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A diagnostic method for herpes simplex keratitis by simultaneous measurement of viral DNA and virus-specific secretory IgA in tears: an evaluation

  • Clinical Investigation
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Abstract

Purpose

We performed simultaneous measurement of herpes simplex virus (HSV) DNA by real-time polymerase chain reaction (real-time PCR) and of HSV-specific secretory IgA antibody (HSV-sIgA) by enzyme-linked immunosorbent assay (ELISA) in tears obtained using Schirmer strips in order to investigate its diagnostic efficacy for herpes simplex keratitis (HSK).

Methods

A total of 59 affected eyes from 59 patients with clinically suspected HSK (HSK group) and 23 eyes from 23 healthy volunteers (control group) were enrolled in this study. The HSK group was divided into five subgroups: dendritic/geographic keratitis, disciform keratitis, necrotizing keratitis, atypical keratitis, and others. The tear samples were taken using Schirmer strips to determine the HSV DNA and HSV-sIgA levels.

Results

The overall sensitivity and specificity were 55.8 and 100 % for HSV DNA and 49.2 and 82.6 % for HSV-sIgA. The HSV DNA levels in the disciform keratitis subgroup (median, 3.1 × 102 copies/sample) were significantly lower than those in the dendritic/geographic keratitis subgroup (median, 2.3 × 104 copies/sample) (P < 0.05, Mann-Whitney test). The HSV-sIgA levels in the disciform keratitis subgroup (median, 50.0 NU/ml) were significantly higher than those in the control group (median, 18.0 NU/ml) (P < 0.05, Steel test). The positive and negative predictive values obtained by simultaneous measurement of HSV DNA and sIgA were 90.9 and 61.3 %, respectively.

Conclusion

The combination of laboratory detection of HSV DNA by real-time PCR and of HSV-sIgA by ELISA using tear samples enables higher reliability in diagnosing the subgroups of HSK, although the HSV DNA value is relatively lower in disciform HSK than in dendritic/geographic HSK.

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References

  1. Kaufman HE, Rayfield MA. Viral conjunctivitis and keratitis: herpes simplex virus. In: Kaufman HE, McDonald MB, Barron BA, Waltman SR, editors. The cornea. New York: Churchill Livingston; 1988. p. 299–321.

    Google Scholar 

  2. Pavan-Langston D. Herpetic infections. In: Smolin G, Thoft RA, editors. The cornea. 3rd ed. Boston: Little Brown; 1994. p. 183–215.

    Google Scholar 

  3. Shimomura Y, The Ocular Herpetic Infection Research Group. New criteria of diagnosis for herpetic epithelial keratitis [in Japanese]. Ganka Ophthalmol. 2002;44:739–42.

    Google Scholar 

  4. Shen YC, Wang CY, Chen YC, Lee YF. Progressive herpetic linear endotheliitis. Cornea. 2007;26:365–7.

    Article  PubMed  Google Scholar 

  5. Inoue Y. Review of clinical and basic approaches to corneal endotheliitis. Cornea. 2014;33(Suppl 11):S3–8.

    Article  PubMed  Google Scholar 

  6. Farhatullah S, Kaza S, Athmanathan S, Garg P, Reddy SB, Sharma S. Diagnosis of herpes simplex virus-1 keratitis using Giemsa stain, immunofluorescence assay, and polymerase chain reaction assay on corneal scrapings. Br J Ophthalmol. 2004;88:142–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Yamamoto S, Shimomura Y, Kinoshita S, Nishida K, Yamamoto R, Tano Y. Detection of herpes simplex virus DNA in human tear film by the polymerase chain reaction. Am J Ophthalmol. 1994;117:160–3.

    Article  CAS  PubMed  Google Scholar 

  8. Madhavan HN, Priya K, Malathi J, Joseph PR. Laboratory methods in the detection of herpes simplex virus (HSV) in keratitis: a 9-year study including polymerase chain reaction during last 4 years. Indian J Pathol Microbiol. 2003;46:109–12.

    CAS  PubMed  Google Scholar 

  9. Khodadoost MA, Sabahi F, Behroz MJ, Roustai MH, Saderi H, Amni-Bavil-Olyaee S, et al. Study of a polymerase chain reaction-based method for detection of herpes simplex virus type 1 DNA among Iranian patients with ocular herpetic keratitis infection. Jpn J Ophthalmol. 2004;48:328–32.

    Article  CAS  PubMed  Google Scholar 

  10. Pramod NP, Dhevahi E, Sudhamathi K, Kannan K, Thyagarajan SP. Tear secretory IgA: evaluation of usefulness as a diagnostic marker in herpetic keratitis. Ocul Immunol Inflamm. 1999;7:61–7.

