J.ophthalmol.(Ukraine).2022;4:49-57.
http://doi.org/10.31288/oftalmolzh202244957
Received: 19.05.2022; Accepted: 14.07.2022; Published on-line: 24.08.2022
Recurrent ocular toxoplasmosis infection in a patient with a selective deficiency of NK T-cells and cytotoxic СD8+ T-cells associated with a genetic folate cycle deficiency
D. V. Maltsev, O. O. Hurzhii
1 Research Institute of Experimental and Clinical Medicin, Bogomolets National Medical University; Kyiv (Ukraine)
2 Visium Clinic; Kyiv (Ukraine)
TO CITE THIS ARTICLE: Maltsev DV, Hurzhii OO. Recurrent ocular toxoplasmosis infection in a patient with a selective deficiency of NK T-cells and cytotoxic СD8+ T-cells associated with a genetic folate cycle deficiency. J.ophthalmol.(Ukraine).2022;4:49-57. http://doi.org/10.31288/oftalmolzh202244957
This paper reports a case of recurrent toxoplasmic chorioretinitis in a patient with cellular immunodeficiency. A 37-year-old male presented to an ophthalmologist with complaints of reduced visual acuity and discomfort in his left eye. He had a history of at least two episodes of acute posterior uveitis without identifying the cause of inflammation. An ophthalmoscopic evaluation revealed a scar in the right retina and signs of acute vitritis and chorioretintis surrounding a scar in the left retina. Paired serology confirmed a diagnosis of toxoplasmosis. A deficiency of NK T-cells and cytotoxic СD8+ T-cells was noted, but there was no evidence of secondary immunosuppression. The Primary Immunodeficiency (PID) panel providing sequencing of 208 genes did not find a disease. A test for genetic folate cycle deficiency was conducted due to persistent hyperhomocysteinemia. The genetic testing identified two pathogenic polymorphisms in the genes coding for folic acid cycle enzymes (heterozygous MTHFR A1298C and homozygous MTRR A66G), which was believed to be associated with a cellular immunity, taking into account the data on immunosuppression and opportunistic infections in the presence of a genetic folate cycle deficiency.
The following treatment was administered: spiramycin, 3.0 mln units orally daily for 14 days, to inhibit toxoplasma; recombinant human alpha2 interferon (3.0 mln units intramuscularly every other day for a month) and oxodihydroacridinylacetate sodium 2.0 mln units intramuscularly every other day for a month, with switching between this agent and interferon, to compensate for a deficiency of NK T-cells and СD8+ T-cells; and daily peribulbar injection of betamethasone 4 mg/mL for 3 days. The first signs of improved visual acuity were seen at day 8, and a complete restoration of vision in the left eye was achieved by the end of one month of combination therapy. In addition, the patient received three one-month courses of alpha2 interferon for compensation of cellular immunodeficiency over two years which prevented a recurrence of toxoplasmosis.
Keywords: toxoplasmic chorioretinitis, vitritis, immunodeficiency, immunotherapy
References
1.Fabiani S, Caroselli C, Menchini M, et al. Ocular toxoplasmosis, an overview focusing on clinical aspects. Acta Trop. 2022 Jan;225:106180.
2.Karanovic D, Michelow IC, Hayward AR, et al. Disseminated and Congenital Toxoplasmosis in a Mother and Child With Activated PI3-Kinase delta Syndrome Type 2 (APDS2): Case Report and a Literature Review of Toxoplasma Infections in Primary Immunodeficiencies. Front Immunol. 2019 Feb 14;10:77.
3.de-la-Torre A, Gómez-Marín J. Disease of the Year 2019: Ocular Toxoplasmosis in HIV-infected Patients. Ocul Immunol Inflamm. 2020 Oct 2;28(7):1031-1039.
4.Srivastava S, Kundu A, Sivakumar H, et al. A case of Toxoplasma gondii and Strongyloides stercoralis coinfection in an immunocompromised patient. Infect. Disord Drug Targets. 2022 Feb 18. Online ahead of print.
5.Parasram M., Arevalo-Perez J. Cerebral toxoplasmosis in a patient with multiple myeloma. Surg Neurol Int. 2022 May 6;13:191.
6.Gioia LV, Bonsall D, Moffett K, et al. Bilateral maculopathy in a patient with ataxia telangiectasia. J AAPOS. 2016 Feb;20(1):85-8.
