遺伝性自己炎症疾患

OBJECTIVES: Medication adherence is a key determinant of treatment effectiveness in chronic inflammatory diseases but data in Behçet's syndrome (BS) remain limited. This study evaluated medication adherence in a real-world cohort of patients with BS and explored demographic and clinical factors associated with reduced adherence. METHODS: We conducted a monocentric cross-sectional study including 125 patients with BS followed at a tertiary referral centre. Adherence was assessed using the validated 8-item Morisky Medication Adherence Scale (MMAS-8). Patients were classified as having high (score=8), intermediate (score 6-<8) or low adherence (score<6). Disease activity was evaluated using the Behçet's Disease Current Activity Form and the Behçet's Disease Activity Index. Associations between adherence and clinical variables were analysed using Spearman correlation and non-parametric tests. RESULTS: The mean MMAS-8 Score was 6.82±1.32. High adherence was observed in 29.6% of patients, intermediate adherence in 48.8% and low adherence in 21.6%. Lower adherence was more frequent among patients in the lower age quartiles. No significant associations were observed between adherence and sex, disease duration, disease activity indices or treatment class. CONCLUSION: Medication adherence in BS appeared generally satisfactory, although a relevant proportion of patients reported suboptimal adherence. These findings confirm, in a BS-specific real-world setting, previously reported associations between age and medication adherence observed in chronic diseases. Routine adherence assessment may help identify patients at higher risk of poor treatment compliance and support personalised management strategies.

BACKGROUND: Recurrent aphthous stomatitis (RAS) is a chronic autoinflammatory condition marked by recurring, painful sores in the mouth. It is often confused with Behcet's disease (BD), a rare systemic vasculitis that also presents with oral ulcers. Despite overlapping symptoms, BD has broader systemic implications, making an accurate diagnosis critical. This study aims to identify unique serum proteins that could reliably distinguish idiopathic RAS from BD. METHODS: We reanalyzed our previous mass spectrometry dataset comprising blood samples from 12 BD patients, 12 individuals with idiopathic RAS, and 21 healthy controls. Differentially expressed proteins (DEPs) related to RAS were identified and examined through Kyoto Encyclopedia of Genes and Genomes and Gene Ontology pathway enrichment. A protein-protein interaction (PPI) network was created to explore functional connections among the DEPs. Validation of three RAS-related proteins was carried out using enzyme-linked immunosorbent assay (ELISA) in a separate cohort of 26 RAS patients, 26 BD patients, and 30 healthy individuals. Their diagnostic utility was then evaluated via receiver operating characteristic (ROC) curve analysis. RESULTS: A total of 99 proteins showed differential expression in RAS samples but not in BD cases when compared to healthy controls-85 were upregulated, and 14 were downregulated. Enrichment analyses indicated these proteins are primarily involved in metabolic and infection-related pathways, particularly influencing keratinocyte differentiation and oxidative stress responses. PPI network analysis highlighted key metabolic and keratinocyte-related proteins as central hubs, suggesting a role in RAS pathology. ELISA validation confirmed significantly elevated levels of ANXA2, ENO1, and S100A7 in RAS patients compared to both BD patients and healthy subjects. CONCLUSION: Our findings identify a set of RAS-related serum proteins with potential diagnostic value. These serum proteins may enhance the clinical differentiation of RAS from BD, aiding in more accurate and timely patient care.

We report the case of a young woman with primary ciliary dyskinesia (PCD) who was also diagnosed with tRNA nucleotidyl transferase 1 (TRNT1)-related autoinflammatory syndrome, characterized by recurrent episodes of fever and arthralgia beginning at age 16. To our knowledge, this is the first documented case of homozygosity for the c.1246A>G variant in the TRNT1 gene. The patient had a milder clinical phenotype than previously reported cases with the same variant in a compound heterozygous state. Etanercept administration effectively controlled autoinflammatory manifestations, consistent with prior literature, and no adverse safety events were observed, despite the elevated risk of infectious pulmonary complications due to concurrent PCD. This case underscores the importance of considering autoinflammatory disease in patients presenting with relevant clinical features, even when manifestations are mild or have a delayed onset.

INTODUCTION: Persistent subclinical inflammation is a hallmark of familial Mediterranean fever (FMF), the most common autoinflammatory disease. Among the key mediators implicated in this chronic inflammatory state are tumor necrosis factor-alpha (TNF-α), oxidized low-density lipoprotein (OxLDL), and apolipoprotein C-II (APOC2), which contribute to the dysregulated immune response characteristic of FMF. The present study aims to evaluate the potential role of TNF-α, OxLDL, and APOC2 as diagnostic biomarkers of disease severity in patients with FMF. METHODS: The study enrolled 66 patients diagnosed with FMF and 60 age- and gender-matched healthy controls. Serum levels of tumor necrosis factor-alpha (TNF-α) and oxidized low-density lipoprotein (OxLDL) were quantified using the enzyme-linked immunosorbent assay (ELISA) technique. However, the apolipoprotein C-II (APOC2) concentrations were measured using an automated biochemistry analyzer. Furthermore, the Carotid intima media was assessed. RESULTS: Serum TNF-α levels were significantly higher in FMF patients than in the control group, emphasizing the protein's role as an important marker of chronic inflammation. Levels of low-density lipoprotein (OxLDL) and apolipoprotein C-II (APOC2) were also notably altered in the FMF cohort. Notably, OxLDL, APOC2 and TNF-α demonstrated strong positive correlation with attack frequency, multiple linear regressions analysis showed that OxLDL (β=1.53, p=0.002) and TNF-α (β=1.38, p=0.003) were significant predictors for higher number of attacks, suggesting their potential role involvement in the inflammatory cascade and their utility as complementary biomarkers in FMF. The carotid intima-media thickness (CIMT) of patients and control subjects did not differ statistically significantly. CONCLUSIONS: TNF-α, oxidized LDL, and APOC2 are key pro-inflammatory mediators that may serve as novel biomarkers for assessing chronic inflammatory status in FMF patients. Their elevated levels could provide valuable insights into disease progression and help guide personalized treatment strategies.

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 × platelet count × 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 < 0.05. Results: PIV levels differed significantly across genotype-defined groups (median: 172, 329.3, and 479.5 in Groups 1-3, respectively; p < 0.001) and were higher in patients with amyloidosis than in those without amyloidosis (540.5 vs. 218.1; p < 0.001). In multivariable logistic regression analysis, PIV remained independently associated with both biallelic pathogenic mutation status (OR = 1.007, 95% CI: 1.003-1.010, p < 0.001) and the presence of amyloidosis (OR = 1.002, 95% CI: 1.001-1.003, p < 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.