Pediatric Infection and Vaccine

The Korean Society of Pediatric Infectious Diseases (대한소아감염학회)
권호 표지
DOI QR코드

DOI QR Code

Opsonophagocytic Antibodies of Intravenous Immunoglobulin Preparations against Seven Streptococcus agalactiae Serotypes

  • Lee, Ji Hyen (Department of Pediatrics, Ewha Womans University Seoul Hospital) ;
  • Kim, Han Wool (Department of Pediatrics, Hallym University Sacred Heart Hospital) ;
  • Cha, Jihei (Department of Pediatrics, Ewha Womans University Mokdong Hospital) ;
  • Kim, Kyung-Hyo (Center for Vaccine Evaluation and Study, Medical Research Institute, Ewha Womans University College of Medicine)
  • Received : 2020.11.30
  • Accepted : 2021.04.18
  • Published : 2021.04.25
Download PDF
⟨ Previous Next ⟩

Abstract

Purpose: Group B streptococcus (GBS) is a causative organism of invasive infections in neonates and pregnant women as well as in non-pregnant adults. Among 10 known serotypes of GBS, uncommon serotypes, such as IV and VI to IX, can cause invasive infections in immunocompromised patients. However, opsonophagocytic antibodies against these serotypes in human sera and intravenous immunoglobulin (IVIG) have not yet been studied. IVIG therapy is used to treat or prevent invasive infections in patients with primary antibody deficiencies. Here, we analyzed the activity of opsonophagocytic antibodies against GBS in IVIG preparations. Methods: Opsonophagocytic antibody activity (opsonic index [OI]) against seven GBS serotypes (II and IV to IX) was evaluated in 16 commercially available IVIG preparations using the opsonophagocytic assay (OPA) in HL-60 cells and baby rabbit complement assay during 2015-2016 in South Korea (UAB GBS OPA, at http://www.vaccine.uab.edu). Results: The estimated serum trough levels of OIs against GBS exceeded the limit of detection (≥4) in all IVIG preparations. For serotype VII, the serum levels of OIs were 6-136, the lowest among all serotypes. An IVIG dose of 400 mg/kg was found to be appropriate for immunocompromised individuals to prevent invasive GBS infections. Conclusions: Most immunoglobulin products displayed high levels of opsonophagocytic activity against GBS, except for serotype VII. IVIG preparations could serve as a therapeutic or immunomodulatory agent for immunocompromised individuals.

목적: Streptococcus agalactiae (group B streptococcus [GBS])은 신생아, 임산부 및 성인에서 침습성 감염의 주요 원인균이다. 면역체계가 손상되거나 약화된 경우, 잘 알려진 10개의 GBS 혈청형 중 흔하지 않은 IV, VI-IX에 의해 침습적인 질환이 발생할 수 있다. 그러나, 지금까지 사람의 혈청 및 정주용 면역글로불린(intravenous immunoglobulin, IVIG) 제제 중 GBS의 흔하지 않은 혈청형에 대한 옵소닌 항체(opsonophagocytic antibody) 활동은 연구되지 않았다. 면역글로불린 치료 요법은 일차항체 결핍증(primary antibody deficiency, PAD) 환자의 침습적 감염을 치료하거나 예방하는 데 사용된다. 이 연구에서는 면역글로불린에서 GBS에 대한 옵소닌 항체 활성을 평가하고자 한다. 방법: 2015-2016년 국내 두 회사에서 사용가능한 16개 면역글로불린에 대하여 7개 GBS 혈청형 (II 및 IV-IX)에 대한 옵소닌 항체 활성도(opsonic index [OI])를 HL-60 세포와 아기토끼 보체를 사용하여 옵소닌 분석법(opsonophagocytic assay)을 통해 분석하였다. (UAB GBS OPA, http://www.vaccine.uab.edu). 결과: 모든 면역글로불린 제제에서 GBS에 대한 OI의 검출 한계점(≥4)을 초과하였다. 혈청형 VII의 경우, OI 값은 6-136으로 모든 혈청형 중에서 가장 낮았다. IVIG의 최저 수준(trough level)을 추정해볼 때, 일반적인 면역글로불린 용량 (400 mg/kg)은 PAD 환자에게 침습성 GBS 감염을 예방하기 위한 적합한 용량으로 보인다. 결론: 국내에서 사용중인 면역글로불린 제품은 GBS에 대한 높은 수준의 옵소닌 항체 활성을 나타냈다. 면역글로불린은 PAD 환자에게 유용한 치료 또는 예방조치가 될 수 있을 것으로 보인다.

