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Table of Contents
ORIGINAL ARTICLE
Year : 2022  |  Volume : 21  |  Issue : 1  |  Page : 37-40

The role of retinol-binding protein 4 in women infected with Toxoplasma gondii


1 Department of Microbiology, College of Medicine, Al-Mustansiriya University, Baghdad, Iraq
2 Department of Obstetrics and Gynecology, College of Medicine, Al-Mustansiriya University, Baghdad, Iraq

Date of Submission25-Aug-2021
Date of Decision13-Sep-2021
Date of Acceptance13-Sep-2021
Date of Web Publication30-Jun-2022

Correspondence Address:
Asst.. Prof. Azhar Hatif Al-Kuraishi
Department of Microbiology, College of Medicine, Al-Mustansiriya University, Bagdad
Iraq
Asst.. Prof. Fatin Shallal Farhan
Department of Obstetrics and Gynecology, College of Medicine, Al-Mustansiriya University, Bagdad
Iraq
Mr. Rajaa Abd Ali
Department of Microbiology, College of Medicine, Al-Mustansiriya University, Bagdad
Iraq
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mj.mj_20_21

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  Abstract 

Background: Ocular toxoplasmosis mainly affected people in the second to fifth decades, as a result of acute or reactivate congenital or postnatally acquired infection. Retinol binding protein 4 (RBP4) is a protein transporter for retinol (Vitamin A) from the liver to peripheral tissue. Because of its function in vision RBP4 has become a target for ophthalmology research. Objectives: Identification of the role of RBP4 parameter in women infected with acute toxoplasmosis. Methodology: One hundred and fifteen blood samples were collected from aborted women, who were suspected of having toxoplasmosis for the period October 2020 to March 2021; in addition, 25 samples were collected from apparently healthy women to use as a healthy control group. All sera were investigated for the presence of anti-Toxoplasma IgM, IgA and IgG antibodies, all IgG-positive samples (50 samples) were neglected. IgM and IgA-positive samples (40 serum samples) out of 115 samples were used as toxoplasmosis case group (acute toxoplasmosis), while the negative IgM, IgA, and IgG aborted women samples were used as aborted nontoxoplasmic control group (25 serum samples). The samples from healthy women that gave negative results for the three antibodies were used as the healthy control group. Results: The RBP4 serum level was reflected a significant decrease 1.84 ± 0.44 ng/ml in aborted toxoplasmic cases when compared with aborted nontoxoplasmic and healthy control groups; 2.85 ± 0.60, 3.90 ± 0.62 ng/ml, respectively. Conclusion: There was a highly significant decrease in RBP4 serum levels in acute toxoplasmosis-infected women. This decreasing may be one of the indirect effects of Toxoplasma gondii infection on their hosts. Furthermore, this level can be used as aid test for the detection for toxoplasmosis.

Keywords: IgA, IgM, retinol-binding protein 4, Toxoplasma gondii infection


How to cite this article:
Ali RA, Al-Kuraishi AH, Farhan FS. The role of retinol-binding protein 4 in women infected with Toxoplasma gondii. Mustansiriya Med J 2022;21:37-40

How to cite this URL:
Ali RA, Al-Kuraishi AH, Farhan FS. The role of retinol-binding protein 4 in women infected with Toxoplasma gondii. Mustansiriya Med J [serial online] 2022 [cited 2022 Aug 16];21:37-40. Available from: https://www.mmjonweb.org/text.asp?2022/21/1/37/349306


  Introduction Top


Toxoplasma gondii is unique parasite among the apicomplexan group because it can invade and multiply in any nucleated cells of virtually all warm-blooded animals, especially, macrophages, muscle cells, epithelial cells, and neurons.[1] Approximately, after 1–3 weeks of infection, the antibodies start to evolve when the tachyzoite begins to localize in cardiac, skeletal muscles, retina, and parenchyma of the brain, as tissue cysts, and disappear from visceral tissues.[2] Wilder was demonstrated T. gondii in adult eyes in 1952.[3] Uveitis is a major cause and can explain more than 60% of chorioretinitis cases in several countries.[4] Ocular toxoplasmosis mainly affected people in the second to fifth decades, as a result of acute or reactivate congenitally or postnatally acquired infection.[5] The clinical image and ocular toxoplasmosis damage depend on the patient's age, location, size, and severity of retinochoroiditis inflammation. Ocular symptoms are dependent on the position of a retinal lesion and include reduced vision, floats, vision blurred, eye redness, and photophobia.[6]

Retinol-binding protein 4 (RBP4) is a protein transporter for retinol (Vitamin A) from the liver to peripheral tissue. RBP4 is composed principally by hepatocytes as well as, is produced in a smaller amount by adipocytes of the adipose tissue and serves as a signal to surrounding cells when plasma glucose is low.[7]. The RBP-retinol complex interacts with transthyretin in plasma, which inhibits its loss via the glomeruli in the kidney.[8] Previous studies have shown that RBP4 is implicated in many human conditions, including ocular disease and impaired vision.[9] Because of its function in vision RBP4 has become a target for ophthalmology research.[10]

Hence, both the infection with toxoplasmosis and deficiency in RBP4 has an effect on eyesight. Therefore, this study was built to clarify the role of RBP4 on toxoplasmosis on one hand, and whether RBP4 level affected (elevation or decline) during toxoplasmosis on the other hand.


