Document Type : Original Article
Authors
1 Department of Biotechnology, Faculty of Biological Sciences, Islamic Azad University of East Tehran, Tehran, Iran
2 Department of Biology, Faculty of Biological Sciences, East Tehran Branch, Islamic Azad University, Tehran, Iran.
3 Department of Biology, Faculty of Basic Sciences, Islamic Azad University of East Tehran, Tehran, Iran
4 Department of Biology, Faculty of Basic Sciences, Islamic Azad University of East Tehran, Tehran, Iran.
Abstract
Due to the lack of reliable biomarkers and a thorough understanding of the etiology of multiple sclerosis (MS), the treatment strategy in MS requires a personalized medicine framework that goes beyond the precision medicine idea. A patient-centered approach is necessary for personalized treatment, and the identification of pathophysiological processes should be employed to help classify diseases. Intracellular aspartic proteinase-A enzyme is expressed by the APR1 gene and is one of the important factors in the development of systemic candidiasis caused by Candida albicans. The aim of this study was molecular detection of fungal DNA in serum of MS patients and to evaluate the expression of the APR1 gene in C. Albicans isolates obtained from patients with multiple sclerosis (MS) and controls. The samples were obtained from 100 MS patients with candidiasis and 100 matched controls of healthy individuals during 2018 - 2019. The evaluation of APR1 gene expression was performed using the reverse transcriptase-polymerase chain reaction (RT-PCR) method. There was a statistically significant difference in APR1 gene expression of C. Albicans strains between MS patients (mean± SD: 0.5008 ± 0.09518) and the control group (mean± SD: 0.7513±0.10505) (P = 0.000). The mean values of EDSS were 1.4074 ± 0.0082 after antifungal treatment and 2.0519 ± 0.1123 before antifungal treatment (P = 0.000). Differences in active fungal infection between patients and controls indicate the importance and possible role of fungi in MS patients. The results suggested that APR1 gene expression in C. Albicans strains isolated from MS patients may be an important factor for invasive C. Albicans strains in the progression of MS disease. Because fungal infections in the serum causes more activity of the body’s immune and defense system and directly affect the activity of the immune system, it further destroys the central nervous system.
Keywords
2.Lajer CB, BUCHWALD CV. The role of human papillomavirus in head and neck cancer. Apmis. 2010 Jun;118(6‐7):510-9.
3.Piri-Gharaghie T, Jegargoshe-Shirin N, Saremi-Nouri S, Khademhosseini SH, Hoseinnezhad-Lazarjani E, Mousavi A, Kabiri H, Rajaei N, Riahi A, Farhadi-Biregani A, Fatehi-Ghahfarokhi S. Effects of Imipenem-containing Niosome nanoparticles against high prevalence methicillin-resistant Staphylococcus Epidermidis biofilm formed. Scientific reports. 2022 Mar 24;12(1):1-3.
4.Piri Gharaghie T, Beiranvand S, Doosti A, Ghadiri AH, Haji Mohammadi S. A review of the epidemiology and clinical signs of SARS-COV-2. New Cellular and Molecular Biotechnology Journal. 2020 Nov 10;11(41):103-20.
5.Venkatesan A, Johnson RT. Infections and multiple sclerosis. Handbook of clinical neurology. 2014 Jan 1;122:151-71.
6.Hube B. From commensal to pathogen: stage-and tissue-specific gene expression of Candida albicans. Current opinion in microbiology. 2004 Aug 1;7(4):336-41.
7.Bagert BA. Epstein-Barr virus in multiple sclerosis. Current neurology and neuroscience reports. 2009 Sep;9(5):405-10.
8.Contini C, Seraceni S, Cultrera R, Castellazzi M, Granieri E, Fainardi E. Molecular detection of Parachlamydia-like organisms in cerebrospinal fluid of patients with multiple sclerosis. Multiple Sclerosis Journal. 2008 May;14(4):564-6.
9.Squiquera L, Galimberti R, Morelli L, Plotkin L, Milicich R, Kowalckzuk A, Leoni J. Antibodies to proteins from Pityrosporum ovale in the sera from patients with psoriasis. Clinical and experimental dermatology. 1994 Jul;19(4):289-93.
