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Lymphocyte transformation test detects a response to Campylobacter jejuni antigens in patients with Guillain-Barré syndrome

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Abstract

Guillain-Barré syndrome (GBS) is an immune-mediated polyneuropathy. Campylobacter jejuni-associated gastrointestinal infection is identified as a major precipitating agent of GBS; however, a standard test to diagnose this infection in patients with GBS is lacking. The aim of the present study was to evaluate an outer membrane protein (OMP)-based lymphocyte transformation test (LTT) for the diagnosis of C. jejuni infection in GBS. Forty patients with GBS, age and gender matched 52 healthy controls (HC) and 46 disease controls (DC) were analyzed for C. jejuni infection by culture, polymerase chain reaction (PCR) and LTT. Lymphocytes at concentration of 1 × 106/well isolated from GBS patients and controls were stimulated with 20 μg/ml of C. jejuni OMP, and 3H-thymidine was incorporated to measure cell proliferation. LTT detected significantly higher C. jejuni infection compared to culture (77.5 vs. 2.5%; P < 0.05) and PCR (77.5 vs. 22.5%; P < 0.05). The cutoff value of lymphocyte proliferation by receiver operating characteristic (ROC) curve of 2.5 had 77.5% sensitivity and 96.5% specificity. Area under ROC curve was 0.92. The mean SI of the cell proliferation for GBS cases was significantly higher than the controls (GBS vs. HC; P < 0.001, GBS vs. DC; P < 0.001). LTT appears to be a sensitive tool for detecting preceding C. jejuni infection in GBS patients with reasonable sensitivity and specificity. It is possible that the activated lymphocytes might play role in the pathogenesis of neuronal damage in GBS.

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References

  1. Govoni V, Granieri E (2001) Epidemiology of the Guillain-Barré syndrome. Curr Opin Neurol 14:605–613

    Article  CAS  PubMed  Google Scholar 

  2. Hughes RA, Rees JH (1997) Clinical and epidemiologic features of Guillain-Barré syndrome. J Infect Dis 176:S92–S98

    Article  PubMed  Google Scholar 

  3. Koga M, Yuki N, Hirata K (2001) Antecedent symptoms in Guillain-Barré syndrome: an important indicator for clinical and serological subgroups. Acta Neurol Scand 103:278–287

    Article  CAS  PubMed  Google Scholar 

  4. Hadden RD, Cornblath DR, Hughes RA, Zielasek J, Hartung HP, Toyka KV, Swan AV (1998) Electrophysiological classification of Guillain-Barré syndrome: clinical associations and outcome. Ann Neurol 44:7–8

    Article  Google Scholar 

  5. Ben-Smith A, Goodall JC, Gaston JSH, Winer JB (1997) Stimulation of peripheral blood lymphocytes with Campylobacter jejuni generates a γδ T cell response in patients with Guillain-Barré syndrome. Clin Exp Immunol 109:121–126

    Article  CAS  PubMed  Google Scholar 

  6. Csurhes PA, Sullivan AA, Green K, Pender MP, McCombe PA (2005) T cell reactivity to P0, P2, PMP-22, and myelin basic protein in patients with Guillain-Barre’ syndrome and chronic inflammatory demyelinating polyradiculoneuropathy. J Neurol Neurosurg Psychiatry 76:1431–1439

    Article  CAS  PubMed  Google Scholar 

  7. Kuroki S, Saida T, Nukina M, Haruta T, Yoshioka M, Kobayashi Y, Nakanishi H (1993) Campylobacter jejuni strains from patients with Guillain-Barre’ syndrome belong mostly to Penner serogroup 19 and contain beta-N-acetylglucosamine residues. Ann Neurol 33:243–247

    Article  CAS  PubMed  Google Scholar 

  8. Zilbauer M, Dorrell N, Wren BW, Elliott MB (2008) Campylobacter jejuni-mediated disease pathogenesis: an update. Trans R Soc Trop Med Hyg 102:123–129