7.Nelwan EJ, Shakinah S, Clarissa G, et al. Rare cardiac complication of toxoplasmosis in immunocompetent host. IDCases. 2022 Jun 15; 29: e01533.
8.Stokkermans TJ, Havens SJ. Toxoplasma Retinochoroiditis. [Updated 2022 Mar 16]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing.
9.Zhang K, Lin G, Han Y, Li J. Serological diagnosis of toxoplasmosis and standardization. Clin Chim Acta. 2016 Oct 1;461:83-9.
10.Chan Y, Martin D, Mace KE, et al. Multiplex Serology for Measurement of IgG Antibodies Against Eleven Infectious Diseases in a National Serosurvey: Haiti 2014-2022. Front Public Health. Jun 9; 10: 897013.
11.Borges HDS, Oliveira-Scussel ACM, Oliveira ÂMM, et al. Comparative Detection of Immunoglobulin Isotypes and Subclasses against Toxoplasma gondii Soluble Antigen in Serum and Colostrum Samples from Puerperal Women. Int J Environ Res Public Health. 2022 Jun 29; 19(13): 7953.
12.Babekir A., Mostafa S., Minor R.C. et al. The Association of Toxoplasma gondii IgG and Liver Injury in US Adults. Int J Environ Res Public Health. 2022 Jun 19;19(12):7515.
13.Combe CL, Curiel TJ, Moretto MM, Khan IA. NK cells help to induce CD8(+)-T-cell immunity against Toxoplasma gondii in the absence of CD4(+) T cells. Infect Immun. 2005 Aug;73(8):4913-21.
14.Khan I.A., Moretto M. Immune responses to Toxoplasma. Curr Opin Immunol. 2022 Jul 1 ;77: 102226.
15.Sana M, Rashid M, Rashid I, et al. Immune response against toxoplasmosis-some recent updates RH: Toxoplasma gondii immune response. Int J Immunopathol Pharmacol. Jan-Dec 2022; 36: 3946320221078436.
16.Sasai M, Yamamoto M. Anti-Toxoplasma host defense systems and the parasitic counterdefense mechanisms. Parasitol Int. 2022 Aug;89:102593.
17.Li WX, Cheng F, Zhang AJ, et al. Folate Deficiency and Gene Polymorphisms of MTHFR, MTR and MTRR Elevate the Hyperhomocysteinemia Risk. Clin Lab. 2017 Mar 1;63(3):523-533.Crossref
18.Zhang L, Yuan XF, Li Q, et al. Correlation between Serum Homocysteine Level, MTHFR Gene Polymorphism and Patients with Hematological Diseases Complicated with Coronary Heart Disease. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2022 Feb;30(1):305-309
19.Van der Weyden MB, Hayman RJ, et al. Folate-deficient human lymphoblasts: changes in deoxynucleotide metabolism and thymidylate cycle activities. Eur J Haematol. 1991 Aug;47(2):109-14.
20.Partearroyo T, Úbeda N, Montero A. Vitamin B(12) and folic acid imbalance modifies NK cytotoxicity, lymphocytes B and lymphoprolipheration in aged rats. Nutrients. 2013 Nov 26;5(12):4836-48.
21.Courtemanche C, Elson-Schwab I, Mashiyama ST. Folate deficiency inhibits the proliferation of primary human CD8+ T lymphocytes in vitro. J Immunol. 2004 Sep 1;173(5):3186-92.
22.Abe I, Shirato K, Hashizume Y. Folate-deficiency induced cell-specific changes in the distribution of lymphocytes and granulocytes in rats. Environ Health Prev Med. 2013 Jan;18(1):78-84.
23.Troen AM, Mitchell B, Sorensen B. Unmetabolized folic acid in plasma is associated with reduced natural killer cell cytotoxicity among postmenopausal women. J Nutr. 2006 Jan;136(1):189-94.
24.Bhatnagar N, Wechalekar A, McNamara C. Pancytopenia due to severe folate deficiency. Intern Med J. 2012 Sep;42(9):1063-4.
25.Maltsev DV, Gorbenko VYu. [HSV-2-associated transverse sacral myelitis in a patient with selective natural killer cell deficiency: a case report]. Ukr Neurol Zh. 2018; №2: 74–80. Ukrainian.
