Detection of ACCPA Levels in Patients with Proteus Mirabilis Urinary Tract Infection: Possible Implications for Rheumatoid Arthritis
DOI:
https://doi.org/10.22317/jcms.v12i1.2094Keywords:
rheumatoid arthritis, urinary tract infection, Proteus mirabilis, anti-citrullinated protein antibodies, molecular mimicryAbstract
Objective: To investigate the anti-citrullinated protein antibodies (ACCPA) value for patients who have urinary tract infection (UTI) with Proteus mirabilis (P. mirabilis) and rheumatoid arthritis (RA) patients.
Methods: Eighty serum samples were analyzed for antibodies to cyclic citrullinated peptides (Anti-CCP) by ELISA. The samples included 40 from patients with RA diagnosed according to the 2010 American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) criteria, 20 from patients with UTI caused by P. mirabilis, and 20 from healthy controls.
Results: ACCPA was significantly higher in RA patients (P<0.001) than in the UTI and control groups; however, ACCPA also showed a significant elevation in the mentioned bacterial UTI group compared to the control group (P<0.001).
Conclusion: P. mirabilis infection is associated with raised ACCPA levels, and early screening and treatment could help to mitigate progression to RA.
References
Shams S, Martinez JM, Dawson JR, Flores J, Gabriel M, Garcia G, Guevara A, Murray K, Pacifici N, Vargas MV, Voelker T. The therapeutic landscape of rheumatoid arthritis: current state and future directions. Frontiers in pharmacology. 2021 May 28; 12:680043.
Jassim HH, Abbas AA, Hadi-Alosami M. MicroRNA-5196 as an Accurate Biomarker of Disease Activity and Response to Treatment in Rheumatoid Arthritis. Journal of Contemporary Medical Sciences. 2024 Mar 1;10(2).
Guo Q, Wang Y, Xu D, Nossent J, Pavlos NJ, Xu J. Rheumatoid arthritis: pathological mechanisms and modern pharmacologic therapies. Bone research. 2018 Apr 27;6(1):15.
Shan F, Rashid MI, Jamal SF, Rahman M, Ahmad I. Environmental and Genetic Etiology of Rheumatoid Arthritis. BioScientific Review. 2025 Mar 7;7(1):77-95.
Azab K. Prevalence and relation of urinary tract infection bacterial pathogens to sex and ages among patients in three arab countries. Al-Azhar Journal of Pharmaceutical Sciences. 2021 Mar 1;63(1):194-206.
Mastrangelo F, Bali N, Mastrangelo F. URINARY TRACT BACTERIAL INFECTIONS: ESCHERICHIA COLI, KLEBSIELLA PNEUMONIAE, PROTEUS MIRABILIS, STAPHYLOCOCCUS SAPROPHYTICUS, ENTEROCOCCUS FAECALIS. International Journal of Infection 2022, Vol. 6, ISSUE 2, May-August.:40.
Abou Heidar NF, Degheili JA, Yacoubian AA, Khauli RB. Management of urinary tract infection in women: A practical approach for everyday practice. Urology annals. 2019 Oct 1;11(4):339-46.
Suzan YJ, Khudhair AB, Rashid AM, Jasim T. Correlation between anti-Proteus antibodies and isolation rates of Proteus mirabilis in rheumatoid arthritis Iraqi patients. Al Mustansiriyah Journal of Pharmaceutical Sciences. 2014 Dec 1;14(2):48-54.
Rashid T, Jayakumar KS, Binder A, Ellis S, Cunningham P, Ebringer A. Rheumatoid arthritis patients have elevated antibodies to cross-reactive and non cross-reactive antigens from Proteus microbes. Clinical and experimental rheumatology. 2007 Mar 1;25(2):259.
Christopoulos G, Christopoulou V, Routsias JG, Babionitakis A, Antoniadis C, Vaiopoulos G. Greek rheumatoid arthritis patients have elevated levels of antibodies against antigens from Proteus mirabilis. Clinical rheumatology. 2017 Mar;36(3):527-35.
Albujassim AS, Al-khateeb SN, Ali H, jabbar Yasir S, Alasady RA, Al-Kraity WR. Bacteriological Study Of Proteus Mirabilis Isolated from Different Clinical Samples. Medical Science. 2024 Mar;5(1).
Zhang S, Li Q, Wang M, Jia R, Chen S, Liu M, Zhu D, Zhao X, Wu Y, Yang Q, Huang J. Genomic analysis of Proteus mirabilis: Unraveling global epidemiology and antimicrobial resistance dissemination− emerging Challenges for public health and Biosecurity. Environment International. 2025 Apr 18:109487.
Grahl MV, Uberti AF, Broll V, Bacaicoa-Caruso P, Meirelles EF, Carlini CR. Proteus mirabilis urease: unsuspected non-enzymatic properties relevant to pathogenicity. International journal of molecular sciences. 2021 Jul 4;22(13):7205.
Abdullah P, Darweesh S, Haydar S. Molecular Detection of hpmA Gene in Proteus mirabilis Isolates and its Association with Inflammatory Biomarkers among Rheumatoid Arthritis Patients. Journal of Life and Bio Sciences Research. 2025 Mar 31;6(01):21-5.
Puntis D, Malik S, Saravanan V, Rynne M, Heycock C, Hamilton J, Kelly CA. Urinary tract infections in patients with rheumatoid arthritis. Clinical rheumatology. 2013 Mar;32(3):355-60.
Steiner G, Toes RE. Autoantibodies in rheumatoid arthritis–rheumatoid factor, anticitrullinated protein antibodies and beyond. Current opinion in rheumatology. 2024 May 1;36(3):217-24.
