Asmanet ENFUMOSA : P. Deviller Urinary eosinophil derived neurotoxin (EDN/EPX) : a useful indicator of in vivo eosinophil activation

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màj 23/07/98

ENFUMOSA
(courriel: Chanez (at) montp.inserm.fr )
The European Network For Understanding
Mechanisms of Severe Asthma
BIOMED 2 Program - European Commission

4th quaterly meeting, with the support of INSERM and
Merck Sharp & Dhome Laboratory
February 13-14th 1998 in Montpellier- France
(see programm, abstracts and experts comments )

Urinary eosinophil derived neurotoxln (EDN/EPX) :
a useful indicator of in vivo eosinophil activation
Deviller P**., Cottin V*., Tardy F., Cordier J-F*
Service de Pneumologie (*) et Laboratoire de Biochimie (**) Hôpital Cardio-vasculaire et Pnenmologique Louis Pradel, 69394 Lyon CEDEX 03.

Samedi 14 Février 1998		Présentateurs		Modérateurs	Experts
9h00-10h00	Marqueurs de l'inflamation	P. Devillers (Lyon) I. Vachier (Montpellier) I. Pin (Grenoble) Discussion	10' 10' 10' 30'	M. Fournier (Paris) B. Crestani (Paris)	S.E. Dahlen (Stockholm, S) A.C. Roldaan (Davos, CH) K. Richter (Grossandorf, D)

Eosinophils are involved in inflamatory processes associated with various disesses including bronchial asthma, parasitic infestations, Carrington's discase (CD) and Churg and Strauss syndrome (CSS). Biological and pathological properties of eosinophils relie upon cellular activation and cytoplasmic granule exocytosis. In general, increase in cell number and cells displaying activated or so called hypodense phenotype are the two marks attesting the participation of eosinophils in a pathological process. If hypereosinophilia can be readily measured, evidence of this activation requires more complex and invasive technics, such as electron microscopic examination of samples from biopsies or bronchoalveolar lavages (BAL).

In this context, measure of the body fluid concentration of cationic protein derived from eosinophil granules (CPE) may represent an alternative of interest. Unlike some other substances, ECP, EPO and EDN are eosinophil-specific. They are resistant to degradation and are responsible for a significant part of the pathogenic capacity of the eosinophils. Therefore a reasonable prediction is that measurement of CPE in plasma or urine should allow to detect activation of eosinophils, whatever the tissue at the origin of such an activation.

For different reasons, EDN is the only of the four main CPE which can be messured in urine. Obviously, advantage of researching EDN relies upon an easy collection of urine samples. This contrasts with the precautions required for blood collection and clotting, in order to avoid in vitro CPE release Our observation (1) concerning the presence in urine of large amounts of EDN in a patient suffering from CD prompted us to develop an EDN assay in urine.

The aim of the present work (2) was to answer the question whether the EDN level in urine is a good index of eosinophil degranulation in vivo, in patients with various pulmonary diseases. Daily EDN excretion in urine was evaluated in three groups of patients and one control group by Enzyme linked immunosorbent assay (ELISA) using a polyclonal rabbit antibody (Table).

Daily excretion of EDN in group 1 was significantly correlated to eosinophil counts in blood and BAL. The highest values were found mainly in patients suffering from CD, CSS, hypereosinophilic idiopathic syndrom (HEIS) or eosinophilic pleuritis.

Results were tentatively expressed as the ratio of daily EDN excretion (mg/d) on peripheral eosinophil cell count (G/L). This ratio was markedly higher (31.4 +/- 94.4 109 mg x L x d-l) in patients with CD than in any of the other pathologies. This was in agreement with the high percentage of hypodense eosinophils present in the BAL of patients with CD.

This work underlines that the semeiological significance of eosinophil count in blood and the level of EDN excretion in urine were not identical. Some patients with marked hypereosinophilia, especially those with parasitological infections, exhibited EDN excretion scoring in normal range. Corticosteroid treatment led to a timecorrelated decrease in eosinophil counts in blood and in EDN excretion in urine, but with different kinetics. In several cases decrease in EDN excretion was progressive and delayed compared to that of eosinophil counts.

Taken together, these observations suggest that measure of EDN excretion.in urine is a simple way to assess and quantify eosinophil activation and degranulation in the body.

Ref (1): Deviller P., Gruart V, Prin L, Tardy F, Bulle C, Capron M, Capron A, Cordier J-F. Detection of an eosinophil-derived neurotoxin in the urine of a patient with idiopathic chronic eosinophilic pneumonia. Clin. Chim. Acta. 201: 105-113 (1991) (partial abstract from http://www.healthy.net/library/search/medline.htm )

Author : Deviller P; Gruart V; Prin L; Tardy F; Bulle C; Capron M; Capron A; Cordier JF
Address : Laboratoire de Biochimie, Hôpital Cardiovasculaire et Pneumologique Louis Pradel, Lyon, France.
Source : Clin Chim Acta, 201(1-2):105-12 1991 Sep 14

Ref (2): Cottin V., Deviller P., Tardy F., Cordier J-F. Urinary eosinophil-derived neurotoxin/Protein X (EDN/EPX): A simple method for assessing eosinophil degranulation in vivo. J. Allergy Clin Immunol à paraitre 1998 (partial abstract from http://www.healthy.net/library/search/medline.htm )

Groups	Number of patients	Blood eosinophil counts (G/L)	Main pathologies	Urine EDN(mg/day)
1	28	> 1	CD, CSS, HEIS, Asthma, Paraneoplasic eosinophilia, Non-hodgkin Iymphoma	2.04 +/-5.11 (0.08 à 27.2) p=0.03 (1/4)
2	32	0.5<-<1G/l	CD, CSS, HEIS, Asthma, Paraneoplasic eosinophilia, Non-hodgkin Iymphoma	0.93+/-1.13 (0.07 à 5.65) p =0 003 (2/4)
3	26	Normal	Pulmonary diseases involving eosinophil activation under treatment or in remission	0.33+/-0.26 (0.01 à 0.97) NS (3/4)
4	13	Normale	Absence	0.39+/-0.33 (0.08 à 0.9)