Risk of atrial fibrillation in primary immunodeficiencies: evaluation of atrial electromechanical delay and P-wave dispersion
Main Article Content
Keywords
arrhythmia, atrial electromechanical delay, atrial fibrillation, inborn errors of immunity, primary immunodeficiency
Abstract
Background: Primary immunodeficiency diseases (PIDs) are an expanding group of rarely observed immune system disorders. Various clinical conditions, such as autoimmunity, immune dysregulation, and inflammation, could affect multiple organ systems in PID patients. The heart may be one of these organs; however, studies on this topic are rare. Atrial fibrillation (AF) is a significant cause of mortality and morbidity in the community and an increased P-wave dispersion (PWD) and atrial electromechanical delay (AED) are well-known markers indicating a predisposition to AF. We aimed to determine whether AED and/or increased PWD predict the early risk of AF in PID patients.
Methods: This single-center, prospective controlled study included 61 PID and 60 control group patients. All participants underwent resting electrocardiography, echocardiography, and atrial electromechanical conduction time (AECT) monitoring using tissue Doppler imaging evaluated by an experienced cardiologist.
Results: The PID group had a statistically significantly higher Pmax, Pmin, and PWD values, compared to the control group (102 [92–108] vs. 88 [82–99] ms, P < 0.001; 74 [70–80] vs. 68 [62–72] ms, P < 0.001; 26 [22–30] vs. 21 [18–26] ms, P = 0.001, respectively). Right atrial delay and interatrial delay were discovered to be statistically significantly higher in PID group (4 [2–6] vs. 2 [2–4] ms, P < 0.001; 6 [4–8] vs. 4 [4–6] ms, P = 0.039, respectively). Left atrial delay was also discovered to be high in the PID group, although this difference was not statistically significant (6 [4–6] vs. 4 [3–6] ms; P = 0.05).
Conclusion: We demonstrated that the well-known predictors of AF, AECT, and PWD were increased in PID patients. This result aids in the follow up and survival of PID patients, who experience multiple complications, by enabling the early identification of AF-related mortality and morbidity risk.
References
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2 Tangye SG, Al-Herz W, Bousfiha A, Cunningham-Rundles C, Franco JL, Holland SM, et al. Human ınborn errors of ımmunity: 2022 update on the classification from the International Union of Immunological Societies Expert Committee. J Clin Immunol. 2022;42(7):1473–507. 10.1007/s10875-022-01289-3
3 Klangkalya N, Fleisher TA, Rosenzweig SD. Diagnostic tests for primary immunodeficiency disorders: Classic and genetic testing. Allergy Asthma Proc. 2024;45(5):355–63. 10.2500/aap.2024.45.240051
4 Bhatt HV, Fischer GW. Atrial fibrillation: Pathophysiology and therapeutic options. J Cardiothorac Vasc Anesth. 2015;29(5):1333–40. 10.1053/j.jvca.2015.05.058
5 Van Gelder IC, Rienstra M, Bunting KV, Casado-Arroyo R, Caso V, Crijns HJGM, et al. ESC Scientific Document Group. 2024 ESC guidelines for the management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2024;45(36):3314–414. 10.1093/eurheartj/ehae176
6 Elsheikh S, Hill A, Irving G, Lip GYH, Abdul-Rahim AH. Atrial fibrillation and stroke: State-of-the-art and future directions. Curr Probl Cardiol. 2024;49(1 Pt C):102181. 10.1016/j.cpcardiol.2023.102181
7 Kahraman E, Keles N, Parsova KE, Bastopcu M, Karatas M. Assessment of atrial conduction times in patients with frequent premature ventricular complex. J Arrhythm. 2023;39(1):34–41. 10.1002/joa3.12806
8 Acar G, Kahraman H, Akkoyun M, Kilinc M, Zencir C, Yusufoglu E, et al. Evaluation of atrial electromechanical delay and its relationship to inflammation and oxidative stress in patients with chronic obstructive pulmonary disease. Echocardiography. 2014;31(5):579–85. 10.1111/echo.12442
