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“Nuts and Bolts” of Laboratory Evaluation of Angioedema

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Abstract

Angioedema, as a distinct disease entity, often becomes a clinical challenge for physicians, because it may cause a life-threatening condition, whereas prompt and accurate laboratory diagnostics may not be available. Although the bedside diagnosis needs to be established based on clinical symptoms and signs, family history, and the therapeutic response, later, laboratory tests are available. Currently, only for five out of the nine different types of angioedema can be diagnosed by laboratory testing, and these occur only in a minority of the patient population. Hereditary angioedema with C1-inhibitor (C1-INH) deficiency type I can be diagnosed by the low C1-INH function and concentration, whereas in type II, C1-INH function is low, but its concentration is normal or even elevated. C1q concentration is normal in both forms. Acquired angioedema with C1-INH deficiency type I is characterized by the low C1-INH function and concentration; however, C1q concentration is also low, and autoantibodies against C1-INH cannot be detected. Complement profile of acquired angioedema with C1-INH deficiency type II is similar to that of type I, but in this form, autoantibodies against C1-INH are present. Hereditary angioedema due to a mutation of the coagulation factor XII can be diagnosed exclusively by mutation analysis of FXII gene. Diagnostic metrics are not available for idiopathic histaminergic acquired angioedema, idiopathic non-histaminergic acquired angioedema, acquired angioedema related to angiotensin-converting enzyme inhibitor, and hereditary angioedema of unknown origin; these angioedemas can be diagnosed by medical and family history, clinical symptoms, and therapeutic response and by excluding the forms previously described. Several potential biomarkers of angioedema are used to date only in research. In the future, they could be utilized into the clinical practice to improve the differential diagnosis, therapy, as well as the prognosis of angioedema.

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References

  1. Cicardi M, Aberer W, Banerji A, Bas M, Bernstein JA, Bork K, Caballero T, Farkas H, Grumach A, Kaplan AP, Riedl MA, Triggiani M, Zanichelli A, Zuraw B (2014) Classification, diagnosis, and approach to treatment for angioedema: consensus report from the Hereditary Angioedema International Working Group. Allergy 69(5):602–616. doi:10.1111/all.12380

    Article  CAS  PubMed  Google Scholar 

  2. Wu MA, Perego F, Zanichelli A, Cicardi M (2016) Angioedema phenotypes: disease expression and classification. Clinic Rev Allerg Immunol. doi:10.1007/s12016-016-8541-z

  3. Farkas H (2010) Management of upper airway edema caused by hereditary angioedema. Allergy Asthma Clin Immunol 6(1):19. doi:10.1186/1710-1492-6-19

    Article  PubMed  PubMed Central  Google Scholar 

  4. Bork K, Meng G, Staubach P, Hardt J (2006) Hereditary angioedema: new findings concerning symptoms, affected organs, and course. Am J Med 119(3):267–274. doi:10.1016/j.amjmed.2005.09.064

    Article  PubMed  Google Scholar 

  5. Farkas H, Harmat G, Kaposi PN, Karadi I, Fekete B, Fust G, Fay K, Vass A, Varga L (2001) Ultrasonography in the diagnosis and monitoring of ascites in acute abdominal attacks of hereditary angioneurotic oedema. Eur J Gastroenterol Hepatol 13(10):1225–1230

    Article  CAS  PubMed  Google Scholar 

  6. Ali MA, Borum ML (2014) Hereditary angioedema: what the gastroenterologist needs to know. Clin Exp Gastroenterol 7:435–445. doi:10.2147/CEG.S50465

    PubMed  PubMed Central  Google Scholar 

  7. Zingale LC, Zanichelli A, Deliliers DL, Rondonotti E, De Franchis R, Cicardi M (2008) Successful resolution of bowel obstruction in a patient with hereditary angioedema. Eur J Gastroenterol Hepatol 20(6):583–587. doi:10.1097/MEG.0b013e3282f1c995

    Article  PubMed  Google Scholar 

  8. Farkas H, Csuka D (2013) An abdominal attack of hereditary angio-oedema. Lancet 381(9875):1404. doi:10.1016/S0140-6736(12)61146-5

