Pan-immune inflammation value as a biomarker in ankylosing spondilitis and associated with disease activity

Abstract

Aims: Ankylosing spondylitis(AS) is the most common and characteristic form of Spondyloarthritis. The pan-immune inflammation value(PIV) is a marker obtained from complete blood count parameters, which has been used as an inflammatory and immune marker. In this study, we aimed to investigate the relationship between inflammation and disease activity in patients with AS and PIV. Methods: In this prospective controlled study a total of 208 participants were included, consisting of 104 AS patients and 104 healthy controls. Complete blood count values, including neutrophils, monocytes, lymphocytes, platelets, and also C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), were measured in all participants. In AS group disease activity was assessed with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). The AS group was divided into two subgroups based on BASDAI score: low disease activity(BASDAI score <4) and high disease activity(BASDAI score ≥4).The pan-immune inflammation value of patients and the control group was calculated as neutrophil count × monocyte count × platelet count/lymphocyte count. Comparative analysis was performed between the two groups, and these values were also compared based on the BASDAI. Results: The AS group exhibited statistically higher values of CRP, monocytes, and PIV compared to the control group (p<0.001 for all). Patients with BASDAI≥4 had a statistically lower disease duration (p<0.001) and lymphocyte count (p:0.012) compared to those with BASDAI<4. Patients with BASDAI ≥ 4 had statistically higher values of CRP, ESR, neutrophils, platelets, and PIV compared to those with BASDAI<4 (p<0.001, p<0.001, p<0.001, p:0.008, p<0.001 respectively). Strong positive correlation was found between PIV and BASDAI (rho=0.790; p<0.001), moderate positive correlation with PIV and CRP (rho=0.467; p<0.001) and also positive correlation was found between PIV and ESR (rho=0.326; p<0.001). The specificity and sensitivity of PIV using a cutoff value of >309,2 were 80.0% and 86.0% respectively, for the active group. Conclusion: Since the parameters comprising PIV are obtained from a complete blood count, it provides an advantage for its use as a simple and cost-effective marker in ankylosing spondylitis patients. In our study, we demonstrated that PIV is sensitive and specific in differentiating disease activity in patients with ankylosing spondylitis from healthy individuals and associated with disease activity.

Keywords

• Ankylosing spondylitis
• Pan-Immune-Inflammation Value
• disease activity

References

1. Stolwijk C, Essers I, van Tubergen A, et al. The epidemiology of extra-articular manifestations in ankylosing spondylitis: a population-based matched cohort study. Ann Rheum Dis. 2015;74(7):1373-1378. doi: 10.1136/annrheumdis-2014-205253
2. Lee JH, Choi M, Rim THT, Lee SC, Lee CS. Clinical characteristics and prognostic factors in ankylosing spondylitis associated uveitis. Ocul Immunol Inflamm. 2019;27(1):64-69. doi: 10.1080/09273948.2017.1359630
3. Mauro D, Thomas R, Guggino G, Lories R, Brown MA, Ciccia F. Ankylosingspondylitis: an autoimmune or autoinflammatory disease? Nat Rev Rheumatol. 2021;17(7):387-404. doi: 10.1038/s41584-021-00625-y
4. Poddubnyy D. Classification vs diagnostic criteria: the challenge of diagnosing axial spondyloarthritis. Rheumatol. 2020;59(Suppl4):iv6-iv17. doi: 10.1093/rheumatology/keaa250
5. Colglazier CL, Sutej PG. Laboratory testing in the rheumatic diseases: a practical review. South Med J. 2005;98(2):185-191. doi: 10.1097/01.SMJ.0000153572.22346.E9
6. Poddubnyy D, Haibel H, Listing J, et al. Baseline radiographic damage, elevated acute‐phase reactant levels, and cigarette smoking status predict spinal radiographic progression in early axial spondylarthritis. Arthritis Rheum. 2012;64(5):1388-1398.
7. Glintborg B, Østergaard M, Krogh NS, Dreyer L, Kristensen HL, Hetland ML. Predictors of treatment response and drug continuation in 842 patients with ankylosing spondylitis treated with anti-tumour necrosis factor: results from 8 years’ surveillance in the Danish nationwide DANBIO registry. Ann Rheum Dis. 2010;69(11):2002-2008.
8. Mandaliya H, Jones M, Oldmeadow C, Nordman IIC. Prognosticbiomarkers in stage IV non-small cell lung cancer (NSCLC): neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR), platelet to lymphocyte ratio (PLR) and advanced lung cancer inflammation index (ALI). Transl Lung Cancer Res. 2019;8(6):886-889.

