Pan-immune-inflammation value and systemic immune-inflammation index: Are they useful markers in sarcoidosis? SII and PIV in sarcoidosis

Adem  Ertürk; Aydın  Balcı

doi:10.28982/josam.7823

Authors

Adem Ertürk Afyonkarahisar Health Sciences University, Department of Rheumatology, Afyonkarahisar, Turkey https://orcid.org/0000-0001-8882-0692
Aydın Balcı Afyonkarahisar Health Sciences University Faculty of Medicine, Department of Chest Diseases, Afyonkarahisar, Turkey https://orcid.org/0000-0002-6723-2418

DOI:

https://doi.org/10.28982/josam.7823

Keywords:

sarcoidosis, pan-immune-inflammation value, systemic immune-inflammation index, pulmonary sarcoidosis

Abstract

Background/Aim: Sarcoidosis is a multisystem inflammatory disease characterized by the infiltration of various organs. Due to the lack of a widely-accepted biomarker, researchers have explored alternative and previously unexplored parameters in sarcoidosis. This study aimed to investigate the utility of various markers, including the systemic immune-inflammation index (SII) and pan-immune-inflammation value (PIV), in patients with sarcoidosis.

Methods: A case-control study was conducted between January 2019 and February 2023. The study included 75 patients diagnosed with sarcoidosis, and 93 healthy individuals matched for age, sex, and body mass index. Sarcoidosis-related features, such as lung stage and extrapulmonary involvement, were recorded. The researchers investigated SII, PIV, procalcitonin, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), other biochemical results, and complete blood counts (including neutrophil, lymphocyte, monocyte, platelet counts, hemoglobin, mean platelet volume [MPV], and red cell distribution width [RDW]).

Results: The age and sex distribution were similar in both the case and control groups (P=0.258 and P=0.196, respectively). The patient group had a significantly lower absolute lymphocyte count than the control group (P=0.035). Patients’ RDW (P=0.007), platelet-to-lymphocyte ratio (P=0.028), and ESR (P<0.001) values were significantly higher compared to controls. No significant difference was observed between the two groups regarding other variables, including PIV and SII. There was a significant weak positive correlation between PIV and lung stage, as well as between MPV and the presence of erythema nodosum.

Conclusion: PIV and SII values in patients with sarcoidosis were similar to controls. The positive correlations between PIV and lung stage and between MPV and erythema nodosum suggest potential relationships with sarcoidosis-related features and demonstrate the value of these readily available and inexpensive markers in patient management. Comprehensive studies are needed to clarify whether SII and/or PIV can be used to assess the characteristics of patients with sarcoidosis.

Downloads

Download data is not yet available.

References

Sève P, Pacheco Y, Durupt F, Jamilloux Y, Gerfaud-Valentin M, Isaac S, et al. Sarcoidosis: A Clinical Overview from Symptoms to Diagnosis. Cells. 2021 Mar 31;10(4):766. DOI: https://doi.org/10.3390/cells10040766

Arkema EV, Cozier YC. Epidemiology of sarcoidosis: current findings and future directions. Ther Adv Chronic Dis. 2018 Nov 24;9(11):227–40. DOI: https://doi.org/10.1177/2040622318790197

Nardi A, Brillet PY, Letoumelin P, Girard F, Brauner M, Uzunhan Y, et al. Stage IV sarcoidosis: comparison of survival with the general population and causes of death. European Respiratory Journal. 2011 Dec 1;38(6):1368–73. DOI: https://doi.org/10.1183/09031936.00187410

Kraaijvanger R, Janssen Bonás M, Vorselaars ADM, Veltkamp M. Biomarkers in the Diagnosis and Prognosis of Sarcoidosis: Current Use and Future Prospects. Front Immunol. 2020 Jul 14;11. DOI: https://doi.org/10.3389/fimmu.2020.01443

Swigris JJ, Olson AL, Huie TJ, Fernandez-Perez ER, Solomon J, Sprunger D, et al. Sarcoidosis-related Mortality in the United States from 1988 to 2007. Am J Respir Crit Care Med. 2011 Jun 1;183(11):1524–30. DOI: https://doi.org/10.1164/rccm.201010-1679OC

