Araştırma Makalesi
BibTex RIS Kaynak Göster

The Effect of Iron Deficiency on Immune Parameters, Including Memory B Cells and Infection Presentations: A Cohort Study in Premenopausal Women

Yıl 2025, Cilt: 35 Sayı: 6, 1165 - 1177, 31.12.2025
https://doi.org/10.54005/geneltip.1694683

Öz

Background: Iron deficiency anemia (IDA) is a condition associated with increased susceptibility to infections in the general population and more common in premenopausal women (PW). Clinical research focussing on humoral immunity and immune memory is limited in contrast to laboratory research.
Objective: This study aims to explore the effects of iron deficiency (ID) and IDA on immune function in PW by assessing immunoglobulins, lymphocyte subsets, memory B cell (MBC) quantities, and infection presentations.
Methods: A total of 180 PW who presented to the immunology outpatient clinic of a tertiary referral center between 2017 and 2024 were included. Infection history data were collected during routine clinical interviews using a six-question screening form designed to identify frequent or severe infections. Patient responses were verified through prescriptions, radiological reports, or physician documentation retrieved from the national health database. Measured parameters included haemoglobin, ferritin, immunoglobulins (IgG, A, M) and IgG subclasses, lymphocyte subsets (CD3+, CD4+, CD8+, CD19+, CD16+56+), and MBCs (CD19+CD27+IgM−IgD−). Subjects were categorized into three groups: IDA, ID, and a control group with normal haemoglobin and ferritin levels.
Results: Total lymphocyte and Natural Killer (NK) cell counts, percentage of MBCs in B lymphocytes and IgG levels were significantly lower in the IDA compared to control group. For MBC and IgG1, IDA had lower levels than both groups. Recurrent pneumonia was a more frequent infection presentation in the IDA compared to control group.
Conclusions: In PW with IDA, reductions in lymphocytes, NKs, IgG, IgG1, and MBCs, along with the higher frequency of recurrent pneumonia, may indicate a reduced capacity of immune responses against pathogens. Given the role of MBCs in maintaining long-term, even lifelong immune responses to infections or vaccinations, the potential relationship between IDA and MBC levels may represent an important and open area for further investigation regarding the sustainability of long-term immunity.