    Article  PubMed  Google Scholar 

  9. Zuberbier T, Aberer W, Asero R, Bindslev-Jensen C, Brzoza Z, Canonica GW, Church MK, Ensina LF, Gimenez-Arnau A, Godse K, Goncalo M, Grattan C, Hebert J, Hide M, Kaplan A, Kapp A, Abdul Latiff AH, Mathelier-Fusade P, Metz M, Nast A, Saini SS, Sanchez-Borges M, Schmid-Grendelmeier P, Simons FE, Staubach P, Sussman G, Toubi E, Vena GA, Wedi B, Zhu XJ, Maurer M (2014) The EAACI/GA(2) LEN/EDF/WAO guideline for the definition, classification, diagnosis, and management of urticaria: the 2013 revision and update. Allergy 69(7):868–887. doi:10.1111/all.12313

    Article  CAS  PubMed  Google Scholar 

  10. Germenis AE, Speletas M (2016) Genetics of hereditary angioedema revisited. Clinic Rev Allerg Immunol. doi:10.1007/s12016-016-8543-x

  11. Nielsen EW, Johansen HT, Holt J, Mollnes TE (1994) C1 inhibitor and diagnosis of hereditary angioedema in newborns. Pediatr Res 35(2):184–187. doi:10.1203/00006450-199402000-00012

    Article  CAS  PubMed  Google Scholar 

  12. Pedrosa M, Boyano-Martinez T, Garcia-Ara C, Caballero T, Quirce S (2015) Utility of specific IgE to Ara h 6 in peanut allergy diagnosis. Ann Allergy Asthma Immunol 115(2):108–112. doi:10.1016/j.anai.2015.05.015

    Article  CAS  PubMed  Google Scholar 

  13. Walker JE, Campbell DM, Ogston D (1982) Blood levels of proteinase inhibitors in pregnancy. Br J Obstet Gynaecol 89(3):208–210

    Article  CAS  PubMed  Google Scholar 

  14. Oltvai ZN, Wong EC, Atkinson JP, Tung KS (1991) C1 inhibitor deficiency: molecular and immunologic basis of hereditary and acquired angioedema. Lab Invest 65(4):381–388

    CAS  PubMed  Google Scholar 

  15. Alsenz J, Bork K, Loos M (1987) Autoantibody-mediated acquired deficiency of C1 inhibitor. N Engl J Med 316(22):1360–1366. doi:10.1056/NEJM198705283162202

    Article  CAS  PubMed  Google Scholar 

  16. Cicardi M, Beretta A, Colombo M, Gioffre D, Cugno M, Agostoni A (1996) Relevance of lymphoproliferative disorders and of anti-C1 inhibitor autoantibodies in acquired angio-oedema. Clin Exp Immunol 106(3):475–480

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Cicardi M, Zingale LC, Pappalardo E, Folcioni A, Agostoni A (2003) Autoantibodies and lymphoproliferative diseases in acquired C1-inhibitor deficiencies. Medicine 82(4):274–281. doi:10.1097/01.md.0000085055.63483.09

    PubMed  Google Scholar 

  18. Bork K, Wulff K, Witzke G, Hardt J (2015) Hereditary angioedema with normal C1-INH with versus without specific F12 gene mutations. Allergy 70(8):1004–1012. doi:10.1111/all.12648

    Article  CAS  PubMed  Google Scholar 

  19. Frazer-Abel A, Giclas PC (2011) Update on laboratory tests for the diagnosis and differentiation of hereditary angioedema and acquired angioedema. Allergy Asthma Proc 32(Suppl 1):S17–21. doi:10.2500/aap.2011.32.3472

    Article  CAS  PubMed  Google Scholar 

  20. Lachmann PJ (2010) Preparing serum for functional complement assays. J Immunol Methods 352(1–2):195–197. doi:10.1016/j.jim.2009.11.003

    Article  CAS  PubMed  Google Scholar 

  21. Wagenaar-Bos IG, Drouet C, Aygoren-Pursun E, Bork K, Bucher C, Bygum A, Farkas H, Fust G, Gregorek H, Hack CE, Hickey A, Joller-Jemelka HI, Kapusta M, Kreuz W, Longhurst H, Lopez-Trascasa M, Madalinski K, Naskalski J, Nieuwenhuys E, Ponard D, Truedsson L, Varga L, Nielsen EW, Wagner E, Zingale L, Cicardi M, van Ham SM (2008) Functional C1-inhibitor diagnostics in hereditary angioedema: assay evaluation and recommendations. J Immunol Methods 338(1–2):14–20. doi:10.1016/j.jim.2008.06.004

