Document Type : original article


1 M.D, Associate Professor of Pediatrics Endocrinology, Pediatrics Health Research Center, Department of Pediatrics, Tabriz University of Medical Sciences, Tabriz, Iran.

2 M.D, Professor of Pediatrics Neurology, Pediatrics Health Research Center, Department of Pediatrics, Tabriz University of Medical Sciences, Tabriz, Iran.

3 M.D, Associate Professor of Pediatrics Neurology, Neurophysiology Research Center, Urmia University of Medical Sciences, Urmia, Iran


Background: Guillain-Barre syndrome (GBS) is an acute immune-mediated disease that affects both adults and children. Many infectious and non-infectious conditions may trigger this disease. Apolipoprotein E (APOE) is a glycosylated protein that has a variety of lipid and non-lipid related functions. The present study aimed to evaluate the serum levels of APOE in children with GBS compared to healthy control subjects to evaluate the diagnostic and pathologic effects of APOE in GBS.
Methods: In a cross-sectional design, 124 participants were divided into the GBS group (n=61) and the control group (n=63). Blood sampling and measurement of APOE were done according to the manual of the Human APOE ELISA kit. Demographic variables and further data about GBS patients were collected from patients' medical records. Weight and height were measured using SECA scales. The analyses were performed using SPSS Statistics 21.0 software and appropriate analytical tests. P-values of <0.05 were considered statistically significant.
Results: Mean ±SD of APOE serum levels was 8.43±3.59 micrograms/ml in the GBS group and 35.28±11.18 micrograms/ml in the comparison group. The difference between the two groups was strongly significant (P<0.001). The mean level of protein in Cerebrospinal Fluid (CSF) in GBS patients was 184.36±19.09 mg/dl. There was not any significant difference in the demographic findings between the two groups.
Conclusion: Our study demonstrated that the serum levels of APOE in children with GBS are lower compared to healthy subjects.