Kaynakça

  • 1. Alem AZ, Efendi F, McKenna L, Felipe-Dimog EB, Chilot D, Tonapa SI, et al. Prevalence and factors associated with anemia in women of reproductive age across low- and middle-income countries based on national data. Scientific reports. 2023;13(1):20335.
  • 2. Bernardi LA, Ghant MS, Andrade C, Recht H, Marsh EE. The association between subjective assessment of menstrual bleeding and measures of iron deficiency anemia in premenopausal African-American women: a cross-sectional study. BMC women's health. 2016;16(1):50.
  • 3. Safiri S, Kolahi AA, Noori M, Nejadghaderi SA, Karamzad N, Bragazzi NL, et al. Burden of anemia and its underlying causes in 204 countries and territories, 1990-2019: results from the Global Burden of Disease Study 2019. Journal of hematology & oncology. 2021;14(1):185.
  • 4. Harding KB, Neufeld LM. Iron deficiency and anemia control for infants and young children in malaria-endemic areas: a call to action and consensus among the research community. Advances in nutrition (Bethesda, Md). 2012;3(4):551-4.
  • 5. Paulino C, Nishijima M, Sarti FM. Association of Iron Supplementation Programs with Iron-Deficiency Anemia Outcomes among Children in Brazil. Nutrients. 2021;13(5).
  • 6. Tam E, Keats EC, Rind F, Das JK, Bhutta AZA. Micronutrient Supplementation and Fortification Interventions on Health and Development Outcomes among Children Under-Five in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis. Nutrients. 2020;12(2).
  • 7. Ni S, Yuan Y, Kuang Y, Li X. Iron Metabolism and Immune Regulation. Frontiers in immunology. 2022;13:816282.
  • 8. Hassan TH, Badr MA, Karam NA, Zkaria M, El Saadany HF, Abdel Rahman DM, et al. Impact of iron deficiency anemia on the function of the immune system in children. Medicine. 2016;95(47):e5395.
  • 9. Warner MJ, Kamran MT. Iron Deficiency Anemia. StatPearls. Treasure Island (FL) ineligible companies. Disclosure: Muhammad Kamran declares no relevant financial relationships with ineligible companies.: StatPearls Publishing LLC.; 2024.
  • 10. Chiang CH, Li CY, Hu KC, Fu YH, Chiu CC, Hsia CC, et al. The Association between Iron-Deficiency Anemia (IDA) and Septic Arthritis (SA): The Real-World Data. Medicina (Kaunas, Lithuania). 2022;58(5).
  • 11. Yildiz E, Çölkesen F, Evcen R, Sadi Aykan F, Kılınç M, Arslan S. Evaluation of the Effectiveness of the 6 Warning Signs of the European Society for Immunodeficiencies for Primary Immunodeficiencies in Older Adults. International archives of allergy and immunology. 2024;185(4):402-10.
  • 12. Littwitz-Salomon E, Moreira D, Frost JN, Choi C, Liou KT, Ahern DK, et al. Metabolic requirements of NK cells during the acute response against retroviral infection. Nature communications. 2021;12(1):5376.
  • 13. Pfeifhofer-Obermair C, Tymoszuk P, Nairz M, Schroll A, Klais G, Demetz E, et al. Regulation of Th1 T Cell Differentiation by Iron via Upregulation of T Cell Immunoglobulin and Mucin Containing Protein-3 (TIM-3). Frontiers in immunology. 2021;12:637809.
  • 14. Jiang Y, Li C, Wu Q, An P, Huang L, Wang J, et al. Iron-dependent histone 3 lysine 9 demethylation controls B cell proliferation and humoral immune responses. Nature communications. 2019;10(1):2935.
  • 15. Weyand AC, McGann PT, Sholzberg M. Sex specific definitions of anaemia contribute to health inequity and sociomedical injustice. The Lancet Haematology. 2022;9(1):e6-e8.
  • 16. Reynolds JH, McDonald G, Alton H, Gordon SB. Pneumonia in the immunocompetent patient. The British journal of radiology. 2010;83(996):998-1009.
  • 17. Shariatzadeh MR, Huang JQ, Tyrrell GJ, Johnson MM, Marrie TJ. Bacteremic pneumococcal pneumonia: a prospective study in Edmonton and neighboring municipalities. Medicine. 2005;84(3):147-61.
  • 18. Mourad S, Rajab M, Alameddine A, Fares M, Ziade F, Merhi BA. Hemoglobin level as a risk factor for lower respiratory tract infections in Lebanese children. North American journal of medical sciences. 2010;2(10):461-6.
  • 19. Stepan D, Dop D, Moroşanu A, Vintilescu B, Niculescu C. Implications of the Iron Deficiency in Lower Tract Respiratory Acute Infections in Toddlers. Current health sciences journal. 2018;44(4):362-7.
  • 20. Ye ZW, Zhang J, Townsend DM, Tew KD. Oxidative stress, redox regulation and diseases of cellular differentiation. Biochimica et biophysica acta. 2015;1850(8):1607-21.
  • 21. AlRajeh L, Zaher A, Alghamdi A, Alsheikh R, AlSultan O. Effects of Iron Deficiency and Its Indicators on Lymphocyte Subsets: A Study at King Fahd Hospital of the University, Saudi Arabia. Journal of blood medicine. 2022;13:61-7.
  • 22. Reza Keramati M, Sadeghian MH, Ayatollahi H, Mahmoudi M, Khajedaluea M, Tavasolian H, et al. Peripheral Blood Lymphocyte Subset Counts in Pre-menopausal Women with Iron-Deficiency Anaemia. The Malaysian journal of medical sciences : MJMS. 2011;18(1):38-44.
  • 23. Gyurova IE, Ali A, Waggoner SN. Natural Killer Cell Regulation of B Cell Responses in the Context of Viral Infection. Viral immunology. 2020;33(4):334-41.
  • 24. Gao N, Dang T, Yuan D. IFN-gamma-dependent and -independent initiation of switch recombination by NK cells. Journal of immunology (Baltimore, Md : 1950). 2001;167(4):2011-8.
  • 25. Lian G, Mak TS, Yu X, Lan HY. Challenges and Recent Advances in NK Cell-Targeted Immunotherapies in Solid Tumors. International journal of molecular sciences. 2021;23(1).
  • 26. Duan S, Liu S. Targeting NK Cells for HIV-1 Treatment and Reservoir Clearance. Frontiers in immunology. 2022;13:842746.
  • 27. Sadeghian MH, Keramati MR, Ayatollahi H, Manavifar L, Enaiati H, Mahmoudi M. Serum immunoglobulins in patients with iron deficiency anemia. Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion. 2010;26(2):45-8.
  • 28. Demmouche A. Iron Deficiency Anemia in Children and Alteration of the Immune System. Journal of Nutrition & Food Sciences. 2014;05.
  • 29. Akkaya M, Kwak K, Pierce SK. B cell memory: building two walls of protection against pathogens. Nature reviews Immunology. 2020;20(4):229-38.
  • 30. Syeda MZ, Hong T, Huang C, Huang W, Mu Q. B cell memory: from generation to reactivation: a multipronged defense wall against pathogens. Cell death discovery. 2024;10(1):117.
  • 31. Lehrke MJ, Shapiro MJ, Rajcula MJ, Kennedy MM, McCue SA, Medina KL, et al. The mitochondrial iron transporter ABCB7 is required for B cell development, proliferation, and class switch recombination in mice. eLife. 2021;10.

