{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T01:47:24Z","timestamp":1782784044380,"version":"3.54.5"},"reference-count":37,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background and Objectives: Familial Mediterranean fever (FMF) is a hereditary autoinflammatory disease characterized by recurrent inflammatory attacks and a risk of AA amyloidosis. Although inflammatory activity may persist during attack-free periods, reliable biomarkers of subclinical inflammation remain limited. The pan-immune-inflammation value (PIV), a composite index derived from circulating immune cell counts, has emerged as a marker of systemic inflammation. This study investigated the association between PIV, MEFV mutation burden, and amyloidosis in patients with FMF during attack-free periods. Materials and Methods: This retrospective cross-sectional study included 386 adult patients with FMF followed at a tertiary rheumatology clinic. Patients were stratified by MEFV mutation status into three groups: Group 1 (genetically non-confirmatory FMF or low-penetrance\/non-causative MEFV variants such as E148Q), Group 2 (single pathogenic mutation), and Group 3 (biallelic pathogenic mutations). Patients were also categorized by amyloidosis status. PIV was calculated as (neutrophil count \u00d7 platelet count \u00d7 monocyte count)\/lymphocyte count using complete blood count parameters obtained during attack-free visits. Associations between PIV and clinical characteristics were evaluated using correlation and logistic regression analyses, and discriminative performance was assessed using receiver operating characteristic (ROC) curve analysis. Statistical significance was set at p &lt; 0.05. Results: PIV levels differed significantly across genotype-defined groups (median: 172, 329.3, and 479.5 in Groups 1\u20133, respectively; p &lt; 0.001) and were higher in patients with amyloidosis than in those without amyloidosis (540.5 vs. 218.1; p &lt; 0.001). In multivariable logistic regression analysis, PIV remained independently associated with both biallelic pathogenic mutation status (OR = 1.007, 95% CI: 1.003\u20131.010, p &lt; 0.001) and the presence of amyloidosis (OR = 1.002, 95% CI: 1.001\u20131.003, p &lt; 0.001). ROC analysis showed an AUC of 0.853 for distinguishing Group 3 from Group 1 (cut-off 337; sensitivity 80.7%, specificity 77.0%) and an AUC of 0.814 for discriminating patients with and without amyloidosis (cut-off 316.4; sensitivity 86.0%, specificity 65.6%). Conclusions: PIV was independently associated with MEFV mutation burden and amyloidosis in patients with FMF during attack-free periods. These findings suggest that PIV may reflect the inflammatory burden associated with genetic mutation load and amyloidosis in FMF. Prospective longitudinal studies are warranted to externally validate these findings and further clarify the relationship between PIV, inflammatory burden, and disease severity in FMF.<\/jats:p>","DOI":"10.3390\/jcm15135058","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:55:11Z","timestamp":1782780911000},"page":"5058","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical Association of Pan-Immune-Inflammation Value with MEFV Mutation Burden and Amyloidosis in Adults with Familial Mediterranean Fever: A Retrospective Cohort Study"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-4976-4771","authenticated-orcid":false,"given":"Ozgur","family":"Yilmaz","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Kanuni Sultan Suleyman Training and Research Hospital, Istanbul 34303, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8676-0136","authenticated-orcid":false,"given":"Osman","family":"Erinc","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Kanuni Sultan Suleyman Training and Research Hospital, Istanbul 34303, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ozan Cemal","family":"Icacan","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Kanuni Sultan Suleyman Training and Research Hospital, Istanbul 34303, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gulseren Goktolga","family":"Erkoca","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Kanuni Sultan Suleyman Training and Research Hospital, Istanbul 34303, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Recep","family":"Demirci","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Kanuni Sultan Suleyman Training and Research Hospital, Istanbul 34303, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sengul","family":"Aydin Yoldemir","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Kanuni Sultan Suleyman Training and Research Hospital, Istanbul 34303, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2675-4252","authenticated-orcid":false,"given":"Murat","family":"Akarsu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Kanuni Sultan Suleyman Training and Research Hospital, Istanbul 34303, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1002\/art.24458","article-title":"Familial mediterranean Fever in the world","volume":"61","author":"Touitou","year":"2009","journal-title":"Arthritis Rheum."},{"key":"ref_2","first-page":"21","article-title":"Familial Mediterranean fever: An updated review","volume":"1","author":"Birlik","year":"2014","journal-title":"Eur. 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