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Intermediate monocytes in ANCA vasculitis: increased surface expression of ANCA autoantigens and IL-1β secretion in response to anti-MPO antibodies.

O'Brien EC, Abdulahad WH, Rutgers A, Huitema MG, O'Reilly VP, Coughlan AM, Harrington M, Heeringa P, Little MA, Hickey FB - Sci Rep (2015)

Bottom Line: Most patients harbour autoantibodies to myeloperoxidase (MPO) or proteinase 3 (PR3).Monocyte subsets respond differently to antibodies directed against MPO and PR3, with anti-MPO but not anti-PR3 leading to increased IL-1β, IL-6 and IL-8 production.These data suggest that monocytes, specifically, the intermediate subset, may play a role in ANCA vasculitis, and also indicate that substantial differences exist between the effect of anti-MPO and anti-PR3 antibodies on these cells.

View Article: PubMed Central - PubMed

Affiliation: Trinity Health Kidney Centre, Department of Clinical Medicine, Trinity College Dublin, St. James' Hospital Campus, Dublin 8, Ireland.

ABSTRACT
ANCA vasculitis encompasses several autoimmune conditions characterised by destruction of small vessels, inflammation of the respiratory tract and glomerulonephritis. Most patients harbour autoantibodies to myeloperoxidase (MPO) or proteinase 3 (PR3). Clinical and experimental data suggest that pathogenesis is driven by ANCA-mediated activation of neutrophils and monocytes. We investigated a potential role for distinct monocyte subsets. We found that the relative proportion of intermediate monocytes is increased in patients versus control individuals, and both MPO and PR3 are preferentially expressed on these cells. We demonstrate that MPO and PR3 are expressed independently of each other on monocytes and that PR3 is not associated with CD177. MPO expression correlates with that of Fc receptor CD16 on intermediate monocytes. Monocyte subsets respond differently to antibodies directed against MPO and PR3, with anti-MPO but not anti-PR3 leading to increased IL-1β, IL-6 and IL-8 production. In concordance with the observed higher surface expression of MPO on intermediate monocytes, this subset produces the highest quantity of IL-1β in response to anti-MPO stimulation. These data suggest that monocytes, specifically, the intermediate subset, may play a role in ANCA vasculitis, and also indicate that substantial differences exist between the effect of anti-MPO and anti-PR3 antibodies on these cells.

No MeSH data available.


Related in: MedlinePlus

Intermediate monocyte subsets are increased in both active and remission AAV patients compared to healthy control individuals.Peripheral blood was collected from healthy control individuals, AAV patients (both patients with active disease and those in remission), and patients with other renal disease (disease controls). Percentages of monocytes in each subset (A–C) were established by flow cytometry based on CD14 and CD16 staining. Each symbol represents a separate individual. Data are presented as the median and interquartile range. (*p < 0.05, ***p < 0.005). HC: healthy control; DC: disease control; Rem: remission.
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f1: Intermediate monocyte subsets are increased in both active and remission AAV patients compared to healthy control individuals.Peripheral blood was collected from healthy control individuals, AAV patients (both patients with active disease and those in remission), and patients with other renal disease (disease controls). Percentages of monocytes in each subset (A–C) were established by flow cytometry based on CD14 and CD16 staining. Each symbol represents a separate individual. Data are presented as the median and interquartile range. (*p < 0.05, ***p < 0.005). HC: healthy control; DC: disease control; Rem: remission.

Mentions: Monocyte subsets were analysed in AAV patients (n = 100, 19 active and 81 remission), disease control patients (n = 18) and healthy control individuals (n = 44) (Table 2). Individual subsets were identified based on cell surface expression of CD14 and CD16 as measured by flow cytometry. We observed no significant difference in the proportion of classical and non-classical monocytes, as a percentage of total monocytes, between healthy controls, disease controls and AAV patients (remission or active) (Fig. 1A,C). Intermediate monocytes were significantly increased in both remission and active AAV patients when compared to healthy control individuals (Fig. 1B). The fraction of intermediate monocytes in the disease control group was numerically similar to the vasculitis groups, but the increase was not significantly different from the healthy control group.