Demir Eksikliğinin Bağışıklık Parametreleri, Bellek B Hücreleri ve Enfeksiyon Bulguları Üzerine Etkisi: Premenopozal Kadınlarda Bir Kohort Çalışması

Yıl 2025, Cilt: 35 Sayı: 6, 1165 - 1177, 31.12.2025
https://doi.org/10.54005/geneltip.1694683

Öz

Giriş: Demir eksikliği anemisi (DEA), genel toplumda enfeksiyon sıklığındaki artışla ilişkilendirilen bir durumdur ve premenopozal kadınlarda daha sık görülmektedir. Humoral immünite ve immün hafıza üzerine yapılan klinik araştırmalar, laboratuvar temelli çalışmalara kıyasla sınırlıdır.
Amaç: Bu çalışmada, premenopozal kadınlarda demir eksikliği (DE) ve DEA'nın immün yanıt üzerindeki etkileri; immünoglobulin düzeyleri, lenfosit alt grupları, bellek B hücresi (BBH) miktarları ve enfeksiyon öyküsü açısından değerlendirilmiştir.
Yöntem: Bir tersiyer referans merkezinin immünoloji polikliniğine 2017 ile 2024 yılları arasında başvuran 180 premenopozal kadın çalışmaya dahil edildi. Enfeksiyon öyküsüne ilişkin veriler, hastalara sık ve ciddi enfeksiyonlara yönelik hazırlanan altı sorudan oluşan bir sorgulama formu ile rutin görüşme sırasında toplanmış ve bu bilgiler reçeteler, radyolojik görüntüler veya ilgili hekim kayıtları üzerinden ulusal sağlık sisteminden doğrulanmıştır. Ölçülen parametreler arasında hemoglobin, ferritin, immünoglobulinler (IgG, A, M), IgG alt grupları, lenfosit alt grupları (CD3+, CD4+, CD8+, CD19+, CD16+56+) ve BBH’ler (CD19+CD27+IgM−IgD−) yer almıştır. Katılımcılar DEA, DE ve hemoglobin ile ferritin düzeyleri normal olan kontrol grubu olmak üzere üç gruba ayrılmıştır.
Bulgular: DEA grubunda toplam lenfosit sayısı, doğal öldürücü hücre (NK) sayısı, B lenfositler içindeki BBH yüzdesi ve IgG düzeyi kontrol grubuna göre anlamlı düzeyde daha düşüktü. BBH ve IgG1 düzeyleri açısından DEA grubu her iki gruptan da daha düşük değerler göstermiştir. DEA grubunda tekrarlayan pnömoni öyküsü diğer gruplara göre daha yaygındı.
Sonuç: DEA’lı premenopozal kadınlarda lenfosit, NK hücreleri, IgG, IgG1 ve BBH düzeylerindeki azalma ile birlikte tekrarlayan pnömoni sıklığındaki artış, patojenlere karşı bağışıklık yanıt kapasitesinde bir azalmaya işaret ediyor olabilir. Bellek B hücrelerinin enfeksiyonlara veya aşılara karşı uzun süreli, hatta ömür boyu sürebilen immün yanıtların oluşumundaki rolü göz önünde bulundurulduğunda, DEA ile BBH düzeyleri arasındaki olası ilişki, uzun vadeli bağışıklığın sürdürülebilirliği açısından araştırmaya açık ve önemli bir alan olarak değerlendirilebilir.