  Methodology Top


One hundred and fifteen blood samples were collected from aborted women, who were suspected of having toxoplasmosis for the period from October 2020 to March 2021, who had attended at the Obstetrics and Gynecology Department of Al-Yarmouk Teaching Hospital, Kamal Al-Samaraie Hospital, and Private Laboratories in Baghdad City. In addition, 25 samples were collected from apparently-healthy women to use as healthy control group, and hence that the total number of samples included in the study is one hundred and forty samples. All sera were investigated for the presence of anti-Toxoplasma IgM and IgG antibodies by (Bio-Medical Com., Ltd, Beijing, China) Rapid Test-Cassette, as well as investigating them also with anti-Toxoplasma IgM, IgG ELISA assay (Foresight. Com., USA) and anti-Toxoplasma IgA ELISA assay (Mybiosource. Com., USA). All positive IgG-Toxoplasma antibodies were neglected (50 samples) because the study was limited only to a recent infection with toxoplasmosis. IgM- and IgA-positive samples (40 samples) were used as toxoplasmosis case group, while the negative IgM, IgG, and IgA aborted women samples (25 samples) were used as aborted control group. In addition, 25, samples from healthy women that give negative results for these tests were used as healthy control group. Then, the RBP4 level was measured using an ELISA kit (Elabscience. Com., USA), which based on sandwich enzyme-linked immune-sorbent assay technology, in each group.

Finally, statistical analysis of data was carried out using SPSS-27. Receiver Operating Characteristic (ROC) curve was applied to determine the application of any parameter as a diagnostic or disease screening tool, and ability to select a Cut-off value that is optimum sensitive and specific for diagnosis.


  Results Top


For toxoplasmosis cases, 40 (34.78%) serum samples out of 115 samples gave results with anti-Toxoplasma IgM, while only 9 (22.5%) cases out of 40 samples was positive for anti-Toxoplasma IgA [Table 1]. There was a highly significant decrease in RBP4 level 1.84 ± 0.44 ng/ml (P < 0.001) in toxoplasmosis cases, when compared with aborted and healthy control groups; 2.85 ± 0.60, 3.90 ± 0.62 ng/ml, respectively, as shown in [Figure 1] and [Figure 2].
Table 1: The Types of anti-Toxoplasma gondii antibodies which detected by ELISA

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Figure 1: The distributions of retinol binding protein 4 values of women infected with Toxoplasma gondii compared with control groups

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Figure 2: The retinol binding protein 4 levels of women infected with Toxoplasma gondii compared with control groups

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The resulting ROC curve and its functional area under the curve, had shown that ELISA IgM still the best tool for the diagnosis of toxoplasmosis then another tool (RBP4) was provided from the current study as simple analytical forms working parameter for prognosis [Table 2] and [Figure 3].
Table 2: The receiver operating characteristic analysis area for selected parameters when used to diagnosis of acute toxoplasmosis as compared with nontoxoplasmosis (both aborted and healthy control groups)

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Figure 3: The receiver operating characteristic curve when use to diagnosis of acute toxoplasmosis as compared with nontoxoplasmosis (both aborted and healthy control groups)

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A comparison of each test showed that cut-off value suggested for ELISA IgM is >0.895 (100% sensitivity and 100% specificity), while RBP4 a cut-off value was <2.78 for 100% sensitivity and 100% specificity [Table 3].
Table 3: The cut-off values, sensitivities, and specificities for early detection of acute toxoplasmosis as compared with nontoxoplasmosis (both aborted and healthy control groups)

