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Impaired clearance of early apoptotic cells mediated by inhibitory IgG antibodies in patients with primary Sjögren's syndrome.

Manoussakis MN, Fragoulis GE, Vakrakou AG, Moutsopoulos HM - PLoS ONE (2014)

Bottom Line: Compared to HBD, approximately half of SS and SLE patients studied (but not RA) manifested significantly reduced ApoCell-phagocytosis (p<0.001) and MB-phagocytosis (p<0.003) by blood-borne phagocytes that correlated inversely with disease activity (p≤0.004).In cross-admixture assays, healthy monocytes showed significantly reduced ApoCell-phagocytosis when fed with apoptotic cells that were pretreated with sera or purified serum IgG preparations from SS and SLE patients (p<0.0001, compared to those from HBD or RA).Such aberrant effect of the SS and SLE sera and IgG preparations correlated linearly with their content of IgG antibodies against apoptotic cells (p≤0.0001).

View Article: PubMed Central - PubMed

Affiliation: Department of Pathophysiology, School of Medicine, University of Athens, Athens, Greece; Hellenic Pasteur Institute, Athens, Greece.

ABSTRACT

Objectives: Deficient efferocytosis (i.e. phagocytic clearance of apoptotic cells) has been frequently reported in systemic lupus erythematosus (SLE). Todate, patients with primary Sjögren's syndrome (SS) have not been assessed for phagocytosis of apoptotic cells (ApoCell-phagocytosis) and of particulate targets (microbeads, MB-phagocytosis).

Design: ApoCell-phagocytosis and MB-phagocytosis were comparatively assessed by flow cytometry in peripheral blood specimens and monocyte-derived macrophage (MDM) preparations from healthy blood donors (HBD) and consecutive SS, SLE and rheumatoid arthritis (RA) patients. Cross-admixture ApoCell-phagocytosis experiments were also performed using phagocytes from HBD or patients, and apoptotic cells pretreated with whole sera or purified serum IgG derived from patients or HBD.

Results: Compared to HBD, approximately half of SS and SLE patients studied (but not RA) manifested significantly reduced ApoCell-phagocytosis (p<0.001) and MB-phagocytosis (p<0.003) by blood-borne phagocytes that correlated inversely with disease activity (p≤0.004). In cross-admixture assays, healthy monocytes showed significantly reduced ApoCell-phagocytosis when fed with apoptotic cells that were pretreated with sera or purified serum IgG preparations from SS and SLE patients (p<0.0001, compared to those from HBD or RA). Such aberrant effect of the SS and SLE sera and IgG preparations correlated linearly with their content of IgG antibodies against apoptotic cells (p≤0.0001). Phagocytic dysfunction maybe also present in certain SS and SLE patients, as supported by deficient capacity of MDM for ApoCell-phagocytosis and MB-phagocytosis under patients' serum-free conditions.

Conclusion: Similarly to SLE, efferocytosis is frequently impaired in SS and is primarily due to the presence of inhibitory IgG anti-ApoCell antibodies and secondarily to phagocytes' dysfunction.

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Related in: MedlinePlus

Impaired MB-phagocytosis by peripheral blood (PB) phagocytes (A; monocytes B; granulocytes) and by monocyte-derived macrophages (MDM, C) obtained from SS and SLE patients, but not from RA patients.The horizontal lines indicate the median levels in each group, whereas the numbers in boxes indicate the percentages of individuals with decreased MB-phagocytosis, as defined by the presence of MB-PhI values that were two standard deviations below the corresponding mean of HBD. Statistically significant comparisons of patient groups to HBD are shown.
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pone-0112100-g003: Impaired MB-phagocytosis by peripheral blood (PB) phagocytes (A; monocytes B; granulocytes) and by monocyte-derived macrophages (MDM, C) obtained from SS and SLE patients, but not from RA patients.The horizontal lines indicate the median levels in each group, whereas the numbers in boxes indicate the percentages of individuals with decreased MB-phagocytosis, as defined by the presence of MB-PhI values that were two standard deviations below the corresponding mean of HBD. Statistically significant comparisons of patient groups to HBD are shown.

Mentions: RA patients displayed similar MB-phagocytosis indices to those of HBD. In direct contrast, both SS and SLE groups were found to manifest highly significantly decreased levels of MB-phagocytosis by granulocytes and by monocytes compared to HBD, as well as to RA (Figure 3A & 3B). Conversely, there were no differences of MB-phagocytosis indices between SS and SLE patients for either granulocytes or monocytes (Figure 3A & 3B). The overall analysis of phagocytosis index values had revealed a highly significant correlation between the levels of MB-phagocytosis and ApoCell-phagocytosis by monocytes in the various groups studied (r = 0.432, p = 0.001).


