Relationship of circulating c5a and complement factor h levels with disease control in pregnant women with asthma

A. Bohács; A. Bikov; I. Ivancsó; I. Czaller; R. Böcskei; V. Müller; Jr. Rigó J.; G. Losonczy; L. Tamási

doi:10.4187/respcare.04339

Relationship of circulating c5a and complement factor h levels with disease control in pregnant women with asthma

A. Bohács, A. Bikov, I. Ivancsó, I. Czaller, R. Böcskei, V. Müller, Jr. Rigó J., G. Losonczy, L. Tamási

Division of Immunology, Immunity to Infection and Respiratory Medicine

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

Abstract

BACKGROUND: Asthma often complicates pregnancy and represents a risk of serious pregnancy complications. The complement system contributes to asthma pathogenesis and is up-regulated in healthy gestation as well. The anaphylatoxin C5a has a major pro-inflammatory role, and the complement factor H is a main soluble regulator protein both in asthma and during pregnancy; however, peripheral levels of these complement factors and their relationship to disease control have not yet been evaluated in pregnant subjects with asthma. METHODS: The present study aimed to investigate circulating C5a and complement factor H levels in asthma (non-pregnant subjects with asthma; n = 19) and in pregnancy with asthma (pregnant subjects with asthma; n = 22), compared with healthy non-pregnant (n = 21) and healthy pregnant women (n = 13) and to test their relationship to clinical parameters of asthma (lung function, airway inflammation, and symptoms). RESULTS: Circulating C5a levels were higher in the pregnant asthma subject group compared with the healthy non-pregnant, healthy pregnant, and non-pregnant asthma groups: median 2.629 (interquartile range [IQR] 2.257–3.052) ng/mL versus 1.84 (IQR 1.576 –2.563), 1.783 (IQR 0.6064 –2.786), and 2.024 (IQR 1.232–2.615) ng/mL, respectively (P =. 02 in all cases). C5a correlated negatively with FEV1 (r = -0.44, P =. 039) and FVC values (r = -0.64, P =. 001) in the pregnant asthma group and positively with fraction of exhaled nitric oxide levels in the nonpregnant asthma group (n = 12, r - 0.78, P =. 004). Complement factor H levels were elevated in both the healthy pregnant and pregnant asthma subject groups compared with the healthy non-pregnant group (median 1,082 [IQR 734.9–1,224] and 910.7 [IQR 614.5–1076] µg/mL vs 559.7 [IQR 388.7– 783.1]µg/mL, P=.002 and P=.004, respectively) but not in the pregnant asthma group compared with the non-pregnant asthma group (median 687.4 [IQR 441.6–947.6] µg/mL, P =. 10). CONCLUSIONS: Asthma during pregnancy increases the circulating level of pro-inflammatory C5a, which is accompanied by impaired lung function and partly counteracted by the gestation-specific elevation of regulatory complement factor H level (detected in pregnancy both in healthy and subjects with asthma). © 2016 Daedalus Enterprises.

Original language	English
Pages (from-to)	502-509
Number of pages	8
Journal	Respiratory Care
Volume	61
Issue number	4
Early online date	25 Mar 2016
DOIs	https://doi.org/10.4187/respcare.04339
Publication status	Published - Apr 2016

Keywords

Asthma
Biomarker
C5a
Complement
Complement factor H
Pregnancy
biological marker
complement component C5a
complement factor H
nitric oxide
regulator protein
complement factor H, human
adult
Article
asthma
clinical article
clinical evaluation
concurrent infection
cross-sectional study
disease control
disease severity
female
gestation period
human
inflammation
lung function
pathogenesis
pregnancy complication
quantitative analysis
respiratory tract inflammation
risk factor
blood
case control study
forced expiratory volume
lung
metabolism
pathophysiology
physiology
pregnancy
vital capacity
Adult
Case-Control Studies
Complement C5a
Complement Factor H
Female
Forced Expiratory Volume
Humans
Inflammation
Lung
Pregnancy Complications
Vital Capacity

