Ponad 7000 publikacji medycznych!
Statystyki za 2021 rok:
odsłony: 8 805 378
Artykuły w Czytelni Medycznej o SARS-CoV-2/Covid-19

Poniżej zamieściliśmy fragment artykułu. Informacja nt. dostępu do pełnej treści artykułu
© Borgis - Postępy Nauk Medycznych 11/2015, s. 760-765
Anna Niemirska1, Jacek Michałkiewicz2, *Mieczysław Litwin1
Przyspieszone dojrzewanie limfocytów krwi obwodowej u dzieci z pierwotnym nadciśnieniem tętniczym
Accelerated maturation of peripheral blood lymphocytes in children with primary hypertension**
1Department of Nephrology and Arterial Hypertension, The Children’s Memorial Health Institute, Warszawa
2Department of Microbiology and Immunology, The Children’s Memorial Health Institute, Warszawa
Wstęp. Nadciśnienie tętnicze pierwotne (NTP) związane jest ze zmianami fenotypu i funkcji limfocytów T. Status limfocytów T można określić poprzez ocenę ekspresji izoform powszechnego antygenu leukocytarnego (CD45 Ag) w limfocytach T CD4+ lub CD8+. Limfocyty T CD45RA+ to tzw. komórki „naiwne”, a limfocyty T CD45RO+ i z ekspresją cząsteczek adhezyjnych to komórki „pamięci immunologicznej”.
Cel pracy. Wykazanie czy u dzieci z NTP dochodzi do zmian subpopulacji limfocytów T i czy koreluje to z wysokością ciśnienia tętniczego i uszkodzeniem narządowym.
Materiał i metody. 68 dzieci z nieleczonym NTP (śr. 15,6 ± 2 lat; 59 chłopców) i 26 dzieci z prawidłowym ciśnieniem tętniczym (śr. 14,8 ± 3,7 roku; 19 chłopców). Izoformy CD45RA+ i CD45RO+ na limfocytach T oceniono techniką cytometrii przepływowej.
Wyniki. Dzieci z NTP miały większą intensywność i więcej limfocytów CD4 i CD8 CD45RO+ w porównaniu do grupy kontrolnej. Stosunek RA+/RO+ na limfocytach CD4 i CD8 był mniejszy w porównaniu z grupą kontrolną. Ekspresja RA+ i RO+ nie korelowała z grubością kompleksu błona środkowa – błona wewnętrzna t. szyjnej wspólnej, ale pacjenci z NTP i przerostem lewej komory serca mieli mniej limfocytów CD4 CD45RA+, więcej limfocytów CD45RO+ i mniejszy stosunek RA+/RO+ w porównaniu do pacjentów z NTP i prawidłową masą lewej komory serca. Odsetek limfocytów CD8 CD45RA+ zmniejszał się ze zmianą statusu ciśnienia tętniczego od stanu przednadciśnieniowego, przez ambulatoryjne nadciśnienie tętnicze do ciężkiego nadciśnienia ambulatoryjnego.
Wnioski. Pacjenci z NTP mieli więcej dojrzałych limfocytów T CD4 i CD8 (o fenotypie komórek pamięci) oraz mniej limfocytów nieaktywnych (naiwnych). Te zaburzenia były związane z ciężkością nadciśnienia i uszkodzeniem narządowym.
Introduction. Primary hypertension (PH) is associated with immune activation. The isoforms of leucocyte common antigen (CD45) in the CD4 and CD8 T cell subsets are markers of T cells status. Naive cells express the RA+ isoform and memory cells express the RO+ isoform. The profile of CD45 isoforms may serve as the marker of T cells functional status and senescence.
Aim. Analysis of distribution of T lymphocytes bearing CD45RA+ (naive) and CD45RO+ (memory) markers and their relationship with hypertension severity and target organ damage (TOD).
Material and methods. 68 children with PH (15.6 ± 2 years, 59 boys) and control group of 26 (14.8 ± 3.7 years, 19 boys) children. The expression of CD45RA+ and CD45RO+ isoforms in the CD4 and CD8 T cell subset was evaluated by flow cytometry technique.
Results. Hypertensive children had greater intensity and percentage of CD45RO+CD4 and CD8 T lymphocytes and lower RA+/RO+ ratio of CD4 and CD8 lymphocytes than controls. T lymphocytes markers expression did not correlate with carotid intima-media-thickness. Children with left ventricular hypertrophy had less CD45RA+CD4 T cells, more CD45RO+ CD4 T cells and lower ratio of RA+/RO+CD4 cells than PH children with normal left ventricular mass index. The percentage of CD45RA+CD8 T cells decreased with increasing blood pressure status from prehypertension, ambulatory hypertension to severe ambulatory hypertension.
Conclusions. PH children had less naive T lymphocytes and more T cells with ‘memory phenotype’. These alterations correlated with hypertension severity and TOD.