9 Yilmaz A, Can S, Perincek G, Kahraman F. Atrial electromechanical delay, neutrophil-to-lymphocyte ratio, and echocardiographic changes in patients with acute and stable chronic obstructive pulmonary disease. J Res Med Sci. 2022;27:64. 10.4103/jrms.JRMS_176_20
10 Okutucu S, Aytemir K, Oto A. P-wave dispersion: What we know till now? JRSM Cardiovasc Dis. 2016;5:2048004016639443. 10.1177/2048004016639443
11 Pekdemir H, Cansel M, Yağmur J, Acikgoz N, Ermis N, Kurtoglu E, et al. Assessment of atrial conduction time by tissue Doppler echocardiography and P-wave dispersion in patients with mitral annulus calcification. J Electrocardiol. 2010;43(4):339–43. 10.1016/j.jelectrocard.2010.02.013
12 Ciftel M, Yılmaz O, Kardelen F, Kahveci H. Assessment of atrial electromechanical delay using tissue Doppler echocardiography in children with asthma. Pediatr Cardiol. 2014;35(5):857–62. 10.1007/s00246-014-0867-9
13 Russo V, Di Meo F, Rago A, Mosella M, Molino A, Russo MG, et al. Impact of continuous positive airway pressure therapy on atrial electromechanical delay in obesity-hypoventilation syndrome patients. J Cardiovasc Electrophysiol. 2016;27(3):327–34. 10.1111/jce.12879
14 Paris K, Wall LA. The treatment of primary ımmune deficiencies: Lessons learned and future opportunities. Clin Rev Allergy Immunol. 2023;65(1):19–30. 10.1007/s12016-022-08950-0
15 Inan MI, Akgul Balaban Y, Yagci AF, Kartal O, Bugan B, Kalkan F, et al. A new perspective on the management of primary ımmunodeficiencies: Evaluation of arrhythmia and cardiac diseases. Cardiology. 2025;150(5):540–548. 10.1159/000543381
16 Clinical Working Party, European Society for Immunodeficiencies. The 6 ESID warning signs for ADULT primary immunodeficiency diseases [Internet]. [cited 2025 Feb 20]. Available from: https://esid.org/updated-and-published-ebmt-esid-guidelines-for-haematopoietic-stem-cell-transplantation-for-pi/
17 Shahreyar M, Fahhoum R, Akinseye O, Bhandari S, Dang G, Khouzam RN. Severe sepsis and cardiac arrhythmias. Ann Transl Med. 2018;6(1):6. 10.21037/atm.2017.12.26
18 Lazzerini PE, Capecchi PL, Laghi-Pasini F. Systemic inflammation and arrhythmic risk: Lessons from rheumatoid arthritis. Eur Heart J. 2017;38(22):1717–27. 10.1093/eurheartj/ehw208
19 Sawaya SE, Rajawat YS, Rami TG, Szalai G, Price RL, Sivasubramanian N, et al. Downregulation of connexin40 and increased prevalence of atrial arrhythmias in transgenic mice with cardiac-restricted overexpression of tumor necrosis factor. Am J Physiol Heart Circ Physiol. 2007;292(3):H1561–7. 10.1152/ajpheart.00285.2006
20 Lazzerini PE, Laghi-Pasini F, Boutjdir M, Capecchi PL. Cardioimmunology of arrhythmias: The role of autoimmune and inflammatory cardiac channelopathies. Nat Rev Immunol. 2019;19(1):63–4. 10.1038/s41577-018-0098-z
21 Swirski FK, Nahrendorf M. Cardioimmunology: The immune system in cardiac homeostasis and disease. Nat Rev Immunol. 2018;18(12):733–44. 10.1038/s41577-018-0065-8
22 Guo Y, Lip GY, Apostolakis S. Inflammation in atrial fibrillation. J Am Coll Cardiol. 2012;60(22):2263–70. 10.1016/j.jacc.2012.04.063
23 Fischer A, Provot J, Jais JP, Alcais A, Mahlaoui N, Members of the CEREDIH French PID study Group. Autoimmune and inflammatory manifestations occur frequently in patients with primary immunodeficiencies. J Allergy Clin Immunol. 2017;140(5):1388–93.e8.
24 Kaplan MY, Ozen S, Akcal O, Gulez N, Genel F. Autoimmune and inflammatory manifestations in pediatric patients with primary immunodeficiencies and their importance as a warning sign. Allergol Immunopathol (Madr). 2020;48(6):701–10. 10.1016/j.aller.2020.02.009
25 Blazina Š, Markelj G, Jeverica AK, Toplak N, Bratanič N, Jazbec J, et al. Autoimmune and ınflammatory manifestations in 247 patients with primary ımmunodeficiency–A report from the Slovenian National Registry. J Clin Immunol. 2016;36(8):764–73. 10.1007/s10875-016-0330-1
26 Aktoz M, Yilmaztepe M, Tatli E, Turan FN, Umit EG, Altun A. Assessment of ventricular and left atrial mechanical functions, atrial electromechanical delay and P-wave dispersion in patients with scleroderma. Cardiol J. 2011;18(3):261–9.
