Correlations between plasma levels of a fibronectin isoform subpopulation and C-reactive protein in patients with systemic inflammatory disease

Abstract

Surrogate markers to detect vasculitic processes prior to organ compromise are lacking. To determine if specific populations among the fibronectin (FN) family of alternatively spliced proteins correlate with parameters of vasculitis in at-risk patients, we retrospectively evaluated the association of plasma levels of total FN (TFN) and FN bearing the alternatively spliced EIIIA segment (A(+)FN) with clinical vasculitis status and with levels of two putative vasculitis markers (C-reactive protein (CRP) and von Willebrand factor) in a previously studied cohort of 27 patients with systemic inflammatory disease. We found that the percentage of TFN composed by A(+)FN (%A(+)) and A(+)FN, but not TFN, correlated with plasma levels of CRP, the prototypic inflammation biomarker used to detect vasculitis. These findings suggest that different FNs may confer distinct clinical information, and that their simultaneous measurement merits further investigation in our efforts to identify soluble biomarker systems to detect vasculitis.

Figure 1

Variation in plasma levels of A⁺FN and vWF between categories of vascular complications in SID, within category, and within person. Box plots show variation for repeated measures on same person; the ends of each box mark the 25^th and 75^th percentile of all observations for the person, and the whiskers show observations in the first and last quartile. Outliers are shown by open circles. Individuals with only one observation are shown by a single line segment. In A, the ordinate is A⁺FN concentration (micrograms/ml), whereas, in B, the ordinate is log of vWF concentration (expressed as % of average concentration in healthy controls). vWF was log transformed to stabilize variance and reduce skewness of data. Patient number 10 is missing from panel B, since no vWF concentration was available for this subject.

Figure 2

Relationship between %A⁺, CRP and vWF in patients with SID. A. The relationship between %A⁺ and CRP is significant and persists after removal of outliers. B. The relationship between %A⁺ and vWF is significant but does not persist after removal of outliers. CRP and vWF are each expressed as the % of the average concentration in healthy controls, whereas %A⁺ represents the ratio of the concentration of A⁺FN to TFN (both in micrograms/ml).