There is an increasing amount of data indicating that primary hypertension (PH) is not only a hemodynamic phenomenon but also a complex syndrome involving abnormal fat tissue distribution, over-activity of the sympathetic nervous system, metabolic abnormalities and activation of the immune system. It has been also reported that accelerated ageing of the immune system may play a role in the pathogenesis of hypertension and atherosclerosis in adults, with the special role of the innate and adaptive immune responses (1, 2). Immune system maturation and ageing is associated with increased populations of memory lymphocytes with highly diverse repertoire of antigenic specificity that enables their wide reactivity against both foreign and auto-antigens possibly including the vascular ones. The role of these cells in the PH pathogenesis is still obscure, especially in humans.
The aim of our study was to find out if the PH children differ from controls in terms of their CD4 and CD8 T cells ‘naive’ and ‘memory’ subsets distribution and if these changes correlate with target organ damage (TOD) or hypertension severity.
Material and methods
The study was performed according to the Declaration of Helsinki and with the approval of the Children’s Memorial Health Institute Ethics Committee. All patients (pts) and parents gave consent to participate in the study.
68 pts (mean age: 15.6 ± 2 years; 59 boys) with newly diagnosed and untreated PH, who underwent full diagnostic approach to exclude secondary hypertension, were included to the study. The exclusion criteria were: the presence of any significant chronic disease (except for PH) including diabetes mellitus, chronic kidney disease, chronic inflammatory disorders, any acute illness including infections in the 6 weeks preceding enrolment, and incomplete data. The control group consisted of 26 (19 boys) normotensive children in mean age 14.8 ± 3.7.
PH was diagnosed according to The Fourth Task Force Report and European Society of Hypertension guidelines and confirmed by 24-hour ambulatory blood pressure monitoring (ABPM) (3-5). Blood pressure status was defined according to the ABPM classification (5, 6). Hypertensive TOD (intima-media thickness of carotid arteries and left ventricular hypertrophy) and metabolic risk profile were assessed in PH group.
ABPM measurements
All ABPM measurements were assessed oscillometrically using SpaceLabs Monitor 90207, and the most appropriate cuff was applied on the non-dominant arm. Readings were taken every 20 minutes during daytime and every 30 minutes at night. Recordings lasting ≥ 20 hours with ≥ 80% of readings were considered as valid and were included to the analysis. We used a recently published classification system based on ABPM to classify patients as having normal blood pressure, ambulatory hypertension and severe ambulatory hypertension (5, 6).
All echocardiography examinations were performed by 1 examiner who knew the clinical diagnosis, but was not aware of the severity of hypertension and the effectiveness of treatment. Echocardiography measurements were performed according to the guidelines of the American Society of Echocardiography (7). To standardize the left ventricular mass to height, left ventricular mass index (LVMI) was calculated according to the de Simone formula (8). Left ventricular hypertrophy (LVH) was defined as a LVMI value above the 95th percentile for age- and sex-based on reference data (9).
Carotid-intima media thickness (cIMT) measurements
cIMT was evaluated by ultrasound, and SD of normal values for cIMT was obtained according to the methodology described previously (10, 11).
Laboratory investigations
The following metabolic cardiovascular risk factors were assessed at diagnosis: plasma glucose level, lipid profile and serum uric acid. Blood samples were taken after 12 hours of fasting.
Evaluation of lymphocyte subsets by flow cytometry
The distribution of CD45RA+ and CD45RO+ isoforms of CD45 common leukocyte antigen in the CD4 and CD8 T cell subsets was determined by conventional three-color direct immuno-fluorescence. The samples of heparinized whole blood (50 ul) were stained for 30 min at room temperature with fluorescein (FITC), phycoerythrin (PE) and R phycoerythrycyanin 5.1 (PC5) conjugated mouse-anti-human monoclonal antibodies (mAbs). After staining, the samples were exposed to lysing solution (OptiLyse C, Beckman-Coulter), then washed and resuspended in PBS containing 2% of FCS and 0.1% sodium azide. The lymphocyte population was gated according to the forward-and side scatter light profile. Fluorescence was measured with a Beckman-Coulter FC-500 flow cytometer. Measurements were made on the FL1-channel (FITC-conjugated mAbs), the Fl-2 channel (PE-conjugated mAbs) and the PC5 mAbs (Fl-4 channel). The gates were adjusted into the appropriate negative control quadrant. A total of 10.000 events was collected. The FITC, PE and PC-5 conjugated mAbs were used in the following combinations, respectively: 1) CD4/CD8/CD3 and CD3/CD56/CD19 (for estimation of the basic lymphocyte subsets distribution), 2) CD45RA+CD4 or CD8, and CD45RO+CD4 or CD8, in combination with CD3 (for evaluation of CD45RA+ and CD45RO+ isoforms expression in the CD4 and CD8 T cell subsets). Simultest Leuco-Gate (CD45-FITC/CD14-PE) as well as gamma-FITC, gamma-PE and gamma-PC5 (Simultest control) were included in each staining panel. The fluorescence intensity (FI) was calculated as a relative mean channel fluorescence (RFI) for each surface molecule as described previously (12, 13).
Statistical analysis
The homogeneity of variance was checked with the Shapiro-Wilk test. Continuous variables with a normal distribution were compared using the Student t-test for independent variables. Continuous values with abnormal distribution were compared using the Wilcoxon test. Variables with normal distribution were presented as mean and SD values, whereas variables with abnormal distribution were presented as median and range values between the 5th and 95th percentiles. The correlation analysis was performed using Spearman test for abnormal distribution. Variables with significant correlation were included in the step-wise multiple regression analysis. P values < 0.05 were considered statistically significant, and values between 0.05 and 0.1 were considered as demonstrating trend toward significance.