27 Erdem FH, Ozturk S, Baltaci D, Donmez I, Alçelik A, Ayhan S, et al. Detection of atrial electromechanical dysfunction in obesity. Acta Cardiol. 2015;70(6):678–84. 10.1080/AC.70.6.3120180
28 El Eraky AZ, Handoka NM, Ghaly MS, Nasef SI, Eldahshan NA, Ibrahim AM, et al. Assessment of left atrial mechanical functions and atrial electromechanical delay in juvenile idiopathic arthritis by tissue Doppler echocardiography. Pediatr Rheumatol Online J. 2016;14(1):62. 10.1186/s12969-016-0122-4
29 Yaman M, Arslan U, Beton O, Asarcıklı LD, Aksakal A, Dogdu O. Atrial electromechanical coupling in patients with lichen planus. Korean Circ J. 2016;46(4):530–5. 10.4070/kcj.2016.46.4.530
30 Yildiz A, Ucmak D, Oylumlu M, Akkurt MZ, Yuksel M, Akil MA, et al. Assessment of atrial electromechanical delay and P-wave dispersion in patients with psoriasis. Echocardiography. 2014;31(9):1071–6. 10.1111/echo.12530
31 Razvi S, Jabbar A, Pingitore A, Danzi S, Biondi B, Klein I, et al. Thyroid hormones and cardiovascular function and diseases. J Am Coll Cardiol. 2018;71(16):1781–96. 10.1016/j.jacc.2018.02.045
32 Marrakchi S, Kanoun F, Idriss S, Kammoun I, Kachboura S. Arrhythmia and thyroid dysfunction. Herz. 2015;40(Suppl 2):101–9. 10.1007/s00059-014-4123-0
33 Baumgartner C, da Costa BR, Collet TH, Feller M, Floriani C, Bauer DC, et al. Thyroid studies collaboration. Thyroid function within the normal range, subclinical hypothyroidism, and the risk of atrial fibrillation. Circulation. 2017;136(22):2100–16. 10.1161/CIRCULATIONAHA.117.028753
34 Ozturk S, Dikbas O, Baltacı D, Ozyasar M, Erdem A, Ayhan SS, et al. Evaulation of atrial conduction abnormalities and left atrial mechanical functions in patients with subclinical thyroid disorders. Endokrynol Pol. 2012;63(4):286–93.
35 Patrawala M, Cui Y, Peng L, Fuleihan RL, Garabedian EK, Patel K, et al. Pulmonary disease burden in primary ımmune deficiency disorders: Data from USIDNET registry. J Clin Immunol. 2020;40(2):340–9. 10.1007/s10875-019-00738-w
36 Nelson RH. Hyperlipidemia as a risk factor for cardiovascular disease. Prim Care. 2013;40(1):195–211. 10.1016/j.pop.2012.11.003
37 Alloubani A, Nimer R, Samara R. Relationship between hyperlipidemia, cardiovascular disease and stroke: A systematic review. Curr Cardiol Rev. 2021;17(6):e051121189015. 10.2174/1573403X16999201210200342
38 Napiórkowska-Baran K, Grześk G, Błażejewski J, Ziętkiewicz M, Więsik-Szewczyk E, Matyja-Bednarczyk A, et al. Trial of cardiovascular risk factor assessment and transthoracic echocardiography results in patients with primary antibody deficiency. Iran J Allergy Asthma Immunol. 2024;23(2):168–81. 10.18502/ijaai.v23i2.15323
39 Macpherson ME, Skarpengland T, Hov JR, Ranheim T, Vestad B, Dahl TB, et al. Increased plasma levels of triglyceride-enriched lipoproteins associate with systemic ınflammation, lipopolysaccharides, and gut dysbiosis in common variable ımmunodeficiency. J Clin Immunol. 2023;43(6):1229–40. 10.1007/s10875-023-01475-x
40 Taborda NA, Blanquiceth Y, Urcuqui-Inchima S, Latz E, Hernandez JC. High-density lipoproteins decrease proinflammatory activity and modulate the ınnate ımmune response. J Interferon Cytokine Res. 2019;39(12):760–70. 10.1089/jir.2019.0029