Kaynakça

  • 1. Alem AZ, Efendi F, McKenna L, Felipe-Dimog EB, Chilot D, Tonapa SI, et al. Prevalence and factors associated with anemia in women of reproductive age across low- and middle-income countries based on national data. Scientific reports. 2023;13(1):20335.
  • 2. Bernardi LA, Ghant MS, Andrade C, Recht H, Marsh EE. The association between subjective assessment of menstrual bleeding and measures of iron deficiency anemia in premenopausal African-American women: a cross-sectional study. BMC women's health. 2016;16(1):50.
  • 3. Safiri S, Kolahi AA, Noori M, Nejadghaderi SA, Karamzad N, Bragazzi NL, et al. Burden of anemia and its underlying causes in 204 countries and territories, 1990-2019: results from the Global Burden of Disease Study 2019. Journal of hematology & oncology. 2021;14(1):185.
  • 4. Harding KB, Neufeld LM. Iron deficiency and anemia control for infants and young children in malaria-endemic areas: a call to action and consensus among the research community. Advances in nutrition (Bethesda, Md). 2012;3(4):551-4.
  • 5. Paulino C, Nishijima M, Sarti FM. Association of Iron Supplementation Programs with Iron-Deficiency Anemia Outcomes among Children in Brazil. Nutrients. 2021;13(5).
  • 6. Tam E, Keats EC, Rind F, Das JK, Bhutta AZA. Micronutrient Supplementation and Fortification Interventions on Health and Development Outcomes among Children Under-Five in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis. Nutrients. 2020;12(2).
  • 7. Ni S, Yuan Y, Kuang Y, Li X. Iron Metabolism and Immune Regulation. Frontiers in immunology. 2022;13:816282.
  • 8. Hassan TH, Badr MA, Karam NA, Zkaria M, El Saadany HF, Abdel Rahman DM, et al. Impact of iron deficiency anemia on the function of the immune system in children. Medicine. 2016;95(47):e5395.
  • 9. Warner MJ, Kamran MT. Iron Deficiency Anemia. StatPearls. Treasure Island (FL) ineligible companies. Disclosure: Muhammad Kamran declares no relevant financial relationships with ineligible companies.: StatPearls Publishing LLC.; 2024.
  • 10. Chiang CH, Li CY, Hu KC, Fu YH, Chiu CC, Hsia CC, et al. The Association between Iron-Deficiency Anemia (IDA) and Septic Arthritis (SA): The Real-World Data. Medicina (Kaunas, Lithuania). 2022;58(5).
  • 11. Yildiz E, Çölkesen F, Evcen R, Sadi Aykan F, Kılınç M, Arslan S. Evaluation of the Effectiveness of the 6 Warning Signs of the European Society for Immunodeficiencies for Primary Immunodeficiencies in Older Adults. International archives of allergy and immunology. 2024;185(4):402-10.
  • 12. Littwitz-Salomon E, Moreira D, Frost JN, Choi C, Liou KT, Ahern DK, et al. Metabolic requirements of NK cells during the acute response against retroviral infection. Nature communications. 2021;12(1):5376.
  • 13. Pfeifhofer-Obermair C, Tymoszuk P, Nairz M, Schroll A, Klais G, Demetz E, et al. Regulation of Th1 T Cell Differentiation by Iron via Upregulation of T Cell Immunoglobulin and Mucin Containing Protein-3 (TIM-3). Frontiers in immunology. 2021;12:637809.
  • 14. Jiang Y, Li C, Wu Q, An P, Huang L, Wang J, et al. Iron-dependent histone 3 lysine 9 demethylation controls B cell proliferation and humoral immune responses. Nature communications. 2019;10(1):2935.
  • 15. Weyand AC, McGann PT, Sholzberg M. Sex specific definitions of anaemia contribute to health inequity and sociomedical injustice. The Lancet Haematology. 2022;9(1):e6-e8.
  • 16. Reynolds JH, McDonald G, Alton H, Gordon SB. Pneumonia in the immunocompetent patient. The British journal of radiology. 2010;83(996):998-1009.
