Impaired phagocytosis and reactive oxygen species production in phagocytes is associated with systemic vasculitis
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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.
CONCLUSION: 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.
|Enheter & grupper|
Ämnesklassifikation (UKÄ) – OBLIGATORISK
|Tidskrift||Arthritis Research & Therapy|
|Status||Published - 2016|
|Peer review utförd||Ja|