41 Grao-Cruces E, Lopez-Enriquez S, Martin ME, Montserrat-de la Paz S. High-density lipoproteins and immune response: A review. Int J Biol Macromol. 2022;195:117–23. 10.1016/j.ijbiomac.2021.12.009
42 Macpherson ME, Halvorsen B, Yndestad A, Ueland T, Mollnes TE, Berge RK, et al. Impaired HDL function amplifies systemic ınflammation in common variable ımmunodeficiency. Sci Rep. 2019;9(1):9427. 10.1038/s41598-019-45861-1
43 Vieira DG, Costa-Carvalho BT, Hix S, da Silva R, Correia MSG, Sarni ROS. Higher cardiovascular risk in common variable ımmunodeficiency and X-linked agammaglobulinaemia patients. Ann Nutr Metab. 2015;66(4):237–41. 10.1159/000435818
2 Tangye SG, Al-Herz W, Bousfiha A, Cunningham-Rundles C, Franco JL, Holland SM, et al. Human ınborn errors of ımmunity: 2022 update on the classification from the International Union of Immunological Societies Expert Committee. J Clin Immunol. 2022;42(7):1473–507. 10.1007/s10875-022-01289-3
3 Klangkalya N, Fleisher TA, Rosenzweig SD. Diagnostic tests for primary immunodeficiency disorders: Classic and genetic testing. Allergy Asthma Proc. 2024;45(5):355–63. 10.2500/aap.2024.45.240051
4 Bhatt HV, Fischer GW. Atrial fibrillation: Pathophysiology and therapeutic options. J Cardiothorac Vasc Anesth. 2015;29(5):1333–40. 10.1053/j.jvca.2015.05.058
5 Van Gelder IC, Rienstra M, Bunting KV, Casado-Arroyo R, Caso V, Crijns HJGM, et al. ESC Scientific Document Group. 2024 ESC guidelines for the management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2024;45(36):3314–414. 10.1093/eurheartj/ehae176
6 Elsheikh S, Hill A, Irving G, Lip GYH, Abdul-Rahim AH. Atrial fibrillation and stroke: State-of-the-art and future directions. Curr Probl Cardiol. 2024;49(1 Pt C):102181. 10.1016/j.cpcardiol.2023.102181
7 Kahraman E, Keles N, Parsova KE, Bastopcu M, Karatas M. Assessment of atrial conduction times in patients with frequent premature ventricular complex. J Arrhythm. 2023;39(1):34–41. 10.1002/joa3.12806
8 Acar G, Kahraman H, Akkoyun M, Kilinc M, Zencir C, Yusufoglu E, et al. Evaluation of atrial electromechanical delay and its relationship to inflammation and oxidative stress in patients with chronic obstructive pulmonary disease. Echocardiography. 2014;31(5):579–85. 10.1111/echo.12442
9 Yilmaz A, Can S, Perincek G, Kahraman F. Atrial electromechanical delay, neutrophil-to-lymphocyte ratio, and echocardiographic changes in patients with acute and stable chronic obstructive pulmonary disease. J Res Med Sci. 2022;27:64. 10.4103/jrms.JRMS_176_20
10 Okutucu S, Aytemir K, Oto A. P-wave dispersion: What we know till now? JRSM Cardiovasc Dis. 2016;5:2048004016639443. 10.1177/2048004016639443
11 Pekdemir H, Cansel M, Yağmur J, Acikgoz N, Ermis N, Kurtoglu E, et al. Assessment of atrial conduction time by tissue Doppler echocardiography and P-wave dispersion in patients with mitral annulus calcification. J Electrocardiol. 2010;43(4):339–43. 10.1016/j.jelectrocard.2010.02.013
12 Ciftel M, Yılmaz O, Kardelen F, Kahveci H. Assessment of atrial electromechanical delay using tissue Doppler echocardiography in children with asthma. Pediatr Cardiol. 2014;35(5):857–62. 10.1007/s00246-014-0867-9