10.Beiranvand S, Doosti A, Mirzaei SA. Putative novel B-cell vaccine candidates identified by reverse vaccinology and genomics approaches to control Acinetobacter baumannii serotypes. Infection, Genetics and Evolution. 2021 Dec 1;96:105138.
11.Picchianti-Diamanti A, Panebianco C, Salemi S, Sorgi ML, Di Rosa R, Tropea A, Sgrulletti M, Salerno G, Terracciano F, D’amelio R, Laganà B. Analysis of gut microbiota in rheumatoid arthritis patients: disease-related dysbiosis and modifications induced by etanercept. International journal of molecular sciences. 2018 Sep 27;19(10):2938.
12.Dai H, Li Z, Zhang Y, Lv P, Gao XM. Elevated levels of serum antibodies against Saccharomyces cerevisiae mannan in patients with systemic lupus erythematosus. Lupus. 2009 Oct;18(12):1087-90.
13.Suchankova M, Paulovicova E, Paulovicova L, Majer I, Tedlova E, Novosadova H, Tibenska E, Tedla M, Bucova M. Increased antifungal antibodies in bronchoalveolar lavage fluid and serum in pulmonary sarcoidosis. Scandinavian journal of immunology. 2015 Apr;81(4):259-64.
14.Dotan I, Fishman S, Dgani Y, Schwartz M, Karban A, Lerner A, Weishauss O, Spector L, Shtevi A, Altstock RT, Dotan N. Antibodies against laminaribioside and chitobioside are novel serologic markers in Crohn’s disease. Gastroenterology. 2006 Aug 1;131(2):366-78.
15.Truss CO. The role of Candida albicans in human illness. J Orthomol Psychiatry. 1981 Jan 1;10(4):228-38.
16.Souod N, Kargar M, Doosti A, Ranjbar R, Sarshar M. Genetic analysis of cagA and vacA genes in Helicobacter pylori isolates and their relationship with gastroduodenal diseases in the west of Iran. Iranian Red Crescent Medical Journal. 2013 May;15(5):371.
17.Benito-León J, Pisa D, Alonso R, Calleja P, Díaz-Sánchez M, Carrasco L. Association between multiple sclerosis and Candida species: evidence from a case-control study. European journal of clinical microbiology & infectious diseases. 2010 Sep;29(9):1139-45.
18.Parra-Ortega B, Cruz-Torres H, Villa-Tanaca L, Hernández-Rodríguez C. Phylogeny and evolution of the aspartyl protease family from clinically relevant Candida species. Memórias do Instituto Oswaldo Cruz. 2009;104:505-12.
19.Kargar M, Ghorbani-Dalini S, Doosti A, Souod N. Real-time PCR for Helicobacter pylori quantification and detection of clarithromycin resistance in gastric tissue from patients with gastrointestinal disorders. Research in microbiology. 2012 Feb 1;163(2):109-13.
20.Doosti A, Ghasemi Dehkordi P, Rahimi E. Molecular assay to fraud identification of meat products. Journal of food science and technology. 2014 Jan;51(1):148-52.
21.Benito-León J, Laurence M. The role of fungi in the etiology of multiple sclerosis. Frontiers in neurology. 2017 Oct 16;8:535.
22.Saroukolaei SA, Ghabaee M, Shokri H, Khosravi A, Badiei A. Evaluation of APR1 gene expression in Candida albicans strains isolated from patients with multiple sclerosis. Jundishapur Journal of Microbiology. 2016 May;9(5).
23.Thiel J, Alter C, Luppus S, Eckstein A, Tan S, Führer D, Pastille E, Westendorf AM, Buer J, Hansen W. MicroRNA-183 and microRNA-96 are associated with autoimmune responses by regulating T cell activation. Journal of autoimmunity. 2019 Jan 1;96:94-103.
24.Oskari Virtanen J, Jacobson S. Viruses and multiple sclerosis. CNS & Neurological Disorders-Drug Targets (Formerly Current Drug Targets-CNS & Neurological Disorders). 2012 Aug 1;11(5):528-44.
