Clinical Significance of Rheumatologic Autoantibodies in Treatment-Naïve Patients with Lymphoma, Breast, and Gastrointestinal Cancers: A Case-Control Study
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Amirhossein Gholamlou
,
Nastaran Khodakarim
,
Marzieh Ghalamkari
,
Fatemeh Tajik Rostami
,
Amineh Salem
Abstract
Background: The production of autoantibodies in cancer patients is a recognized phenomenon, yet their clinical significance and diagnostic yield remain debated. This study evaluated the frequency of rheumatologic autoantibodies in treatment-naïve patients and their association with clinical parameters.
Materials and Methods: In this case-control study, 150 treatment-naïve cancer patients (50 lymphoma, 50 breast cancer, 50 GI cancers) and 150 matched healthy controls were enrolled. A broad rheumatologic panel was performed. Clinical staging and molecular subtyping were recorded, and the 24-month progression-free survival (PFS) was also evaluated in a DLBCL subgroup to assess the prognostic weight of ANA and RF positivity.
Results: ANA and RF positivity were significantly more prevalent in cancer patients (particularly breast and lymphoma) than in controls. However, specific markers (anti-dsDNA, anti-CCP) were almost entirely negative. In lymphoma, aggressive types showed higher numerical autoantibody positivity than indolent forms, though not reaching statistical significance (p‑value <0.05). ANA and RF positivity were not significantly associated with 2-year PFS in the DLBCL subgroup (p > 0.05). In breast and GI cancers, no consistent correlation was found between ANA status and molecular subtypes or histology.
Conclusion: While ANA and RF may be positive in malignancy due to immune dysregulation, these findings are largely non-specific. In the absence of clinical rheumatic symptoms, extensive autoantibody screening does not provide additional diagnostic or prognostic value and should neither prompt a diagnosis of a rheumatic disease nor alter the oncological treatment plan.
2. De Cock D, Hyrich K. Malignancy and rheumatoid arthritis: epidemiology, risk factors and management. Best Pract Res Clin Rheumatol. 2018;32(6):869-86.
3.Wilton KM, Matteson EL. Malignancy Incidence, Management, and Prevention in Patients with Rheumatoid Arthritis. Rheumatol Ther. 2017;4(2):333-47.
4. Verma N, Jaffer MH, Kolli AS, et al. Updates in the Management of Paraneoplastic Syndrome. Semin Neurol. 2024;44(1):36-46.
5. Azar L, Khasnis A. Paraneoplastic rheumatologic syndromes. Curr Opin Rheumatol. 2013;25(1):44-9.
6. Fam AG. Paraneoplastic rheumatic syndromes. Baillieres Best Pract Res Clin Rheumatol. 2000;14(3):515-33.
7. Liang ZZ, He JH, Han ZP, et al. Analysis of antinuclear antibody pattern distribution and correlation in patients with colorectal cancer. World J Gastrointest Surg. 2025;17(12):112038.
8. Kumar M, Prakash G, Bal A, et al. Impact of Anti-nuclear Antibody Seropositivity on Clinicopathological Parameters, Treatment Response, and Survival in Lymphoma Patients. Asian Pac J Cancer Prev. 2024;25(1):73-8.
9. Nisihara R, Machoski MCC, Neppel A, et al. Anti-nuclear antibodies in patients with breast cancer. Clin Exp Immunol. 2018;193(2):178-82.
10. Maverakis E, Goodarzi H, Wehrli LN, et al. The etiology of paraneoplastic autoimmunity. Clin Rev Allergy Immunol. 2012;42(2):135-44.
11. Khanmohammadi S, Shabani M, Tabary M, et al. Lymphoma in the setting of autoimmune diseases: A review of association and mechanisms. Crit Rev Oncol Hematol. 2020;150:102945.
12. Chen C, Guo W, Zhao Y, et al. Autoimmune disease-associated lymphomas: research progress and review. Front Immunol. 2026;16:1719391.
13. Kuksin CA, Minter LM. The link between autoimmunity and lymphoma: does NOTCH signaling play a contributing role?. Front Oncol. 2015;5:51.
14. Frost E, Hofmann JN, Huang WY, et al. Antinuclear Antibodies Are Associated with an Increased Risk of Diffuse Large B-Cell Lymphoma. Cancers (Basel). 2023;15(21): 5231.