    Article  CAS  PubMed  Google Scholar 

  11. Fox PD, Khaw PT, McBride BW, McGill JI, Ward KA. Tear and serum antibody levels in ocular herpetic infection: diagnostic precision of secretory IgA. Br J Ophthalmol. 1986;70:584–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Harada N, Shoji J, Inada N, Kato H, Sawa M. Evaluation of herpes simplex virus specific IgA anti-body in tears of patients with herpes simplex keratitis [in Japanese]. Ganka. 2010;52:1819–27.

    Google Scholar 

  13. Sawa M. Development of non-invasive clinical examination methods for the anterior segment of the eye and their clinical significance [in Japanese]. Nihon Ganka Gakkai Zasshi. 2011;115:177–211.

    PubMed  Google Scholar 

  14. Fukuda M, Deai T, Hibino T, Higaki S, Hayashi K, Shimomura Y. Quantitative analysis of herpes simplex virus genome in tears from patients with herpetic keratitis. Cornea. 2003;22(Suppl 7):S55–60.

    Article  PubMed  Google Scholar 

  15. Kakimaru-Hasegawa A, Kuo CH, Komatsu N, Komatsu K, Miyazaki D, Inoue Y. Clinical application of real-time polymerase chain reaction for diagnosis of herpetic diseases of the anterior segment of the eye. Jpn J Ophthalmol. 2008;52:24–31.

    Article  PubMed  Google Scholar 

  16. Pedersen B, Møller Andersen S, Klauber A, Ottovay E, Prause JU, Zhong CU, et al. Secretory IgA specific for herpes simplex virus in lacrimal fluid from patients with herpetic keratitis: a possible diagnostic parameter. Br J Ophthalmol. 1982;66:648–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Tomasi TB Jr, Larson L, Challacombe S, McNabb P. Mucosal immunity: the origin and migration patterns of cells in the secretory system. J Allergy Clin Immunol. 1980;65:12–9.

    Article  PubMed  Google Scholar 

  18. Shoji J, Inada N, Saito K, Takaura N, Iwasaki Y, Sawa M. Immunohistochemical study on follicular dendritic cell of conjunctiva-associated lymphoid tissue. Jpn J Ophthalmol. 1998;42:1–7.

    Article  CAS  PubMed  Google Scholar 

  19. Sakimoto T, Shoji J, Inada N, Saito K, Iwasaki Y, Sawa M. Histological study of conjunctiva-associated lymphoid tissue in mouse. Jpn J Ophthalmol. 2002;46:364–9.

    Article  CAS  PubMed  Google Scholar 

  20. Knop E, Knop N, Claus P. Local production of secretory IgA in the eye-associated lymphoid tissue (EALT) of the normal human ocular surface. Invest Ophthalmol Vis Sci. 2008;49:2322–9.

    Article  PubMed  Google Scholar 

  21. Knop E, Knop N. The role of eye-associated lymphoid tissue in corneal immune protection. J Anat. 2005;206:271–85.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Inoue T, Inoue Y, Hayashi K, Yoshida A, Nishida K, Shimomura Y, et al. Topical administration of HSV gD-IL-2 DNA is highly protective against murine herpetic stromal keratitis. Cornea. 2002;21:106–10.

    Article  PubMed  Google Scholar 

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Acknowledgments

We wish to thank Mrs. Akiko Tomioka (Department of Visual Sciences, Division of Ophthalmology, Nihon University School of Medicine) and Mr. Hiroshi Kato for their expert technical assistance.

Conflicts of interest

J. Shoji, Lecture fees (Santen Pharmaceutical); T. Sakimoto, None; N. Inada, None; Y. Kamei, None; M. Matsubara, None; E. Takamura, None; M. Sawa, Grant (Santen Pharmaceutical), P (Copyright for Ishihara Test for Colour Deficiency).

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Authors and Affiliations

  1. Division of Ophthalmology, Department of Visual Sciences, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi-ku, Tokyo, 173-8610, Japan

    Jun Shoji, Tohru Sakimoto, Noriko Inada & Mitsuru Sawa

  2. Department of Ophthalmology, Tokyo Women’s Medical University Medical Center East, Tokyo, Japan

    Yuko Kamei & Masao Matsubara

  3. Department of Ophthalmology, Tokyo Women’s Medical University School of Medicine, Tokyo, Japan

    Etsuko Takamura

Authors
  1. Jun Shoji
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  2. Tohru Sakimoto
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  3. Noriko Inada
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  4. Yuko Kamei
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  5. Masao Matsubara
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  6. Etsuko Takamura
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  7. Mitsuru Sawa
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Correspondence to Jun Shoji.

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Shoji, J., Sakimoto, T., Inada, N. et al. A diagnostic method for herpes simplex keratitis by simultaneous measurement of viral DNA and virus-specific secretory IgA in tears: an evaluation. Jpn J Ophthalmol 60, 294–301 (2016). https://doi.org/10.1007/s10384-016-0448-y

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  • DOI: https://doi.org/10.1007/s10384-016-0448-y

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