Keywords

Acknowledgement

We appreciate Green Cross Corp. (Yongin, the Republic of Korea) and SK Chemicals (Seongnam, the Republic of Korea) for providing intravenous immunoglobulin (IVIG) preparations.

References

  1. Phares CR, Lynfield R, Farley MM, Mohle-Boetani J, Harrison LH, Petit S, et al. Epidemiology of invasive group B streptococcal disease in the United States, 1999-2005. JAMA 2008;299:2056-65. https://doi.org/10.1001/jama.299.17.2056
  2. Le Doare K, Heath PT. An overview of global GBS epidemiology. Vaccine 2013;31 Suppl 4:D7-12. https://doi.org/10.1016/j.vaccine.2013.01.009
  3. Baker CJ, Kasper DL. Correlation of maternal antibody deficiency with susceptibility to neonatal group B streptococcal infection. N Engl J Med 1976;294:753-6. https://doi.org/10.1056/NEJM197604012941404
  4. Edwards MS, Lane HJ, Hillier SL, Rench MA, Baker CJ. Persistence of functional antibodies to group B streptococcal capsular polysaccharides following immunization with glycoconjugate vaccines. Vaccine 2012;30:4123-6. https://doi.org/10.1016/j.vaccine.2012.04.048
  5. Harrison LH, Dwyer DM, Johnson JA. Emergence of serotype V group B streptococcal infection among infants and adults. J Infect Dis 1995;171:513. https://doi.org/10.1093/infdis/171.2.513
  6. Lin FY, Clemens JD, Azimi PH, Regan JA, Weisman LE, Philips JB 3rd, et al. Capsular polysaccharide types of group B streptococcal isolates from neonates with early-onset systemic infection. J Infect Dis 1998;177:790-2. https://doi.org/10.1086/517810
  7. Ferrieri P, Lynfield R, Creti R, Flores AE. Serotype IV and invasive group B streptococcus disease in neonates, Minnesota, USA, 2000-2010. Emerg Infect Dis 2013;19:551-8. https://doi.org/10.3201/eid1904.121572
  8. Melin P, Efstratiou A. Group B streptococcal epidemiology and vaccine needs in developed countries. Vaccine 2013;31 Suppl 4:D31-42. https://doi.org/10.1016/j.vaccine.2013.05.012
  9. Lamagni TL, Keshishian C, Efstratiou A, Guy R, Henderson KL, Broughton K, et al. Emerging trends in the epidemiology of invasive group B streptococcal disease in England and Wales, 1991-2010. Clin Infect Dis 2013;57:682-8. https://doi.org/10.1093/cid/cit337
  10. Lachenauer CS, Kasper DL, Shimada J, Ichiman Y, Ohtsuka H, Kaku M, et al. Serotypes VI and VIII predominate among group B streptococci isolated from pregnant Japanese women. J Infect Dis 1999;179:1030-3. https://doi.org/10.1086/314666
  11. Lee JH, Cho HK, Kim KH, Kim CH, Kim DS, Kim KN, et al. Etiology of invasive bacterial infections in immunocompetent children in Korea (1996-2005): a retrospective multicenter study. J Korean Med Sci 2011;26:174-83. https://doi.org/10.3346/jkms.2011.26.2.174
  12. Cho HK, Lee H, Kang JH, Kim KN, Kim DS, Kim YK, et al. The causative organisms of bacterial meningitis in Korean children in 1996-2005. J Korean Med Sci 2010;25:895-9. https://doi.org/10.3346/jkms.2010.25.6.895
  13. Yoon IA, Jo DS, Cho EY, Choi EH, Lee HJ, Lee H. Clinical significance of serotype V among infants with invasive group B streptococcal infections in South Korea. Int J Infect Dis 2015;38:136-40. https://doi.org/10.1016/j.ijid.2015.05.017
  14. Fischer GW. Immunoglobulin therapy for neonatal sepsis: an overview of animal and clinical studies. J Clin Immunol 1990;10:40S-46S. https://doi.org/10.1007/BF00918690