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.4187/respcare.04339

Cite this

@article{bdb76f03cc2544b3a8107a07a71f892d,

title = "Relationship of circulating c5a and complement factor h levels with disease control in pregnant women with asthma",

abstract = "BACKGROUND: Asthma often complicates pregnancy and represents a risk of serious pregnancy complications. The complement system contributes to asthma pathogenesis and is up-regulated in healthy gestation as well. The anaphylatoxin C5a has a major pro-inflammatory role, and the complement factor H is a main soluble regulator protein both in asthma and during pregnancy; however, peripheral levels of these complement factors and their relationship to disease control have not yet been evaluated in pregnant subjects with asthma. METHODS: The present study aimed to investigate circulating C5a and complement factor H levels in asthma (non-pregnant subjects with asthma; n = 19) and in pregnancy with asthma (pregnant subjects with asthma; n = 22), compared with healthy non-pregnant (n = 21) and healthy pregnant women (n = 13) and to test their relationship to clinical parameters of asthma (lung function, airway inflammation, and symptoms). RESULTS: Circulating C5a levels were higher in the pregnant asthma subject group compared with the healthy non-pregnant, healthy pregnant, and non-pregnant asthma groups: median 2.629 (interquartile range [IQR] 2.257–3.052) ng/mL versus 1.84 (IQR 1.576 –2.563), 1.783 (IQR 0.6064 –2.786), and 2.024 (IQR 1.232–2.615) ng/mL, respectively (P =. 02 in all cases). C5a correlated negatively with FEV1 (r = -0.44, P =. 039) and FVC values (r = -0.64, P =. 001) in the pregnant asthma group and positively with fraction of exhaled nitric oxide levels in the nonpregnant asthma group (n = 12, r - 0.78, P =. 004). Complement factor H levels were elevated in both the healthy pregnant and pregnant asthma subject groups compared with the healthy non-pregnant group (median 1,082 [IQR 734.9–1,224] and 910.7 [IQR 614.5–1076] µg/mL vs 559.7 [IQR 388.7– 783.1]µg/mL, P=.002 and P=.004, respectively) but not in the pregnant asthma group compared with the non-pregnant asthma group (median 687.4 [IQR 441.6–947.6] µg/mL, P =. 10). CONCLUSIONS: Asthma during pregnancy increases the circulating level of pro-inflammatory C5a, which is accompanied by impaired lung function and partly counteracted by the gestation-specific elevation of regulatory complement factor H level (detected in pregnancy both in healthy and subjects with asthma). {\textcopyright} 2016 Daedalus Enterprises.",

keywords = "Asthma, Biomarker, C5a, Complement, Complement factor H, Pregnancy, biological marker, complement component C5a, complement factor H, nitric oxide, regulator protein, complement factor H, human, adult, Article, asthma, clinical article, clinical evaluation, concurrent infection, cross-sectional study, disease control, disease severity, female, gestation period, human, inflammation, lung function, pathogenesis, pregnancy complication, quantitative analysis, respiratory tract inflammation, risk factor, blood, case control study, forced expiratory volume, lung, metabolism, pathophysiology, physiology, pregnancy, vital capacity, Adult, Case-Control Studies, Complement C5a, Complement Factor H, Female, Forced Expiratory Volume, Humans, Inflammation, Lung, Pregnancy Complications, Vital Capacity",

author = "A. Boh{\'a}cs and A. Bikov and I. Ivancs{\'o} and I. Czaller and R. B{\"o}cskei and V. M{\"u}ller and {Rig{\'o} J.}, Jr. and G. Losonczy and L. Tam{\'a}si",