Powyżej zamieściliśmy fragment artykułu, do którego możesz uzyskać pełny dostęp.
Mam kod dostępu
  • Aby uzyskać płatny dostęp do pełnej treści powyższego artykułu albo wszystkich artykułów (w zależności od wybranej opcji), należy wprowadzić kod.
  • Wprowadzając kod, akceptują Państwo treść Regulaminu oraz potwierdzają zapoznanie się z nim.
  • Aby kupić kod proszę skorzystać z jednej z poniższych opcji.

Opcja #1


  • dostęp do tego artykułu
  • dostęp na 7 dni

uzyskany kod musi być wprowadzony na stronie artykułu, do którego został wykupiony

Opcja #2


  • dostęp do tego i pozostałych ponad 7000 artykułów
  • dostęp na 30 dni
  • najpopularniejsza opcja

Opcja #3


  • dostęp do tego i pozostałych ponad 7000 artykułów
  • dostęp na 90 dni
  • oszczędzasz 28 zł
1. Abais-Battad JM, Rudemiller NP, Mattson DL: Hypertension and immunity: mechanisms of T cell activation and pathways of hypertension. Curr Opin Nephrol Hypertens 2015; 24: 470-474.
2. Rodríguez-Iturbe B, Pons H, Quiroz Y et al.: The immunological basis of hypertension. Am J Hypertens 2014; 27: 1327-1337.
3. National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. The fourth report on diagnosis, evaluation and treatment of high blood pressure in children and adolescents. Pediatrics 2004; 114: 555-576.
4. Lurbe E, Cifkova R, Cruickshank JK et al.: European Society of Hypertension. Management of high blood pressure in children and adolescents: recommendations of the European Society of Hypertension. J Hypertens 2009; 27: 1719-1742.
5. Urbina E, Alpert B, Flynn J et al.: American Heart Association Atherosclerosis, Hypertension, and Obesity in Youth Committee. Ambulatory blood pressure monitoring in children and adolescents: recommendations for standard assessment: a scientific statement from the American Heart Association Atherosclerosis, Hypertension and Obesity in Youth Committee of the Council on Cardiovascular Disease in the Young and the Council for High Blood Pressure Research. Hypertension 2008; 52: 433-451.
6. Flynn JT, Daniels SR, Hayman LL et al.: American Heart Association Atherosclerosis, Hypertension and Obesity in Youth Committee of the Council on Cardiovascular Disease in the Young. Update: ambulatory blood pressure monitoring in children and adolescents: a scientific statement from the American Heart Association. Hypertension 2014; 63: 1116-1135.
7. Nagueh SF, Appleton CP, Gillebert TC et al.: Recommendations for the evaluation of left ventricular diastolic function by echocardiography. J Am Soc Echocardiogr 2009; 22: 107-133.
8. De Simone G, Deveraux RB, Daniels SR et al.: Effect of growth on variability of left ventricular mass: assessment of allometric signals in adults and children and their capacity to predict cardiovascular risk. J Am Coll Cardiol 1995; 25: 1056-1062.
9. Khoury PR, Mitsnefes M, Daniels SR et al.: Age-specific reference intervals for indexed left ventricular mass in children. J Am Soc Echocardiogr 2009; 22: 709-714.