Wu CY, Yang HY, Luo SF, Lai JH. From rheumatoid factor to anti-citrullinated protein antibodies and anti-carbamylated protein antibodies for diagnosis and prognosis prediction in patients with rheumatoid arthritis. International Journal of Molecular Sciences. 2021 Jan 12;22(2):686.
Lima I, Santiago M. Antibodies against cyclic citrullinated peptides in infectious diseases—a systematic review. Clinical rheumatology. 2010 Dec;29(12):1345-51.
Arleevskaya MI, Novikov AA, Valeeva AR, Korovina MO, Serdiuk IL, Popov VA, Carlé C, Renaudineau Y. At Early Rheumatoid Arthritis Stage, the Infectious Spectrum Is Driven by Non-Familial Factors and Anti-CCP Immunization. Journal of Clinical Medicine. 2024 May 9;13(10):2796.
Jin J, Li J, Hou M, Ding X, Zhong Y, He J, Sun X, Ye H, Li R, Wu L, Wang J. A shifted urinary microbiota associated with disease activity and immune responses in rheumatoid arthritis. Microbiology Spectrum. 2023 Jun 15;11(3): e03662-22.
Magdy AK, Hamid FA, Nasser YK, Awaid IK, Jawad AA. Molecular detection of urease and hemolysin genes in Proteus mirabilis bacteria isolated from urine of Rheumatoid arthritis patients in Najaf province. Journal of Medical Genetics and Clinical Biology. 2024;1(6):30-9.
Ebringer A, Rashid T. Rheumatoid arthritis is an autoimmune disease triggered by Proteus urinary tract infection. Journal of Immunology Research. 2006;13(1):41-8.
Ebringer A, Rashid T. Rheumatoid arthritis is caused by a Proteus urinary tract infection. Apmis. 2014 May;122(5):363-8.
Newkirk MM, Goldbach-Mansky R, Senior BW, Klippel J, Schumacher Jr HR, El-Gabalawy HS. Elevated levels of IgM and IgA antibodies to Proteus mirabilis and IgM antibodies to Escherichia coli are associated with early rheumatoid factor (RF)-positive rheumatoid arthritis. Rheumatology. 2005 Nov 1;44(11):1433-41.
Coelho B, Marrafa M, Esteves R, Ribeiro E. Association between rheumatoid arthritis and urinary tract infections caused by Proteus spp.: a review. Saúde & Tecnologia. 2021 Apr 16(24):11-20.
Sangha MS, Wright ML, Ciurtin C. Strongly positive anti‐CCP antibodies in patients with sacroiliitis or reactive arthritis post‐E. coli infection: A mini case‐series based review. International Journal of Rheumatic Diseases. 2018 Jan;21(1):315-21.
Kharbanda H, Khanna M, Thakrar K, Basak M, Dwivedi M, Das PP. Effect of DMARD Therapy on Inflammatory Biomarkers and Disease Activity in Rheumatoid Arthritis Patients. Journal of Orthopaedic Case Reports. 2025 Apr;15(4):299.
Venetsanopoulou AI, Alamanos Y, Voulgari PV, Drosos AA. Epidemiology and risk factors for rheumatoid arthritis development. Mediterranean journal of rheumatology. 2023 Dec 30;34(4):404.
Nielen MM, van Schaardenburg D, Reesink HW, Van de Stadt RJ, van der Horst‐Bruinsma IE, de Koning MH, Habibuw MR, Vandenbroucke JP, Dijkmans BA. Specific autoantibodies precede the symptoms of rheumatoid arthritis: a study of serial measurements in blood donors. Arthritis & Rheumatism: Official Journal of the American College of Rheumatology. 2004 Feb;50(2):380-6.
Wilson C, Tiwana H, Ebringer A. Molecular mimicry between HLA-DR alleles associated with rheumatoid arthritis and Proteus mirabilis as the aetiological basis for autoimmunity. Microbes and infection. 2000 Oct 1;2(12):1489-96.
Fehringer M, Vogl T. Molecular mimicry in the pathogenesis of autoimmune rheumatic diseases. Journal of Translational Autoimmunity. 2025 Jan 7:100269.
Ebringer A, Rashid T, Wilson C. Rheumatoid arthritis, Proteus, anti-CCP antibodies and Karl Popper. Autoimmunity reviews. 2010 Feb 1;9(4):216-23.
Ahmed MA, Ahmed MM, Ali AJ. Levels of IL-6 and IL-8 in Complicated versus Uncomplicated Urinary Tract Infection. Journal of Chemistry Studies. 2024 May 15;3(1):21-5.
Drake M, Kiely J, Luxton R, Barnett J. 291-Interleukin-8 and lactoferrin as potential biomarkers for urinary tract infection. Continence. 2025 Jan 1;15:102215.
Khandpur R, Carmona-Rivera C, Vivekanandan-Giri A, Gizinski A, Yalavarthi S, Knight JS, Friday S, Li S, Patel RM, Subramanian V, Thompson P. NETs are a source of citrullinated autoantigens and stimulate inflammatory responses in rheumatoid arthritis. Science translational medicine. 2013 Mar 27;5(178):178ra40-.
Chen J, Cao Y, Xiao J, Hong Y, Zhu Y. The emerging role of neutrophil extracellular traps in the progression of rheumatoid arthritis. Frontiers in Immunology. 2024 Aug 16;15:1438272.
Wright HL, Moots RJ, Edwards SW. The multifactorial role of neutrophils in rheumatoid arthritis. Nature Reviews Rheumatology. 2014 Oct;10(10):593-601.
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