9. Kadihasanoglu M, Karabay E, Yucetas U, Erkan E, Ozbek E. Relation between monocyteto high-density lipoprotein cholesterol ratio and presence and severity of erectile dysfunction. Aktuelle Urol. 2018;7(03):256-261.
10. Elyan M, Khan MA. Diagnosing ankylosing spondylitis. J Rheumatol Suppl. 2006;78:12-23.
11. Ulutaş F, Çobankara V. Pan-immune-inflammation value (PIIV) in lupus nephritis. Med Sci Discov. 2023;10(4):234-238. 10.36472/msd.v10i4.918
12. Baba Y, Nakagawa S, Toihata T, et al. Pan-immune-inflammation value and prognosis in patients with esophageal cancer. Ann Surg Open. 2022;3(1):e113.
13. Yang XC, Liu H, Liu DC, Tong C, Liang XW, Chen RH. Prognostic value of pan-immune-inflammation value in colorectal cancer patients: a systematic review and meta-analysis. Front Oncol. 2022;12:1036890
14. Truffi M, Sottotetti F, Gafni N, et al. Prognostic potential of immune inflammatory biomarkers in breast cancer patients treated with neoadjuvant chemotherapy. Cancers. 2022;14(21):5287.
15. Lin F, Zhang LP, Xie SY, et al. Pan-immune-inflammation value: a new prognostic index in operative breast cancer. Front Oncol. 2022;12:830138
16. Van der Heijde D, Lie E, Kvien TK, et al. Assessment of SpondyloArthritis international Society (ASAS). ASDAS, a highly discriminatory ASAS-endorsed disease activity score in patients with ankylosing spondylitis. Ann Rheum Dis. 2009;68(12):1811-1818. doi:10.1136/ard.2008.100826
17. Van der Heijde D, Sieper J, Maksymowych WP, et al; Assessment of SpondyloArthritis International Society. 2010 update of the international ASAS recommendations for the use of anti-TNF agents in patients with axial spondyloarthritis. Ann Rheum Dis. 2011;70(6):905-908. doi: 10.1136/ard.2011.151563
18. Braun J, Pham T, Sieper J, et al. International ASAS consensus statement for the use of anti-tumour necrosis factor agents in patients with ankylosing spondylitis. Ann Rheum Dis. 2003; 62(9):817-824.
19. Kayhan S, Aydın Isak O. The significance of pan-immune inflammation value and systemic immune inflammation index in colorectal cancer screening. Turk J Clin Lab. 2021;12(3):273-277
20. Wiley. CMT Level II 2018: Theory and Analysis. John Wiley & Sons:2018
21. Wright GC, Kaine J, Deodhar A. Understanding differences between men and women with axial spondyloarthritis. Semin Arthritis Rheum. 2020;50(4):687-694. doi:10.1016/ j.semarthrit .2020.05.005
22. Mantovani A, Cassatella MA, Costantini C, Jaillon S. Neutrophils in the activation and regulation of innate and adaptive immunity. Nat Rev Immunol. 2011;11(8):519-531. doi:10.1038/nri3024
23. Wu J, Yan L, Chai K. Systemic immune-inflammation index is associated with disease activity in patients with ankylosing spondylitis. J Clin Lab Anal. 2021;35(9):e23964. doi: 10.1002/jcla.23964
24. Shanshan Xu, Yubo Ma, Meng Wu, et al. Neutrophil lymphocyte ratio in patients with ankylosing spondylitis: a systematic review and meta-analysis. Modern Rheumatol. 2020;30(1):141-148. doi.org/10.1080/14397595.2018.1564165
25. Boyraz I, Koç B, Boyacı A, Tutoğlu A, Sarman H, Ozkan H. Ratio of neutrophil/lymphocyte and platelet/lymphocyte in patient with ankylosing spondylitis that are treating with anti-TNF. Int J Clin Exp Med. 2014;7(9):2912-2915.
26. Doğan M, Boyacıoğlu Z, Doğan AG. Evaluation of neutrophyl/lymphocyte ratio, platelet/lymphocyte ratio and mean platelet volume according to the disease activity index in patients of ankylosing spondylitis. J Health Sci Med. 2022;5(1):247-251.
27. Spoorenberg A, van der Heijde D, de Klerk E, et al. Relative value of erythrocyte sedimentation rate and C-reactive protein in assessment of disease activity in ankylosing spondylitis. J Rheumatol. 1999;26(4):980-984.
28. Ruof J, Stucki G. Validity aspects of erythrocyte sedimentation rate and C-reactive protein in ankylosing spondylitis: a literature review. J Rheumatol. 1999;26(4):966-970.
29. Ruof J, Stucki G. Validity aspects of erythrocyte sedimentation rate and C-reactive protein in ankylosing spondylitis: a literature review. J Rheumatol. 1999;26(4):966-970.
30. Baba Y, Nakagawa S, Toihata T, et al. Pan-immune-inflammation value and prognosis in patients with esophageal cancer. Ann Surg Open. 2021;3(1):e113. doi:10.1097/AS9.0000000000000113
31. Truffi M, Sottotetti F, Gafni N, et al. Prognostic potential of immune inflammatory biomarkers in breast cancer patients treated with neoadjuvant chemotherapy. Cancers. 2022;14(21):5287. doi:10.3390/cancers14215287
32. Guven DC, Sahin TK, Erul E, Kilickap S, Gambichler T, Aksoy S. The association between the pan-immune-inflammation value and cancer prognosis: a systematic review and meta-analysis. Cancers. 2022;14(11):2675. doi:10.3390/cancers14112675
33. Zhang F, Li L, Wu X, et al. Pan-immune-inflammation value is associated with poor prognosis in patients undergoing peritoneal dialysis. Ren Fail. 2023;45(1):2158103. doi:10.1080/0886022X. 2022.2158103
34. Kazan DE, Kazan S. Systemic immune inflammation index and pan-immune inflammation value as prognostic markers in patients with idiopathic low and moderate risk membranous nephropathy. Eur Rev Med Pharmacol Sci. 2023;27(2):642-648. doi:10.26355/eurrev_202301_31065
35. Rudwaleit M, Haibel H, Baraliakos X, et al. The early disease stage in axial spondylarthritis: results from the German Spondyloarthritis Inception Cohort. J Am College Rheumatol. 2009;60(3):717-727.
36. Tutan D, Doğan AG. Pan-immune-inflammation index as a biomarker for rheumatoid arthritis progression and diagnosis. Cureus. 2023;15(10):e46609
37. Lee LE, Ahn SS, Pyo JY, Song JJ, Park YB, Lee SW. Pan-immune-inflammation value at diagnosis independently predicts all-cause mortality in patients with antineutrophil cytoplasmic antibody-associated vasculitis. Clin Exp Rheumatol. 2021;39(2):S88-S93.
38. Ulutaş F, Aydın M. Pan-immune-inflammation value in FMF patients. Med Sci Discov. 2023;10(6):364-367.