Crouser ED, Maier LA, Wilson KC, Bonham CA, Morgenthau AS, Patterson KC, et al. Diagnosis and Detection of Sarcoidosis. An Official American Thoracic Society Clinical Practice Guideline. Am J Respir Crit Care Med. 2020 Apr 15;201(8):e26–51. DOI: https://doi.org/10.1164/rccm.202002-0251ST

Drent M, Lower EE, De Vries J. Sarcoidosis-associated fatigue. European Respiratory Journal. 2012 Jul;40(1):255–63. DOI: https://doi.org/10.1183/09031936.00002512

Judson MA. The Diagnosis of Sarcoidosis. Clin Chest Med. 2008 Sep;29(3):415–27. DOI: https://doi.org/10.1016/j.ccm.2008.03.009

Kobak S, Semiz H, Akyildiz M, Gokduman A, Atabay T, Vural H. Serum adipokine levels in patients with sarcoidosis. Clin Rheumatol. 2020 Jul 14;39(7):2121–5. DOI: https://doi.org/10.1007/s10067-020-04980-1

Jabbari P, Sadeghalvad M, Rezaei N. An inflammatory triangle in Sarcoidosis: PPAR-γ, immune microenvironment, and inflammation. Expert Opin Biol Ther. 2021 Nov 2;21(11):1451–9. DOI: https://doi.org/10.1080/14712598.2021.1913118

Mousapasandi A, Herbert C, Thomas P. Potential Use of Biomarkers for the Clinical Evaluation of Sarcoidosis. Journal of Investigative Medicine. 2021 Apr 5;69(4):804–13. DOI: https://doi.org/10.1136/jim-2020-001659

Iliaz S, Iliaz R, Ortakoylu G, Bahadir A, Bagci B, Caglar E. Value of neutrophil/lymphocyte ratio in the differential diagnosis of sarcoidosis and tuberculosis. Ann Thorac Med. 2014;9(4):232. DOI: https://doi.org/10.4103/1817-1737.140135

Ramos-Casals M, Retamozo S, Sisó-Almirall A, Pérez-Alvarez R, Pallarés L, Brito-Zerón P. Clinically-useful serum biomarkers for diagnosis and prognosis of sarcoidosis. Expert Rev Clin Immunol. 2019 Apr 3;15(4):391–405. DOI: https://doi.org/10.1080/1744666X.2019.1568240

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 May 19;39(2):88–93. DOI: https://doi.org/10.55563/clinexprheumatol/m46d0v

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 (Basel). 2022 May 27;14(11):2675. DOI: https://doi.org/10.3390/cancers14112675

Murat B, Murat S, Ozgeyik M, Bilgin M. Comparison of pan-immune-inflammation value with other inflammation markers of long-term survival after ST-segment elevation myocardial infarction. Eur J Clin Invest. 2023 Jan;53(1):e13872. doi: 10.1111/eci.13872. Epub 2022 Sep 20. PMID: 36097823. DOI: https://doi.org/10.1111/eci.13872

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 Jan;27(2):642–8.

Şahin AB, Cubukcu E, Ocak B, Deligonul A, Oyucu Orhan S, Tolunay S, et al. Low pan-immune-inflammation-value predicts better chemotherapy response and survival in breast cancer patients treated with neoadjuvant chemotherapy. Sci Rep. 2021 Jul 19;11(1):14662. DOI: https://doi.org/10.1038/s41598-021-94184-7

Tunca O, Kazan ED. A new parameter predicting steroid response in idiopathic IgA nephropathy: a pilot study of pan-immune inflammation value. Eur Rev Med Pharmacol Sci. 2022 Nov;26(21):7899–904.

Zhong JH, Huang DH, Chen ZY. Prognostic role of systemic immune-inflammation index in solid tumors: a systematic review and meta-analysis. Oncotarget. 2017 Sep 26;8(43):75381–8. DOI: https://doi.org/10.18632/oncotarget.18856

Yun S, Yi HJ, Lee DH, Sung JH. Systemic Inflammation Response Index and Systemic Immune-inflammation Index for Predicting the Prognosis of Patients with Aneurysmal Subarachnoid Hemorrhage. Journal of Stroke and Cerebrovascular Diseases. 2021 Aug;30(8):105861. DOI: https://doi.org/10.1016/j.jstrokecerebrovasdis.2021.105861

As AK, Abanoz M, Ozyazicioglu A. Effect of systemic immune inflammation index on symptom development in patients with moderate to severe carotid stenosis. Journal of Surgery and Medicine. 2022 Jan 1;6(2):149–53. DOI: https://doi.org/10.28982/josam.1055846