note = "Export Date: 31 October 2018 CODEN: RECAC Correspondence Address: Tam{\'a}si, L.; Department of Pulmonology, Semmelweis University, Di{\'o}s {\'a}rok u. 1/c, Hungary; email: [email protected] Chemicals/CAS: complement factor H, 80295-65-4; nitric oxide, 10102-43-9; Complement C5a; Complement Factor H; complement factor H, human References: Global Initiative for Asthma (GINA) 2015, , http://www.ginasthma.org/, Accessed September 17, 2014; Charlton, R.A., Hutchison, A., Davis, K.J., De Vries, C.S., Asthma management in pregnancy (2013) Plos One, 8 (4), p. e60247; Demissie, K., Breckenridge, M.B., Rhoads, G.G., Infant and maternal outcomes in the pregnancies of asthmatic women (1998) Am J Respir Crit Care Med, 158 (4), pp. 1091-1095; Breton, M.C., Beauchesne, M.F., Lemi{\`e}re, C., Rey, E., Forget, A., Blais, L., Risk of perinatal mortality associated with asthma during pregnancy (2009) Thorax, 64 (2), pp. 101-106; Murphy, V.E., Clifton, V.L., Gibson, P.G., Asthma exacerbations during pregnancy: Incidence and association with adverse pregnancy outcomes (2006) Thorax, 61 (2), pp. 169-176; Tam{\'a}si, L., Horv{\'a}th, I., Boh{\'a}cs, A., M{\"u}ller, V., Losonczy, G., Schatz, M., Asthma in pregnancy: Immunological changes and clinical management (2011) Respir Med, 105 (2), pp. 159-164; Grindheim, G., Toska, K., Estensen, M.E., Rosseland, L.A., Changes in pulmonary function during pregnancy: A longitudinal cohort study (2012) BJOG, 119 (1), pp. 94-101; Ivancs{\'o}, I., Toldi, G., Boh{\'a}cs, A., Eszes, N., M{\"u}ller, V., Rig{\'o}, J., Jr., Relationship of circulating soluble urokinase plasminogen activator receptor (SuPAR) levels to disease control in asthma and asthmatic pregnancy (2013) Plos One, 8 (4), p. e60697; Eszes, N., Toldi, G., Boh{\'a}cs, A., Ivancs{\'o}, I., M{\"u}ller, V., Rig{\'o}, J., Jr., Relationship of circulating hyaluronic acid levels to disease control in asthma and asthmatic pregnancy (2014) Plos One, 9 (4), p. e94678; Ricklin, D., Hajishengallis, G., Yang, K., Lambris, J.D., Complement: A key system for immune surveillance and homeostasis (2010) Nat Immunol, 11 (9), pp. 785-797; Zhang, X., K{\"o}hl, J., A complex role for complement in allergic asthma (2010) Expert Rev Clin Immunol, 6 (2), pp. 269-277; Laumonnier, Y., Schmudde, I., K{\"o}hl, J., The role of complement in the diagnosis and management of allergic rhinitis and allergic asthma (2011) Curr Allergy Asthma Rep, 11 (2), pp. 122-130; Krug, N., Tschernig, T., Erpenbeck, V.J., Hohlfeld, J.M., K{\"o}hl, J., Complement factors C3a and C5a are increased in bronchoalveolar lavage fluid after segmental allergen provocation in subjects with asthma (2001) Am J Respir Crit Care Med, 164 (10), pp. 1841-1843; Marc, M.M., Korosec, P., Kosnik, M., Kern, I., Flezar, M., Suskovic, S., Sorli, J., Complement factors c3a, c4a, and c5a in chronic obstructive pulmonary disease and asthma (2004) Am J Respir Cell Mol Biol, 31 (2), pp. 216-219; Bowser, C., Erstein, D.P., Silverberg, J.I., Nowakowski, M., Joks, R., Correlation of plasma complement split product levels with allergic respiratory disease activity and relation to allergen immunotherapy (2010) Ann Allergy Asthma Immunol, 104 (1), pp. 42-49; Kopp, A., Hebecker, M., Svobodov{\'a}, E., J{\'o}zsi, M., Factor H: A complement regulator in health and disease, and a mediator of cellular interactions (2012) Biomolecules, 7 (1), pp. 46-75; Weiszh{\'a}r, Z., Bikov, A., G{\'a}lffy, G., Tam{\'a}si, L., Ungv{\'a}ri, I., Szalai, C., Elevated complement factor H levels in asthmatic sputa (2013) J Clin Immunol, 33 (2), pp. 496-505; Richani, K., Soto, E., Romero, R., Espinoza, J., Chaiworapongsa, T., Nien, J.K., Normal pregnancy is characterized by systemic activation of the complement system (2005) J Matern Fetal Neonatal Med, 17 (4), pp. 239-245; Derzsy, Z., Proh{\'a}szka, Z., Rig{\'o}, J., Jr., F{\"u}st, G., Molvarec, A., Activation of the complement system in normal pregnancy and preeclampsia (2010) Mol Immunol, 47 (7), pp. 