TL;DR
Elevated PIV is non-linearly associated with thyroid autoantibody positivity, particularly TgAb, with stronger effects observed in women and hypertensive individuals, with stronger effects observed in women and hypertensive individuals.
Graves’ disease is an organ-specific autoimmune disorder driven by thyrotropin receptor antibody (TRAb) and accompanied by persistent immune and inflammatory activation. Peripheral blood inflammatory indices are readily available and have been increasingly used to assess inflammation in autoimmune diseases. However, their clinical significance in Graves’ disease across different thyroid functional states is unknown. In this retrospective study, 687 patients with Graves’ disease were enrolled. Five peripheral blood inflammatory indices were calculated, including the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and pan-immune-inflammation value (PIV). Patients were stratified and compared according to thyroid functional status. Because sex distribution differed among the groups, sex-adjusted median regression models were additionally fitted, and group-by-sex interactions were examined. Correlation analysis, logistic regression, and receiver operating characteristic (ROC) curve analysis were used to evaluate associations of these indices with clinical characteristics, liver biochemical abnormalities, and hyperthyroid relapse. The outcome models were internally validated using bootstrap resampling and repeated 10-fold cross-validation. Sex distribution differed significantly among the thyroid functional groups. After adjustment for sex, MLR, SIRI, and PIV remained significantly higher in the overt hyperthyroid group than in the subclinical hyperthyroid and euthyroid groups. In patients with overt hyperthyroidism, MLR was positively correlated with age, FT3, FT4, ALT, and AST (r s = 0.152–0.206, all P < 0.05). Multivariable logistic regression identified TRAb, hemoglobin, and standardized MLR as independent factors associated with liver biochemical abnormalities, and the resulting model showed limited-to-moderate discrimination (apparent AUC, 0.703; optimism-corrected AUC, 0.692; cross-validated AUC, 0.680). Among the five inflammatory indices, PIV showed the highest individual discrimination for hyperthyroid relapse (AUC, 0.734). The TRAb–PIV model showed relatively good internal discrimination (apparent AUC, 0.815; optimism-corrected AUC, 0.805; cross-validated AUC, 0.788). Compared with NLR and SII, the monocyte-containing indices MLR, SIRI, and PIV showed clearer differences across thyroid functional states in Graves’ disease and may provide complementary inflammation-related information. Among them, MLR was associated with liver biochemical abnormalities, whereas PIV showed potential adjunctive value for hyperthyroid relapse risk assessment.
Diabetes is a major global health burden, with chronic inflammation playing a central role in its progression and complications. The pan-immune-inflammation value (PIV) is a novel composite biomarker reflecting systemic immune inflammation. However, its prognostic value for mortality in individuals with diabetes remains unclear. We conducted a retrospective cohort analysis using the nationally representative National Health and Nutrition Examination Survey (NHANES) data, including participants aged ≥ 20 with available PIV data. PIV was calculated using a validated equation and then log-transformed (ln) before analysis. Multivariable Cox regression models were employed to evaluate this association. We further explored the dose-response relationship using restricted cubic splines (RCS) and threshold analysis to identify potential non-linear effects. The robustness of findings was confirmed through subgroup and sensitivity analyses, and the potential mediating role of estimated glomerular filtration rate (eGFR) was investigated. During a median follow-up of 94.9 months, 2,549 deaths were recorded, including 727 attributable to cardiovascular diseases. Elevated lnPIV levels were strongly associated with increased all-cause and cardiovascular mortality. Critical thresholds were identified at lnPIV values of 5.056 for all-cause mortality and 5.586 for cardiovascular mortality. These core associations were stable across all subgroup and sensitivity analyses. Furthermore, mediation analysis estimated that eGFR accounted for 5.1% and 6.4% of the lnPIV-associated risk for all-cause and cardiovascular mortality, respectively. Pan-immune-inflammation value was found to be independently associated with increased risks of all-cause and cardiovascular mortality in individuals with diabetes, characterized by a nonlinear association and a distinct threshold effect. These findings suggest that PIV could serve as a practical biomarker for risk stratification, potentially identifying patients who may benefit from more intensive management of both inflammation and renal function.