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  Discussion Top


To our knowledge, this is the first study in the world to measure RBP4 serum levels in women with toxoplasmosis. The results of the current study showed that there is a highly significant decrease in this parameter (1.84 at P < 0.001) in women with this disease compared with control groups. To clarify the role of T. gondii in changing the levels of RBP4 in the body, compared to the control groups, this can be explained by the estimation of vitamin A and its relationship to each of them. RBP4 has a key role in the transport of Vitamin A, which is an important, fat-soluble nutrient, for embryogenesis, also, plays an important role in vision, cellular immunity function, reproduction and proliferation, regulation, and differentiation of cells.[11] Several studies have investigated the relationship between RBP4 and Vitamin A.[12],[13],[14] An in vivo study,[15] which revealed that RBP4 required for hepatic retinol mobilization and that mobilization is important for ocular and visual function development. Another study[16] showed that steatohepatitis in mice severely effects Vitamin A metabolism in the liver, resulting in decreased retinol due to the accumulation of retinyl esters in healthy hepatocytes and hepatic RBP4 levels are also decreased. Thus, steatohepatitis does not result in true Vitamin A deficiency as indicated by previous studies, but it leads to hepatic retinol deficiency due to metabolic changes. Another study showed that RBP4 normally supplies retinol to peripheral tissues, including the placenta and fetal eye, from liver reserves, therefore, Vitamin A deficiency increases the risk of congenital eye abnormalities and blindness during pregnancy.[17] A studies conducted by Al-Fartusie et al.[18] and Khaleel et al.,[19] showed that serum Vitamin A was significantly decreased in infected women with toxoplasmosis compared to those control groups. A recent study showed decrease, but nonsignificant in the level of Vitamin A during the pregnancy period in the placental of women with toxoplasmosis.[20] Therefore, the present finding contributed to the association between circulating RBP4 (carrier of this vitamin) and toxoplasmosis, especially in the acute form. In addition, other evidence that one of the symptoms of toxoplasmosis is a change in the retina that leads to blindness.[21] In vitro studies have demonstrated the ability of tachyzoites to cross retinal pigmented epithelial cells with dendritic cells after systemic infection in which Vitamin A metabolism occurs within these cells in addition to controlling intra-retinal homeostasis and immune regulation.[22],[23]

It can be concluded that there was a highly significant decrease in RBP4 serum levels in acute toxoplasmosis-infected women. This decreasing may be one of the indirect effects of T. gondii infection on their hosts. Furthermore, this level can be used as aid test for the detection of toxoplasmosis.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

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Cioffi CL, Dobri N, Freeman EE, Conlon MP, Chen P, Stafford DG, et al. Design, synthesis, and evaluation of nonretinoid retinol binding protein 4 antagonists for the potential treatment of atrophic age-related macular degeneration and Stargardt disease. J Med Chem 2014;57:7731-57.  Back to cited text no. 10
    
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Kawaguchi R, Yu J, Honda J, Hu J, Whitelegge J, Ping P, et al. A membrane receptor for retinol binding protein mediates cellular uptake of Vitamin A. Science 2007;315:820-5.  Back to cited text no. 12
    
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Hermsdorff HH, Zulet MÁ, Puchau B, Bressan J, Martínez JA. Association of retinol-binding protein-4 with dietary selenium intake and other lifestyle features in young healthy women. Nutrition 2009;25:392-9.  Back to cited text no. 13
    
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Alapatt P, Guo F, Komanetsky SM, Wang S, Cai J, Sargsyan A, et al. Liver retinol transporter and receptor for serum retinol-binding protein (RBP4). J. Bio. Chem 2013;288:1250-65.  Back to cited text no. 14
    
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Shen J, Shi D, Suzuki T, Xia Z, Zhang H, Araki K, et al. Severe ocular phenotypes in Rbp4-deficient mice in the C57BL/6 genetic background. Lab Invest 2016;96:680-91.  Back to cited text no. 15
    
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Saeed A, Bartuzi P, Heegsma J, Dekker D, Kloosterhuis N, de Bruin A, et al. Impaired hepatic Vitamin A metabolism in NAFLD mice leading to Vitamin A accumulation in hepatocytes. Cell Mol Gastroenterol Hepatol 2021;11:309-25.  Back to cited text no. 16
    
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Chou CM, Nelson C, Tarlé SA, Pribila JT, Bardakjian T, Woods S, et al. Biochemical basis for dominant inheritance, variable penetrance, and maternal effects in RBP4 congenital eye disease. Cell 2015;161:634-46.  Back to cited text no. 17
    
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Al-Fartusie FS, Marzook AT, Morad TS. Study of some trace elements and antioxidant vitamins in sera of Iraqi women with toxoplasmosis. Al-Mustansiriyah J Sci 2012;23:199-206.  Back to cited text no. 18
    
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Khaleel FM, Hameed AS, Dawood AS. Evaluation of antioxidant (GSH, Vitamin A, E, C) and MDA in Iraqi women with toxoplasmosis. Indian J Forensic Med Toxicol 2020;14:1447.  Back to cited text no. 19
    
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Ibraheem MI, Mustafa LA, Ismail AY. Effect of some biochemical parameters such as antioxidants in placenta of infected pregnant woman with toxoplasmosis. J. Education Sci 2020;29:58-67.  Back to cited text no. 20
    
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Furtado JM, Bharadwaj AS, Ashander LM, Olivas A, Smith JR. Migration of Toxoplasma gondii–infected dendritic cells across human retinal vascular endothelium. Invest Ophthalmol Visual Sci 2012;53:6856-62.  Back to cited text no. 22
    
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    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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