  15. Shehata N, Palda V, Bowen T, Haddad E, Issekutz TB, Mazer B, et al. The use of immunoglobulin therapy for patients with primary immune deficiency: an evidence-based practice guideline. Transfus Med Rev 2010;24 Suppl 1:S28-50. https://doi.org/10.1016/j.tmrv.2009.09.011
  16. Baker CJ, Noya FJ. Potential use of intravenous immune globulin for group B streptococcal infection. Rev Infect Dis 1990;12 Suppl 4:S476-82. https://doi.org/10.1093/clinids/12.Supplement_4.S476
  17. Baker CJ, Rench MA, Noya FJ, Garcia-Prats JA. Role of intravenous immunoglobulin in prevention of late-onset infection in low-birth-weight neonates. The Neonatal IVIG Study Group. Rev Infect Dis 1990;12 Suppl 4:S463-9. https://doi.org/10.1093/clinids/12.Supplement_4.S463
  18. Kim HW, Lee JH, Cho HK, Lee H, Seo HS, Lee S, et al. Opsonophagocytic antibodies to serotype Ia, Ib, and III group B streptococcus among Korean infants and in intravenous immunoglobulin products. J Korean Med Sci 2017;32:737-43. https://doi.org/10.3346/jkms.2017.32.5.737
  19. Lee S, Kim HW, Kim KH. Functional antibodies to Haemophilus influenzae type b, Neisseria meningitidis, and Streptococcus pneumoniae contained in intravenous immunoglobulin products. Transfusion 2017;57:157-65. https://doi.org/10.1111/trf.13869
  20. Schuchat A. Group B streptococcus. Lancet 1999;353:51-6. https://doi.org/10.1016/S0140-6736(98)07128-1
  21. Kwatra G, Adrian PV, Shiri T, Buchmann EJ, Cutland CL, Madhi SA. Natural acquired humoral immunity against serotype-specific group B streptococcus rectovaginal colonization acquisition in pregnant women. Clin Microbiol Infect 2015;21:568.e13-21. https://doi.org/10.1016/j.cmi.2015.01.030
  22. Francois Watkins LK, McGee L, Schrag SJ, Beall B, Jain JH, Pondo T, et al. Epidemiology of invasive group B streptococcal infections among nonpregnant adults in the United States, 2008-2016. JAMA Intern Med 2019;179:479-88. https://doi.org/10.1001/jamainternmed.2018.7269
  23. Madzivhandila M, Adrian PV, Cutland CL, Kuwanda L, Schrag SJ, Madhi SA. Serotype distribution and invasive potential of group B streptococcus isolates causing disease in infants and colonizing maternalnewborn dyads. PLoS One 2011;6:e17861. https://doi.org/10.1371/journal.pone.0017861
  24. Mikolajczyk MG, Concepcion NF, Wang T, Frazier D, Golding B, Frasch CE, et al. Characterization of antibodies to capsular polysaccharide antigens of Haemophilus influenzae type b and Streptococcus pneumoniae in human immune globulin intravenous preparations. Clin Diagn Lab Immunol 2004;11:1158-64. https://doi.org/10.1128/CDLI.11.6.1158-1164.2004
  25. Takahashi Y, Ishiwada N, Hishiki H, Tanaka J, Akeda Y, Shimojo N, et al. IgG levels against 13-valent pneumococcal conjugate vaccine serotypes in non pneumococcal conjugate vaccine immunized healthy Japanese and intravenous immunoglobulin preparations. J Infect Chemother 2014;20:794-8. https://doi.org/10.1016/j.jiac.2014.08.027
  26. Adam E, Church JA. Antibody levels to Bordetella pertussis and Neisseria meningitidis in immunodeficient patients receiving immunoglobulin replacement therapy. J Clin Immunol 2015;35:213-7. https://doi.org/10.1007/s10875-015-0131-y
  27. Imbach P, Barandun S, d'Apuzzo V, Baumgartner C, Hirt A, Morell A, et al. High-dose intravenous gammaglobulin for idiopathic thrombocytopenic purpura in childhood. Lancet 1981;1:1228-31.
