Anti-LGALS3 monoclonal antibody, clone N4/49 [Biotin]

Aims Cardiac specificity provides an advantage in correlating heart failure (HF) biomarker plasma levels with indices of cardiac function and remodelling, as shown for natriuretic peptides. Using bioinformatics, we explored the cardiac specificity of secreted proteins and investigated in more detail the relationship of Dickkopf-3 (DKK3) gene expression and DKK3 plasma concentrations with cardiac function and remodelling in (pre)clinical studies. Methods and results The cardiac specificity of secreted proteins was determined using RNAseq data for a large panel of organs and tissues. This showed that natriuretic peptides (NPPAandNPPB) are highly cardiac-specific (>99%), whereas other HF biomarkers, including galectin-3 (Gal-3,LGALS3) and growth differentiation factor-15 (GDF-15), lack cardiac specificity (<4%).DKK3was cardiac-enriched (44%), warranting further investigation. In three different HF mouse models, cardiacDkk3expression was altered, but DKK3 plasma concentrations were not. In humans, DKK3 plasma concentrations were higher in HF patients (n = 2090) in comparison with age- and sex-matched controls without HF (n = 240) (46.4 ng/mL vs. 36.3 ng/mL;P < 0.001). Multivariate regression analysis revealed that DKK3 was strongly associated with HF risk factors and comorbidities, including age, kidney function and atrial fibrillation. After correction for existing prediction models, DKK3 did not independently predict HF outcome [all-cause mortality/HF hospitalization, hazard ratio 1.13 (0.79-1.61) per DKK3 doubling;P = 0.503]. Conclusions Of actively secreted HF biomarkers, only natriuretic peptides showed high cardiac specificity. Despite a cardiac specificity of 44%, secreted DKK3 had limited additional diagnostic and prognostic value.

The diagnosis of thyroid tumors is critical for clinical management; however, tumors with follicular architecture often present problems. We evaluated the diagnostic use of the protein expression of four genes that were found to be upregulated in papillary thyroid carcinoma compared to normal thyroid (LGALS3, FN1, CITED1 and KRT19), and of the mesothelial cell surface protein recognized by monoclonal antibody HBME1 in thyroid tumors. Tissues from 85 carcinomas ( 67 papillary, six follicular, eight Hurthle cell and four anaplastic) and 21 adenomas were evaluated by immunohistochemistry for the expression of these gene protein products, for example, galectin-3 (GAL3), fibronectin-1 ( FN1), CITED1, cytokeratin-19 (CK19) and HBME1. Non-neoplastic thyroids ( 29 adenomatous and 14 thyrotoxic hyperplasia, and 59 normal) were also studied. The expression of all five proteins was significantly associated with malignancy, and highly specific (greater than or equal to90%) for carcinoma compared to adenoma. GAL3, FN1 and/or HBME1 expression was seen in 100% of carcinomas (85/85) and in 24% of adenomas (5/21). Coexpression of multiple proteins was seen in 95% of carcinomas and only 5% of adenomas (P<0.0001). Coexpression of FN1 and GAL3 ( FN1+GAL3+, 70/85) or FN1 and HBME1 (FN1+HBME1+, 53/85) was restricted to carcinomas, while their concurrent absence ( FN1 - GAL3 - or FN1 - HBME1 -, 18/21 adenoma) was highly specific (96%) for benign lesions. Among non-neoplastic thyroids, adenomatous hyperplasia frequently expressed GAL3 ( n = 16), CK19 ( n = 9) and CITED1 ( n = 7), but the expression was predominantly focal in contrast to the diffuse expression in carcinomas. An immunohistochemical panel consisting of GAL3, FN1 and HBME1 may be useful in the diagnosis of follicular cell-derived thyroid tumors.