    Article  CAS  PubMed  Google Scholar 

  22. Malentacchi F, Pizzamiglio S, Ibrahim-Gawel H, Pazzagli M, Verderio P, Ciniselli CM, Wyrich R, Gelmini S (2015) Second SPIDIA-DNA External Quality Assessment (EQA): influence of pre-analytical phase of blood samples on genomic DNA quality. Clin Chim Acta. doi:10.1016/j.cca.2015.12.032

    Google Scholar 

  23. Li HH, Busse P, Lumry WR, Frazer-Abel A, Levy H, Steele T, Dayno J, Riedl M (2015) Comparison of chromogenic and ELISA functional C1 inhibitor tests in diagnosing hereditary angioedema. J Allergy Clin Immunol In Pract 3(2):200–205. doi:10.1016/j.jaip.2014.08.002

    Article  Google Scholar 

  24. Gompels MM, Lock RJ, Morgan JE, Osborne J, Brown A, Virgo PF (2002) A multicentre evaluation of the diagnostic efficiency of serological investigations for C1 inhibitor deficiency. J Clin Pathol 55(2):145–147

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Joseph K, Bains S, Tholanikunnel BG, Bygum A, Aabom A, Koch C, Farkas H, Varga L, Ghebrehiwet B, Kaplan AP (2015) A novel assay to diagnose hereditary angioedema utilizing inhibition of bradykinin-forming enzymes. Allergy 70(1):115–119. doi:10.1111/all.12520

    Article  CAS  PubMed  Google Scholar 

  26. Tarzi MD, Hickey A, Forster T, Mohammadi M, Longhurst HJ (2007) An evaluation of tests used for the diagnosis and monitoring of C1 inhibitor deficiency: normal serum C4 does not exclude hereditary angio-oedema. Clin Exp Immunol 149(3):513–516. doi:10.1111/j.1365-2249.2007.03438.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Gompels MM, Lock RJ, Unsworth DJ, Johnston SL, Archer CB, Davies SV (2003) Misdiagnosis of hereditary angio-oedema type 1 and type 2. Br J Dermatol 148(4):719–723

    Article  CAS  PubMed  Google Scholar 

  28. Varga L, Szeplaki G, Visy B, Fust G, Harmat G, Miklos K, Nemeth J, Cervenak L, Karadi I, Farkas H (2007) C1-inhibitor (C1-INH) autoantibodies in hereditary angioedema. Strong correlation with the severity of disease in C1-INH concentrate naive patients. Mol Immunol 44(6):1454–1460. doi:10.1016/j.molimm.2006.04.020

    Article  CAS  PubMed  Google Scholar 

  29. Cicardi M, Bergamaschini L, Cugno M, Beretta A, Zingale LC, Colombo M, Agostoni A (1998) Pathogenetic and clinical aspects of C1 inhibitor deficiency. Immunobiology 199(2):366–376. doi:10.1016/S0171-2985(98)80041-7

    Article  CAS  PubMed  Google Scholar 

  30. Engel R, Rensink I, Roem D, Brouwer M, Kalei A, Perry D, Zeerleder S, Wouters D, Hamann D (2015) ELISA to measure neutralizing capacity of anti-C1-inhibitor antibodies in plasma of angioedema patients. J Immunol Methods 426:114–119. doi:10.1016/j.jim.2015.08.011

    Article  CAS  PubMed  Google Scholar 

  31. Strimbu K, Tavel JA (2010) What are biomarkers? Curr Opin HIV AIDS 5(6):463–466. doi:10.1097/COH.0b013e32833ed177

    Article  PubMed  PubMed Central  Google Scholar 

  32. Deroux A, Vilgrain I, Dumestre-Perard C, Boccon-Gibod I, Bouillet L (2015) Towards a specific marker for acute bradykinin-mediated angioedema attacks: a literature review. Eur J Dermatol EJD 25(4):290–295. doi:10.1684/ejd.2015.2547

