Autoimmune Crossroads Revisited: A Systematic Review and Meta-Analysis of Molecular Pathogenesis in Rheumatoid Arthritis and Systemic Lupus Erythematosus

Authors

  • Sadaf Andleeb Buraidah Central Hospital Buraidah, Saudi Arabia,KSA.
  • Mostafa Ahmed Abdellah Ahmed Frimley Health NHS Foundation Trust
  • Seemi Tanvir Margalla Institute of Health Sciences, Rawalpindi , Pakistan.
  • Madeeha Minhas College of Science and Health Professions ,King Saud bin Abdul-Aziz University for Health sciences, Jeddah, Saudi Arabia.
  • Durga Devi Liaquat University of Medical and Health Sciences, Jamshoro, Sindh, Pakistan.
  • Muhammad Hussain University of Florence ,Italy. https://orcid.org/0009-0002-9282-8587

DOI:

https://doi.org/10.36283/ziun-pjmd14-4/094

Keywords:

Rheumatoid Arthritis , Systemic Lupus Erythematosus , Systematic Review, Meta-Analysis, Molecular markers, Translational Medicine, Pathology

Abstract

Background: According to their aetiology, RA and SLE are both autoimmune diseases that share similarities in their molecular manifestations and the immunological responses. Objective: This study aimed to review and measure the molecular evidence that connects systemic lupus erythematosus and rheumatoid arthritis. Methods: According to the PRISMA 2020 guidelines, a systematic review and a meta-analysis were carried out. Up until February 2025, searches were conducted in Web of Science, PubMed, Embase, and Scopus. Original studies that reported concurrent molecular-level data on RA and SLE were among the eligible studies. Using RoB 2.0, ROBINS-I, and modified criteria for in silico research, two reviewers independently carried out screening, data extraction, and risk of bias assessment. A random-effects meta-analysis and narrative synthesis were used to combine the data. I2 statistics were utilised to assess heterogeneity. The GRADE framework was used to evaluate the evidence's certainty. Results: Ten of the 120 identified studies were included that contained more than 58,000 participants. Common molecular characteristics included the transcriptional regulators like GATA1 and PBX1, as well as the dysregulation of the PI3K, MAPK, and interferon pathways. There was moderate heterogeneity (I2 ≈58%) and a pooled odds ratio of 3.0 (95% CI: 2.1–4.2) for the shared molecular marker association. Evidence certainty ranged from moderate to high. Conclusion: There was a great deal of molecular overlap between RA and SLE, especially in immune signalling and transcriptional regulation. Researchers can develop shared biomarkers and treatments that complement precision autoimmune medical techniques thanks to these shared characteristics.

Author Biographies

  • Sadaf Andleeb, Buraidah Central Hospital Buraidah, Saudi Arabia,KSA.

    Department of Rheumatology,

  • Mostafa Ahmed Abdellah Ahmed, Frimley Health NHS Foundation Trust

    Department of General Surgery,

  • Seemi Tanvir, Margalla Institute of Health Sciences, Rawalpindi , Pakistan.

    Department of Pathology,


  • Madeeha Minhas, College of Science and Health Professions ,King Saud bin Abdul-Aziz University for Health sciences, Jeddah, Saudi Arabia.

    Department of Basic Sciences-Pathology,

  • Durga Devi, Liaquat University of Medical and Health Sciences, Jamshoro, Sindh, Pakistan.

    Department of Pathology, 

  • Muhammad Hussain, University of Florence ,Italy.

    Department of Biomedical Sciences,

References

References

He P, Cao RR, Deng FY, Lei SF. Identification of Potential Pleiotropic Genes for Immune and Skeletal Diseases Using Multivariate MetaCCA Analysis. Curr Genomics. 2021 Dec 31;22(8):596-606. doi: 10.2174/1389202923666211223115214.

Jia X, Shi N, Feng Y, Li Y, Tan J, Xu F, et al. Identification of 67 Pleiotropic Genes Associated With Seven Autoimmune/Autoinflammatory Diseases Using Multivariate Statistical Analysis. Front Immunol. 2020 Feb 3;11:30. doi: 10.3389/fimmu.2020.00030.

Ghosh S, Mohanty R, Santra A, Saha A, Agrawal A, Shrivastava S, et al. Unlocking the genetic tapestry of autoimmune diseases: Unveiling common genes across multiple conditions. Int J Rheum Dis. 2024 May;27(5):e15185. doi: 10.1111/1756-185X.15185.

Toro-Domínguez D, Alarcón-Riquelme ME. Precision medicine in autoimmune diseases: fact or fiction. Rheumatology (Oxford). 2021 Sep 1;60(9):3977-3985. doi: 10.1093/rheumatology/keab448.