13 Russo V, Di Meo F, Rago A, Mosella M, Molino A, Russo MG, et al. Impact of continuous positive airway pressure therapy on atrial electromechanical delay in obesity-hypoventilation syndrome patients. J Cardiovasc Electrophysiol. 2016;27(3):327–34. 10.1111/jce.12879
14 Paris K, Wall LA. The treatment of primary ımmune deficiencies: Lessons learned and future opportunities. Clin Rev Allergy Immunol. 2023;65(1):19–30. 10.1007/s12016-022-08950-0
15 Inan MI, Akgul Balaban Y, Yagci AF, Kartal O, Bugan B, Kalkan F, et al. A new perspective on the management of primary ımmunodeficiencies: Evaluation of arrhythmia and cardiac diseases. Cardiology. 2025;150(5):540–548. 10.1159/000543381
16 Clinical Working Party, European Society for Immunodeficiencies. The 6 ESID warning signs for ADULT primary immunodeficiency diseases [Internet]. [cited 2025 Feb 20]. Available from: https://esid.org/updated-and-published-ebmt-esid-guidelines-for-haematopoietic-stem-cell-transplantation-for-pi/
17 Shahreyar M, Fahhoum R, Akinseye O, Bhandari S, Dang G, Khouzam RN. Severe sepsis and cardiac arrhythmias. Ann Transl Med. 2018;6(1):6. 10.21037/atm.2017.12.26
18 Lazzerini PE, Capecchi PL, Laghi-Pasini F. Systemic inflammation and arrhythmic risk: Lessons from rheumatoid arthritis. Eur Heart J. 2017;38(22):1717–27. 10.1093/eurheartj/ehw208
19 Sawaya SE, Rajawat YS, Rami TG, Szalai G, Price RL, Sivasubramanian N, et al. Downregulation of connexin40 and increased prevalence of atrial arrhythmias in transgenic mice with cardiac-restricted overexpression of tumor necrosis factor. Am J Physiol Heart Circ Physiol. 2007;292(3):H1561–7. 10.1152/ajpheart.00285.2006
20 Lazzerini PE, Laghi-Pasini F, Boutjdir M, Capecchi PL. Cardioimmunology of arrhythmias: The role of autoimmune and inflammatory cardiac channelopathies. Nat Rev Immunol. 2019;19(1):63–4. 10.1038/s41577-018-0098-z
21 Swirski FK, Nahrendorf M. Cardioimmunology: The immune system in cardiac homeostasis and disease. Nat Rev Immunol. 2018;18(12):733–44. 10.1038/s41577-018-0065-8
22 Guo Y, Lip GY, Apostolakis S. Inflammation in atrial fibrillation. J Am Coll Cardiol. 2012;60(22):2263–70. 10.1016/j.jacc.2012.04.063
23 Fischer A, Provot J, Jais JP, Alcais A, Mahlaoui N, Members of the CEREDIH French PID study Group. Autoimmune and inflammatory manifestations occur frequently in patients with primary immunodeficiencies. J Allergy Clin Immunol. 2017;140(5):1388–93.e8.
24 Kaplan MY, Ozen S, Akcal O, Gulez N, Genel F. Autoimmune and inflammatory manifestations in pediatric patients with primary immunodeficiencies and their importance as a warning sign. Allergol Immunopathol (Madr). 2020;48(6):701–10. 10.1016/j.aller.2020.02.009
25 Blazina Š, Markelj G, Jeverica AK, Toplak N, Bratanič N, Jazbec J, et al. Autoimmune and ınflammatory manifestations in 247 patients with primary ımmunodeficiency–A report from the Slovenian National Registry. J Clin Immunol. 2016;36(8):764–73. 10.1007/s10875-016-0330-1
26 Aktoz M, Yilmaztepe M, Tatli E, Turan FN, Umit EG, Altun A. Assessment of ventricular and left atrial mechanical functions, atrial electromechanical delay and P-wave dispersion in patients with scleroderma. Cardiol J. 2011;18(3):261–9.