25.Yoshitomi H, Sakaguchi N, Kobayashi K, Brown GD, Tagami T, Sakihama T, Hirota K, Tanaka S, Nomura T, Miki I, Gordon S. A role for fungal β-glucans and their receptor Dectin-1 in the induction of autoimmune arthritis in genetically susceptible mice. The Journal of experimental medicine. 2005 Mar 21;201(6):949-60.
26.Medically reviewed by Heidi Moawad, M.D. — Written by Jenna Fletcher on April 28, 2022.
27.Becher B, Bechmann I, Greter M. Antigen presentation in autoimmunity and CNS inflammation: how T lymphocytes recognize the brain. Journal of molecular medicine. 2006 Jul;84(7):532-43.
28.Rahimi E, Ameri M, Momtaz H. Prevalence and antimicrobial resistance of Listeria species isolated from milk and dairy products in Iran. Food Control. 2010 Nov 1;21(11):1448-52.
29.Fang H, Ohlsson AK, Jiang GX, Ullberg M. Screening for vancomycin-resistant enterococci: an efficient and economical laboratory-developed test. European journal of clinical microbiology & infectious diseases. 2012 Mar;31(3):261-5.
30.Laín A, Elguezabal N, Moragues MD, García-Ruiz JC, Del Palacio A, Pontón J. Contribution of serum biomarkers to the diagnosis of invasive candidiasis. Expert review of molecular diagnostics. 2008 May 1;8(3):315-25.
31.Lipton SA, Hickey WF, Morris JH, Loscalzo J. Candidal infection in the central nervous system. The American journal of medicine. 1984 Jan 1;76(1):101-8.
32.Gangneux JP, Bougnoux ME, Dannaoui E, Cornet M, Zahar JR. Invasive fungal diseases during COVID-19: we should be prepared. Journal de mycologie medicale. 2020 Jun 1;30(2):100971.
33.Alfaresi M, Elkosh A. Rapid identification of clinically relevant Nocardia species using real-time PCR with SYBR Green and melting-curve analysis. Journal of medical microbiology. 2006 Dec 1;55(12):1711-5.
34.Aloisi F, Ria F, Columba‐Cabezas S, Hess H, Penna G, Adorini L. Relative efficiency of microglia, astrocytes, dendritic cells and B cells in naive CD4+ T cell priming and Th1/Th2 cell restimulation. European journal of immunology. 1999 Sep;29(9):2705-14.
35.Ascherio A, Munger KL. Environmental risk factors for multiple sclerosis. Part II: Noninfectious factors. Annals of Neurology: Official Journal of the American Neurological Association and the Child Neurology Society. 2007 Jun;61(6):504-13.
36.Becher B, Bechmann I, Greter M. Antigen presentation in autoimmunity and CNS inflammation: how T lymphocytes recognize the brain. Journal of molecular medicine. 2006 Jul;84(7):532-43.
37.De Andrade DC, Rodrigues CL, Abraham R, Castro LH, Livramento JA, Machado LR, Leite CC, Caramelli P. Cognitive impairment and dementia in neurocysticercosis: a cross-sectional controlled study. Neurology. 2010 Apr 20;74(16):1288-95..
38.Berthelot L, Laplaud DA, Pettré S, Ballet C, Michel L, Hillion S, Braudeau C, Connan F, Lefrère F, Wiertlewski S, Guillet JG. Blood CD8+ T cell responses against myelin determinants in multiple sclerosis and healthy individuals. European journal of immunology. 2008 Jul;38(7):1889-99.
39.Brex PA, Ciccarelli O, O’Riordan JI, Sailer M, Thompson AJ, Miller DH. A longitudinal study of abnormalities on MRI and disability from multiple sclerosis. New England Journal of Medicine. 2002 Jan 17;346(3):158-64.
40.Zarinnezhad A, Shahhoseini MH, Piri Gharaghie T. Evaluating the Relative Frequency of Fungal Infections in the Serum of Patients with Multiple Sclerosis and Healthy Subjects Using PCR. Biological Journal of Microorganism. 2021 Mar 21;10(37):37-50.
41.Piri Gharaghie T, Doosti A, Mirzaei SA. Prevalence and antibiotic resistance pattern of Acinetobacter spp.nfections in Shahrekord medical centers. Developmental Biology. 2021 Nov 22;13(4):35-46.
