increased bone marrow release and prolonged survival. An increased percentage of AAV PMN expressed CD177 but no other signs of activation were seen. A decreased production of reactive oxygen species was observed in AAV phagocytes, which was associated with disease activity. Moreover, granulocytes from patients with microscopic polyangiitis showed lower oxidative burst capacity compared to patients with granulomatosis with polyangiitis or eosinophilic granulomatosis with polyangiitis. In addition, decreased phagocytosis capacity was seen in PMN and monocytes.


CONCLUSIONS
Our results indicate that phagocytes from AAV patients have impaired function, are easily mobilized from bone marrow but are not particularly activated. The association between low reactive oxygen species formation in PMN and disease severity is consistent with findings in other autoimmune diseases and might be considered as a risk factor.
Department of Haematology, Lund University and Skåne University Hospital, BMC B13, 221 84, Lund, Sweden. asa.johansson@med.lu.se.|University and Regional Laboratories Region Skåne, Clinical Immunology and Transfusion Medicine, Skåne, 221 85, Lund, Sweden. asa.johansson@med.lu.se.
Åsa Cm
ÅC
Johansson
Department of Clinical Sciences Lund, Nephrology, Lund University, Skane University Hospital, Lund, Sweden.
Sophie
S
Ohlsson
Department of Clinical Sciences Lund, Nephrology, Lund University, Skane University Hospital, Lund, Sweden.
Åsa
Å
Pettersson
Department of Clinical Sciences, Lund, Rheumatology, Lund University, Skåne University Hospital, Lund, Sweden.
Anders A
AA
Bengtsson
Department of Clinical Sciences Lund, Nephrology, Lund University, Skane University Hospital, Lund, Sweden.
Daina
D
Selga
Department of Haematology, Lund University and Skåne University Hospital, BMC B13, 221 84, Lund, Sweden.
Markus
M
Hansson
Department of Clinical Sciences Lund, Nephrology, Lund University, Skane University Hospital, Lund, Sweden.
Thomas
T
Hellmark
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology*; D017382:Reactive Oxygen Species / Q000276:immunology / Q000378:metabolism*; D055815:Young Adult
D017382:Reactive Oxygen Species
ANCA; Monocytes; Oxidative burst; PMN; Phagocytosis; Vasculitis