J.ophthalmol.(Ukraine).2020;3:23-28.

http://doi.org/10.31288/oftalmolzh202032328

Received: 20 February 2020; Published on-line: 24 June 2020


ICAM-1 expression on blood lymphocytes in patients with stromal herpes keratitis at different periods of disease

N.I. Khramenko, T.B. Gaidamaka, G.I. Drozhzhyna, L.N. Velychko, A.V. Bogdanova

SI “The Filatov Institute of Eye Diseases and Tissue Therapy of the National Academy of Medical Sciences of Ukraine”;  Odesa (Ukraine)

E-mail: khramenkon@gmail.com

TO CITE THIS ARTICLE: Khramenko N.I., Gaidamaka T.B., Drozhzhyna G.I., Velychko L.N., Bogdanova A.V. ICAM-1 expression on blood lymphocytes in patients with stromal herpes keratitis at different periods of disease. J.ophthalmol.(Ukraine).2020;3:23-28. http://doi.org/10.31288/oftalmolzh202032328


Background: In spite of intensive antiviral and anti-inflammatory therapy, recovery is not always achieved in patients with stromal herpes keratitis (HK). Inflammatory host response and a complex immune defense system play a major role among the numerous factors involved in herpes simplex virus (HSV) reactivation from latency. Inter-Cellular Adhesion Molecule (ICAM-1) is best known for its role in mediating leukocyte adhesion to endothelial cells and guiding leukocytes across the vascular wall. This factor is considered as an inflammatoty biomarker. Given that signs of inflammation in recurrent stromal keratitis are not always clinically manifest, additional diagnostics is required for well-founded anti-inflammatory treatment decisions.

Purpose: To assess the expression of ICAM-1 on blood lymphocytes in patients with primary stromal HK and patients experiencing one or more annual recurrences of stromal HK at different periods of disease.

Material and Methods: Fifty-six patients (age, 20 to 60 years) who had been consulted and treated for stromal HK at the Department of Corneal Disorders and 27 systemically and ophthalmologically healthy controls (age, 20 to 64 years) were involved in the study. Of the 56 patients, 10 had primary HK with disease duration ≤ 6 months, and 46 had recurrent HK with disease duration ≤ 20 years. Individuals experiencing more than one recurrence annually were defined as those with frequent recurrences. Absolute and relative ICAM-1 expression on lymphocytes was examined. Immunohistochemical staining with monoclonal antibodies for ICAM-1 (CD-54) was performed.

Results: The median and interquartile range of the absolute expression level of ICAM, and the mean (standard deviation) of the relative ICAM-1 expression on peripheral blood lymphocytes in controls were 113.3 cells/μL, 87-168 cells/μL, and 8.5 (2.0)%, respectively. Total patients with HSV keratitis exhibited significantly (4.0 times; p = 0.0001) higher absolute counts of peripheral blood lymphocytes expressing ICAM-1 (median, 450 cells/μL; interquartile range, 326-552 cells/μL) compared to controls. In patients in remission with recurrent stromal HK, the relative ICAM-1 expression did not depend on the frequency of recurrence and was 23.4 (4.0)%, which was 2.8 times higher than in controls (p = 0.000). Patients with active keratitis experiencing one recurrence annually had practically the same  relative ICAM-1 expression as those experiencing more than one recurrence annually, with a mean value of 26.8 (4.6)%. This was 3.3 times higher than in controls (p = 0.000) and 15.8% higher than in patients in remission with recurrent HK (23.4 (4.1)%; p = 0.001). The relative ICAM-1 expression in patients with primary keratitis was 16% higher than in patients on remission, and there was no significant difference in this parameter between patients with primary keratitis and patients with active recurrent HK.

Conclusion: The absolute and relative ICAM-1 expression on peripheral blood lymphocytes in patients with HSV keratitis was 4.0 times and 3.1 times, respectively, higher than in controls. The relative expression of ICAM on lymphocytes in patients with active recurrent disease and in patients with primary keratitis was 16% higher than in patients on remission.

Keywords: recurrent herpes keratitis, ICAM-1, lymphocytes


References 

1.Pflugfelder SC, Stern M, Zhang S, Shojaei A. LFA-1/ICAM-1 Interaction as a Therapeutic Target in Dry Eye Disease. J Ocul Pharmacol Ther. 2017 Jan/Feb;33(1):5-12.

Crossref  PubMed

2.Roebuck KA, Finnegan A. Regulation of intercellular adhesion molecule-1 (CD54) gene expression. J Leukoc Biol. 1999 Dec;66(6):876-88.