    CAS  PubMed  Google Scholar 

  33. Kaplan AP, Joseph K (2010) The bradykinin-forming cascade and its role in hereditary angioedema. Ann Allergy Asthma Immunol 104(3):193–204. doi:10.1016/j.anai.2010.01.007

    Article  CAS  PubMed  Google Scholar 

  34. Spath PJ, Wuthrich B, Butler R (1984) Quantification of C1-inhibitor functional activities by immunodiffusion assay in plasma of patients with hereditary angioedema—evidence of a functionally critical level of C1-inhibitor concentration. Complement 1(3):147–159

    CAS  PubMed  Google Scholar 

  35. Kelemen Z, Moldovan D, Mihaly E, Visy B, Szeplaki G, Csuka D, Fust G, Farkas H, Varga L (2010) Baseline level of functional C1-inhibitor correlates with disease severity scores in hereditary angioedema. Clin Immunol 134(3):354–358. doi:10.1016/j.clim.2009.11.002

    Article  CAS  PubMed  Google Scholar 

  36. Csuka D, Fust G, Farkas H, Varga L (2011) Parameters of the classical complement pathway predict disease severity in hereditary angioedema. Clin Immunol 139(1):85–93. doi:10.1016/j.clim.2011.01.003

    Article  CAS  PubMed  Google Scholar 

  37. Cugno M, Hack CE, de Boer JP, Eerenberg AJ, Agostoni A, Cicardi M (1993) Generation of plasmin during acute attacks of hereditary angioedema. J Lab Clin Med 121(1):38–43

    CAS  PubMed  Google Scholar 

  38. Varga L, Szeplaki G, Laki J, Kocsis A, Kristof K, Gal P, Bajtay Z, Wieslander J, Daha MR, Garred P, Madsen HO, Fust G, Farkas H (2008) Depressed activation of the lectin pathway of complement in hereditary angioedema. Clin Exp Immunol 153(1):68–74. doi:10.1111/j.1365-2249.2008.03671.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Csuka D, Munthe-Fog L, Hein E, Zotter Z, Prohaszka Z, Farkas H, Varga L, Garred P (2014) Activation of the ficolin-lectin pathway during attacks of hereditary angioedema. J Allergy Clin Immunol 134(6):1388–1393 e1381. doi:10.1016/j.jaci.2014.05.030

    Article  CAS  PubMed  Google Scholar 

  40. Hansen CB, Csuka D, Munthe-Fog L, Varga L, Farkas H, Hansen KM, Koch C, Skjodt K, Garred P, Skjoedt MO (2015) The levels of the lectin pathway serine protease MASP-1 and its complex formation with C1 inhibitor are linked to the severity of hereditary angioedema. J Immunol 195(8):3596–3604. doi:10.4049/jimmunol.1402838

    Article  CAS  PubMed  Google Scholar 

  41. Csuka D, Veszeli N, Imreh E, Zotter Z, Skopal J, Prohaszka Z, Varga L, Farkas H (2015) Comprehensive study into the activation of the plasma enzyme systems during attacks of hereditary angioedema due to C1-inhibitor deficiency. Orphanet J Rare Dis 10:132. doi:10.1186/s13023-015-0351-5

    Article  PubMed  PubMed Central  Google Scholar 

  42. Joseph K, Tuscano TB, Kaplan AP (2008) Studies of the mechanisms of bradykinin generation in hereditary angioedema plasma. Ann Allergy Asthma Immunol 101(3):279–286. doi:10.1016/S1081-1206(10)60493-0

    Article  CAS  PubMed  Google Scholar 

  43. Cugno M, Cicardi M, Coppola R, Agostoni A (1996) Activation of factor XII and cleavage of high molecular weight kininogen during acute attacks in hereditary and acquired C1-inhibitor deficiencies. Immunopharmacology 33(1–3):361–364

    Article  CAS  PubMed  Google Scholar 

  44. Konings J, Cugno M, Suffritti C, Ten Cate H, Cicardi M, Govers-Riemslag JW (2013) Ongoing contact activation in patients with hereditary angioedema. PLoS One 8(8):e74043. doi:10.1371/journal.pone.0074043