10. Jourdan C, Wuhl E, Litwin M et al.: Normative values of intima-media thickness and distensibility of large arteries in healthy adolescents. J Hypertens 2005; 23: 1707-1715.
11. Doyon A, Kracht D, Bayazit AK et al.: 4C Study Consortium. Carotid artery intima-media thickness and distensibility in children and adolescents: reference values and role of body dimensions. Hypertension 2013; 62: 550-556.
12. Motkowski R, Michałkiewicz J, Mikołuć B et al.: Peripheral blond T lymphocyte subsets in children with congenital asplenia. Human Immunology 2012; 7(3): 1091-1097.
13. Michałkiewicz J, Barth C, Weemaes C et al.: Abnormalities in the T and NK lymphocyte phenotype in patients with Nijmegen breakage syndrome. Clin Exp Immunol 2003; 134: 482-490.
14. Lee VW, Wang Y, Harris DC: The role of the immune system in the pathogenesis of hypertension. Curr Hypertens Rev 2013; 9: 76-84.
15. Libby P, Ridker PM, Maseri A: Inflammation and atherosclerosis. Circulation 2002; 105: 1135-1143.
16. Ammirati E, Cianflone D, Vecchio V et al.: Effector memory T cells are associated with atherosclerosis in humans and animal models. J Am Heart Assoc 2012; 1: 27-41.
17. Harrison DG, Guzik TJ, Lob HE et al.: Inflammation, immunity and hypertension. Hypertension 2011; 57: 132-140.
18. Verlohren S, Muller DN, Luft FC et al.: Immunology in hypertension, preeclampsia, and target-organ damage. Hypertension 2009; 54: 439-443.
19. Litwin M, Feber J, Niemirska A et al.: Primary hypertension is a disease of premature vascular aging associated with neuro-immuno-metabolic abnormalities. Pediatr Nephrol 2015 Feb 28 [Epub ahead of print].
20. Chae CU, Lee RT, Rifai N et al.: Blood pressure and inflammation in apparently healthy man. Hypertension 2001; 38: 399-403.
21. Lande MB, Pearson TA, Vermilion RP et al.: Elevated blood pressure, race/ethnicity, and C-reactive protein levels in children and adolescents. Pediatrics 2008; 122: 1252-1257.
22. Litwin M, Michalkiewicz J, Niemirska A et al.: Inflammatory activation in children with primary hypertension. Pediatr Nephrol 2010; 25: 2489-2499.
23. Litwin M, Michalkiewicz J, Trojanek J et al.: Altered genes profile of renin-angiotensin system, immune system, and adipokines receptors in leukocytes of children with primary hypertension. Hypertension 2013; 61(2): 431-436.
24. Litwin M, Michałkiewicz J, Gackowska L: Primary hypertension in children and adolescents is an immuno-metabolic disease with hemodynamic consequences. Curr Hypertens Rep 2013; 15: 331-339.
25. Harrison DG, Vinch A, Lob H et al.: Role of adaptive immune system in hypertension. Curr Opin Pharmacol 2010; 10: 203-207.
26. Jurewicz M, McDermott DH, Sechler JM et al.: Human T and natural killer cells possess a functional renin-angiotensin system: further mechanisms of angiotensin induced inflammation. J Am Soc Nephrol 2007; 18: 1093-1102.
27. Hoch NE, Guzik TJ, Chen W et al.: Regulation of T cell function by endogenously produced angiotensin II. Am J Physiol Regul Integr Comp Physiol 2009; 296: 208-216.
