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. 2015 Jun 29:5:11685.
doi: 10.1038/srep11685.

The antimicrobial propeptide hCAP-18 plasma levels in neutropenia of various aetiologies: a prospective study

Ying Ye  1 , Göran Carlsson  2 , Jenny M T Karlsson-Sjöberg  3 , Niels Borregaard  4 , Thomas U Modéer  5 , Mats L Andersson  3 , Katrin L-A Pütsep  3
Affiliations

The antimicrobial propeptide hCAP-18 plasma levels in neutropenia of various aetiologies: a prospective study

Ying Ye et al. Sci Rep. .

Abstract

The underlying cause of neutropenia may be difficult to determine due to similar clinical presentation in many neutropenic conditions. The neutrophil protein hCAP-18 (pro-LL-37) is a major component of neutrophil secondary granules and in this prospective study we assessed the use of hCAP-18 levels in blood plasma for differential diagnosis of neutropenic patients (n = 133) of various aetiologies. Plasma levels of hCAP-18 were determined using immunoblot and ELISA. Patients with severe congenital neutropenia (n = 23) presented with the lowest levels of plasma hCAP-18 and differential diagnostic accuracy revealed high sensitivity (100%) and specificity (98.8%) for hCAP-18 ELISA. The correlation coefficient of the hCAP-18 ELISA versus immunoblotting was (R = 0.831) and that of the peptide LL-37 ELISA versus immunoblotting was (R = 0.405) (P < 0.001). Plasma hCAP-18 levels thus displayed high diagnostic value in differential diagnosis of chronic neutropenia. Neutropenic patients with Shwachman-Diamond syndrome, Barth syndrome, Cohen syndrome, acute myeloid leukaemia and specific granule deficiency presented with reduced plasma hCAP-18 levels as well. The blood plasma level of hCAP-18 was thus low in conditions in which the neutrophil antibacterial propeptide hCAP-18 is deficient, i.e. severe congenital neutropenia and neutrophil-specific granule deficiency, and in conditions in which bone marrow myelopoiesis is negatively affected.

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Conflict of interest statement

M.L-A.A., G.C., K.L-A.P. are inventors in a patent (# 7591997) owned by the company Mabtech (Sweden) "Method for determining the susceptibility of a subject to infection". Mabtech had no part in initiating the present study, had no influence on study design, data collection and analysis of data, writing the report or in the decision to submit this report for publication. The company has no part in funding of this study. The other authors (T.U.M., N.B., Y.Y., J.M.T.K.) have no conflicts of interest to declare.

Figures

Figure 1
Figure 1. Plasma h-CAP18 levels and absolute neutrophil counts.
Plasma hCAP-18 levels (% of standard) assessed by immunoblotting (a) and absolute neutrophil count (ANC) (b) for patients with chronic neutropenia as the main clinical presentation. SCN, severe congenital neutropenia; AIN, autoimmune neutropenia; IN, idiopathic neutropenia; EN, ethnic neutropenia; ns, no significance. *P < 0.05, ***P < 0.001.
Figure 2
Figure 2. Plasma hCAP-18 levels determined by ELISA.
Plasma hCAP-18 levels assessed by hCAP-18 ELISA for patients with chronic neutropenia as the main clinical presentation. SCN, severe congenital neutropenia; AIN, autoimmune neutropenia; IN, idiopathic neutropenia; EN, ethnic neutropenia; ns, no significance. ***P < 0.001.
Figure 3
Figure 3. Differential diagnostic accuracy by (ROC) analysis.
Receiver operating characteristic (ROC) curves showing performance of plasma hCAP-18 and plasma LL-37 analysis in diagnosis of severe congenital neutropenia for the patient cohort with chronic neutropenia as the main clinical presentation (AIN, IN, SCN, EN).
Figure 4
Figure 4. Correlation analysis of plasma hCAP-18 or LL-37 levels versus immunoblotting.
The regression lines are between hCAP-18 levels analysed by immunoblot and hCAP-18 ELISA (a), and between hCAP-18 levels analysed by immunoblot and LL-37 levels analysed by LL-37 ELISA (b).
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