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Suffritti C, Zanichelli A, Maggioni L, Bonanni E, Cugno M, Cicardi M (2014) High-molecular-weight kininogen cleavage correlates with disease states in the bradykinin-mediated angioedema due to hereditary C1-inhibitor deficiency. Clin Exp Allergy 44(12):1503–1514. doi:10.1111/cea.12293

    Article  CAS  PubMed  Google Scholar 

  46. Hoover T, Lippmann M, Grouzmann E, Marceau F, Herscu P (2010) Angiotensin converting enzyme inhibitor induced angio-oedema: a review of the pathophysiology and risk factors. Clin Exp Allergy 40(1):50–61. doi:10.1111/j.1365-2222.2009.03323.x

    CAS  PubMed  Google Scholar 

  47. Nussberger J, Cugno M, Amstutz C, Cicardi M, Pellacani A, Agostoni A (1998) Plasma bradykinin in angio-oedema. Lancet 351(9117):1693–1697. doi:10.1016/S0140-6736(97)09137-X

    Article  CAS  PubMed  Google Scholar 

  48. Defendi F, Charignon D, Ghannam A, Baroso R, Csopaki F, Allegret-Cadet M, Ponard D, Favier B, Cichon S, Nicolie B, Fain O, Martin L, Drouet C, National Reference Centre for Angioedema C (2013) Enzymatic assays for the diagnosis of bradykinin-dependent angioedema. PLoS One 8(8), e70140. doi:10.1371/journal.pone.0070140

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Duan QL, Nikpoor B, Dube MP, Molinaro G, Meijer IA, Dion P, Rochefort D, Saint-Onge J, Flury L, Brown NJ, Gainer JV, Rouleau JL, Agostoni A, Cugno M, Simon P, Clavel P, Potier J, Wehbe B, Benarbia S, Marc-Aurele J, Chanard J, Foroud T, Adam A, Rouleau GA (2005) A variant in XPNPEP2 is associated with angioedema induced by angiotensin I-converting enzyme inhibitors. Am J Hum Genet 77(4):617–626. doi:10.1086/496899

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Drouet C, Desormeaux A, Robillard J, Ponard D, Bouillet L, Martin L, Kanny G, Moneret-Vautrin DA, Bosson JL, Quesada JL, Lopez-Trascasa M, Adam A (2008) Metallopeptidase activities in hereditary angioedema: effect of androgen prophylaxis on plasma aminopeptidase P. J Allergy Clin Immunol 121(2):429–433. doi:10.1016/j.jaci.2007.10.048

    Article  CAS  PubMed  Google Scholar 

  51. Byrd JB, Touzin K, Sile S, Gainer JV, Yu C, Nadeau J, Adam A, Brown NJ (2008) Dipeptidyl peptidase IV in angiotensin-converting enzyme inhibitor associated angioedema. Hypertension 51(1):141–147. doi:10.1161/HYPERTENSIONAHA.107.096552

    Article  CAS  PubMed  Google Scholar 

  52. Grouzmann E, Livio F, Buclin T (2009) Angiotensin-converting enzyme and dipeptidyl peptidase IV inhibitors: an increased risk of angioedema. Hypertension 54(3):468–470. doi:10.1161/HYPERTENSIONAHA.109.135244

    Article  CAS  PubMed  Google Scholar 

  53. Lefebvre J, Murphey LJ, Hartert TV, Jiao Shan R, Simmons WH, Brown NJ (2002) Dipeptidyl peptidase IV activity in patients with ACE-inhibitor-associated angioedema. Hypertension 39(2 Pt 2):460–464

    Article  CAS  PubMed  Google Scholar 

  54. Joseph K, Tholanikunnel BG, Wolf B, Bork K, Kaplan AP (2015) Deficiency of plasminogen activator inhibitor 2 in plasma of patients with hereditary angioedema with normal C1 inhibitor levels. J Allergy Clin Immunol. doi:10.1016/j.jaci.2015.07.041

    PubMed Central  Google Scholar 

  55. Cugno M, Cicardi M, Bottasso B, Coppola R, Paonessa R, Mannucci PM, Agostoni A (1997) Activation of the coagulation cascade in C1-inhibitor deficiencies. Blood 89(9):3213–3218

