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. 2020 Dec 17;71(10):e580-e586.
doi: 10.1093/cid/ciaa233.

Strongyloides stercoralis Infection in Solid Organ Transplant Patients Is Associated With Eosinophil Activation and Intestinal Inflammation: A Cross-sectional Study

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Strongyloides stercoralis Infection in Solid Organ Transplant Patients Is Associated With Eosinophil Activation and Intestinal Inflammation: A Cross-sectional Study

Eva Clark et al. Clin Infect Dis. .

Abstract

Background: Strongyloidiasis can cause devastating morbidity and death in immunosuppressed patients. Identification of reliable biomarkers for strongyloidiasis in immunosuppressed patients is critical for the prevention of severe disease.

Methods: In this cross-sectional study of solid organ transplant (SOT) candidates and recipients, we quantified Strongyloides-specific IgG to the recombinant NIE-Strongyloides antigen and/or to a soluble extract of S. stercoralis somatic antigens ("crude antigen") using enzyme-linked immunosorbent assays (ELISAs). We also measured peripheral eosinophilia, 4 different eosinophil granule proteins, and intestinal fatty acid-binding protein (IFABP).

Results: We evaluated serum biomarkers in 149 individuals; 77 (52%) pre-SOT and 72 (48%) post-SOT. Four percent (6/149) tested positive by NIE ELISA and 9.6% (11/114) by crude antigen ELISA (overall seropositivity of 9.4% [14/149]). Seropositive patients had higher absolute eosinophil counts (AECs) than seronegative patients (P = .004). AEC was positively correlated to the levels of eosinophil granule proteins eosinophil cationic protein (ECP) and eosinophil peroxidase (EPO) (P < .05), while IFABP was positively related to the 2 other eosinophil granule proteins (major basic protein [MBP] and eosinophil-derived neurotoxin [EDN]; Spearman's r = 0.3090 and 0.3778, respectively; P < .05; multivariate analyses slopes = 0.70 and 2.83, respectively).

Conclusions: This study suggests that, in SOT patients, strongyloidiasis triggers both eosinophilia and eosinophil activation, the latter being associated with intestinal inflammation. These data provide insight into the pathogenesis of S. stercoralis infection in the immunocompromised population at high risk of severe strongyloidiasis syndromes.

Keywords: Strongyloides stercoralis; eosinophil granule protein; eosinophils; intestinal fatty acid–binding protein; solid organ transplant.

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Figures

Figure 1.
Figure 1.
A, Absolute eosinophil counts were elevated for Strongyloides-seropositive versus -seronegative patients (320 vs 122 cells/mL, P = .004). B, Peripheral eosinophilia is associated with S. stercoralis seropositivity. AEC increased by an estimated 36.86 cells/mL for every 1 unit/mL S. stercoralis IgG (95% CI, 20.99–52.73; P < .001). Abbreviations: AEC, absolute eosinophil count; CI, confidence interval; IgG, immunoglobulin G.
Figure 2.
Figure 2.
Strongyloides seropositivity is associated with increased eosinophil granule proteins. A, Strongyloides stercoralis–seropositive patients had eosinophilia associated with increased ECP and EPO compared with seronegative patients. B, For every 1-unit/mL increase in S. stercoralis IgG, ECP increased by 251.9 ng/mL, and EPO increased by 1.2 ng/mL. Multivariate analysis results for all eosinophil granule proteins were compared to S. stercoralis IgG concentration (see Supplementary Figure 2). Abbreviations: ECP, eosinophil cationic protein; Eos, eosinophil; EPO, eosinophil peroxidase; IgG, immunoglobulin G; Strongy, Strongyloides stercoralis.
Figure 3.
Figure 3.
Increased eosinophil granule proteins MBP and EDN (data not shown) correlated with increasing IFABP, a marker of intestinal inflammation. This correlation was validated with both univariate and multivariate testing (see Supplementary Figure 3). Abbreviations: EDN, eosinophil-derived neurotoxin; IFABP, intestinal fatty acid–binding protein; MBP, major basic protein.
Figure 4.
Figure 4.
Solid organ transplant patients with strongyloidiasis had elevated eosinophils and increased ECP and EPO, while MBP and EDN correlated with increasing IFABP. Increasing Strongyloides-specific IgG was associated with increasing eosinophils and ECP, EPO in Strongyloides-seropositive patients (P < .05). Abbreviations: ECP, eosinophil cationic protein; EDN, eosinophil-derived neurotoxin; EPO, eosinophil peroxidase; IFABP, intestinal fatty acid–binding protein; IgG, immunoglobulin G; MBP, major basic protein.

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