Anti-phospholipid antibodies are elevated and functionally active in chronic rhinosinusitis with nasal polyps

Jacob G. Eide; Jeffanie Wu; Whitney W. Stevens; Junqin Bai; Songwang Hou; Julia H. Huang; Jacob Rosenberg; Paul Utz; Stephanie Shintani-Smith; David B. Conley; Kevin C. Welch; Robert C. Kern; Kathryn E. Hulse; Anju T. Peters; Leslie C. Grammer; Ming Zhao; Paul Lindholm; Robert P. Schleimer; Bruce K. Tan

doi:10.1111/cea.14120

Anti-phospholipid antibodies are elevated and functionally active in chronic rhinosinusitis with nasal polyps

Jacob G. Eide, Jeffanie Wu, Whitney W. Stevens, Junqin Bai, Songwang Hou, Julia H. Huang, Jacob Rosenberg, Paul Utz, Stephanie Shintani-Smith, David B. Conley, Kevin C. Welch, Robert C. Kern, Kathryn E. Hulse, Anju T. Peters, Leslie C. Grammer, Ming Zhao, Paul Lindholm, Robert P. Schleimer, Bruce K. Tan^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

Abstract

Background: Polyps from patients with chronic rhinosinusitis with nasal polyps (CRSwNP) contain increased levels of autoreactive antibodies, B cells and fibrin deposition. Anti-phospholipid antibodies (APA) are autoantibodies known to cause thrombosis but have not been implicated in chronic rhinosinusitis (CRS). Objective: To compare APA levels (anti-cardiolipin, anti-phosphatidylethanolamine (anti-PE), and anti-β₂-glycoprotein (anti-B2GP)) in nasal polyp (NP) tissue with tissue from control and CRS without nasal polyp (CRSsNP) patients, we tested whether NP antibodies affect coagulation, and correlate APAs with anti-dsDNA IgG and markers of coagulation. Methods: Patient specimens were assayed for APA IgG, anti-dsDNA IgG and thrombin-anti-thrombin (TaT) complex by ELISA. Antibodies from a subset of specimens were tested for modified activated partial thromboplastin time (aPTT) measured on an optical-mechanical coagulometer. Results: Anti-cardiolipin IgG in NP was 5-fold higher than control tissue (p <.0001). NP antibodies prolonged aPTT compared to control tissue antibodies at 400 µg/mL (36.7 s vs. 33.8 s, p =.024) and 600 µg/mL (40.9 s vs. 34.7 s, p =.0037). Anti-PE IgG antibodies were increased in NP (p =.027), but anti-B2GP IgG was not significantly higher (p =.084). All APAs correlated with anti-dsDNA IgG levels, which were also elevated (R =.77,.71 and.54, respectively, for anti-cardiolipin, anti-PE, and anti-B2GP; all p <.001), but only anti-cardiolipin (R =.50, p =.0185) and anti-PE (R = 0.45, p =.037) correlated with TaT complex levels. Conclusions: APA IgG antibodies are increased in NP and correlate with autoreactive tissue antibodies. NP antibodies have in vitro anti-coagulant activity similar to those observed in anti-phospholipid syndrome, suggesting that they may have pro-coagulant effects in polyp tissue.

Original language	English (US)
Pages (from-to)	954-964
Number of pages	11
Journal	Clinical and Experimental Allergy
Volume	52
Issue number	8
DOIs	https://doi.org/10.1111/cea.14120
State	Published - Aug 2022

Funding

Robert C. Kern is a consultant of Lyra Therapeutics, Sanofi Regeneron, GlaxoSmithKline, and Genentech. Anju T. Peters reports personal fees from Sanofi Regeneron, grants and personal fees from AstraZeneca and Optinose, outside the submitted work. Leslie C. Grammar III has received grants from the National Institutes of Health and Bazley Foundation to support her research. She has received grants for the institution from the National Institute of Health Food Allergy Network, AstraZeneca, and Sanofi Regeneron. She is a consultant for Astellas Pharmaceuticals. She has received royalties and payment for lectures from the American Academy of Allergy, Asthma and Immunology (AAAAI), Mount Sinai, Lippincott, UpToDate, Elsevier, Kluwers Wolter. Whitney W. Stevens has served on an advisory board for GlaxoSmithKline. Robert P. Schleimer is a consultant for Intersect ENT, GlaxoSmithKline, Merck, Sanofi, AstraZeneca/Medimmune, Genentech, Otsuka, Actobio Therapeutics, Lyra Therapeutics, Astellas Pharm Inc, Genzyme/Sanofi Corp, and Celgene Corp. He is also a consultant with stock/stock options with Allakos, Aurasense, BioMarck, Exicure, and Aqualung Therapeutics Corp. He has a patent with Allakos related to Siglec‐8 and Siglec‐8 ligand related products that have not been developed yet. He has also received grants from the National Institutes of Health to support this and other research. Bruce K. Tan has received grants from the National Institutes of Health to support this research. He has served on advisory boards for Sanofi/Genzyme. All other authors have no conflicts of interest to report. This work was supported by NIH grant R01 AI134952, R01 DC016645, and K23 DC012067 (BKT) and the Chronic Rhinosinusitis Integrative Studies Program 2 (CRISP2) P01 AI145818.