    Article  CAS  PubMed  Google Scholar 

  9. Nachamkin I, Murray EJ, Baron MA, Pfaller FC, Tenover F, Yolken RH (1995) Campylobacter and Arcobacter. In: Murray PR, Baron EJ, Pfaller MA, Jorgensen JH, Yolken RH (eds) Manual of clinical microbiology, 6th edn. American Society for Microbiology, Washington, DC, pp 483–491

    Google Scholar 

  10. Zhu J, Link H, Mix E, Olsson T, Huang WX (1994) Th1-like cell responses to peripheral nerve myelin components over the course of experimental allergic neuritis in Lewis rats. Acta Neurol Scand 90:19–25

    Article  CAS  PubMed  Google Scholar 

  11. Christiansen J, Farm G, Eid-Forest R, Anderson C, Cederbrant K, Hultman P (2006) Interferon-gamma secreted from peripheral blood mononuclear cells as a possible diagnostic marker for allergic contact dermatitis to gold. Contact Dermatitis 55:101–112

    Article  CAS  PubMed  Google Scholar 

  12. Fujimoto S, Yuki N, Itoh T, Amako K (1992) Specific serotype of Campylobacter jejuni associated with Guillain-Barre’ syndrome. J Infect Dis 165:183

    CAS  PubMed  Google Scholar 

  13. Sinha S, Prasad KN, Pradhan S, Jain D, Jha S (2004) Detection of preceding Campylobacter jejuni infection by polymerase chain reaction in patients with Guillain-Barré syndrome. Trans Roy Soc Trop Med Hyg 98:342–346

    Article  CAS  PubMed  Google Scholar 

  14. Yuki N, Taki T, Takahashi M, Saito K, Tai T, Miyatake T, Handa S (1994) Penner’s serotype 4 of Campylobacter jejuni has a lipopolysaccharide that bears a GM1 ganglioside epitope as well as one that bears a GD1a epitope. Infect Immun 62:2101–2103

    CAS  PubMed  Google Scholar 

  15. Nachamkin I, Mishu AB, Ho T (1998) Campylobacter species and Guillain-Barré syndrome. Clin Microbiol Rev 11:555–567

    CAS  PubMed  Google Scholar 

  16. Linton D, Lawson AJ, Owen RJ, Stanley J (1997) PCR detection, identification to species level, and fingerprinting to Campylobacter jejuni and Campylobacter coli direct from diarrheic samples. J Clin Microbiol 35:2568–2572

    CAS  PubMed  Google Scholar 

  17. Honavar M, Tharakan JK, Hughes RAC, Leibowitz S, Winer JB (1991) A clinicopathological study of the Guillain-Barre’ syndrome. Nine cases and literature review. Brain 114:1245–1269

    Article  PubMed  Google Scholar 

  18. Nachamkin I, Allos BM, Ho TW (2000) Campylobacter jejuni infection and the association with Guillain Barré syndrome. In: Nachamkin I, Blaser MJ (eds) Campylobacter, 2nd edn. American Society for Microbiology, Washington, DC, pp 155–175

    Google Scholar 

  19. Winer JB, Hughes RAC, Anderson MJ, Jones DM, Kangro H, Watkins RP (1988) A prospective study of acute idiopathic neuropathy: II. Antecedent events. J Neurol Neurosurg Psychiatry 51:613–618

    Article  CAS  PubMed  Google Scholar 

  20. Asbury AK, Cornblath DR (1990) Assessment of current diagnostic criteria for Guillain-Barré syndrome. Ann Neurol 27:S21–S24

    Article  PubMed  Google Scholar 

  21. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin reagent. J Biol Chem 193:265–275

    CAS  PubMed  Google Scholar 

  22. Prasad A, Prasad KN, Yadav A, Gupta RK, Pradhan S, Jha S, Tripathi M, Husain M (2008) Lymphocyte transformation test: a new method for diagnosis of neurocysticercosis. Diagn Microbiol Infect Dis 61:198–202

    Article  CAS  PubMed  Google Scholar 

  23. Kaluza W, Meyer zum Büschenfelde KH, Galle PR, Märker-Hermann E (2000) Synovial fluid lymphocyte proliferation in response to crude microbial antigens is not useful as a diagnostic test to specifically indicate a bacterial cause of arthritis. Clin Exp Rheumatol 18:39–46