Gok M, Kurtul A. A novel marker for predicting severity of acute pulmonary embolism: systemic immune-inflammation index. Scandinavian Cardiovascular Journal. 2021 Apr 5;55(2):91–6. DOI: https://doi.org/10.1080/14017431.2020.1846774

Kemal CT, Aylin OA, Volkan K, Seda M, Recep B, Can S. The importance of PET/CT findings and hematological parameters in prediction of progression in sarcoidosis cases. Sarcoidosis Vasc Diffuse Lung Dis. 2017;34(3):242–50.

Bekir SA, Yalcinsoy M, Gungor S, Tuncay E, Akyil FT, Sucu P, et al. Prognostic value of inflammatory markers determined during diagnosis in patients with sarcoidosis: chronic versus remission. Rev Assoc Med Bras. 2021 Nov;67(11):1575–80. DOI: https://doi.org/10.1590/1806-9282.20210627

Statement on Sarcoidosis. Am J Respir Crit Care Med. 1999 Aug 1;160(2):736–55. DOI: https://doi.org/10.1164/ajrccm.160.2.ats4-99

Caplan A, Rosenbach M, Imadojemu S. Cutaneous Sarcoidosis. Semin Respir Crit Care Med. 2020 Oct 27;41(05):689–99. DOI: https://doi.org/10.1055/s-0040-1713130

Pasadhika S, Rosenbaum JT. Ocular Sarcoidosis. Clin Chest Med. 2015 Dec;36(4):669–83. DOI: https://doi.org/10.1016/j.ccm.2015.08.009

Fritz D, van de Beek D, Brouwer MC. Clinical features, treatment and outcome in neurosarcoidosis: systematic review and meta-analysis. BMC Neurol. 2016 Dec 15;16(1):220. DOI: https://doi.org/10.1186/s12883-016-0741-x

Design of A Case Control Etiologic Study of Sarcoidosis (ACCESS). J Clin Epidemiol. 1999 Dec;52(12):1173–86. DOI: https://doi.org/10.1016/S0895-4356(99)00142-0

Gerke AK. Treatment of Sarcoidosis: A Multidisciplinary Approach. Front Immunol. 2020 Nov 19;11. DOI: https://doi.org/10.3389/fimmu.2020.545413

Yücel KB, Yekedüz E, Karakaya S, Tural D, Ertürk İ, Erol C, et al. The relationship between systemic immune inflammation index and survival in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors. Sci Rep. 2022 Oct 3;12(1):16559. DOI: https://doi.org/10.1038/s41598-022-20056-3

Furman D, Campisi J, Verdin E, Carrera-Bastos P, Targ S, Franceschi C, et al. Chronic inflammation in the etiology of disease across the life span. Nat Med. 2019 Dec 5;25(12):1822–32. DOI: https://doi.org/10.1038/s41591-019-0675-0

Yalcinkaya R, Öz FN, Durmuş SY, Fettah A, Kaman A, Teke TA, et al. Is There a Role for Laboratory Parameters in Predicting Coronary Artery Involvement in Kawasaki Disease? Klin Padiatr. 2022 Nov 4;234(06):382–7. DOI: https://doi.org/10.1055/a-1816-6754

Vaena S, Chakraborty P, Lee HG, Janneh AH, Kassir MF, Beeson G, et al. Aging-dependent mitochondrial dysfunction mediated by ceramide signaling inhibits antitumor T cell response. Cell Rep. 2021 May;35(5):109076. DOI: https://doi.org/10.1016/j.celrep.2021.109076

Selroos O, Koivunen E. Prognostic Significance of Lymphopenia in Sarcoidosis. Acta Med Scand. 2009 Apr 24;206(1–6):259–62. DOI: https://doi.org/10.1111/j.0954-6820.1979.tb13507.x

Jones NP, Tsierkezou L, Patton N. Lymphopenia as a predictor of sarcoidosis in patients with uveitis. British Journal of Ophthalmology. 2016 Oct;100(10):1393–6. DOI: https://doi.org/10.1136/bjophthalmol-2015-307455

Karataş M, Öztürk A. The utility of RDW in discrimination of sarcoidosis and tuberculous lymphadenitis diagnosed by ebus. Tuberk Toraks. 2018 Jun 30;66(2):93–100. DOI: https://doi.org/10.5578/tt.66993