42.Piri-Gharaghie T. Polycystic ovary syndrome and genetic factors influencing its development: A review article. Personalized Medicine Journal. 2021 Dec 1;6(23):25-9.
43.Correale J, Peirano I, Romano L. Benign multiple sclerosis: a new definition of this entity is needed. Multiple Sclerosis Journal. 2012 Feb;18(2):210-8.
44.Cox RA. Immunosuppression by cell wall antigens of Coccidioides immitis. Reviews of Infectious Diseases. 1988 Jul 1:S415-8.
45.Derfuss T, Meinl E. Identifying autoantigens in demyelinating diseases: valuable clues to diagnosis and treatment?. Current opinion in neurology. 2012 Jun 1;25(3):231-8.
46.Arshi A, Sharifi FS, Ghahfarokhi MK, Faghih Z, Doosti A, Ostovari S, Maymand EM, Seno MM. Expression analysis of MALAT1, GAS5, SRA, and NEAT1 lncRNAs in breast cancer tissues from young women and women over 45 years of age. Molecular Therapy-Nucleic Acids. 2018 Sep 7;12:751-7.
47.Lapinski PE, Doosti A, Salato V, North P, Burrows PE, King PD. Somatic second hit mutation of RASA1 in vascular endothelial cells in capillary malformation-arteriovenous malformation. European journal of medical genetics. 2018 Jan 1;61(1):11-6.
48.Kargar M, Mohammadalipour Z, Doosti A, Lorzadeh S, Japoni-Nejad A. High prevalence of class 1 to 3 integrons among multidrug-resistant diarrheagenic Escherichia coli in southwest of Iran. Osong public health and research perspectives. 2014 Aug 1;5(4):193-8.
49.Eskandarian٫ Z. Roghanian٫R. Zarkesh Esfahani٫S.H. HadiMaghzi٫A (2012). Detection of Chlamydia Pneumoniae in the Cerebrospinal Fluid of Multiple Sclerosis Patients and other Neurological Disorders. Advanced Studies in Biology. 2012;7: 307 – 316.
50.Etemadifar M, Abtahi SH, Akbari M, Murray RT, Ramagopalan SV, Fereidan-Esfahani M. Multiple sclerosis in Isfahan, Iran: an update. Multiple Sclerosis Journal. 2014 Jul;20(8):1145-7.
51.Evans C, Beland SG, Kulaga S, Wolfson C, Kingwell E, Marriott J, Koch M, Makhani N, Morrow S, Fisk J, Dykeman J. Incidence and prevalence of multiple sclerosis in the Americas: a systematic review. Neuroepidemiology. 2013;40(3):195-210.
52.Faure E. Multiple sclerosis and hepatitis B vaccination: could minute contamination of the vaccine by partial hepatitis B virus polymerase play a role through molecular mimicry?. Medical hypotheses. 2005 Jan 1;65(3):509-20.
53.Fetler L, Amigorena S. Brain under surveillance: the microglia patrol. Science. 2005 Jul 15;309(5733):392-3.
54.Ferrante P, Mancuso R, Pagani E, Guerini FR, Calvo MG, Saresella M, Speciale L, Caputo D. Molecular evidences for a role of HSV-1 in multiple sclerosis clinical acute attack. Journal of neurovirology. 2000 May 1;6(2):S109.
55.Ferrò MT, Franciotta D, Prelle A, Bestetti A, Cinque P. Active intrathecal herpes simplex virus type 1 (HSV-1) and human herpesvirus-6 (HHV-6) infection at onset of multiple sclerosis. Journal of neurovirology. 2012 Oct;18(5):437-40.
56.Heidari-soureshjani E, Heidari M, Doosti A. Epidemiology of urinary tract infection and antibiotic resistance pattern of E. coli in patients referred to Imam Ali hospital in Farokhshahr, Chaharmahal va Bakhtiari, Iran. Journal of Shahrekord Uuniversity of Medical Sciences. 2013;15.
57.Goldenberg MM. Multiple sclerosis review. Pharmacy and therapeutics. 2012 Mar;37(3):175.
)