CEACAM1 and MICA as novel serum biomarkers in patients with acute and recurrent pericarditis

Abstract

Background: The immune response plays a significant role in pericarditis, but the mechanisms of disease are poorly defined. Further, efficient monitoring and predictive clinical tools are unavailable. Carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) is an immune-inhibitory protein, while MHC class I chain related protein A (MICA) and B (MICB) have an immune-stimulating function.

Methods and results: Serum CEACAM1, MICA and MICB concentrations were measured by ELISA in ~50 subjects of each group: acute pericarditis (AP), recurrent pericarditis (RP) and lupus (SLE) patients, metastatic melanoma patients as well as healthy donors. Serum CEACAM1 was dramatically elevated in AP and RP patients, but not in SLE patients, and displayed a highly accurate profile in ROC curve analyses. MICA and MICB were elevated in some pericarditis patients. All markers were enhanced in metastatic melanoma patients irrespective of neoplastic pericardial involvement. Etiology-guided analysis of RP patients showed that very low MICA levels were associated with idiopathic RP, while high MICA was associated with autoimmune and post-operative RP. Importantly, MICA was significantly associated with recurrences, independently of other potentially confounding parameters such as age, time of follow up or treatment modality.

Conclusions: Here we report for the first time on CEACAM1 as a potentially novel biomarker for pericarditis, as well as on MICA as an innovative prognostic marker in these patients. Determination of the roles of these immune factors, as well as their diagnostic and prognostic values should be determined in future prospective studies.

Keywords: MICA; MICB; biomarkers; pericarditis; serum.

Figure 1. Distribution analysis of inflammatory biomarkers

Distribution analysis of each of the indicated biomarkers according to serum concentrations (y-axis) in each group of subjects: healthy donors (Healthy), acute pericarditis patients (AP), recurrent pericarditis patients (RP), systemic lupus erythematosis patients (SLE), metastatic melanoma (Mel) with or without pericardial involvement (+/− eff). Boxes and Whiskers present all data, horizontal line reflects the median value. Statistical significance was tested with Kruskal-Wallis test: ***denotes P < 0.0001, **denotes P < 0.01 and *denotes P < 0.05.

Figure 2. Distribution analysis of biomarkers in healthy donors

(A) Distribution analysis of each of the indicated biomarkers according to serum concentrations (X-axis). Y-axis denotes the number of patients (frequency); (B) Correlation of each biomarker with age among the healthy donors. Correlation was tested with Spearman's test, the R and P values are indicated in each plot.

Figure 3. Comparison of biomarker levels between healthy donors and patients

(A) Serum levels of CEACAM1, MICA and MICB among four subject populations: healthy donors (Healthy), acute pericarditis patients (AP), recurrent pericarditis patients (RP), systemic lupus erythematosis patients (SLE) and metastatic melanoma (MM) with or without pericardial involvement (+/− eff). Each dot represents a patient. Statistical significance was tested with Kruskal-Wallis test: ***denotes P < 0.0001, **denotes P < 0.01 and *denotes P < 0.05; (B–D) ROC curves of each biomarker (indicate in the top of the Figure) for each group of patients (indicated in the left). Area Under the Curve (AUC) is indicated in each plot.

Figure 4. Distribution of RP patients exhibiting high values of biomarkers according to etiological groups

Figure shows the percentage of RP patients exhibiting biomarker values in the highest tertile. Patients are categorized in each of the indicated etiological groups.