POS1188 SERUM LEVELS OF CITRULLINATED HISTONE H3 AS A MARKER OF NEUTROPHIL EXTRACELLULAR TRAPS AMONG PATIENTS WITH FAMILIAL MEDITERRANEAN FEVER
Authors: S. Ugurlu, O. C. Kilinc, T. Ayalti, S. Karup, F. N. Azman, E. Hacioglu, H. Guney, Z. Taskin, O. Er, I. M. Bolayirli
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Familial Mediterranean Fever (FMF) is the most frequent autoinflammatory disease stemming from mutations in the MEFV gene. The disease is characterized by overactivation of innate immune system. Neutrophil extracellular traps (NETs) are shown to play a role in the pathogenesis of FMF [1]. Citrullinated Histone H3 (CitH3) is a specific marker of NETosis [2]. <h3>Objectives:</h3> This study aims to evaluate formation of NETs among FMF patients with and without attack and FMF patients with amyloidosis by assessing serum levels of CitH3. <h3>Methods:</h3> Blood samples (n=79) were collected from four groups, including FMF patients during attack (n=18), the same FMF patients during the attack-free period (n=12), FMF patients with amyloidosis (n=28) and healthy volunteers (n=21). CitH3levels were determined in duplicate by the enzyme linked immunoabsorbent assay (ELISA). <h3>Results:</h3> Serum levels of CitH3, CRP, NLR, urea, and creatinine are summarized in the Table 1. Males constituted 55.2% of the FMF patients and the average age was 37.5 ± 11.8. All FMF patients had at least one Exon-10 mutation. Median level of CitH3 was 82.9 (IQR, 59.9-106.6) among FMF patients with attack and 65.4 (IQR, 53.85-76.0) among healthy volunteers (p-value: 0.043). FMF patients without attack had a significantly increased median CitH3 level compared to healthy controls (74.75 [IQR, 67.7-79.0] vs. 65.4 [IQR, 53.85-76.0], p-value: 0.048). Median CitH3 level of FMF patients with amyloidosis was significantly higher than healthy volunteers (77.2 [IQR, 69.48-90.53] vs. 65.4 [IQR, 53.85-76.0], p-value: 0.004). Serum CitH3 levels were higher during attacks compared to attack-free period, but the difference did not reach statistical significance (p-value: 0.42) (Figure 1). Serum CitH3 levels positively correlated with NLR (p-value &lt; 0.001, r: 0.748). Age, gender, genotype (M694V homozygous or not) and usage of anti-IL-1 treatment were non-significant variables regarding serum levels of CitH3. <h3>Conclusion:</h3> The results showed increased CitH3 levels among FMF patients during attack and attack-free periods indicating formation of NETs. Additionally, patients with amyloidosis had increased CitH3 levels which remarks increased formation of NETs in FMF patients with amyloidosis. <h3>REFERENCES:</h3> [1] Apostolidou E, Skendros P, Kambas K, Mitroulis I, Konstantinidis T, Chrysanthopoulou A, Nakos K, Tsironidou V, Koffa M, Boumpas DT, Ritis K. Neutrophil extracellular traps regulate IL-1β-mediated inflammation in familial Mediterranean fever. Ann Rheum Dis. 2016 Jan;75(1):269-77. [2] Pan B, Alam HB, Chong W, Mobley J, Liu B, Deng Q, Liang Y, Wang Y, Chen E, Wang T, Tewari M, Li Y. CitH3: a reliable blood biomarker for diagnosis and treatment of endotoxic shock. Sci Rep. 2017 Aug 21;7(1):8972. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>