Keywords

anti-phospholipid antibodies
nasal polyps
rhinosinusitis

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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10.1111/cea.14120

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Eide, J. G., Wu, J., Stevens, W. W., Bai, J., Hou, S., Huang, J. H., Rosenberg, J., Utz, P., Shintani-Smith, S., Conley, D. B., Welch, K. C., Kern, R. C., Hulse, K. E., Peters, A. T., Grammer, L. C., Zhao, M., Lindholm, P., Schleimer, R. P., & Tan, B. K. (2022). Anti-phospholipid antibodies are elevated and functionally active in chronic rhinosinusitis with nasal polyps. Clinical and Experimental Allergy, 52(8), 954-964. https://doi.org/10.1111/cea.14120

@article{143cf5055fcd4655b1699dd74db8ab2f,

title = "Anti-phospholipid antibodies are elevated and functionally active in chronic rhinosinusitis with nasal polyps",

abstract = "Background: Polyps from patients with chronic rhinosinusitis with nasal polyps (CRSwNP) contain increased levels of autoreactive antibodies, B cells and fibrin deposition. Anti-phospholipid antibodies (APA) are autoantibodies known to cause thrombosis but have not been implicated in chronic rhinosinusitis (CRS). Objective: To compare APA levels (anti-cardiolipin, anti-phosphatidylethanolamine (anti-PE), and anti-β2-glycoprotein (anti-B2GP)) in nasal polyp (NP) tissue with tissue from control and CRS without nasal polyp (CRSsNP) patients, we tested whether NP antibodies affect coagulation, and correlate APAs with anti-dsDNA IgG and markers of coagulation. Methods: Patient specimens were assayed for APA IgG, anti-dsDNA IgG and thrombin-anti-thrombin (TaT) complex by ELISA. Antibodies from a subset of specimens were tested for modified activated partial thromboplastin time (aPTT) measured on an optical-mechanical coagulometer. Results: Anti-cardiolipin IgG in NP was 5-fold higher than control tissue (p <.0001). NP antibodies prolonged aPTT compared to control tissue antibodies at 400 µg/mL (36.7 s vs. 33.8 s, p =.024) and 600 µg/mL (40.9 s vs. 34.7 s, p =.0037). Anti-PE IgG antibodies were increased in NP (p =.027), but anti-B2GP IgG was not significantly higher (p =.084). All APAs correlated with anti-dsDNA IgG levels, which were also elevated (R =.77,.71 and.54, respectively, for anti-cardiolipin, anti-PE, and anti-B2GP; all p <.001), but only anti-cardiolipin (R =.50, p =.0185) and anti-PE (R = 0.45, p =.037) correlated with TaT complex levels. Conclusions: APA IgG antibodies are increased in NP and correlate with autoreactive tissue antibodies. NP antibodies have in vitro anti-coagulant activity similar to those observed in anti-phospholipid syndrome, suggesting that they may have pro-coagulant effects in polyp tissue.",

keywords = "anti-phospholipid antibodies, nasal polyps, rhinosinusitis",

author = "Eide, {Jacob G.} and Jeffanie Wu and Stevens, {Whitney W.} and Junqin Bai and Songwang Hou and Huang, {Julia H.} and Jacob Rosenberg and Paul Utz and Stephanie Shintani-Smith and Conley, {David B.} and Welch, {Kevin C.} and Kern, {Robert C.} and Hulse, {Kathryn E.} and Peters, {Anju T.} and Grammer, {Leslie C.} and Ming Zhao and Paul Lindholm and Schleimer, {Robert P.} and Tan, {Bruce K.}",

note = "Publisher Copyright: {\textcopyright} 2022 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.",

year = "2022",

month = aug,

doi = "10.1111/cea.14120",

language = "English (US)",

volume = "52",

pages = "954--964",

journal = "Clinical and Experimental Allergy",

issn = "0954-7894",

publisher = "Wiley-Blackwell Publishing Ltd",

number = "8",

}

Eide, JG, Wu, J, Stevens, WW, Bai, J, Hou, S, Huang, JH, Rosenberg, J, Utz, P, Shintani-Smith, S , Conley, DB , Welch, KC , Kern, RC, Hulse, KE, Peters, AT , Grammer, LC , Zhao, M , Lindholm, P , Schleimer, RP & Tan, BK 2022, 'Anti-phospholipid antibodies are elevated and functionally active in chronic rhinosinusitis with nasal polyps', Clinical and Experimental Allergy, vol. 52, no. 8, pp. 954-964. https://doi.org/10.1111/cea.14120

TY - JOUR

T1 - Anti-phospholipid antibodies are elevated and functionally active in chronic rhinosinusitis with nasal polyps

AU - Eide, Jacob G.

AU - Wu, Jeffanie

AU - Stevens, Whitney W.

AU - Bai, Junqin

AU - Hou, Songwang

AU - Huang, Julia H.