  • 17. Shariatzadeh MR, Huang JQ, Tyrrell GJ, Johnson MM, Marrie TJ. Bacteremic pneumococcal pneumonia: a prospective study in Edmonton and neighboring municipalities. Medicine. 2005;84(3):147-61.
  • 18. Mourad S, Rajab M, Alameddine A, Fares M, Ziade F, Merhi BA. Hemoglobin level as a risk factor for lower respiratory tract infections in Lebanese children. North American journal of medical sciences. 2010;2(10):461-6.
  • 19. Stepan D, Dop D, Moroşanu A, Vintilescu B, Niculescu C. Implications of the Iron Deficiency in Lower Tract Respiratory Acute Infections in Toddlers. Current health sciences journal. 2018;44(4):362-7.
  • 20. Ye ZW, Zhang J, Townsend DM, Tew KD. Oxidative stress, redox regulation and diseases of cellular differentiation. Biochimica et biophysica acta. 2015;1850(8):1607-21.
  • 21. AlRajeh L, Zaher A, Alghamdi A, Alsheikh R, AlSultan O. Effects of Iron Deficiency and Its Indicators on Lymphocyte Subsets: A Study at King Fahd Hospital of the University, Saudi Arabia. Journal of blood medicine. 2022;13:61-7.
  • 22. Reza Keramati M, Sadeghian MH, Ayatollahi H, Mahmoudi M, Khajedaluea M, Tavasolian H, et al. Peripheral Blood Lymphocyte Subset Counts in Pre-menopausal Women with Iron-Deficiency Anaemia. The Malaysian journal of medical sciences : MJMS. 2011;18(1):38-44.
  • 23. Gyurova IE, Ali A, Waggoner SN. Natural Killer Cell Regulation of B Cell Responses in the Context of Viral Infection. Viral immunology. 2020;33(4):334-41.
  • 24. Gao N, Dang T, Yuan D. IFN-gamma-dependent and -independent initiation of switch recombination by NK cells. Journal of immunology (Baltimore, Md : 1950). 2001;167(4):2011-8.
  • 25. Lian G, Mak TS, Yu X, Lan HY. Challenges and Recent Advances in NK Cell-Targeted Immunotherapies in Solid Tumors. International journal of molecular sciences. 2021;23(1).
  • 26. Duan S, Liu S. Targeting NK Cells for HIV-1 Treatment and Reservoir Clearance. Frontiers in immunology. 2022;13:842746.
  • 27. Sadeghian MH, Keramati MR, Ayatollahi H, Manavifar L, Enaiati H, Mahmoudi M. Serum immunoglobulins in patients with iron deficiency anemia. Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion. 2010;26(2):45-8.
  • 28. Demmouche A. Iron Deficiency Anemia in Children and Alteration of the Immune System. Journal of Nutrition & Food Sciences. 2014;05.
  • 29. Akkaya M, Kwak K, Pierce SK. B cell memory: building two walls of protection against pathogens. Nature reviews Immunology. 2020;20(4):229-38.
  • 30. Syeda MZ, Hong T, Huang C, Huang W, Mu Q. B cell memory: from generation to reactivation: a multipronged defense wall against pathogens. Cell death discovery. 2024;10(1):117.
  • 31. Lehrke MJ, Shapiro MJ, Rajcula MJ, Kennedy MM, McCue SA, Medina KL, et al. The mitochondrial iron transporter ABCB7 is required for B cell development, proliferation, and class switch recombination in mice. eLife. 2021;10.
Toplam 31 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular İç Hastalıkları
Bölüm Araştırma Makalesi
Yazarlar

Tuğba Önalan 0000-0003-2427-5925

Fatih Çölkesen 0000-0002-6595-1267

Mehmet Emin Gerek 0000-0003-4792-0544

Fatma Arzu Akkuş 0000-0003-0519-7132

Recep Evcen 0000-0002-6124-5816

Mehmet Kılınç 0000-0003-1117-6872

Filiz Sadi Aykan 0000-0002-8941-5573

Şevket Arslan 0000-0002-0343-0159

Gönderilme Tarihi 7 Mayıs 2025
Kabul Tarihi 7 Ekim 2025
Yayımlanma Tarihi 31 Aralık 2025
Yayımlandığı Sayı Yıl 2025 Cilt: 35 Sayı: 6

Kaynak Göster

Vancouver Önalan T, Çölkesen F, Gerek ME, Akkuş FA, Evcen R, Kılınç M, vd. The Effect of Iron Deficiency on Immune Parameters, Including Memory B Cells and Infection Presentations: A Cohort Study in Premenopausal Women. Genel Tıp Derg. 2025;35(6):1165-77.