Intermediate monocytes in ANCA vasculitis: increased surface expression of ANCA autoantigens and IL-1β secretion in response to anti-MPO antibodies.

O'Brien EC, Abdulahad WH, Rutgers A, Huitema MG, O'Reilly VP, Coughlan AM, Harrington M, Heeringa P, Little MA, Hickey FB - Sci Rep (2015)

Intermediate monocyte subsets are increased in both active and remission AAV patients compared to healthy control individuals.Peripheral blood was collected from healthy control individuals, AAV patients (both patients with active disease and those in remission), and patients with other renal disease (disease controls). Percentages of monocytes in each subset (A–C) were established by flow cytometry based on CD14 and CD16 staining. Each symbol represents a separate individual. Data are presented as the median and interquartile range. (*p < 0.05, ***p < 0.005). HC: healthy control; DC: disease control; Rem: remission.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4493694&req=5

f1: Intermediate monocyte subsets are increased in both active and remission AAV patients compared to healthy control individuals.Peripheral blood was collected from healthy control individuals, AAV patients (both patients with active disease and those in remission), and patients with other renal disease (disease controls). Percentages of monocytes in each subset (A–C) were established by flow cytometry based on CD14 and CD16 staining. Each symbol represents a separate individual. Data are presented as the median and interquartile range. (*p < 0.05, ***p < 0.005). HC: healthy control; DC: disease control; Rem: remission.
Mentions: Monocyte subsets were analysed in AAV patients (n = 100, 19 active and 81 remission), disease control patients (n = 18) and healthy control individuals (n = 44) (Table 2). Individual subsets were identified based on cell surface expression of CD14 and CD16 as measured by flow cytometry. We observed no significant difference in the proportion of classical and non-classical monocytes, as a percentage of total monocytes, between healthy controls, disease controls and AAV patients (remission or active) (Fig. 1A,C). Intermediate monocytes were significantly increased in both remission and active AAV patients when compared to healthy control individuals (Fig. 1B). The fraction of intermediate monocytes in the disease control group was numerically similar to the vasculitis groups, but the increase was not significantly different from the healthy control group.

Bottom Line: Most patients harbour autoantibodies to myeloperoxidase (MPO) or proteinase 3 (PR3).Monocyte subsets respond differently to antibodies directed against MPO and PR3, with anti-MPO but not anti-PR3 leading to increased IL-1β, IL-6 and IL-8 production.These data suggest that monocytes, specifically, the intermediate subset, may play a role in ANCA vasculitis, and also indicate that substantial differences exist between the effect of anti-MPO and anti-PR3 antibodies on these cells.

View Article: PubMed Central - PubMed

Affiliation: Trinity Health Kidney Centre, Department of Clinical Medicine, Trinity College Dublin, St. James' Hospital Campus, Dublin 8, Ireland.

ABSTRACT
ANCA vasculitis encompasses several autoimmune conditions characterised by destruction of small vessels, inflammation of the respiratory tract and glomerulonephritis. Most patients harbour autoantibodies to myeloperoxidase (MPO) or proteinase 3 (PR3). Clinical and experimental data suggest that pathogenesis is driven by ANCA-mediated activation of neutrophils and monocytes. We investigated a potential role for distinct monocyte subsets. We found that the relative proportion of intermediate monocytes is increased in patients versus control individuals, and both MPO and PR3 are preferentially expressed on these cells. We demonstrate that MPO and PR3 are expressed independently of each other on monocytes and that PR3 is not associated with CD177. MPO expression correlates with that of Fc receptor CD16 on intermediate monocytes. Monocyte subsets respond differently to antibodies directed against MPO and PR3, with anti-MPO but not anti-PR3 leading to increased IL-1β, IL-6 and IL-8 production. In concordance with the observed higher surface expression of MPO on intermediate monocytes, this subset produces the highest quantity of IL-1β in response to anti-MPO stimulation. These data suggest that monocytes, specifically, the intermediate subset, may play a role in ANCA vasculitis, and also indicate that substantial differences exist between the effect of anti-MPO and anti-PR3 antibodies on these cells.

No MeSH data available.


Related in: MedlinePlus