Hereditary Angioedema (HAE) with a mutation in the plasminogen gene: a retrospective study of a cohort of 14 patients from Russia

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Abstract

BACKGROUND: In 2018, a new form of hereditary angioedema without C1-inhibitor deficiency — hereditary angioedema with a mutation in the plasminogen gene — was identified. The world scientific literature describes a small number of patients with this form of the disease and, therefore, new research is relevant.

AIMS: To identify the sociodemographic and clinical features of patients with hereditary angioedema with plasminogen gene mutation; to evaluate the treatment efficacy; to conduct a comparative analysis in a group of patients with hereditary angioedema type I/II.

MATERIAL AND METHODS: 14 patients (1 male and 13 females, mean age 51.64±13.55 years) with hereditary angioedema with c.988A>G mutation in the plasminogen gene (p.Lys330Glu; K330E) were enrolled in a retrospective study. The comparison group included 194 patients with hereditary angioedema type I/II (56 males and 138 females, mean age 37.03±16.23 years).

RESULTS: The average age at disease onset in patients with hereditary angioedema with a mutation in the plasminogen gene is 25.07±10.46 years, which is significantly higher than in patients with hereditary angioedema type I/II — 11.58±8.92 years (p <0.001). Peripheral angioedema was reported in 21.4% of patients with hereditary angioedema with a mutation in the plasminogen gene, abdominal attacks in 28.6%, which is less common than in patients with hereditary angioedema type I/II (peripheral edema 97.4%, p <0.001; abdominal attacks 86.6%, p <0.001). Face and neck angioedema was observed in all patients with hereditary angioedema with a mutation in the plasminogen gene (100%) and in 72.2% of patients in the group of hereditary angioedema type I/II (p=0.023). 85.7% of patients with hereditary angioedema with a mutation in the plasminogen gene had edema of the tongue. A decrease in the severity and duration of 28 out of 29 attacks by an average of 71.4% was reported by 4/5 of patients who used icatibant (Firazyr); 3/4 of patients reported a decrease in the frequency of attacks during treatment with tranexamic acid.

CONCLUSIONS: The disease’s manifestation in adulthood, the predominance of face and tongue angioedema are common features of hereditary angioedema with a mutation in the plasminogen gene. The efficacy of tranexamic acid and icatibant was demonstrated in the observed cohort of patients.

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About the authors

Irina A. Manto

National Research Center – Institute of Immunology Federal Medical-Biological Agency

Author for correspondence.
Email: irina.manto@yandex.ru
ORCID iD: 0000-0001-6432-394X
SPIN-code: 7944-5159

MD, Cand. Sci. (Med.)

Russian Federation, 24, Kashirskoye shosse, Moscow, 115522

Elena A. Latysheva

National Research Center – Institute of Immunology Federal Medical-Biological Agency of Russia; Pirogov Russian National Research Medical University

Email: ealat@mail.ru
ORCID iD: 0000-0002-1606-205X
SPIN-code: 2063-7973

MD, Dr. Sci. (Med.)

Russian Federation, 24, Kashirskoye shosse, Moscow, 115522; 1, Moskvorechye str., Moscow, 115578

Elena A. Bliznetz

Federal State Budgetary Institution, Research Centre for Medical Genetics

Email: bliznetzelena@mail.ru
ORCID iD: 0000-0002-5339-5566
SPIN-code: 8451-3075

Cand. Sci. (Med.)

Russian Federation, 1, Moskvorechye str., Moscow, 115578

Daria O. Timoshenko

Pirogov Russian National Research Medical University (Pirogov Medical University)

Email: d.o.timoshenko@gmail.com
ORCID iD: 0000-0002-7585-1390
SPIN-code: 2714-0906

MD

Russian Federation, 1, Ostrovityanova, Moscow, 117997

Liubov V. Aleshina

Saratov State Medical University named by Razumovsky

Email: Lubov-sk@mail.ru
ORCID iD: 0000-0002-3281-7379

Cand. Sci. (Med.)