    CAS  PubMed  Google Scholar 

  56. van Geffen M, Cugno M, Lap P, Loof A, Cicardi M, van Heerde W (2012) Alterations of coagulation and fibrinolysis in patients with angioedema due to C1-inhibitor deficiency. Clin Exp Immunol 167(3):472–478. doi:10.1111/j.1365-2249.2011.04541.x

    Article  PubMed  PubMed Central  Google Scholar 

  57. Cugno M, Zanichelli A, Bellatorre AG, Griffini S, Cicardi M (2009) Plasma biomarkers of acute attacks in patients with angioedema due to C1-inhibitor deficiency. Allergy 64(2):254–257. doi:10.1111/j.1398-9995.2008.01859.x

    Article  CAS  PubMed  Google Scholar 

  58. Nielsen EW, Johansen HT, Hogasen K, Wuillemin W, Hack CE, Mollnes TE (1996) Activation of the complement, coagulation, fibrinolytic and kallikrein-kinin systems during attacks of hereditary angioedema. Scand J Immunol 44(2):185–192

    Article  CAS  PubMed  Google Scholar 

  59. Bas M, Hoffmann TK, Bier H, Kojda G (2005) Increased C-reactive protein in ACE-inhibitor-induced angioedema. Br J Clin Pharmacol 59(2):233–238. doi:10.1111/j.1365-2125.2004.02268.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Joseph K, Tholanikunnel TE, Kaplan AP (2010) Treatment of episodes of hereditary angioedema with C1 inhibitor: serial assessment of observed abnormalities of the plasma bradykinin-forming pathway and fibrinolysis. Ann Allergy Asthma Immunol 104(1):50–54. doi:10.1016/j.anai.2009.11.014

    Article  CAS  PubMed  Google Scholar 

  61. Reshef A, Zanichelli A, Longhurst H, Relan A, Hack CE (2015) Elevated D-dimers in attacks of hereditary angioedema are not associated with increased thrombotic risk. Allergy 70(5):506–513. doi:10.1111/all.12587

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Czucz J, Schaffer G, Csuka D, Walentin S, Kunde J, Prohaszka Z, Farkas H, Cervenak L (2012) Endothelial cell function in patients with hereditary angioedema: elevated soluble E-selectin level during inter-attack periods. J Clin Immunol 32(1):61–69. doi:10.1007/s10875-011-9606-7

    Article  CAS  PubMed  Google Scholar 

  63. Kajdacsi E, Jani PK, Csuka D, Varga LA, Prohaszka Z, Farkas H, Cervenak L (2014) Endothelial cell activation during edematous attacks of hereditary angioedema types I and II. J Allergy Clin Immunol 133(6):1686–1691. doi:10.1016/j.jaci.2013.12.1072

    Article  CAS  PubMed  Google Scholar 

  64. Kajdacsi E, Jani PK, Csuka D, Varga L, Prohaszka Z, Farkas H, Cervenak L (2016) Novel vasoregulatory aspects of hereditary angioedema: the role of arginine vasopressin, adrenomedullin and endothelin-1. J Clin Immunol. doi:10.1007/s10875-016-0239-8

    PubMed  Google Scholar 

  65. Kajdacsi E, Varga L, Prohaszka Z, Farkas H, Cervenak L (2016) Atrial natriuretic peptide as a novel biomarker of hereditary angioedema. Clin Immunol. doi:10.1016/j.clim.2016.03.007

    PubMed  Google Scholar 

  66. Loffredo S, Bova M, Suffritti C, Borriello F, Zanichelli A, Petraroli A, Varricchi G, Triggiani M, Cicardi M, Marone G (2016) Elevated plasma levels of vascular permeability factors in C1 inhibitor-deficient hereditary angioedema. Allergy. doi:10.1111/all.12862

    Google Scholar 

  67. Hofman ZL, Relan A, Hack CE (2014) C-reactive protein levels in hereditary angioedema. Clin Exp Immunol 177(1):280–286. doi:10.1111/cei.12314

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Veszeli N, Csuka D, Zotter Z, Imreh E, Jozsi M, Benedek S, Varga L, Farkas H (2015) Neutrophil activation during attacks in patients with hereditary angioedema due to C1-inhibitor deficiency. Orphanet J Rare Dis 10(1):156. doi:10.1186/s13023-015-0374-y