    CAS  PubMed  Google Scholar 

  24. Valentine-Thon E, Ilsemann K, Sandkamp M (2007) A novel lymphocyte transformation test (LTT-MELISA) for lyme borreliosis. Diagn Microbiol Infect Dis 57:27–34

    Article  CAS  PubMed  Google Scholar 

  25. Pichler WJ, Tilch J (2004) The lymphocyte transformation test in the diagnosis of drug hypersensitivity. Allergy 59:809–820

    Article  CAS  PubMed  Google Scholar 

  26. Moran AP, Prendergast MM (2001) Molecular mimicry in Campylobacter jejuni and Helicobacter pylori lipopolysaccharides: Contribution of gastrointestinal infections to Autoimmunity. J Autoimmun 16:241–256

    Article  CAS  PubMed  Google Scholar 

  27. Rhijn V, Bleumink-Pluym N, Van Putten J, Van den Berg L (2002) Campylobacter DNA is present in circulating myelomonocytic cells of healthy persons and in persons with Guillain-Barre’ Syndrome. J Infect Dis 185:262–268

    Article  PubMed  Google Scholar 

  28. Jacobs BC, Rothbarth PH, vander Mechq FG, Herbrink P, Schmitz PIM, de Klerk MA, van Doorn PA (1998) The spectrum of antecedent infections in Guillain-Barré syndrome: a case control study. Neurology 51:1110–1115

    CAS  PubMed  Google Scholar 

  29. Sinha S, Prasad KN, Jain D, Pandey CM, Jha S, Pradhan S (2007) Preceding infections and anti-ganlioside antibodies in patients with Guillain-Barré syndrome: a single centre prospective case-control study. Clin Microbiol Infect 13:334–337

    Article  CAS  PubMed  Google Scholar 

  30. Ho TW, Mishu B, Li CY, Gao CY, Cornblath DR, Griffin JW, Asbury AK, Blaser MJ, McKhann GM (1995) Guillain-Barré syndrome in northern China: relationship to Campylobacter jejuni infection and anti-glycolipid antibodies. Brain 118:597–605

    Article  PubMed  Google Scholar 

  31. Ogawara K, Kuwabara S, Mori M, Hattori T, Koga M, Yuki N (2000) Axonal Guillain-Barre’ syndrome: relation to anti-ganglioside antibodies and Campylobacter jejuni infection in Japan. Ann Neurol 48:624–631

    Article  CAS  PubMed  Google Scholar 

  32. Rees JH, Soudain SE, Gergson NA, Hughes RAC (1995) Campylobacter jejuni infection and Guillain-Barre’ syndrome. N Eng J Med 333:1374–1379

    Article  CAS  Google Scholar 

  33. Ghoshal UC, Tripathi S, Chourasia D (2007) Principle of statistical analysis in clinical research: a primer. In: Mehta R (ed) Clinical gastroenterology. Paras Publishing, Hyderabad, pp 372–386

    Google Scholar 

  34. Zhu J, Mix E, Link H (1998) Cytokine production and the pathogenesis of experimental autoimmune neuritis and Guillain-Barré syndrome. J Neuroimmunol 84:40–52

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The study was supported by the Indian Council of Medical Research (ICMR), Govt. of India, New Delhi, India (5/3/3/24/2006-ECD-I). The senior research fellows: K K Nyati (80/569/2007-ECD-I) and A Verma (09/590 (0138)/2007-EMR-I) acknowledge the financial assistance from the ICMR and the Council of Scientific and Industrial Research, Govt. of India, New Delhi, India, respectively.

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The authors declare that they have no conflict of interest.

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Correspondence to Kashi N. Prasad.

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Nyati, K.K., Prasad, K.N., Rizwan, A. et al. Lymphocyte transformation test detects a response to Campylobacter jejuni antigens in patients with Guillain-Barré syndrome. Med Microbiol Immunol 199, 109–116 (2010). https://doi.org/10.1007/s00430-010-0144-3

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