Russian Federation, 22, Proviantskata str., Saratov, 410028

Yulia A. Bocherova

Tambov Regional Clinical Hospital named after V.D. Babenko

Email: dum_spiro.spero@inbox.ru
ORCID iD: 0000-0003-4182-0008
Russian Federation, 29, Moskovskaya str., Tambov, 392023

Elvira R. Gilvanova

Bashkir State Medical University; Bashkir State University; State Medical Institution of the Republic of Bashkortostan City Hospital 2

Email: elvira_rer@mail.ru
ORCID iD: 0000-0002-0188-8625

Cand. Sci. (Med.)

Russian Federation, 3, Lenina str., Ufa, 450008; 32, Zaki Validi str., Ufa, 450076; 59, Patrioticheskaya str., Sterlitamak, 453130

Galina A. Kameneva

Аrkhangelsk Regional Clinical Hospital

Email: gaakam@mail.ru
ORCID iD: 0000-0002-2328-9420
Russian Federation, 292, Prospect Lomonosova, Arkhangelsk, 163045

Maria A. Platonova

Laboratory MedLab

Email: drmaria65@mail.ru
ORCID iD: 0000-0001-9669-8391
Russian Federation, 46, corp. 2, lit. B, Tambovskaya str., Saint Petersburg

Valentina A. Fedorova

Tula Regional Clinical Hospital

Email: valentina1957efanova@rambler.ru

Chief freelance specialist of The Ministry of Health of Tula oblast

Russian Federation, 1a, st. Yablochkova, Tula, 300053

Aleksander V. Polyakov

Federal State Budgetary Institution, Research Centre for Medical Genetics

Email: apol@dnalab.ru
ORCID iD: 0000-0002-0105-1833
SPIN-code: 6453-3097

Dr. Sci. (Bio), Professor

Russian Federation, 1, Moskvorechye str., Moscow, 115578

Tatiana V. Latysheva

National Research Center – Institute of Immunology Federal Medical-Biological Agency of Russia; Moscow State University of Medicine and Dentistry named after A.I. Evdokimov

Email: tvlat@mail.ru
ORCID iD: 0000-0003-1508-0640
SPIN-code: 8929-7644

MD, Dr. Sci. (Med.), Professor

Russian Federation, 24, Kashirskoye shosse, Moscow, 115522; 20/1, Delegatskaya st., Moscow, 127473

