Disease-specific biomarker value of C-reactive protein and its composite indices in autoinflammatory diseases: an integrated study of multi-modal omics and population cohorts
Aug 2026· Frontiers in Immunology· Vol 17· 0 citations· 39 references
Medicine
TL;DR
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.
Abstract
Background Autoinflammatory diseases (AIDs) are a heterogeneous group of innate immune-driven disorders whose prevalence is rising globally, yet the lack of disease-specific biomarkers continues to hamper accurate disease activity assessment, phenotype stratification, and risk evaluation. C-reactive protein (CRP) is one of the most widely used markers of systemic inflammation, yet its disease-specific expression, clinical correlations, network connectivity, and cellular origin across both adult and pediatric AIDs have not been systematically examined. Methods We established a single-center retrospective cohort including 11 adult and pediatric AIDs and age matched healthy controls. Baseline CRP measurements were obtained before anti-inflammatory or immunosuppressive therapy. We performed multivariate regression and subgroup analyses to examine the associations of CRP and its composite indices, the CRP to lymphocyte ratio (CLR) and CRP to albumin ratio (CAR), with different AIDs. We integrated a public serum proteomic dataset to construct CRP centered protein interaction networks in macrophage activation syndrome. We also analyzed single cell CITE seq and spatial transcriptomic data from healthy human liver to determine the cellular origin of CRP. Results Serum CRP levels showed a disease specific distribution across AIDs, with the highest levels in hyperinflammatory conditions such as AOSD and MAS. CRP correlated with fever, rash, and arthralgia in AOSD, but showed no association with mucosal or articular phenotypes in other diseases. Both CLR and CAR showed stronger associations with disease risk than CRP alone in regression models. Proteomic network analysis positioned CRP as a prominently connected node in the MAS inflammatory interactome. Single cell and spatial transcriptomic data confirmed hepatocytes as the exclusive source of CRP transcripts in healthy human liver. Conclusions These findings indicate a positive association of CRP and its composite indices with AIDs, suggesting their potential as disease-specific biomarkers. Yet, given the single-center retrospective design and lack of external validation, further multi-center prospective studies are required before clinical implementation.
Background: Psoriasis is a chronic inflammatory skin disorder affecting approximately 2-4% of the global population, characterized by immune dysregulation and keratinocyte hyperproliferation. Although multiple investigations have identified potential biomarkers, no validated panel exists for assessing disease severity. Objectives of the study were to determine levels of serum uric acid (SUA), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), CRP/albumin ratio (CAR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) in psoriasis patients versus controls, and assess their correlation with disease severity using psoriasis area severity index (PASI).
Methods: This case-control study included 50 psoriasis patients and 50 age- and sex-matched controls. Participants underwent complete blood count, CRP, ESR, serum albumin, and SUA measurements. Disease severity was categorized as mild (PASI <7), moderate (PASI 7-15), or severe (PASI >15).
Results: ESR was significantly elevated in cases versus controls (33.24±22.75 versus 19.44±11.50 mm/hour, p<0.001). CAR distribution differed significantly (p<0.001), with 56% of cases having CAR ≤0.1 mg/l versus 2% of controls. SUA showed no overall difference between groups (p=0.468) but significantly correlated with disease severity (p=0.028), increasing from mild (4.76±0.97 mg/dl) to moderate (5.47±1.50 mg/dl) to severe disease (5.77±1.01 mg/dl). CRP, albumin, NLR, and PLR showed no significant differences.
Conclusions: ESR and CAR significantly differentiate psoriasis patients from controls. SUA, while not discriminating between cases and controls, correlates with disease severity. These cost-effective biomarkers can complement clinical assessment in psoriasis management.
Akhila Pandigunta, H. Yadalla· International Journal of Res...· 0 citations
Objective: Celiac disease (CD) is a chronic immune-mediated enteropathy diagnosed using serological tests and histopathological evaluation of duodenal biopsies according to the Marsh classification. Because biopsy is invasive, attention has shifted toward simple inflammatory biomarkers derived from routine laboratory parameters, such as the Systemic Immune-Inflammation Index (SII) and hemoglobin–albumin–lymphocyte–platelet (HALP) score, which reflect systemic inflammatory and immune-nutritional status. This study evaluated the diagnostic value of SII and HALP and their ability to predict the histopathological severity in patients with CD.Methods: This retrospective observational study included 112 participants: 51 patients with newly diagnosed CD and 61 age- and sex-matched controls. CD was confirmed according to the European Society for the Study of Coeliac Disease criteria, and patients were classified as having Marsh 2 or Marsh 3 disease. SII and HALP indices were derived from routine laboratory parameters. Comparative analyses, ROC curve assessments, and multivariate logistic regression were conducted, with significance set at p < 0.05.Results: Patients with CD showed significantly lower hemoglobin, ferritin, and total iron-binding capacity than controls (p < 0.05), whereas SII and HALP did not differ significantly between groups. Tissue transglutaminase IgA and anti-endomysial IgA positivity were markedly higher in Marsh 3 than in Marsh 2 patients. ROC analysis showed limited diagnostic utility for HALP (AUC = 0.589) and no significant performance for SII (AUC = 0.479). Neither index predicted advanced villous atrophy (HALP AUC = 0.623; SII AUC = 0.611) nor emerged as an independent predictor in the regression analysis.Conclusion: In this single-center retrospective cohort, SII and HALP scores showed limited diagnostic and prognostic utility in newly diagnosed CD and, on the basis of the present data, did not reliably forecast histopathological severity.