Elevated RCII levels were significantly elevated in ACPA-negative RA, ACPA-positive RA, undifferentiated inflammatory arthritis, dermatomyositis, and systemic lupus erythematosus compared with HCs, with the highest levels observed in ACPA-negative RA.
Introduction: Autoimmune thyroid diseases (AITDs), including Hashimoto’s thyroiditis (HT) and Graves’ disease (GD), are characterized by immune-mediated thyroid dysfunction. However, whether systemic inflammatory burden differs among thyroid disease phenotypes remains unclear.Methods: In this cross-sectional study, 100 adult patients (HT n=60, GD n=11, goiter n=29) were evaluated. Serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), neutrophil-to-lymphocyte ratio (NLR), and procalcitonin levels were compared among groups using the Kruskal–Wallis test with Bonferroni-adjusted post-hoc analyses. General linear models adjusted for age, sex, and disease duration were applied. Associations between inflammatory markers and thyroid parameters were assessed using Spearman correlation analysis.Results: CRP (p=0.638), ESR (p=0.135), and NLR (p=0.466) did not differ significantly among the three thyroid phenotypes. Although statistically significant differences in procalcitonin levels were observed between groups (p=0.031), lower measurable values were observed in the Graves’ disease group, and this difference remained significant after adjustment for confounders (adjusted p=0.041). Correlation analyses demonstrated generally weak associations between inflammatory markers and thyroid autoantibodies, with only a modest correlation between procalcitonin and TRAb reaching statistical significance (r=0.22, p=0.048).Conclusions: Routine systemic inflammatory markers do not meaningfully distinguish autoimmune from non-autoimmune thyroid disease phenotypes. Although procalcitonin demonstrated a phenotype-related difference, its clinical relevance remains uncertain. These findings support the concept that autoimmune thyroid diseases predominantly reflect localized rather than systemic inflammatory activation.
Serum CRP levels showed a disease specific distribution across AIDs, with the highest levels in hyperinflammatory conditions such as AOSD and MAS, suggesting their potential as disease-specific biomarkers.
Introduction Smoking is the first recognized modifiable risk factor for IgG4-related disease (IgG4-RD) and a driver of rheumatoid arthritis (RA)-associated interstitial lung disease, yet whether it is associated with IgG4-positive cell infiltration in RA lung tissue remains unclear. Methods We analyzed 28 RA patients with abnormal chest CT findings undergoing bronchoalveolar lavage (BAL) and transbronchial lung biopsy; tissue IgG and IgG4 were quantified immunohistochemically. An exploratory IgG4/IgG ratio ≥10% defined IgG4-rich infiltration (only one patient met the conventional ≥40% pathology threshold). BAL and peripheral blood were phenotyped by flow cytometry. Comparisons used non-parametric tests, exploratory Firth penalized logistic regression to address quasi-complete separation, and exploratory subgroup and sensitivity analyses. Results Six patients (21%) had IgG4/IgG ratio ≥10%; all were male ever-smokers with higher ACPA (343.1 vs 96.2 U/mL, p=0.015), although serum IgG4 did not differ (p=0.194). BAL fluid showed lower CD4/CD8 ratio, higher CD8, higher CD22+ B cells, and a trend toward higher Treg; peripheral blood T-helper subsets did not differ. IgG4-rich patients had more interstitial lung disease, more frequent reported probable UIP, higher emphysema scores, and lower baseline %FEV1.0. Tissue IgG4/IgG ratio correlated with ACPA and inversely with %FEV1.0. In an exploratory Firth analysis, male sex and log(ACPA) were associated with tissue IgG4 positivity; because all IgG4-rich cases were male ever-smokers, smoking and male sex could not be disentangled. Discussion In this exploratory cohort, tissue IgG4-positive cell infiltration was observed only among male ever-smokers and was accompanied by a distinct BAL immune-cell profile without parallel peripheral-blood changes. Given the small sample size, the exploratory cutoff, and the unresolved confounding between sex and smoking, these findings should be regarded as hypothesis-generating and require validation in larger prospective studies.