References

  1. Union of Pediatricians of Russia, et al. Hereditary angioedema. Clinical guidelines (D84. 1). Moscow; 2020. 46 p. (In Russ).
  2. Maurer M, Magerl M, Ansotegui I, et al. The international WAO/EAACI guideline for the management of hereditary angioedema – The 2017 revision and update. World Allergy Organ J. 2018;11(1):1–20. doi: 10.1186/s40413-017-0180-1
  3. Reshef A, Kidon M, Leibovich I. The story of angioedema: from quincke to bradykinin. Clin Rev Allergy Immunol. 2016;51(2):121–139. doi: 10.1007/s12016-016-8553-8
  4. Dewald G, Bork K. Missense mutations in the coagulation factor XII (Hageman factor) gene in hereditary angioedema with normal C1 inhibitor. Biochem Biophys Res Commun. 2006;343(4):1286–1289. doi: 10.1016/j.bbrc.2006.03.092
  5. Bork K, Wulff K, Meinke P, et al. A novel mutation in the coagulation factor 12 gene in subjects with hereditary angioedema and normal C1-inhibitor. Clin Immunol Elsevier Inc. 2011;141(1):31–35. doi: 10.1016/j.clim.2011.07.002
  6. Kiss N, Barabás E, Várnai K, et al. Novel duplication in the F12 gene in a patient with recurrent angioedema. Clin Immunol Elsevier Inc. 2013;149(1):142–145. doi: 10.1016/j.clim.2013.08.001
  7. Bork K, Wulff K, Steinmüller-Magin L, et al. Hereditary angioedema with a mutation in the plasminogen gene. Allergy Eur J Allergy Clin Immunol. 2018;73(2):442–450. doi: 10.1111/all.13270
  8. Bafunno V, Firinu D, D’Apolito M, et al. Mutation of the angiopoietin-1 gene (ANGPT1) associates with a new type of hereditary angioedema. J Allergy Clin Immunol Elsevier Inc. 2018;141(3):1009–1017. doi: 10.1016/j.jaci.2017.05.020
  9. Bork K, Wulff K, Rossmann H, et al. Hereditary angioedema cosegregating with a novel kininogen 1 gene mutation changing the N-terminal cleavage site of bradykinin. Allergy Eur J Allergy Clin Immunol. 2019;74(12):2479–2481. doi: 10.1111/all.13869
  10. Ariano A, D’Apolito M, Bova M, et al. A myoferlin gain-of-function variant associates with a new type of hereditary angioedema. Allergy Eur J Allergy Clin Immunol. 2020;75(11):2989–2992. doi: 10.1111/all.14454
  11. Bork K, Machnig T, Wulff K, et al. Clinical features of genetically characterized types of hereditary angioedema with normal C1 inhibitor: a systematic review of qualitative evidence. Orphanet J Rare Dis. 2020;15(1):1–14. doi: 10.1186/s13023-020-01570-x
  12. Recke A, Massalme EG, Jappe U, et al. Identification of the recently described plasminogen gene mutation p.Lys330Glu in a family from Northern Germany with hereditary angioedema. Clin Transl Allergy BioMed Central. 2019;9(1):4–7. doi: 10.1186/s13601-019-0247-x
  13. Bork K, Zibat A, Ferrari DM, et al. Hereditary angioedema in a single family with specific mutations in both plasminogen and SERPING1 genes. J Ger Soc Dermatology. 2020;18(3):215–223. doi: 10.1111/ddg.14036
  14. Bork K, Wulff K, Witzke G, et al. Treatment of patients with hereditary angioedema with the c.988A>G (p.Lys330Glu) variant in the plasminogen gene. Orphanet J Rare Dis. 2020;15(1):1–10. doi: 10.1186/s13023-020-1334-8
  15. Belbézier A, Hardy G, Marlu R, et al. Plasminogen gene mutation with normal C1 inhibitor hereditary angioedema: Three additional French families. Allergy Eur J Allergy Clin Immunol. 2018;3(11):2237–2239. doi: 10.1111/all.13543
  16. Germenis AE, Loules G, Zamanakou M, et al. On the pathogenicity of the plasminogen K330E mutation for hereditary angioedema. Allergy Eur J Allergy Clin Immunol. 2018;73(8):1751–1753. doi: 10.1111/all.13324
  17. Yakushiji H, Hashimura C, Fukuoka K, et al. A missense mutation of the plasminogen gene in hereditary angioedema with normal C1 inhibitor in Japan. Allergy Eur J Allergy Clin Immunol. 2018;73(11):2244–2247. doi: 10.1111/all.13550
  18. Bodian DL, Vilboux T, Hauser NS. Genotype-first analysis of a generally healthy population cohort supports genetic testing for diagnosis of hereditary angioedema of unknown cause. Allergy Asthma Clin Immunol BioMed Central. 2019;15(1):1–4. doi: 10.1186/s13223-019-0346-1
  19. Banday AZ, Kaur A, Jindal AK, et al. An update on the genetics and pathogenesis of hereditary angioedema. Genes Dis Elsevier Ltd. 2020;7(1):75–83. doi: 10.1016/j.gendis.2019.07.002