Nunes-Santos CJ, Uzel G, Rosenzweig SD. PI3K pathway defects leading to immunodeficiency and immune dysregulation. J Allergy Clin Immunol. 2019 May;143(5):1676-1687. doi: 10.1016/j.jaci.2019.03.017.

Ding Q, Hu W, Wang R, Yang Q, Zhu M, Li M, et al. Signaling pathways in rheumatoid arthritis: implications for targeted therapy. Signal Transduct Target Ther. 2023 Feb 17;8(1):68. doi: 10.1038/s41392-023-01331-9.

Gu S, Zhang J, Han X, Ding H, Yao C, Ye Z, et al. Involvement of Transcriptional Factor Pbx1 in Peripheral B Cell Homeostasis to Constrain Lupus Autoimmunity. Arthritis Rheumatol. 2023 Aug;75(8):1381-1394. doi: 10.1002/art.42487.

Takasaki K, Chou ST. GATA1 in Normal and Pathologic Megakaryopoiesis and Platelet Development. Adv Exp Med Biol. 2024;1459:261-287. doi: 10.1007/978-3-031-62731-6_12.

Nowak K, Gumkowska-Sroka O, Kotyla P. Adhesion molecules: a way to understand lupus. Reumatologia. 2022;60(2):133-141. doi: 10.5114/reum.2022.115664.

Wang Y, Xie X, Zhang C, Su M, Gao S, Wang J, et al. Rheumatoid arthritis, systemic lupus erythematosus and primary Sjögren's syndrome shared megakaryocyte expansion in peripheral blood. Ann Rheum Dis. 2022 Mar;81(3):379-385. doi: 10.1136/annrheumdis-2021-220066.

Assawasaksakul T, Sathitratanacheewin S, Vichaiwattana P, Wanlapakorn N, Poovorawan Y, Avihingsanon Y, et al. Immunogenicity of the third and fourth BNT162b2 mRNA COVID-19 boosters and factors associated with immune response in patients with SLE and rheumatoid arthritis. Lupus Sci Med. 2022 Jul;9(1):e000726. doi: 10.1136/lupus-2022-000726.

Lu H, Zhang J, Jiang Z, Zhang M, Wang T, Zhao H, et al. Detection of Genetic Overlap Between Rheumatoid Arthritis and Systemic Lupus Erythematosus Using GWAS Summary Statistics. Front Genet. 2021 Mar 18;12:656545. doi: 10.3389/fgene.2021.656545.

Fang Q, Li T, Chen P, Wu Y, Wang T, Mo L, et al. Comparative Analysis on Abnormal Methylome of Differentially Expressed Genes and Disease Pathways in the Immune Cells of RA and SLE. Front Immunol. 2021 May 17;12:668007. doi: 10.3389/fimmu.2021.668007.

Balog JÁ, Zvara Á, Bukovinszki V, Puskás LG, Balog A, Szebeni GJ. Comparative single-cell multiplex immunophenotyping of therapy-naive patients with rheumatoid arthritis, systemic sclerosis, and systemic lupus erythematosus shed light on disease-specific composition of the peripheral immune system. Front Immunol. 2024 Apr 25;15:1376933. doi: 10.3389/fimmu.2024.1376933.

Zhang Y, Lee TY. Revealing the Immune Heterogeneity between Systemic Lupus Erythematosus and Rheumatoid Arthritis Based on Multi-Omics Data Analysis. Int J Mol Sci. 2022 May 5;23(9):5166. doi: 10.3390/ijms23095166.

Bartels LE, Ammitzbøll C, Andersen JB, Vils SR, Mistegaard CE, Johannsen AD, et al. Local and systemic reactogenicity of COVID-19 vaccine BNT162b2 in patients with systemic lupus erythematosus and rheumatoid arthritis. Rheumatol Int. 2021 Nov;41(11):1925-1931. doi: 10.1007/s00296-021-04972-7.

Jensen MK, Andersen SS, Andersen SS, Liboriussen CH, Kristensen S, Jochumsen M. Modulating Heart Rate Variability through Deep Breathing Exercises and Transcutaneous Auricular Vagus Nerve Stimulation: A Study in Healthy Participants and in Patients with Rheumatoid Arthritis or Systemic Lupus Erythematosus. Sensors (Basel). 2022 Oct 17;22(20):7884. doi: 10.3390/s22207884.