15. Rugienė R, Dadonienė J, Aleknavičius E, et al. Prevalence of paraneoplastic rheumatic syndromes and their antibody profile among patients with solid tumours. Clin Rheumatol. 2011;30(3):373-80.
16. Islam MA. Antiphospholipid antibodies and antiphospholipid syndrome in cancer: Uninvited guests in troubled times. Semin Cancer Biol. 2020;64:108-113.
17. Abdel-Wahab N, Tayar JH, Fa'ak F, et al. Systematic review of observational studies reporting antiphospholipid antibodies in patients with solid tumors. Blood Adv. 2020;4(8):1746-55.
18. Kim JY, Kim MJ, Lee EB, et al. Musculoskeletal pain and the prevalence of rheumatoid arthritis in breast cancer patients during cancer treatment: a retrospective study. J Breast Cancer. 2022;25(5):404-414.
19. Schattner A, Shani A, Talpaz M, et al. Rheumatoid factors in the sera of patients with gastrointestinal carcinoma. Cancer. 1983;52(11):2156-61.
20. Simon TA, Thompson A, Gandhi KK, et al. Incidence of malignancy in adult patients with rheumatoid arthritis: a meta-analysis. Arthritis Res Ther. 2015;17(1):212.
21. 21. Fong S, Chen PP, Crowley JJ, et al. Idiotypes and the structural diversity of human rheumatoid factors. Springer Semin Immunopathol. 1988;10(2-3):189-201.
22. Euler N, Hellbacher E, af Klint E, et al. Diffuse large B cell lymphoma in rheumatoid arthritis patients is associated with elevated B-cell driving factors including CXCL13. Clin Immunol. 2025;275:110476.
23. Chen K, Guo B, Liu R, et al. Serum autoantibody profiles in cancer patients treated with immune checkpoint inhibitors: a cross-sectional study. Front Oncol. 2025;15:1716014.
24. Zou HY, Gu X, Yu WZ, et al. Detection of serum antinuclear antibodies in lymphoma patients. Genet Mol Res. 2015;14(4):16546-52.
25. Vassalo J, Spector N, de Meis E, et al. Antiphospholipid antibodies in critically ill patients with cancer: a prospective cohort study. J Crit Care. 2014;29(4):533-8.
26. Kraev K, Hristov B, Uchikov P, et al. Comprehensive exploration of antinuclear antibodies (ANAs): unveiling clinical significance, associations with Cancer, and the nuances of differential diagnosis in positive ANA patients. Diagnostics (Basel). 2024;14(3):320.
27. Vlagea A, Falagan S, Gutiérrez-Gutiérrez G, et al. Antinuclear antibodies and cancer: a literature review. Crit Rev Oncol Hematol. 2018; 127:42-9.
28. Lang J, Ma K, Guo J, et al. Clinical significance of elevated antinuclear antibodies in patients with diffuse large B-cell lymphoma: a single center study. J Cancer Res Ther. 2018;14(1):213-219.
29. Ortona E, Pierdominici M, Berstein L. Autoantibodies to estrogen receptors and their involvement in autoimmune diseases and cancer. J Steroid Biochem Mol Biol. 2014;144 Pt B:260-7.
30. Chapman C, Murray A, Chakrabarti J, et al. Autoantibodies in breast cancer: their use as an aid to early diagnosis. Ann Oncol. 2007;18(5):868-73.
31. Tan HT, Low J, Lim SG, et al. Serum autoantibodies as biomarkers for early cancer detection. FEBS J. 2009;276(23):6880-904.
32. Erkanli A, Taylor DD, Dean D, et al. Application of Bayesian modeling of autologous antibody responses against ovarian tumor-associated antigens to cancer detection. Cancer Res. 2006;66(3):1792-8.
33. Autenshlyus A, Davletova K, Varaksin N, et al. Cytokines in various molecular subtypes of breast cancer. Int J Immunopathol Pharmacol. 2021;35:20587384211034089.
| Files | ||
| Issue | Vol 20 No 3 (2026) | |
| Section | Original Article(s) | |
| Keywords | ||
| Autoantibodies; Neoplasms; Lymphoma; Rheumatoid factor | ||
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