1500-1506; Banadakoppa, M., Chauhan, M.S., Havemann, D., Balakrishnan, M., Dominic, J.S., Yallampalli, C., Spontaneous abortion is associated with elevated systemic C5a and reduced mRNA of complement inhibitory proteins in placenta (2014) Clin Exp Immunol, 177 (3), pp. 743-749; Denny, K.J., Coulthard, L.G., Finnell, R.H., Callaway, L.K., Taylor, S.M., Woodruff, T.M., Elevated complement factor C5a in maternal and umbilical cord plasma in preeclampsia (2013) J Reprod Immunol, 97 (2), pp. 211-216; Soto, E., Romero, R., Richani, K., Espinoza, J., Chaiworapongsa, T., Nien, J.K., Preeclampsia and pregnancies with small-for-gestational age neonates have different profiles of complement split products (2010) J Matern Fetal Neonatal Med, 23 (7), pp. 646-657; Miller, M.R., Hankinson, J., Brusasco, V., Burgos, F., Casaburi, R., Coates, A., Standardisation of spirometry (2005) Eur Respir J, 26 (2), pp. 319-338; ATS/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide (2005) Am J Respir Crit Care Med, 171 (8), pp. 912-930; Wong, E.K., Kavanagh, D., Anticomplement C5 therapy with eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome (2015) Transl Res, 165 (2), pp. 306-320; Tan, L.A., Yu, B., Sim, F.C., Kishore, U., Sim, R.B., Complement activation by phospholipids: The interplay of factor H and C1q (2010) Protein Cell, 1 (11), pp. 1033-1049; K{\"o}hl, J., The role of complement in danger sensing and transmission (2006) Immunol Res, 34 (2), pp. 157-176; Khan, M.A., Nicolls, M.R., Surguladze, B., Saadoun, I., Complement components as potential therapeutic targets for asthma treatment (2014) Respir Med, 108 (4), pp. 543-549; Smith, S.G., Watson, B., Clark, G., Gauvreau, G.M., Eculizumab for treatment of asthma (2012) Expert Opin Biol Ther, 12 (4), pp. 529-537; Baelder, R., Fuchs, B., Bautsch, W., Zwirner, J., K{\"o}hl, J., Hoymann, H.G., Pharmacological targeting of anaphylatoxin receptors during the effector phase of allergic asthma suppresses airway hyperresponsiveness and airway inflammation (2005) J Immunol, 174 (2), pp. 783-789; Tam{\'a}si, L., Boh{\'a}cs, A., Bikov, A., Orka, C., Rig{\'o}, J., Jr., Losonczy, G., Horv{\'a}th, I., Exhaled nitric oxide in pregnant healthy and asthmatic women (2009) J Asthma, 46 (8), pp. 786-791; Lee, J., Oh, J., Choi, E., Park, I., Han, C., Kim Do, H., Differentially expressed genes implicated in unexplained recurrent spontaneous abortion (2007) Int J Biochem Cell Biol, 39 (12), pp. 2265-2277; Lappas, M., Woodruff, T.M., Taylor, S.M., Permezel, M., Complement C5A regulates prolabor mediators in human placenta (2012) Biol Reprod, 86 (6), p. 190; Soto, E., Romero, R., Richani, K., Yoon, B.H., Chaiworapongsa, T., Vaisbuch, E., Evidence for complement activation in the amniotic fluid of women with spontaneous preterm labor and intra-amniotic infection (2009) J Matern Fetal Neonatal Med, 22 (11), pp. 983-992; Burwick, R.M., Feinberg, B.B., Eculizumab for the treatment of preeclampsia/ HELLP syndrome (2013) Placenta, 34 (2), pp. 201-203; Kelly, R., Arnold, L., Richards, S., Hill, A., Bomken, C., Hanley, J., The management of pregnancy in paroxysmal nocturnal haemoglobinuria on long term eculizumab (2010) Br J Haematol, 149 (3), pp. 446-450; Ardissino, G., Wally Ossola, M., Baffero, G.M., Rigotti, A., Cugno, M., Eculizumab for atypical hemolytic uremic syndrome in pregnancy (2013) Obstet Gynecol, 122 (2), pp. 487-489; Buurma, A., Cohen, D., Veraar, K., Schonkeren, D., Claas, F.H., Bruijn, J.A., Preeclampsia is characterized by placental complement dysregulation (2012) Hypertension, 60 (5), pp. 1332-1337; Salmon, J.E., Heuser, C., Triebwasser, M., Liszewski, M.K., Kavanagh, D., Roumenina, L., Mutations in complement regulatory proteins predispose to preeclampsia: A genetic analysis of the PROMISSE cohort (2011) Plos Med, 8 (3); Fakhouri, F., Jablonski, M., Lepercq, J., Blouin, J., Benachi, A., Hourmant, M., Factor H, membrane cofactor protein, and factor I mutations in patients with hemolysis, elevated liver enzymes, and low platelet count syndrome (2008) Blood, 112 (12), pp. 4542-4545",