Assawasaksakul T, Lertussavavivat T, Sathitratanacheewin S, Oudomying N, Vichaiwattana P, Wanlapakorn N, et al. Comparison of Immunogenicity and Safety of Inactivated, Adenovirus-Vectored, and Heterologous Adenovirus-Vectored/mRNA Vaccines in Patients with Systemic Lupus Erythematosus and Rheumatoid Arthritis: A Prospective Cohort Study. Vaccines (Basel). 2022 May 26;10(6):853. doi: 10.3390/vaccines10060853.

Walbi IA, Albarqi HA, Alghanim NS, Albadi MA, Al Maimouni HM, Alkahtani SA, et al. Effect of chronic hydroxychloroquine use on COVID-19 risk in patients with rheumatoid arthritis and systemic lupus erythematosus: a multicenter retrospective cohort. J Int Med Res. 2022 Apr;50(4):3000605221090363. doi: 10.1177/03000605221090363.

Antonatos C, Panoutsopoulou M, Georgakilas GK, Evangelou E, Vasilopoulos Y. Gene Expression Meta-Analysis of Potential Shared and Unique Pathways between Autoimmune Diseases under Anti-TNFα Therapy. Genes (Basel). 2022 Apr 27;13(5):776. doi: 10.3390/genes13050776.

Mena-Vázquez N, Manrique-Arija S, Ordoñez-Cañizares MC, Redondo-Rodriguez R, Rioja Villodres J, Cano-Garcia L, et al. Relationship between polyautoimmunity and sarcopenic obesity in rheumatoid arthritis patients. Reumatol Clin (Engl Ed). 2022 Nov;18(9):531-537. doi: 10.1016/j.reumae.2021.06.002.

Liu Z, Ke SR, Shi ZX, Zhou M, Sun L, Sun QH, et al. Dynamic transition of Tregs to cytotoxic phenotype amid systemic inflammation in Graves' ophthalmopathy. JCI Insight. 2024 Nov 22;9(22):e181488. doi: 10.1172/jci.insight.181488.

Marcoux G, Laroche A, Espinoza Romero J, Boilard E. Role of platelets and megakaryocytes in adaptive immunity. Platelets. 2021 Apr 3;32(3):340-351. doi: 10.1080/09537104.2020.1786043.

Fechner J, Lausen J. Transcription Factor TAL1 in Erythropoiesis. Adv Exp Med Biol. 2024;1459:243-258. doi: 10.1007/978-3-031-62731-6_11.

Cooles FAH, Isaacs JD. The interferon gene signature as a clinically relevant biomarker in autoimmune rheumatic disease. Lancet Rheumatol. 2022 Jan;4(1):e61-e72. doi: 10.1016/S2665-9913(21)00254-X.

Niebel D, de Vos L, Fetter T, Brägelmann C, Wenzel J. Cutaneous Lupus Erythematosus: An Update on Pathogenesis and Future Therapeutic Directions. Am J Clin Dermatol. 2023 Jul;24(4):521-540. doi: 10.1007/s40257-023-00774-8.

Cheng X, Meng X, Chen R, Song Z, Li S, Wei S, et al. The molecular subtypes of autoimmune diseases. Comput Struct Biotechnol J. 2024 Mar 28;23:1348-1363. doi: 10.1016/j.csbj.2024.03.026.

Yasmeen F, Pirzada RH, Ahmad B, Choi B, Choi S. Understanding Autoimmunity: Mechanisms, Predisposing Factors, and Cytokine Therapies. Int J Mol Sci. 2024 Jul 12;25(14):7666. doi: 10.3390/ijms25147666.

Lincoln MR, Connally N, Axisa PP, Gasperi C, Mitrovic M, van Heel D, et al. Genetic mapping across autoimmune diseases reveals shared associations and mechanisms. Nat Genet. 2024 May;56(5):838-845. doi: 10.1038/s41588-024-01732-8.

Kim HY, Kim HR, Lee SH. Advances in systems biology approaches for autoimmune diseases. Immune Netw. 2014 Apr;14(2):73-80. doi: 10.4110/in.2014.14.2.73.

Downloads

Published

2025-09-29

Metrics

How to Cite

1.
Andleeb S, Ahmed MAA, Tanvir S, Minhas M, Devi D, Hussain M. Autoimmune Crossroads Revisited: A Systematic Review and Meta-Analysis of Molecular Pathogenesis in Rheumatoid Arthritis and Systemic Lupus Erythematosus. PJMD [Internet]. 2025 Sep. 29 [cited 2026 Jun. 4];14(4). Available from: https://ojs.zu.edu.pk/pjmd/article/view/3726

Similar Articles

91-100 of 607

You may also start an advanced similarity search for this article.

Most read articles by the same author(s)

1 2 > >>