27 Erdem FH, Ozturk S, Baltaci D, Donmez I, Alçelik A, Ayhan S, et al. Detection of atrial electromechanical dysfunction in obesity. Acta Cardiol. 2015;70(6):678–84. 10.1080/AC.70.6.3120180
28 El Eraky AZ, Handoka NM, Ghaly MS, Nasef SI, Eldahshan NA, Ibrahim AM, et al. Assessment of left atrial mechanical functions and atrial electromechanical delay in juvenile idiopathic arthritis by tissue Doppler echocardiography. Pediatr Rheumatol Online J. 2016;14(1):62. 10.1186/s12969-016-0122-4
29 Yaman M, Arslan U, Beton O, Asarcıklı LD, Aksakal A, Dogdu O. Atrial electromechanical coupling in patients with lichen planus. Korean Circ J. 2016;46(4):530–5. 10.4070/kcj.2016.46.4.530
30 Yildiz A, Ucmak D, Oylumlu M, Akkurt MZ, Yuksel M, Akil MA, et al. Assessment of atrial electromechanical delay and P-wave dispersion in patients with psoriasis. Echocardiography. 2014;31(9):1071–6. 10.1111/echo.12530
31 Razvi S, Jabbar A, Pingitore A, Danzi S, Biondi B, Klein I, et al. Thyroid hormones and cardiovascular function and diseases. J Am Coll Cardiol. 2018;71(16):1781–96. 10.1016/j.jacc.2018.02.045
32 Marrakchi S, Kanoun F, Idriss S, Kammoun I, Kachboura S. Arrhythmia and thyroid dysfunction. Herz. 2015;40(Suppl 2):101–9. 10.1007/s00059-014-4123-0
33 Baumgartner C, da Costa BR, Collet TH, Feller M, Floriani C, Bauer DC, et al. Thyroid studies collaboration. Thyroid function within the normal range, subclinical hypothyroidism, and the risk of atrial fibrillation. Circulation. 2017;136(22):2100–16. 10.1161/CIRCULATIONAHA.117.028753
34 Ozturk S, Dikbas O, Baltacı D, Ozyasar M, Erdem A, Ayhan SS, et al. Evaulation of atrial conduction abnormalities and left atrial mechanical functions in patients with subclinical thyroid disorders. Endokrynol Pol. 2012;63(4):286–93.
35 Patrawala M, Cui Y, Peng L, Fuleihan RL, Garabedian EK, Patel K, et al. Pulmonary disease burden in primary ımmune deficiency disorders: Data from USIDNET registry. J Clin Immunol. 2020;40(2):340–9. 10.1007/s10875-019-00738-w
36 Nelson RH. Hyperlipidemia as a risk factor for cardiovascular disease. Prim Care. 2013;40(1):195–211. 10.1016/j.pop.2012.11.003
37 Alloubani A, Nimer R, Samara R. Relationship between hyperlipidemia, cardiovascular disease and stroke: A systematic review. Curr Cardiol Rev. 2021;17(6):e051121189015. 10.2174/1573403X16999201210200342
38 Napiórkowska-Baran K, Grześk G, Błażejewski J, Ziętkiewicz M, Więsik-Szewczyk E, Matyja-Bednarczyk A, et al. Trial of cardiovascular risk factor assessment and transthoracic echocardiography results in patients with primary antibody deficiency. Iran J Allergy Asthma Immunol. 2024;23(2):168–81. 10.18502/ijaai.v23i2.15323
39 Macpherson ME, Skarpengland T, Hov JR, Ranheim T, Vestad B, Dahl TB, et al. Increased plasma levels of triglyceride-enriched lipoproteins associate with systemic ınflammation, lipopolysaccharides, and gut dysbiosis in common variable ımmunodeficiency. J Clin Immunol. 2023;43(6):1229–40. 10.1007/s10875-023-01475-x
40 Taborda NA, Blanquiceth Y, Urcuqui-Inchima S, Latz E, Hernandez JC. High-density lipoproteins decrease proinflammatory activity and modulate the ınnate ımmune response. J Interferon Cytokine Res. 2019;39(12):760–70. 10.1089/jir.2019.0029
41 Grao-Cruces E, Lopez-Enriquez S, Martin ME, Montserrat-de la Paz S. High-density lipoproteins and immune response: A review. Int J Biol Macromol. 2022;195:117–23. 10.1016/j.ijbiomac.2021.12.009
42 Macpherson ME, Halvorsen B, Yndestad A, Ueland T, Mollnes TE, Berge RK, et al. Impaired HDL function amplifies systemic ınflammation in common variable ımmunodeficiency. Sci Rep. 2019;9(1):9427. 10.1038/s41598-019-45861-1
43 Vieira DG, Costa-Carvalho BT, Hix S, da Silva R, Correia MSG, Sarni ROS. Higher cardiovascular risk in common variable ımmunodeficiency and X-linked agammaglobulinaemia patients. Ann Nutr Metab. 2015;66(4):237–41. 10.1159/000435818