  1. Nasiri J, Ghazavi M, Yaghini O, Chaldavi M. Clinical Features and Outcome of Guillain-Barré Syndrome in Children. Iranian journal of child neurology. 2018; 12(2):49-57.
  2. Chung A, Deimling M. Guillain-Barré Syndrome. Pediatr Rev. 2018 Jan; 39(1):53-54.
  3. Karalok ZS, Taskin BD, Yanginlar ZB, Gurkhas E, Given A, Degerliyurt A, Unlu E, Kose G. Guillain-Barré syndrome in children: subtypes and outcome. Childs Nerv Syst. 2018 Nov; 34(11):2291-2297.
  4. Sejvar JJ, Baughman AL, Wise M, Morgan OW. Population incidence of Guillain-Barre syndrome: a systematic review and meta-analysis. Neuroepidemiology. 2011; 36(2):123-33.
  5. Karalok ZS, Taskin BD, Yanginlar ZB, Gurkhas E, Given A, Degerliyurt A, Unlu E, Kose G. Guillain-Barre syndrome in children: subtypes and outcome. Child's nervous system: ChNS: official journal of the International Society for Pediatric Neurosurgery. 2018; 34(11):2291-7.
  6. Ashrafi, M. R., Mohammadalipoor, A., Naeini, A. R., Amanat, M., Tavasoli, A. R., Heidari, M., & Akbari, M. G. (2020). Clinical Characteristics and Electrodiagnostic Features of Guillain-Barré Syndrome among the Pediatric Population. Journal of child neurology, 35(7), 448-455.
  7. Singh, S., Gupta, N., Gupta, A. M., Chandel, A. S., Waghela, S., & Sample, P. (2020). Clinical profile and predictors for outcome in children presenting with Guillain–Barré syndrome. Journal of Family Medicine and Primary Care, 9(10), 5316.
  8. Zhang HL, Wu J, Zhu J. The role of apolipoprotein E in Guillain-Barre syndrome and experimental autoimmune neuritis. J Biomed Biotechnol. 2010; 2010:357412.
  9. Park, J., Kim, Y., & Woo, M. (2021). Physical Fitness and Apolipoprotein E Genotype Influence Cortical Networking and Intelligence in Adolescents. The Journal of Prevention of Alzheimer's disease, 8(1), 92-99.
  10. Zhang H, Wu LM, Wu J. Cross-talk between apolipoprotein E and cytokines. Mediators of inflammation. 2011; 2011:949072.
  11. Ethemoglu O, Calik M. Effect of serum inflammatory markers on the prognosis of adult and pediatric patients with Guillain-Barré syndrome. Neuropsychiatric disease and treatment. 2018; 14:1255-60.
  12. D'Aguanno S, Franciotta D, Lupisella S, Barassi A, Pieragostino D, Lugaresi A, D'Eril GM, Bernardini S, Federici G, Urbani A. Protein profiling of Guillain-Barre syndrome cerebrospinal fluid by two-dimensional electrophoresis and mass spectrometry. Neuroscience letters. 2010; 485(1):49-54.
  13. Duan RS, Jin T, Yang X, Mix E, Adem A, Zhu J. Apolipoprotein E deficiency enhances the antigen-presenting capacity of Schwann cells. Glia. 2007; 55(7):772-6.
  14. Pritchard J, Hughes RA, Rees JH, Willison HJ, Nicoll JA. Apolipoprotein E genotypes and clinical outcome in Guillain-Barre syndrome. J Neurol Neurosurg Psychiatry. 2003; 74(7):971-3.
  15. Vitek MP, Brown CM, Colton CA. APOE genotype-specific differences in the innate immune response. Neurobiology of aging. 2009; 30(9):1350-60.
  16. Willison HJ, Jacobs BC, van Doorn PA. Guillain-Barre syndrome. Lancet. 2016; 388(10045):717-27.
  17. Zhang HL, Gao SJ, Yang Y, Wu J. Detection of autoantibodies against gangliosides in Guillain-Barre syndrome. Iranian journal of immunology: IJI. 2010; 7(3):198-9.
  18. Chang KH, Lyu RK, Tseng MY, Ro LS, Wu YR, Chang HS, Hsu WC, Kuo HC, Huang CC, Chu CC, Hsieh SY, Chen CM. Elevated haptoglobin level of cerebrospinal fluid in Guillain-Barre syndrome revealed by proteomics analysis. Proteomics Clinical applications. 2007; 1(5):467-75.
  19. Nyati KK, Prasad KN. Role of cytokines and Toll-like receptors in the immunopathogenesis of Guillain-Barré syndrome. Mediators of inflammation. 2014; 2014:758639.
  20. Hartung HP, Schwenke C, Bitter-Suermann D, Toyka KV. Guillain-Barre syndrome: activated complement components C3a and C5a in CSF. Neurology. 1987; 37(6):1006-9.
  21. Lu MO, Zhu J. The role of cytokines in Guillain-Barre syndrome. Journal of neurology. 2011; 258(4):533-48.
  22. Fazekas F, Strasser-Fuchs S, Kollegger H, Berger T, Kristoferitsch W, Schmidt H, Enzinger C, Schiefermeier M, Schwarz C, Kornek B, Reindl M, Huber K, Grass R, Wimmer G, Vass K, H Pfeiffer K, Hartung HP, Schmidt R. Apolipoprotein E epsilon 4 is associated with rapid progression of multiple sclerosis. Neurology. 2001; 57(5):853-7.
  23. Chen, Y., Strickland, M. R., Soranno, A., & Holtzman, D. M. (2020). Apolipoprotein E: Structural insights and links to Alzheimer disease pathogenesis. Neuron.
  24. Horsburgh K, McCarron MO, White F, Nicoll JA. The role of apolipoprotein E in Alzheimer's disease, acute brain injury and cerebrovascular disease: evidence of common mechanisms and utility of animal models. Neurobiology of aging. 2000; 21(2):245-55.
  25. Krasemann S, Madore C, Celiac R, Baufeld C, Calcagno N, El Fatimy R, Beckers L, O'Loughlin E, Xu Y, Fanek Z, Greco DJ, Smith ST, Tweet G, Humulock Z, Zrzavy T, Conde-Sanroman P, Gacias M, Weng Z, Chen H, Tjon E, Mazaheri F, Hartmann K, Madi A, Ulrich JD, Glatzel M, Worthmann A, Heeren J, Budnik B, Lemere C, Ikezu T, Heppner FL, Litvak V, Holtzman DM, Lassmann H, Weiner H, Ochando J, Haass C, Butovsky O. The TREM2-APOE Pathway Drives the Transcriptional Phenotype of Dysfunctional Microglia in Neurodegenerative Diseases. Immunity. 2017; 47(3):566-81.e9.
  26. Bedlack RS, Strittmatter WJ, Morgenlander JC. Apolipoprotein E and neuromuscular disease: a critical review of the literature. Archives of neurology. 2000; 57(11):1561-5.
  27. Siddiqui R, Suzu S, Ueno M, Nasser H, Koba R, Bhuyan F, Noyori O, Hamidi S, Sheng G, Yasuda-Inoue M, Hishiki T, Sukegawa S, Miyagi E, Strebel K, Matsushita S, Shimotohno K, Ariumi Y. Apolipoprotein E is an HIV-1-inducible inhibitor of viral production and infectivity in macrophages. PLoS pathogens. 2018; 14(11):e1007372.
  28. Mahley RW. Apolipoprotein E: cholesterol transport protein with expanding role in cell biology. Science (New York, NY). 1988; 240(4852):622-30.
  29. Laurat E, Poirier B, Tupin E, Caligiuri G, Hansson GK, Variety J, Nicoletti A. In vivo downregulation of T helper cell 1 immune responses reduces atherogenesis in apolipoprotein E-knockout mice. Circulation. 2001; 104(2):197-202.
  30. Laskowitz DT, Lee DM, Schmechel D, Staats HF. Altered immune responses in apolipoprotein E-deficient mice. Journal of lipid research. 2000; 41(4):613-20.
  31. Yu S, Duan RS, Chen Z, Quezada HC, Bao L, Nennesmo I, Zhu SW, Winblad B, Ljunggren HG, Zhu J. Increased susceptibility to experimental autoimmune neuritis after upregulation of the autoreactive T cell response to peripheral myelin antigen in apolipoprotein E-deficient mice. Journal of neuropathology and experimental neurology. 2004; 63(2):120-8.
  32. Sipila JOT, Soilu-Hanninen M, Ruuskanen JO, Rautava P, Kyto V. Epidemiology of Guillain-Barre syndrome in Finland 2004-2014. J Peripher Nerv Syst. 2017; 22(4):440-5.
  33. Ryan MM. Guillain-Barre syndrome in childhood. Journal of pediatrics and child health. 2005; 41(5-6):237-41.
  34. Sadek AA, Abou-Taleb A, Ali WA. Outcome of Guillain - Barre Syndrome in Children: A prospective cohort study in a tertiary hospital in Upper Egypt. Electronic physician. 2016; 8(12):3318-24.
  35. Jin T, Hu LS, Chang M, Wu J, Winblad B, Zhu J. Proteomic identification of potential protein markers in cerebrospinal fluid of GBS patients. European journal of neurology. 2007; 14(5):563-8.
  36. Yang YR, Liu SL, Qin ZY, Liu FJ, Qin YJ, Bai SM, et al. Comparative proteomics analysis of cerebrospinal fluid of patients with Guillain-Barre syndrome. Cellular and molecular neurobiology. 2008; 28(5):737-44.