year = "2016",

month = apr,

doi = "10.4187/respcare.04339",

language = "English",

volume = "61",

pages = "502--509",

journal = "Respiratory Care",

issn = "0020-1324",

publisher = "Daedalus Enterprises Inc",

number = "4",

}

TY - JOUR

T1 - Relationship of circulating c5a and complement factor h levels with disease control in pregnant women with asthma

AU - Bohács, A.

AU - Bikov, A.

AU - Ivancsó, I.

AU - Czaller, I.

AU - Böcskei, R.

AU - Müller, V.

AU - Rigó J., Jr.

AU - Losonczy, G.

AU - Tamási, L.

N1 - Export Date: 31 October 2018 CODEN: RECAC Correspondence Address: Tamási, L.; Department of Pulmonology, Semmelweis University, Diós árok u. 1/c, Hungary; email: [email protected] Chemicals/CAS: complement factor H, 80295-65-4; nitric oxide, 10102-43-9; Complement C5a; Complement Factor H; complement factor H, human References: Global Initiative for Asthma (GINA) 2015, , http://www.ginasthma.org/, Accessed September 17, 2014; Charlton, R.A., Hutchison, A., Davis, K.J., De Vries, C.S., Asthma management in pregnancy (2013) Plos One, 8 (4), p. e60247; Demissie, K., Breckenridge, M.B., Rhoads, G.G., Infant and maternal outcomes in the pregnancies of asthmatic women (1998) Am J Respir Crit Care Med, 158 (4), pp. 1091-1095; Breton, M.C., Beauchesne, M.F., Lemière, C., Rey, E., Forget, A., Blais, L., Risk of perinatal mortality associated with asthma during pregnancy (2009) Thorax, 64 (2), pp. 101-106; Murphy, V.E., Clifton, V.L., Gibson, P.G., Asthma exacerbations during pregnancy: Incidence and association with adverse pregnancy outcomes (2006) Thorax, 61 (2), pp. 169-176; Tamási, L., Horváth, I., Bohács, A., Müller, V., Losonczy, G., Schatz, M., Asthma in pregnancy: Immunological changes and clinical management (2011) Respir Med, 105 (2), pp. 159-164; Grindheim, G., Toska, K., Estensen, M.E., Rosseland, L.A., Changes in pulmonary function during pregnancy: A longitudinal cohort study (2012) BJOG, 119 (1), pp. 94-101; Ivancsó, I., Toldi, G., Bohács, A., Eszes, N., Müller, V., Rigó, J., Jr., Relationship of circulating soluble urokinase plasminogen activator receptor (SuPAR) levels to disease control in asthma and asthmatic pregnancy (2013) Plos One, 8 (4), p. e60697; Eszes, N., Toldi, G., Bohács, A., Ivancsó, I., Müller, V., Rigó, J., Jr., Relationship of circulating hyaluronic acid levels to disease control in asthma and asthmatic pregnancy (2014) Plos One, 9 (4), p. e94678; Ricklin, D., Hajishengallis, G., Yang, K., Lambris, J.D., Complement: A key system for immune surveillance and homeostasis (2010) Nat Immunol, 11 (9), pp. 785-797; Zhang, X., Köhl, J., A complex role for complement in allergic asthma (2010) Expert Rev Clin Immunol, 6 (2), pp. 269-277; Laumonnier, Y., Schmudde, I., Köhl, J., The role of complement in the diagnosis and management of allergic rhinitis and allergic asthma (2011) Curr Allergy Asthma Rep, 11 (2), pp. 122-130; Krug, N., Tschernig, T., Erpenbeck, V.J., Hohlfeld, J.M., Köhl, J., Complement factors C3a and C5a are increased in bronchoalveolar lavage fluid after segmental allergen provocation in subjects with asthma (2001) Am J Respir Crit Care Med, 164 (10), pp. 1841-1843; Marc, M.M., Korosec, P., Kosnik, M., Kern, I., Flezar, M., Suskovic, S., Sorli, J., Complement factors c3a, c4a, and c5a in chronic obstructive pulmonary disease and asthma (2004) Am J Respir Cell Mol Biol, 31 (2), pp. 216-219; Bowser, C., Erstein, D.P., Silverberg, J.I., Nowakowski, M., Joks, R., Correlation of plasma complement split product levels with allergic respiratory disease activity and relation to allergen immunotherapy (2010) Ann Allergy Asthma Immunol, 104 (1), pp. 42-49; Kopp, A., Hebecker, M., Svobodová, E., Józsi, M., Factor H: A complement regulator in health and disease, and a mediator of cellular interactions (2012) Biomolecules, 7 (1), pp. 46-75; Weiszhár, Z., Bikov, A., Gálffy, G., Tamási, L., Ungvári, I., Szalai, C., Elevated complement factor H levels in asthmatic sputa (2013) J Clin Immunol, 33 (2), pp. 496-505; Richani, K., Soto, E., Romero, R., Espinoza, J., Chaiworapongsa, T., Nien, J.K., Normal pregnancy is characterized by systemic activation of the complement system (2005) J Matern Fetal Neonatal Med, 17 (4), pp. 