    Article  PubMed  PubMed Central  Google Scholar 

  69. Arcoleo F, Salemi M, La Porta A, Selvaggio V, Mandala V, Muggeo V, Misiano G, Milano S, Romano GC, Cillari E (2014) Upregulation of cytokines and IL-17 in patients with hereditary angioedema. Clin Chem Lab Med 52(5):e91–93. doi:10.1515/cclm-2013-1008

    Article  CAS  PubMed  Google Scholar 

  70. Salemi M, Mandala V, Muggeo V, Misiano G, Milano S, Colonna-Romano G, Arcoleo F, Cillari E (2015) Growth factors and IL-17 in hereditary angioedema. Clin Exp Med. doi:10.1007/s10238-015-0340-y

    PubMed  Google Scholar 

  71. Visy B, Fust G, Varga L, Szendei G, Takacs E, Karadi I, Fekete B, Harmat G, Farkas H (2004) Sex hormones in hereditary angioneurotic oedema. Clin Endocrinol 60(4):508–515. doi:10.1111/j.1365-2265.2004.02009.x

    Article  CAS  Google Scholar 

  72. Shoemaker LR, Schurman SJ, Donaldson VH, Davis AE 3rd (1994) Hereditary angioneurotic oedema: characterization of plasma kinin and vascular permeability-enhancing activities. Clin Exp Immunol 95(1):22–28

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Cugno M, Nussberger J, Cicardi M, Agostoni A (2003) Bradykinin and the pathophysiology of angioedema. Int Immunopharmacol 3(3):311–317. doi:10.1016/S1567-5769(02)00162-5

    Article  CAS  PubMed  Google Scholar 

  74. Cichon S, Martin L, Hennies HC, Muller F, Van Driessche K, Karpushova A, Stevens W, Colombo R, Renne T, Drouet C, Bork K, Nothen MM (2006) Increased activity of coagulation factor XII (Hageman factor) causes hereditary angioedema type III. Am J Hum Genet 79(6):1098–1104. doi:10.1086/509899

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Bork K, Wulff K, Hardt J, Witzke G, Staubach P (2009) Hereditary angioedema caused by missense mutations in the factor XII gene: clinical features, trigger factors, and therapy. J Allergy Clin Immunol 124(1):129–134. doi:10.1016/j.jaci.2009.03.038

    Article  CAS  PubMed  Google Scholar 

  76. Byrd JB, Woodard-Grice A, Stone E, Lucisano A, Schaefer H, Yu C, Eyler AE, Salloum NE, Brown NJ (2010) Association of angiotensin-converting enzyme inhibitor-associated angioedema with transplant and immunosuppressant use. Allergy 65(11):1381–1387. doi:10.1111/j.1398-9995.2010.02398.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Materson BJ, Bernal EM (2009) Inherent inaccuracies and potential utility of race/ethnicity labeling in the treatment of hypertension. J Am Soc Hypertens JASH 3(5):291–294. doi:10.1016/j.jash.2009.08.001

    Article  PubMed  Google Scholar 

  78. Grouzmann E, Buclin T (2008) Is dipeptidylpeptidase IV the missing link in angiotensin-converting enzyme inhibitor—induced angioedema? Hypertension 51(1):45–47. doi:10.1161/HYPERTENSIONAHA.107.101329

    Article  CAS  PubMed  Google Scholar 

  79. Moreau ME, Garbacki N, Molinaro G, Brown NJ, Marceau F, Adam A (2005) The kallikrein-kinin system: current and future pharmacological targets. J Pharmacol Sci 99(1):6–38

    Article  CAS  PubMed  Google Scholar 

  80. Moholisa RR, Rayner BR, Patricia Owen E, Schwager SL, Stark JS, Badri M, Cupido CL, Sturrock ED (2013) Association of B2 receptor polymorphisms and ACE activity with ACE inhibitor-induced angioedema in black and mixed-race South Africans. J Clin Hypertens (Greenwich) 15(6):413–419. doi:10.1111/jch.12104