Ayça Acet, S. Coşgun, C. Koçak et al.· Turkish Journal of Internal...· 0 citations
Objectives: Individuals with type 2 diabetes (T2D) remain at high cardiovascular disease (CVD) risk. The pan-immune-inflammation value (PIV) integrates circulating neutrophils, monocytes, platelets, and lymphocytes but does not capture albumin-related nutritional and inflammatory reserve. We investigated associations between the PIV-to-albumin ratio (PIVA) and incident CVD, cardiovascular mortality, and disease progression in individuals with T2D. Methods: This prospective study included 15,355 UK Biobank participants with T2D and no baseline CVD. PIVA was calculated from peripheral blood cell counts and serum albumin and was natural log-transformed. Fine–Gray competing-risk and cause-specific Cox models were used to evaluate incident CVD and cardiovascular mortality. Multi-state models characterized transitions from T2D to CVD and death. We also examined nonlinear associations, renal biomarker mediation, joint associations with the CVD polygenic risk score and triglyceride–glucose index, sensitivity analyses, and external validation of cardiovascular mortality in the National Health and Nutrition Examination Survey. Results: During median follow-ups of 12.94 years for incident CVD and 14.49 years for cardiovascular mortality, 4829 incident CVD events and 514 cardiovascular deaths occurred. Each 1-unit increase in lnPIVA was associated with higher risks of incident CVD (subdistribution hazard ratio [sHR], 1.140; 95% confidence interval [CI], 1.088–1.194) and cardiovascular mortality (sHR, 1.449; 95% CI, 1.247–1.684). Associations were nonlinear. Higher lnPIVA was also associated with transitions from T2D to CVD, from T2D directly to cardiovascular death, and from incident CVD to cardiovascular death. Cystatin C explained a larger proportion of these associations than creatinine. Elevated lnPIVA identified excess cardiovascular risk across strata of genetic susceptibility and insulin resistance, and the findings were generally supported by sensitivity and external validation analyses. Conclusions: lnPIVA was associated with incident CVD, cardiovascular mortality, and adverse cardiovascular transitions in individuals with T2D. As an immune-inflammatory and albumin-based index, PIVA may help identify high-risk individuals beyond conventional cardiometabolic and genetic risk profiles.
Fangkun Liu, Xinghua Yang, Bo Gao et al.· Biomedicines· 0 citations
Background The C‐reactive protein–albumin–lymphocyte (CALLY) index, a novel composite marker derived from lymphocyte count, serum albumin, and C‐reactive protein (CRP) levels, is commonly used to assess nutritional and inflammatory status. However, existing studies have not clarified the association between the CALLY index and prognosis in patients with chronic inflammatory airway diseases (CIADs). This study aims to elucidate the relationship between the CALLY index and the risks of all‐cause and cardiovascular mortality among CIAD patients in the United States. Methods This investigation included 4128 patients with CIAD from the National Health and Nutrition Examination Survey (NHANES, 1999–2010). The CALLY index was measured only at baseline. We employed weighted Cox proportional hazards regression models to assess the association between the CALLY index and risks of all‐cause and cardiovascular mortality across three progressively adjusted models. To evaluate potential nonlinear dose–response relationships, we applied restricted cubic spline (RCS) models. Additionally, subgroup analyses and sensitivity analyses were conducted to verify the robustness of our findings. Results Multivariable‐adjusted Model 3 demonstrated that, compared with the lowest quartile, the highest CALLY index quartile showed a significant inverse association with both all‐cause and cardiovascular mortality, with corresponding HRs of 0.36 (95% CI: 0.27–0.47) and 0.33 (95% CI: 0.21–0.51), respectively (both p < 0.05). Conclusions The CALLY index showed a significant inverse association with all‐cause and cardiovascular mortality among U.S. adults with CIAD, suggesting its potential value as a prognostic tool for risk stratification in this group.
Yuting Fan, Zhao Chen, Mingshan Xue et al.· Mediators of Inflammation· 0 citations
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.