  20. Zanichelli A, Longhurst HJ, Maurer M, et al. Misdiagnosis trends in patients with hereditary angioedema from the real-world clinical setting. Ann Allergy Asthma Immunol. 2016;117(4):394–398. doi: 10.1016/j.anai.2016.08.014
  21. Banerji A, Busse P, Christiansen SC, et al. Current state of hereditary angioedema management: A patient survey. Allergy Asthma Proc. 2015;36(3):213–217. doi: 10.2500/aap.2015.36.3824
  22. Lunn ML, Santos CB, Craig TJ. Is there a need for clinical guidelines in the United States for the diagnosis of hereditary angioedema and the screening of family members of affected patients? Ann Allergy Asthma Immunol. 2010;104(3):211–214. doi: 10.1016/j.anai.2009.12.004
  23. Riedl M, Gower RG, Chrvala CA. Current medical management of hereditary angioedema: Results from a large survey of US physicians. Ann Allergy Asthma Immunol. 2011;106(4):316–322. doi: 10.1016/j.anai.2010.12.012
  24. Agostini A, Aygorenpursun E, Binkley K, et al. Hereditary and acquired angioedema: Problems and progress: Proceedings of the third C1 esterase inhibitor deficiency workshop and beyond. J Allergy Clin Immunol. 2004;114(3):51–131. doi: 10.1016/j.jaci.2004.06.047
  25. Bork K, Wulff K, Witzke G, et al. Hereditary angioedema with normal C1-INH with versus without specific F12 gene mutations. Allergy Eur J Allergy Clin Immunol. 2015;70(8):1004–1012. doi: 10.1111/all.12648
  26. Germenis AE, Speletas M. Genetics of hereditary angioedema revisited. Clin Rev Allergy Immunol. 2016;51(2):170–182. doi: 10.1007/s12016-016-8543-x
  27. Zuraw BL, Christiansen SC. HAE pathophysiology and underlying mechanisms. Clin Rev Allergy Immunol. 2016;51(2):216–229. doi: 10.1007/s12016-016-8561-8
  28. Bork K, Fischer B, Dewald G. Recurrent episodes of skin angioedema and severe attacks of abdominal pain induced by oral contraceptives or hormone replacement therapy. Am J Med. 2003;114(4):294–298. doi: 10.1016/S0002-9343(02)01526-7
  29. Saule C, Boccon-Gibod I, Fain O, et al. Benefits of progestin contraception in non-allergic angioedema. Clin Exp Allergy J. 2013;43(4):475–482. doi: 10.1111/cea.12055
  30. Bouillet L, Longhurst H, Boccon-Gibod I, et al. Disease expression in women with hereditary angioedema. Am J Obstet Gynecol. 2008;199(5):484.e1–4. doi: 10.1016/j.ajog.2008.04.034
  31. Bork K, Wulff K, Witzke G, et al. Treatment for hereditary angioedema with normal C1-INH and specific mutations in the F12 gene (HAE-FXII). Allergy Eur J Allergy Clin Immunol. 2017;72(2):320–324. doi: 10.1111/all.13076
  32. Bouillet L, Boccon-Gibod I, Launay D, et al. Hereditary angioedema with normal C1 inhibitor in a French cohort: Clinical characteristics and response to treatment with icatibant. Clinical Immunity Inflamm Dis. 2017;5(1):29–36. doi: 10.1002/iid3.137
  33. Bouillet L, Boccon-Gibod I, Gompel A, et al. Hereditary angioedema with normal C1 inhibitor: Clinical characteristics and treatment response with plasma-derived human C1 inhibitor concentrate (Berinert®) in a french cohort. Eur J Dermatology. 2017;27(2):155–159. doi: 10.1684/ejd.2016.2948
  34. Dewald G. A missense mutation in the plasminogen gene, within the plasminogen kringle 3 domain, in hereditary angioedema with normal C1 inhibitor. Biochem Biophys Res Commun Elsevier Ltd. 2018;498(1):193–198. doi: 10.1016/j.bbrc.2017.12.060
  35. Saule C, Boccon-Gibod I, Fain O, et al. Benefits of progestin contraception in non-allergic angioedema. Clin Exp Allergy. 2013;43(4):475–482. doi: 10.1111/cea.12055
  36. Depetri F, Tedeschi A, Cugno M. Angioedema and emergency medicine: From pathophysiology to diagnosis and treatment. Eur J Intern Med Elsevier. 2019;59:8–13. doi: 10.1016/j.ejim.2018.09.004

Supplementary files

Supplementary Files
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1. Fig. 1. Current classification of hereditary angioedema.

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2. Fig. 2. Comparative analysis of angioedema localization in patients with hereditary angioedema with C1-inhibitor deficiency (n=194) and HAE-PLG (n=14),%.

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