rpcardioRational Pharmacotherapy in CardiologyРациональная Фармакотерапия в Кардиологии1819-64462225-3653«SILICEA-POLIGRAF» LLC10.20996/1819-6446-2012-8-5-647-654rpcardio-576Research ArticleORIGINAL STUDIESОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯTITERS OF ANTIBODIES TO Β1-ADRENOCEPTOR AND M2 CHOLINERGIC RECEPTORS IN PATIENTS WITH VENTRICULAR ARRHYTHMIAS WITHOUT AN ORGANIC CARDIOVASCULAR DISEASE AND THEIR POSSIBLE CLINICAL SIGNIFICANCEТИТРЫ АНТИТЕЛ К β1-АДРЕНОРЕЦЕПТОРАМ И М2-ХОЛИНОРЕЦЕПТОРАМ У БОЛЬНЫХ С ЖЕЛУДОЧКОВЫМИ НАРУШЕНИЯМИ РИТМА СЕРДЦА БЕЗ ПРИЗНАКОВ ОРГАНИЧЕСКОГО ЗАБОЛЕВАНИЯ СЕРДЕЧНО-СОСУДИСТОЙ СИСТЕМЫ И ИХ ВОЗМОЖНОЕ КЛИНИЧЕСКОЕ ЗНАЧЕНИЕРоговаМ. М.RogovaM. M.

аспирант отдела клинической электрофизиологии и рентгенохирургических методов лечения нарушений ритма и проводимости сердца

amble@inbox.ruМироноваН. А.MironovaN. A.

к.м.н., научный сотрудник отдела клинической электрофизиологии и рентгенохирургических методов лечения нарушений ритма и проводимости сердца

РодионоваЕ. С.RodionovaE. S.

аспирант отдела клинической электрофизиологии и рентгенохирургических методов лечения нарушений ритма и проводимости сердца

МалкинаТ. А.MalkinaT. A.

к.м.н., научный сотрудник отдела клинической электрофизиологии и рентгенохирургических методов лечения нарушений ритма и проводимости сердца

ЗыковК. А.ZykovK. A.

д.м.н., руководитель лаборатории иммунопатологии сердечно-сосудистых заболеваний

БеспаловаЖ. Д.BespalovaZh. D.

к.м.н., руководитель лаборатории синтеза пептидов НИИ экспериментальной кардиологии

БибилашвилиР. Ш.BibilashviliR. Sh.

к.ф.-м.н., руководитель лаборатории генной инженерии

ЕфремовЕ. Е.EfremovE. E.

к.б.н., руководитель лаборатории иммунохимии

ГолицынС. П.GolitsynS. P.

д.м.н., профессор, руководитель отдела клинической электрофизиологии и рентгенохирургических методов лечения нарушений ритма и проводимости сердца

Российский кардиологический научно-производственный комплексРоссияRussian Cardiology Research and Production ComplexRussian Federation20120401201685647654Copyright © Rogova M.M., Mironova N.A., Rodionova E.S., Malkina T.A., Zykov K.A., Bespalova Z.D., Bibilashvili R.S., Efremov E.E., Golitsyn S.P., 20152015Рогова М.М., Миронова Н.А., Родионова Е.С., Малкина Т.А., Зыков К.А., Беспалова Ж.Д., Бибилашвили Р.Ш., Ефремов Е.Е., Голицын С.П.Rogova M.M., Mironova N.A., Rodionova E.S., Malkina T.A., Zykov K.A., Bespalova Z.D., Bibilashvili R.S., Efremov E.E., Golitsyn S.P.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.rpcardio.online/jour/article/view/576