239-245; Derzsy, Z., Prohászka, Z., Rigó, J., Jr., Füst, G., Molvarec, A., Activation of the complement system in normal pregnancy and preeclampsia (2010) Mol Immunol, 47 (7), pp. 1500-1506; Banadakoppa, M., Chauhan, M.S., Havemann, D., Balakrishnan, M., Dominic, J.S., Yallampalli, C., Spontaneous abortion is associated with elevated systemic C5a and reduced mRNA of complement inhibitory proteins in placenta (2014) Clin Exp Immunol, 177 (3), pp. 743-749; Denny, K.J., Coulthard, L.G., Finnell, R.H., Callaway, L.K., Taylor, S.M., Woodruff, T.M., Elevated complement factor C5a in maternal and umbilical cord plasma in preeclampsia (2013) J Reprod Immunol, 97 (2), pp. 211-216; Soto, E., Romero, R., Richani, K., Espinoza, J., Chaiworapongsa, T., Nien, J.K., Preeclampsia and pregnancies with small-for-gestational age neonates have different profiles of complement split products (2010) J Matern Fetal Neonatal Med, 23 (7), pp. 646-657; Miller, M.R., Hankinson, J., Brusasco, V., Burgos, F., Casaburi, R., Coates, A., Standardisation of spirometry (2005) Eur Respir J, 26 (2), pp. 319-338; ATS/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide (2005) Am J Respir Crit Care Med, 171 (8), pp. 912-930; Wong, E.K., Kavanagh, D., Anticomplement C5 therapy with eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome (2015) Transl Res, 165 (2), pp. 306-320; Tan, L.A., Yu, B., Sim, F.C., Kishore, U., Sim, R.B., Complement activation by phospholipids: The interplay of factor H and C1q (2010) Protein Cell, 1 (11), pp. 1033-1049; Köhl, J., The role of complement in danger sensing and transmission (2006) Immunol Res, 34 (2), pp. 157-176; Khan, M.A., Nicolls, M.R., Surguladze, B., Saadoun, I., Complement components as potential therapeutic targets for asthma treatment (2014) Respir Med, 108 (4), pp. 543-549; Smith, S.G., Watson, B., Clark, G., Gauvreau, G.M., Eculizumab for treatment of asthma (2012) Expert Opin Biol Ther, 12 (4), pp. 529-537; Baelder, R., Fuchs, B., Bautsch, W., Zwirner, J., Köhl, J., Hoymann, H.G., Pharmacological targeting of anaphylatoxin receptors during the effector phase of allergic asthma suppresses airway hyperresponsiveness and airway inflammation (2005) J Immunol, 174 (2), pp. 783-789; Tamási, L., Bohács, A., Bikov, A., Orka, C., Rigó, J., Jr., Losonczy, G., Horváth, I., Exhaled nitric oxide in pregnant healthy and asthmatic women (2009) J Asthma, 46 (8), pp. 786-791; Lee, J., Oh, J., Choi, E., Park, I., Han, C., Kim Do, H., Differentially expressed genes implicated in unexplained recurrent spontaneous abortion (2007) Int J Biochem Cell Biol, 39 (12), pp. 2265-2277; Lappas, M., Woodruff, T.M., Taylor, S.M., Permezel, M., Complement C5A regulates prolabor mediators in human placenta (2012) Biol Reprod, 86 (6), p. 190; Soto, E., Romero, R., Richani, K., Yoon, B.H., Chaiworapongsa, T., Vaisbuch, E., Evidence for complement activation in the amniotic fluid of women with spontaneous preterm labor and intra-amniotic infection (2009) J Matern Fetal Neonatal Med, 22 (11), pp. 983-992; Burwick, R.M., Feinberg, B.B., Eculizumab for the treatment of preeclampsia/ HELLP syndrome (2013) Placenta, 34 (2), pp. 201-203; Kelly, R., Arnold, L., Richards, S., Hill, A., Bomken, C., Hanley, J., The management of pregnancy in paroxysmal nocturnal haemoglobinuria on long term eculizumab (2010) Br J Haematol, 149 (3), pp. 446-450; Ardissino, G., Wally Ossola, M., Baffero, G.M., Rigotti, A., Cugno, M., Eculizumab for atypical hemolytic uremic syndrome in pregnancy (2013) Obstet Gynecol, 122 (2), pp. 487-489; Buurma, A., Cohen, D., Veraar, K., Schonkeren, D., Claas, F.H., Bruijn, J.A., Preeclampsia is characterized by placental complement dysregulation (2012) Hypertension, 60 (5), pp. 1332-1337; Salmon, J.E., Heuser, C., Triebwasser, M., Liszewski, M.K., Kavanagh, D., Roumenina, L., Mutations in complement regulatory proteins predispose to preeclampsia: A genetic analysis of the PROMISSE cohort (2011) Plos Med, 8 (3); Fakhouri, F., Jablonski, M., Lepercq, J., Blouin, J., Benachi, A., Hourmant, M., Factor H, membrane cofactor protein, and factor I mutations in patients with hemolysis, elevated liver enzymes, and low platelet count syndrome (2008) Blood, 112 (12), pp. 4542-4545