Crossref  PubMed  

3.Johnson LA, Clasper S, Holt AP, Lalor PF, Baban D, Jackson DG. An inflammation-induced mechanism for leukocyte transmigration across lymphatic vessel endothelium. J Exp Med. 2006 Nov 27;203(12):2763-77. 

Crossref  PubMed

4.Wiesolek HL, Bui TM, Lee JJ, Dalal P, Finkielsztein A, Batra A, et al. ICAM-1 functions as an efferocytosis receptor in inflammatory macrophages. Am J Pathol. 2020 Apr;190(4):874-85. doi: 10.1016/j.ajpath.2019.12.006.

Crossref  PubMed

5.Hocaoglu-Emre FS, Saribal D, Yenmis G, Guvenen G. Vascular Cell Adhesion Molecule 1, Intercellular Adhesion Molecule 1, and Cluster of Differentiation 146 Levels in Patients with Type 2 Diabetes with Complications. Endocrinol Metab (Seoul). 2017 Mar;32(1):99-105.

Crossref  PubMed

6.Shtein RM, Garcia DD, Musch DC, Elner VM. HSV keratitis: histopathologic predictors of corneal allograft complications. Trans Am Ophthalmol Soc. 2008;106:161-8; discussion 168-70.

7.van de Stolpe A, van der Saag PT. Intercellular adhesion molecule-1. J Mol Med (Berl). 1996 Jan;74(1):13-33. 

Crossref  PubMed

8.Brankin B, Hart MN, Cosby SL, Fabry Z, Allen IV. Adhesion molecule expression and lymphocyte adhesion to cerebral endothelium: effects of measles virus and herpes simplex 1 virus. J Neuroimmunol. 1995 Jan;56(1):1-8.

Crossref 

9.Zhang T, Wang N, Lou B, Yuan Z. The role of adhesion molecules ICAM-1 and VCAM-1 in herpes simplex keratitis. Eye Sci. 2011 Jun;26(2):61-4. 

10.Elner VM, Dutt S, Pavilack MA, Sugar A, Foster CS, Elner SG. Intercellular adhesion molecule-1 (ICAM-1) and HLA-DR antigens in herpes keratitis. Ophthalmology. 1992 Sep;99(9):1400-7. 

Crossref  

11.Shtein RM, Garcia DD, Musch DC, Elner VM. Herpes simplex virus keratitis: histopathologic inflammation and corneal allograft rejection. Оphthalmology. 2009 Jul;116(7):1301-5.

Crossref  PubMed

12.Gluzman DF, Skliarenko LM, Nadgornaia VA, Kriachok IA.  [Immunocytochemistry in tumor diagnosis]. Kyiv: Morion;2003. Russian. 

13.Toma HS, Murina AT, Areaux RG Jr, Neumann DM, Bhattacharjee PS, Foster TP, Kaufman HE, Hill JM. Ocular HSV-1 latency, reactivation and recurrent disease. Semin Ophthalmol. 2008 Jul-Aug;23(4):249-73.

Crossref  PubMed

14.Gaidamaka TB, Chaura AG, Khramenko NI. [State of the autonomous nervous system and psychoemotional status in patients with herpetic keratitis]. Oftalmol Zh. 2009;1-2:70-2. Ukrainian.

Crossref  

15.Khramenko NI, Ponomarchuk VS, Drozhzhyna GI. [State of the autonomous nervous system and effect of the latter on regional ocular hemodynamics in patients with different courses of recurrent herpetic keratitis]. Oftalmol Zh. 2013;6:5-11. Ukrainian.

16.Kim YC, Bang D, Lee S, Lee KH. The effect of herpesvirus infection on the expression of cell adhesion molecules on cultured human dermal microvascular endothelial cells. J Dermatol Sci. 2000 Sep;24(1):38-47.

Crossref  

17.Jung HW, Jung CR, Choi BK, Vinay DS, Hill JM, Gebhardt BM, Kwon BS.Herpesvirus infection of ICAM-1-deficient mice. Curr Eye Res. 2004 Aug-Sep;29(2-3):201-8.

Crossref  PubMed

18.Noisakran S, Härle P, Carr DJ. ICAM-1 is required for resistance to herpes simplex virus type 1 but not interferon-alpha1 transgene efficacy. Virology. 2001 Apr 25;283(1):69-77.

Crossref  PubMed

 

The authors certify that they have no conflicts of interest in the subject matter or materials discussed in this manuscript.