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Case report
Department of Diagnostic Services, Pathology and Legal Medicine, Section of Pathology, University of Modena and Reggio Emilia, Modena, Italy
Department of Clinical Pathology, Section of Immunopathology and Allergology, SantAgostino Estense Hospital, Baggiovara, Modena, Italy
c
Department of General Surgery and Surgical Specialties, Section of Anaesthesiology and Intensive Care, University of Modena and Reggio Emilia, Modena, Italy
b
A R T I C L E I N F O
A B S T R A C T
Article history:
Received 24 November 2012
Received in revised form 5 February 2013
Accepted 25 February 2013
Available online 26 March 2013
Keywords:
Anaphylaxis
Thymoglobulin
Mannitol
Carbohydrate cross-reactive determinants
(CCDs)
Basophil activation test (BAT)
2D7 antibody
1. Introduction
Immediate response: In this phase, subsequent to the sensitization period (usually of 1530 days), the immune system
identies the allergen again, through one of the exposure routes
which binds to IgE on cell membranes. This triggers the
degranulation of mast cells and basophils with the release of
preformed mediators contained in their granules (histamine,
adenosine, chymase, tryptase, heparin) within 530 min of
exposure [5]. These preformed mediators are responsible for
clinical manifestations which, in ascending order of severity,
include: rhinitis, conjunctivitis, urticaria, bronchial asthma,
laryngospastic angioedema and anaphylactic shock.
Delayed response: After a few hours from allergen exposure,
regardless of its persistence, secondary mediators (autacoids,
cytokines), synthesized de novo, are released from various
inammatory cells. These include Major Basic Protein (MBP) and
Eosinophil Cationic Protein (ECP), which are the main causes of
tissue damage.
The term anaphylaxis refers to a severe whole-body immunoallergic reaction against a foreign substance denominated allergen,
giving rise to immediate hypersensitivity which, if not promptly
treated, can lead to the patients death [13]. The immediate (type
I) hypersensitivity consists of three stages:
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observed, particularly in the explanted liver; which was characterized by extensive areas of centrilobular (zone III) necrosis.
3.4. Serology and biochemistry
therapy, from the intra-operative administration of Thymoglobulin during cadaveric renal transplantation [15]. Each Thymoglobulin vial (10 ml) contained 25 mg anti-thymocyte globulin
(rabbit), as well as 10 mg sodium chloride, 50 mg glycine and
50 mg mannitol. Among these excipients, mannitol (sorbitol
isomer) is classied as a sugar alcohol, usually derived from
The post-mortem serological test performed with ImmunoCAPTM 100 system (Phadia, Uppsala, Sweden) on a preserved sample
of the patients pre-OLT blood, obtained the day before the
admission to the operating theater, showed high levels of specic
IgE against graminaceae, canine grass and peanuts, whereas no
signicant IgE values were detected for different classes of
antibiotics (penicillins and cephalosporins) and natural latex
rubber. Moreover, the test revealed the presence of specic IgE
against CCDs from bromelin (MUXF3) and native extract bromelin
(nAna c 2). Finally, tryptase-level evaluation in preserved sera
conrmed the anaphylactic reaction: pre-OLT tryptasemia was
5.72 mg/l while post-OLT tryptasemia, evaluated at the end of the
surgical operation, was four times higher.
4. Discussion
On the basis of the post-mortem serological test, this is the rst
reported case of fatal anaphylactic shock from prolonged intraoperative infusion of Thymoglobulin in an atopic patient with
specic IgE against CCDs. Hitherto, only one case has been
described of non-fatal anaphylactic shock, well controlled by
Fig. 5. Original liver. Degranulated mast cells and basophils are noticeable (original
magnication 40); in the insert degranulated basophils (black arrows) are weakly
stained by hematoxylin, used for counterstaining Pagoda red (original
magnication 100).
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Acknowledgments
The authors would like to express their thanks to Paul Angus,
who revised the manuscript in its nal version, and to Luca
Fabbiani, for his technical support.
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1
CD63 protein (MLA1, LAMP3), encoded by the CD63 gene, is a transmembrane
protein belonging to the tetraspanin family, and is characterized by the presence of
four hydrophobic domains, mainly situated on the internal membranous surface of
basophil granules. During the degranulation process, the granules membrane
merges with the cell membrane and, consequently, CD63 protein is exposed on the
external surface of the cell membrane. For this reason, the CD63 protein is
considered a molecular marker of activated and degranulated basophils.
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