26.Maltsev DV. Features of folate cycle disorders in children with ASD. Bangladesh J Med Sci. 2020; Vol. 19(4): 737–742.
27.Maltsev DV. [The results of the study of the microbial spectrum in children with autism spectrum disorders associated with genetic deficiency of the folate cycle]. Choloviche zdorov’ia, genderna ta psyhosomatychna medycyna. 2021; № 1-2: 26–39. Ukrainian.
28.Yamagiwa S, Matsuda Y, Ichida T, et al. Sustained response to interferon-alpha plus ribavirin therapy for chronic hepatitis C is closely associated with increased dynamism of intrahepatic natural killer and natural killer T cells. Hepatol Res. 2008 Jul;38(7):664-72.
29.Okumura A, Ishikawa T, Maeno T, et al. Changes in natural killer T cells subsets during therapy in type C hepatitis and hepatocellular carcinoma. Hepatol Res. 2005 Aug;32(4):213-7.
30.Maltsev DV. [New discoveries in the mechanisms of interferon-dependent control of latent alpha-herpes virus in sensory ganglia and the experience of using an inducer of interferon overin for the restoration of such control]. Choloviche zdorov’ia, genderna ta psyhosomatychna medycyna. 2018; № 2: 19–32. Ukrainian.
31.Skariah S, Sultan AA., Mordue DG. IFN-induced cell-autonomous immune mechanisms in the control of intracellular protozoa. Parasitol Res. 2022 Jun;121(6):1559-1571.
32.Maltsev DV, Hurzhii OO. Toxoplasma chorioretinitis in primary myeloperoxidase MPO deficiency: A case report. J Ophthalmol (Ukraine). 2019; Vol. 4: 75-81.
33.Maltsev DV, Hurzhii OO. ANA-associated uveitis in the presence of reactivated HHV-7 infection in a patient with MBL deficiency. J Ophthalmol. (Ukraine). 2020; Vol. 6 (497): 64–9.
34.Maltsev DV. A case of persistent recurrent herpes zoster ophthalmicus in a patient with primary mannose binding lectin deficiency. J Ophthalmol (Ukraine). 2021; Vol. 6 (503): 64–68.
35.Shachor J, Shneyour A., Radnay J. et al. Toxoplasmosis in a patient with common variable immunodeficiency. Am J Med Sci. May-Jun 1984;287(3):36-8.
36.Liu X, Zhou K, Yu D, et al. A delayed diagnosis of X-linked hyper IgM syndrome complicated with toxoplasmic encephalitis in a child: A case report and literature review. Medicine (Baltimore). 2017 Dec;96(49):e8989.
37.Le Deist F, Hivroz C, Partiseti M, et al. A primary T-cell immunodeficiency associated with defective transmembrane calcium influx. Blood. 1995 Feb 15;85(4):1053-62.
38.Yong PF, Post FA, Gilmour KC, et al. Cerebral toxoplasmosis in a middle-aged man as first presentation of primary immunodeficiency due to a hypomorphic mutation in the CD40 ligand gene. J Clin Pathol. 2008 Nov;61(11):1220-2.
39.Sasson SC, Davies S, Chan R, et al. Cerebral toxoplasmosis in a patient with myasthenia gravis and thymoma with immunodeficiency/Good's syndrome: a case report. BMC Infect Dis. 2016 Aug 30;16(1):457.
40.Kalogeropoulos D, Sakkas H, Mohammed B, et al. Ocular toxoplasmosis: a review of the current diagnostic and therapeutic approaches. Int Ophthalmol. 2022 Jan;42(1):295-321.
41.McDermott DH, Heusinkveld LE, Zein WM, et al. Case Report: Ocular toxoplasmosis in a WHIM syndrome immunodeficiency patient. F1000Res. 2019 Jan 2;8:2.
42.Meyer L, Magierowska M, Hubert JB, et al. CCR5 delta32 deletion and reduced risk of toxoplasmosis in persons infected with human immunodeficiency virus type 1. The SEROCO-HEMOCO-SEROGEST Study Groups. J Infect Dis. 1999 Sep;180(3):920-4.
Disclosures
Corresponding Author: Maltsev D.V., email: dmaltsev@ukr.net
Conflict of Interests: The author certifies that there is no conflict of interest that could influence his opinion regarding the subject matter or materials described and discussed in this manuscript.