Aim. To identify the most promising epitopes that simulate various sites β1-adrenergic and M2-cholinergic receptors, and to evaluate their possible contribution to the development and maintenance of cardiac arrhythmias, particularly idiopathic ventricular arrhythmia. Material and methods. Patients with ventricular arrhythmias without organic cardiovascular disease (the study group; n=70) were included in the study. The control group consisted of 20 healthy volunteers. Evaluation of levels of antibodies to antigenic determinants, modeling various sites β1-adrenergic and M2-cholinergic performed in all patients. Causal treatment with clarithromycin and valacyclovir performed in part of patients. Results. Antibodies to different peptide sequences of β1-adrenergic and M2-cholinergic receptors have been identified in 25% of main group patients. A direct correlation between the frequency of episodes of ventricular tachycardia and IgG levels to MRI-MRIV (p=0.02) revealed. Increase in titre of antibodies to β1-adrenoceptors, to a peptide sequence β8 (p=0.02), and lower titers of antibodies to the M2 acetylcholine receptor — chimera MRI-MRIV IgM (p=0.06) and ARI-MRIV IgM (p=0.07) were observed when assessing the efficacy of the therapy in the causal dynamics in the group of "untreated" patients. IgG titer reduction of ARI-MRIV (p=0.02), which is 4 times out of 10 with reduction of ventricular ectopic activity , recorded after valacyclovir therapy. Clarithromycin therapy on the level of antibodies exerted no significant effect. Conclusion. Possible involvement of antibodies to β1-adrenoceptor and M2-cholinergic receptors in the development of idiopathic ventricular arrhythmias demonstrated. The relationship between the frequency of episodes of ventricular tachycardia and levels of antibody titers to M2-cholinergic receptors found. Attempt of causal treatment, depending on the possible mechanisms of the autoimmune process is executed. Further studies to confirm or refute the results to the larger sample of patients are needed.

Цель. Определить наиболее перспективные антигенные детерминанты, моделирующие различные участки β1-адренорецепторов и М2-холинорецепторов, а также оценить их возможный вклад в развитие и поддержание нарушений ритма сердца, в частности, идиопатической желудочковой экстрасистолии. Материал и методы. В исследование включено 70 больных с желудочковыми нарушениями ритма без признаков органических заболеваний со стороны сердечно-сосудистой системы (основная группа). Группу контроля составили 20 здоровых добровольцев. Всем пациентам выполнено определение уровней антител к антигенным детерминантам, моделирующим различные участки β1-адренорецепторов и М2-холинорецепторов. Части пациентов по показаниям проводилась этиотропная терапия кларитромицином и валацикловиром. Результаты. При обследовании пациентов основной группы в 25% случаев были выявлены антитела к различным пептидным последовательностям β1-адренорецепторов и М2-холинорецепторов. Выявлена прямая корреляционная связь между частотой эпизодов желудочковой тахикардии и уровнями IgG к MRI-MRIV (p=0,02). При оценке эффективности проводимой этиотропной терапии в динамике в группе «нелеченных» больных отмечался рост титра антител к β1-адренорецепторам, к пептидной последовательности β8 (р=0,02), а также снижение титра антител к М2-холинорецептора — химере MRI-MRIV IgM (р=0,06) и ARI-MRIV IgM (р=0,07). На фоне терапии валацикловиром зарегистрировано снижение титра IgG к ARI-MRIV (р=0,02), что в 4 случаях из 10 сопровождалось уменьшением желудочковой эктопической активности. Терапия кларитромицином на уровень антител достоверного влияния не оказывала. Заключение. Продемонстрировано вероятное участие антител к β1-адренорецепторам и М2-холинорецепторам в развитии идиопатических желудочковых аритмий. Отмечено наличие взаимосвязи между частотой эпизодов желудочковых тахикардий и уровнями титров антител к М2-холинорецепторам. Выполнена попытка проведения этиотропной терапии в зависимости от возможных механизмов развития аутоиммунного процесса. Из-за малочисленности групп наблюдения необходимы дальнейшие исследования для подтверждения или опровержения полученных результатов на большей выборке больных.

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The authors declare that there are no conflicts of interest present.