  28. Garcia-Lloret M, McGhee S, Chatila TA. Immunoglobulin replacement therapy in children. Immunol Allergy Clin North Am 2008;28:833-49. https://doi.org/10.1016/j.iac.2008.07.001
  29. Quinti I, Soresina A, Guerra A, Rondelli R, Spadaro G, Agostini C, et al. Effectiveness of immunoglobulin replacement therapy on clinical outcome in patients with primary antibody deficiencies: results from a multicenter prospective cohort study. J Clin Immunol 2011;31:315-22. https://doi.org/10.1007/s10875-011-9511-0
  30. Lucas M, Lee M, Lortan J, Lopez-Granados E, Misbah S, Chapel H. Infection outcomes in patients with common variable immunodeficiency disorders: relationship to immunoglobulin therapy over 22 years. J Allergy Clin Immunol 2010;125:1354-60. https://doi.org/10.1016/j.jaci.2010.02.040
  31. Radosevich M, Burnouf T. Intravenous immunoglobulin G: trends in production methods, quality control and quality assurance. Vox Sang 2010;98:12-28. https://doi.org/10.1111/j.1423-0410.2009.01226.x
  32. Uh Y, Choi SJ, Jang IH, Lee KS, Cho HM, Kwon O, et al. Colonization rate, serotypes, and distributions of macrolide-lincosamide-streptograminB resistant types of group B streptococci in pregnant women. Korean J Clin Microbiol 2009;12:174-9. https://doi.org/10.5145/KJCM.2009.12.4.174
  33. Oh CE, Jang HO, Kim NH, Lee J, Choi EH, Lee HJ. Molecular serotyping of group B streptococcus isolated from the pregnant women by polymerase chain reaction and sequence analysis. Korean J Pediatr Infect Dis 2009;16:47-53. https://doi.org/10.14776/kjpid.2009.16.1.47
  34. Hong JS, Choi CW, Park KU, Kim SN, Lee HJ, Lee HR, et al. Genital group B streptococcus carrier rate and serotype distribution in Korean pregnant women: implications for group B streptococcal disease in Korean neonates. J Perinat Med 2010;38:373-7. https://doi.org/10.1515/JPM.2010.05
  35. Edwards JM, Watson N, Focht C, Wynn C, Todd CA, Walter EB, et al. Group B streptococcus (GBS) colonization and disease among pregnant women: a historical cohort study. Infect Dis Obstet Gynecol 2019;2019:5430493. https://doi.org/10.1155/2019/5430493
  36. Zhu Y, Huang J, Lin XZ, Chen C. Group B streptococcus colonization in late pregnancy and invasive infection in neonates in China: a population-based 3-year study. Neonatology 2019;115:301-9. https://doi.org/10.1159/000494133
  37. Norrby-Teglund A, Haque KN, Hammarstrom L. Intravenous polyclonal IgM-enriched immunoglobulin therapy in sepsis: a review of clinical efficacy in relation to microbiological aetiology and severity of sepsis. J Intern Med 2006;260:509-16. https://doi.org/10.1111/j.1365-2796.2006.01726.x
  38. Romero-Steiner S, Frasch CE, Carlone G, Fleck RA, Goldblatt D, Nahm MH. Use of opsonophagocytosis for serological evaluation of pneumococcal vaccines. Clin Vaccine Immunol 2006;13:165-9. https://doi.org/10.1128/CVI.13.2.165-169.2006
  39. Baker CJ, Carey VJ, Rench MA, Edwards MS, Hillier SL, Kasper DL, et al. Maternal antibody at delivery protects neonates from early onset group B streptococcal disease. J Infect Dis 2014;209:781-8. https://doi.org/10.1093/infdis/jit549
  40. Dangor Z, Kwatra G, Izu A, Adrian P, Cutland CL, Velaphi S, et al. Correlates of protection of serotype-specific capsular antibody and invasive group B streptococcus disease in South African infants. Vaccine 2015;33:6793-9. https://doi.org/10.1016/j.vaccine.2015.10.019