AU - Rosenberg, Jacob

AU - Utz, Paul

AU - Shintani-Smith, Stephanie

AU - Conley, David B.

AU - Welch, Kevin C.

AU - Kern, Robert C.

AU - Hulse, Kathryn E.

AU - Peters, Anju T.

AU - Grammer, Leslie C.

AU - Zhao, Ming

AU - Lindholm, Paul

AU - Schleimer, Robert P.

AU - Tan, Bruce K.

PY - 2022/8

Y1 - 2022/8

N2 - Background: Polyps from patients with chronic rhinosinusitis with nasal polyps (CRSwNP) contain increased levels of autoreactive antibodies, B cells and fibrin deposition. Anti-phospholipid antibodies (APA) are autoantibodies known to cause thrombosis but have not been implicated in chronic rhinosinusitis (CRS). Objective: To compare APA levels (anti-cardiolipin, anti-phosphatidylethanolamine (anti-PE), and anti-β2-glycoprotein (anti-B2GP)) in nasal polyp (NP) tissue with tissue from control and CRS without nasal polyp (CRSsNP) patients, we tested whether NP antibodies affect coagulation, and correlate APAs with anti-dsDNA IgG and markers of coagulation. Methods: Patient specimens were assayed for APA IgG, anti-dsDNA IgG and thrombin-anti-thrombin (TaT) complex by ELISA. Antibodies from a subset of specimens were tested for modified activated partial thromboplastin time (aPTT) measured on an optical-mechanical coagulometer. Results: Anti-cardiolipin IgG in NP was 5-fold higher than control tissue (p <.0001). NP antibodies prolonged aPTT compared to control tissue antibodies at 400 µg/mL (36.7 s vs. 33.8 s, p =.024) and 600 µg/mL (40.9 s vs. 34.7 s, p =.0037). Anti-PE IgG antibodies were increased in NP (p =.027), but anti-B2GP IgG was not significantly higher (p =.084). All APAs correlated with anti-dsDNA IgG levels, which were also elevated (R =.77,.71 and.54, respectively, for anti-cardiolipin, anti-PE, and anti-B2GP; all p <.001), but only anti-cardiolipin (R =.50, p =.0185) and anti-PE (R = 0.45, p =.037) correlated with TaT complex levels. Conclusions: APA IgG antibodies are increased in NP and correlate with autoreactive tissue antibodies. NP antibodies have in vitro anti-coagulant activity similar to those observed in anti-phospholipid syndrome, suggesting that they may have pro-coagulant effects in polyp tissue.

AB - Background: Polyps from patients with chronic rhinosinusitis with nasal polyps (CRSwNP) contain increased levels of autoreactive antibodies, B cells and fibrin deposition. Anti-phospholipid antibodies (APA) are autoantibodies known to cause thrombosis but have not been implicated in chronic rhinosinusitis (CRS). Objective: To compare APA levels (anti-cardiolipin, anti-phosphatidylethanolamine (anti-PE), and anti-β2-glycoprotein (anti-B2GP)) in nasal polyp (NP) tissue with tissue from control and CRS without nasal polyp (CRSsNP) patients, we tested whether NP antibodies affect coagulation, and correlate APAs with anti-dsDNA IgG and markers of coagulation. Methods: Patient specimens were assayed for APA IgG, anti-dsDNA IgG and thrombin-anti-thrombin (TaT) complex by ELISA. Antibodies from a subset of specimens were tested for modified activated partial thromboplastin time (aPTT) measured on an optical-mechanical coagulometer. Results: Anti-cardiolipin IgG in NP was 5-fold higher than control tissue (p <.0001). NP antibodies prolonged aPTT compared to control tissue antibodies at 400 µg/mL (36.7 s vs. 33.8 s, p =.024) and 600 µg/mL (40.9 s vs. 34.7 s, p =.0037). Anti-PE IgG antibodies were increased in NP (p =.027), but anti-B2GP IgG was not significantly higher (p =.084). All APAs correlated with anti-dsDNA IgG levels, which were also elevated (R =.77,.71 and.54, respectively, for anti-cardiolipin, anti-PE, and anti-B2GP; all p <.001), but only anti-cardiolipin (R =.50, p =.0185) and anti-PE (R = 0.45, p =.037) correlated with TaT complex levels. Conclusions: APA IgG antibodies are increased in NP and correlate with autoreactive tissue antibodies. NP antibodies have in vitro anti-coagulant activity similar to those observed in anti-phospholipid syndrome, suggesting that they may have pro-coagulant effects in polyp tissue.

KW - anti-phospholipid antibodies

KW - nasal polyps

KW - rhinosinusitis

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U2 - 10.1111/cea.14120

DO - 10.1111/cea.14120

M3 - Article

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AN - SCOPUS:85126256036

SN - 0954-7894

VL - 52

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EP - 964

JO - Clinical and Experimental Allergy

JF - Clinical and Experimental Allergy

IS - 8

ER -

Anti-phospholipid antibodies are elevated and functionally active in chronic rhinosinusitis with nasal polyps

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