Impaired clearance of early apoptotic cells mediated by inhibitory IgG antibodies in patients with primary Sjögren's syndrome.

Manoussakis MN, Fragoulis GE, Vakrakou AG, Moutsopoulos HM - PLoS ONE (2014)

Impaired MB-phagocytosis by peripheral blood (PB) phagocytes (A; monocytes B; granulocytes) and by monocyte-derived macrophages (MDM, C) obtained from SS and SLE patients, but not from RA patients.The horizontal lines indicate the median levels in each group, whereas the numbers in boxes indicate the percentages of individuals with decreased MB-phagocytosis, as defined by the presence of MB-PhI values that were two standard deviations below the corresponding mean of HBD. Statistically significant comparisons of patient groups to HBD are shown.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4232361&req=5

pone-0112100-g003: Impaired MB-phagocytosis by peripheral blood (PB) phagocytes (A; monocytes B; granulocytes) and by monocyte-derived macrophages (MDM, C) obtained from SS and SLE patients, but not from RA patients.The horizontal lines indicate the median levels in each group, whereas the numbers in boxes indicate the percentages of individuals with decreased MB-phagocytosis, as defined by the presence of MB-PhI values that were two standard deviations below the corresponding mean of HBD. Statistically significant comparisons of patient groups to HBD are shown.
Mentions: RA patients displayed similar MB-phagocytosis indices to those of HBD. In direct contrast, both SS and SLE groups were found to manifest highly significantly decreased levels of MB-phagocytosis by granulocytes and by monocytes compared to HBD, as well as to RA (Figure 3A & 3B). Conversely, there were no differences of MB-phagocytosis indices between SS and SLE patients for either granulocytes or monocytes (Figure 3A & 3B). The overall analysis of phagocytosis index values had revealed a highly significant correlation between the levels of MB-phagocytosis and ApoCell-phagocytosis by monocytes in the various groups studied (r = 0.432, p = 0.001).

Bottom Line: Compared to HBD, approximately half of SS and SLE patients studied (but not RA) manifested significantly reduced ApoCell-phagocytosis (p<0.001) and MB-phagocytosis (p<0.003) by blood-borne phagocytes that correlated inversely with disease activity (p≤0.004).In cross-admixture assays, healthy monocytes showed significantly reduced ApoCell-phagocytosis when fed with apoptotic cells that were pretreated with sera or purified serum IgG preparations from SS and SLE patients (p<0.0001, compared to those from HBD or RA).Such aberrant effect of the SS and SLE sera and IgG preparations correlated linearly with their content of IgG antibodies against apoptotic cells (p≤0.0001).

View Article: PubMed Central - PubMed

Affiliation: Department of Pathophysiology, School of Medicine, University of Athens, Athens, Greece; Hellenic Pasteur Institute, Athens, Greece.

ABSTRACT

Objectives: Deficient efferocytosis (i.e. phagocytic clearance of apoptotic cells) has been frequently reported in systemic lupus erythematosus (SLE). Todate, patients with primary Sjögren's syndrome (SS) have not been assessed for phagocytosis of apoptotic cells (ApoCell-phagocytosis) and of particulate targets (microbeads, MB-phagocytosis).

Design: ApoCell-phagocytosis and MB-phagocytosis were comparatively assessed by flow cytometry in peripheral blood specimens and monocyte-derived macrophage (MDM) preparations from healthy blood donors (HBD) and consecutive SS, SLE and rheumatoid arthritis (RA) patients. Cross-admixture ApoCell-phagocytosis experiments were also performed using phagocytes from HBD or patients, and apoptotic cells pretreated with whole sera or purified serum IgG derived from patients or HBD.

Results: Compared to HBD, approximately half of SS and SLE patients studied (but not RA) manifested significantly reduced ApoCell-phagocytosis (p<0.001) and MB-phagocytosis (p<0.003) by blood-borne phagocytes that correlated inversely with disease activity (p≤0.004). In cross-admixture assays, healthy monocytes showed significantly reduced ApoCell-phagocytosis when fed with apoptotic cells that were pretreated with sera or purified serum IgG preparations from SS and SLE patients (p<0.0001, compared to those from HBD or RA). Such aberrant effect of the SS and SLE sera and IgG preparations correlated linearly with their content of IgG antibodies against apoptotic cells (p≤0.0001). Phagocytic dysfunction maybe also present in certain SS and SLE patients, as supported by deficient capacity of MDM for ApoCell-phagocytosis and MB-phagocytosis under patients' serum-free conditions.

Conclusion: Similarly to SLE, efferocytosis is frequently impaired in SS and is primarily due to the presence of inhibitory IgG anti-ApoCell antibodies and secondarily to phagocytes' dysfunction.

Show MeSH
Related in: MedlinePlus