    Article  CAS  Google Scholar 

  81. Bjorkqvist J, de Maat S, Lewandrowski U, Di Gennaro A, Oschatz C, Schonig K, Nothen MM, Drouet C, Braley H, Nolte MW, Sickmann A, Panousis C, Maas C, Renne T (2015) Defective glycosylation of coagulation factor XII underlies hereditary angioedema type III. J Clin Invest 125(8):3132–3146. doi:10.1172/JCI77139

    Article  PubMed  PubMed Central  Google Scholar 

  82. Speletas M, Szilagyi A, Csuka D, Koutsostathis N, Psarros F, Moldovan D, Magerl M, Kompoti M, Varga L, Maurer M, Farkas H, Germenis AE (2015) F12-46C/T polymorphism as modifier of the clinical phenotype of hereditary angioedema. Allergy. doi:10.1111/all.12714

    PubMed  Google Scholar 

  83. Pare G, Kubo M, Byrd JB, McCarty CA, Woodard-Grice A, Teo KK, Anand SS, Zuvich RL, Bradford Y, Ross S, Nakamura Y, Ritchie M, Brown NJ (2013) Genetic variants associated with angiotensin-converting enzyme inhibitor-associated angioedema. Pharmacogenet Genomics 23(9):470–478. doi:10.1097/FPC.0b013e328363c137

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Demirturk M, Polat N, Guz G, Gurdal A, Altun I, Gelincik A, Toz B, Oflaz H, Colakoglu B, Dal M, Buyukozturk S (2012) There is an increased risk of atherosclerosis in hereditary angioedema. Int Immunopharmacol 12(1):212–216. doi:10.1016/j.intimp.2011.11.013

    Article  CAS  PubMed  Google Scholar 

  85. Lopez-Lera A, Cabo FS, Garrido S, Dopazo A, Lopez-Trascasa M (2013) Disease-modifying factors in hereditary angioedema: an RNA expression-based screening. Orphanet J Rare Dis 8:77. doi:10.1186/1750-1172-8-77

    Article  PubMed  PubMed Central  Google Scholar 

  86. Bouillet L, Mannic T, Arboleas M, Subileau M, Massot C, Drouet C, Huber P, Vilgrain I (2011) Hereditary angioedema: key role for kallikrein and bradykinin in vascular endothelial-cadherin cleavage and edema formation. J Allergy Clin Immunol 128(1):232–234. doi:10.1016/j.jaci.2011.02.017

    Article  PubMed  Google Scholar 

  87. Cai S, Dole VS, Bergmeier W, Scafidi J, Feng H, Wagner DD, Davis AE 3rd (2005) A direct role for C1 inhibitor in regulation of leukocyte adhesion. J Immunol 174(10):6462–6466

    Article  CAS  PubMed  Google Scholar 

  88. Cimbollek SH, Gonzalez-Quevedo T, Diaz Fernandez M (2005) CA 125: marker of serosal inflammation in hereditary angioedema? Allergy 60(6):835–836. doi:10.1111/j.1398-9995.2005.00792.x

    Article  PubMed  Google Scholar 

  89. Joseph K, Tholanikunnel BG, Kaplan AP (2002) Activation of the bradykinin-forming cascade on endothelial cells: a role for heat shock protein 90. Int Immunopharmacol 2(13–14):1851–1859

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The study was supported by the grant of the Hungarian Scientific Research Fund (OTKA) 100886 (HF). All authors have equally contributed to this work.

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Authors and Affiliations

  1. Research Laboratory, 3rd Department of Internal Medicine, Semmelweis University, Kútvölgyi út 4, H-1125, Budapest, Hungary

    Henriette Farkas, Nóra Veszeli, Erika Kajdácsi, László Cervenak & Lilian Varga

  2. Hungarian Angioedema Center, 3rd Department of Internal Medicine, Semmelweis University, Kútvölgyi út 4, H-1125, Budapest, Hungary

    Henriette Farkas, Nóra Veszeli & Lilian Varga

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  1. Henriette Farkas
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  2. Nóra Veszeli
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Correspondence to Henriette Farkas.

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Farkas, H., Veszeli, N., Kajdácsi, E. et al. “Nuts and Bolts” of Laboratory Evaluation of Angioedema. Clinic Rev Allerg Immunol 51, 140–151 (2016). https://doi.org/10.1007/s12016-016-8539-6

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