28. Youn J-C, Yu HT, Lim BJ et al.: Immunosenescent CD8? T cells and CXC chemokine receptor type 3 chemokines are increased in human hypertension. Hypertension 2013; 62: 126-133.
29. Guzik TJ, Hoch NE, Brown KA et al.: Role of the T cell in the genesis of angiotensin II induced hypertension and vascular dysfunction. J Exp Med 2007; 204: 2449-2460.
30. Vinh A, Chen W, Blinder Y et al.: Inhibition and genetic ablation of the B7/CD28 T-cell costimulation axis prevents experimental hypertension. Circulation 2010; 122: 2529-2537.
31. Svendsen UG: Spontaneous hypertension and hypertensive vascular disease in the NZB strain of mice. Acta Pathol Microbiol Scand A 1977; 85: 548-554.
32. Barhoumi T, Kasal DA, Li MW et al.: T regulatory lymphocytes prevent angiotensin II-induced hypertension and vascular injury. Hypertension 2011; 57: 469-476.
33. Svendsen UG: The role of thymus for the development and prognosis of hypertension and hypertensive vascular disease in mice following renal infarction. Acta Pathol Microbiol Scand A 1976; 84: 235-243.
34. Marvar PJ, Thabet SR, Guzik TJ et al.: Central and peripheral mechanisms of T-lymphocyte activation and vascular inflammation produced by angiotensin II-induced hypertension. Circ Res 2010; 107: 263-270.
35. Madhur MS, Harrison DG: Senescent T cells and hypertension new ideas about old cells. Hypertension 2013; 62: 13-15.
36. Park S, Youn J-C, Yu HT et al.: Immunosenescent CD8+ T cells and CXCR3 Chemokines Are Increased in Human Hypertension. Hypertension 2013, 62: 126-133.
37. Yu HT, Park S, Shin EC et al.: T cell senescence and cardiovascular diseases. Clin Exp Med 2015 Jul 19 [Epub ahead of print].
38. Weng NP, Akbar AN, Goronzy J: CD28(–) T cells: their role in the age-associated decline of immune function. Trends Immunol 2009; 30: 306-312.
39. Pludowski P, Litwin M, Niemirska A et al.: Accelerated skeletal maturation in children with primary hypertension. Hypertension 2009; 54: 1234-1239.
40. Bravo Y, Quiroz Y, Ferrebuz A et al.: Mycophenolate mofetil administration reduces renal inflammation, oxidative stress, and arterial pressure in rats with lead induced hypertension. Am J Physiol Renal Physiol 2007; 293: 616-623.
41. Herrera J, Ferrebuz A, MacGregor EG et al.: Mycophenolate mofetil treatment improves hypertension in patients with psoriasis and rheumatoid arthritis. J Am Soc Nephrol 2007; 17: 218-225.
42. Baradaran A, Nasri H, Rafieian-Kopaei M: Oxidative stress and hypertension: Possibility of hypertension therapy with antioxidants. J Res Med 2014; 19: 358-367.
43. Benicky J, Sanchez-Lemus E, Pavel J et al.: Anti-inflammatory effects of angiotensin receptor blockers in the brain and the periphery. Cell Moll Neurobiol 2009; 29: 781-792.
otrzymano: 2015-09-08
zaakceptowano do druku: 2015-09-30

Adres do korespondencji:
*Mieczysław Litwin
Department of Nephrology and Arterial Hypertension The Children’s Memorial Health Institute
Aleja Dzieci Polskich 20, 04-730 Warszawa
tel. +48 (22) 815-15-40,
fax +48 (22) 815-15-39

Postępy Nauk Medycznych 11/2015
Strona internetowa czasopisma Postępy Nauk Medycznych