PY - 2016/4

Y1 - 2016/4

N2 - BACKGROUND: Asthma often complicates pregnancy and represents a risk of serious pregnancy complications. The complement system contributes to asthma pathogenesis and is up-regulated in healthy gestation as well. The anaphylatoxin C5a has a major pro-inflammatory role, and the complement factor H is a main soluble regulator protein both in asthma and during pregnancy; however, peripheral levels of these complement factors and their relationship to disease control have not yet been evaluated in pregnant subjects with asthma. METHODS: The present study aimed to investigate circulating C5a and complement factor H levels in asthma (non-pregnant subjects with asthma; n = 19) and in pregnancy with asthma (pregnant subjects with asthma; n = 22), compared with healthy non-pregnant (n = 21) and healthy pregnant women (n = 13) and to test their relationship to clinical parameters of asthma (lung function, airway inflammation, and symptoms). RESULTS: Circulating C5a levels were higher in the pregnant asthma subject group compared with the healthy non-pregnant, healthy pregnant, and non-pregnant asthma groups: median 2.629 (interquartile range [IQR] 2.257–3.052) ng/mL versus 1.84 (IQR 1.576 –2.563), 1.783 (IQR 0.6064 –2.786), and 2.024 (IQR 1.232–2.615) ng/mL, respectively (P =. 02 in all cases). C5a correlated negatively with FEV1 (r = -0.44, P =. 039) and FVC values (r = -0.64, P =. 001) in the pregnant asthma group and positively with fraction of exhaled nitric oxide levels in the nonpregnant asthma group (n = 12, r - 0.78, P =. 004). Complement factor H levels were elevated in both the healthy pregnant and pregnant asthma subject groups compared with the healthy non-pregnant group (median 1,082 [IQR 734.9–1,224] and 910.7 [IQR 614.5–1076] µg/mL vs 559.7 [IQR 388.7– 783.1]µg/mL, P=.002 and P=.004, respectively) but not in the pregnant asthma group compared with the non-pregnant asthma group (median 687.4 [IQR 441.6–947.6] µg/mL, P =. 10). CONCLUSIONS: Asthma during pregnancy increases the circulating level of pro-inflammatory C5a, which is accompanied by impaired lung function and partly counteracted by the gestation-specific elevation of regulatory complement factor H level (detected in pregnancy both in healthy and subjects with asthma). © 2016 Daedalus Enterprises.