Balcı A, Aydın S. A novel approach in the diagnosis and follow-up of sarcoidosis. Journal of Surgery and Medicine. 2020 Nov 1;4(11):1077–81. DOI: https://doi.org/10.28982/josam.811687

Yalnız E, Karadeniz G, Üçsular FD, Erbay Polat G, Şahin GV. Predictive value of platelet-to-lymphocyte ratio in patients with sarcoidosis. Biomark Med. 2019 Feb;13(3):197–204. DOI: https://doi.org/10.2217/bmm-2018-0252

Korkmaz C, Demircioglu S. The Association of Neutrophil/Lymphocyte and Platelet/Lymphocyte Ratios and Hematological Parameters with Diagnosis, Stages, Extrapulmonary Involvement, Pulmonary Hypertension, Response to Treatment, and Prognosis in Patients with Sarcoidosis. Can Respir J. 2020 Sep 24;2020:1–8. DOI: https://doi.org/10.1155/2020/1696450

Dirican N, Anar C, Kaya S, Bircan HA, Colar HH, Cakir M. The clinical significance of hematologic parameters in patients with sarcoidosis. Clin Respir J. 2016 Jan;10(1):32–9. DOI: https://doi.org/10.1111/crj.12178

Bera D, Shanthi Naidu K, Kaur Saggu D, Yalagudri S, Kishor Kadel J, Sarkar R, et al. Serum angiotensin converting enzyme, Erythrocyte sedimentation rate and high sensitive-C reactive protein levels in diagnosis of cardiac sarcoidosis- where do we stand? Indian Pacing Electrophysiol J. 2020 Sep;20(5):184–8. DOI: https://doi.org/10.1016/j.ipej.2020.05.002

Ungprasert P, Ryu JH, Matteson EL. Clinical Manifestations, Diagnosis, and Treatment of Sarcoidosis. Mayo Clin Proc Innov Qual Outcomes. 2019 Sep;3(3):358–75. DOI: https://doi.org/10.1016/j.mayocpiqo.2019.04.006

Sweiss NJ, Salloum R, Ghandi S, Alegre ML, Sawaqed R, Badaracco M, et al. Significant CD4, CD8, and CD19 Lymphopenia in Peripheral Blood of Sarcoidosis Patients Correlates with Severe Disease Manifestations. PLoS One. 2010 Feb 5;5(2):e9088. DOI: https://doi.org/10.1371/journal.pone.0009088

Valeyre D, Casassus P, Battesti JP. [Clinical value of the blood lymphocyte count in thoracic sarcoidosis in adults. Apropos of 123 cases]. Rev Pneumol Clin. 1984;40(1):13–9.

Morell F, Levy G, Orriols R, Ferrer J, De Gracia J, Sampol G. Delayed Cutaneous Hypersensitivity Tests and Lymphopenia as Activity Markers in Sarcoidosis. Chest. 2002 Apr;121(4):1239–44. DOI: https://doi.org/10.1378/chest.121.4.1239

Cohen-Aubart F, Galanaud D, Grabli D, Haroche J, Amoura Z, Chapelon-Abric C, et al. Spinal Cord Sarcoidosis. Medicine. 2010 Mar;89(2):133–40. DOI: https://doi.org/10.1097/MD.0b013e3181d5c6b4

Mirsaeidi M, Mortaz E, Omar HR, Camporesi EM, Sweiss N. Association of Neutrophil to Lymphocyte Ratio and Pulmonary Hypertension in Sarcoidosis Patients. Tanaffos. 2016;15(1):44–7. DOI: https://doi.org/10.1155/2016/2402515

Ozsu S, Ozcelik N, Oztuna F, Ozlu T. Prognostic value of red cell distribution width in patients with sarcoidosis. Clin Respir J. 2015 Jan;9(1):34–8. DOI: https://doi.org/10.1111/crj.12101

Vorselaars AD, van Moorsel CH, Zanen P, Ruven HJ, Claessen AM, van Velzen-Blad H, Grutters JC. ACE and sIL-2R correlate with lung function improvement in sarcoidosis during methotrexate therapy. Respir Med. 2015 Feb;109(2):279-85. DOI: https://doi.org/10.1016/j.rmed.2014.11.009