AB - BACKGROUND: Asthma often complicates pregnancy and represents a risk of serious pregnancy complications. The complement system contributes to asthma pathogenesis and is up-regulated in healthy gestation as well. The anaphylatoxin C5a has a major pro-inflammatory role, and the complement factor H is a main soluble regulator protein both in asthma and during pregnancy; however, peripheral levels of these complement factors and their relationship to disease control have not yet been evaluated in pregnant subjects with asthma. METHODS: The present study aimed to investigate circulating C5a and complement factor H levels in asthma (non-pregnant subjects with asthma; n = 19) and in pregnancy with asthma (pregnant subjects with asthma; n = 22), compared with healthy non-pregnant (n = 21) and healthy pregnant women (n = 13) and to test their relationship to clinical parameters of asthma (lung function, airway inflammation, and symptoms). RESULTS: Circulating C5a levels were higher in the pregnant asthma subject group compared with the healthy non-pregnant, healthy pregnant, and non-pregnant asthma groups: median 2.629 (interquartile range [IQR] 2.257–3.052) ng/mL versus 1.84 (IQR 1.576 –2.563), 1.783 (IQR 0.6064 –2.786), and 2.024 (IQR 1.232–2.615) ng/mL, respectively (P =. 02 in all cases). C5a correlated negatively with FEV1 (r = -0.44, P =. 039) and FVC values (r = -0.64, P =. 001) in the pregnant asthma group and positively with fraction of exhaled nitric oxide levels in the nonpregnant asthma group (n = 12, r - 0.78, P =. 004). Complement factor H levels were elevated in both the healthy pregnant and pregnant asthma subject groups compared with the healthy non-pregnant group (median 1,082 [IQR 734.9–1,224] and 910.7 [IQR 614.5–1076] µg/mL vs 559.7 [IQR 388.7– 783.1]µg/mL, P=.002 and P=.004, respectively) but not in the pregnant asthma group compared with the non-pregnant asthma group (median 687.4 [IQR 441.6–947.6] µg/mL, P =. 10). CONCLUSIONS: Asthma during pregnancy increases the circulating level of pro-inflammatory C5a, which is accompanied by impaired lung function and partly counteracted by the gestation-specific elevation of regulatory complement factor H level (detected in pregnancy both in healthy and subjects with asthma). © 2016 Daedalus Enterprises.

KW - Asthma

KW - Biomarker

KW - C5a

KW - Complement

KW - Complement factor H

KW - Pregnancy

KW - biological marker

KW - complement component C5a

KW - complement factor H

KW - nitric oxide

KW - regulator protein

KW - complement factor H, human

KW - adult

KW - Article

KW - asthma

KW - clinical article

KW - clinical evaluation

KW - concurrent infection

KW - cross-sectional study

KW - disease control

KW - disease severity

KW - female

KW - gestation period

KW - human

KW - inflammation

KW - lung function

KW - pathogenesis

KW - pregnancy complication

KW - quantitative analysis

KW - respiratory tract inflammation

KW - risk factor

KW - blood

KW - case control study

KW - forced expiratory volume

KW - lung

KW - metabolism

KW - pathophysiology

KW - physiology

KW - pregnancy

KW - vital capacity

KW - Adult

KW - Case-Control Studies

KW - Complement C5a

KW - Complement Factor H

KW - Female

KW - Forced Expiratory Volume

KW - Humans

KW - Inflammation

KW - Lung

KW - Pregnancy Complications

KW - Vital Capacity

U2 - 10.4187/respcare.04339

DO - 10.4187/respcare.04339

M3 - Article

SN - 0020-1324

VL - 61

SP - 502

EP - 509

JO - Respiratory Care

JF - Respiratory Care

IS - 4

ER -

Relationship of circulating c5a and complement factor h levels with disease control in pregnant women with asthma

Abstract

Keywords

UN SDGs

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