Occupational and food allergy - RePub - Erasmus Universiteit

127 Pages·2004·2.23 MB·English

Occupational and food allergy:
focus on allergen extracts
Cover illustration: Levien Willemse, Rotterdam
Printed by: Optima Grafische Communicatie, Rotterdam

ISBN 90-77595-73-2

No part of this thesis may be reproduced or transmitted in any form by means, electronic or mechanical,
including photocopying, recording or any information storage and retrieval system, without permission in
writing from the publisher (N.W. de Jong, Department of Allergology, Erasmus MC, Dr. Molewaterplein 40,
3015 GD, Rotterdam, the Netherlands)
Occupational and food allergy:
focus on allergen extracts

Beroeps - en voedselallergieën:
aandacht voor allergeen extracten

Proefschrift

Ter verkrijging van de graad van doctor aan de
Erasmus Universiteit Rotterdam
op gezag van de
Rector magnificus

Prof.dr. S.W.J. Lamberts

en volgens besluit van het College voor promoties.

De openbare verdediging zal plaatsvinden op
Woensdag 17 November 2004 om 15.45 uur

door

Nicolette Wilma de Jong

Geboren te Rotterdam
Promotiecommissie

Promotor:
Prof.dr. H.A.P.Pols

Overige leden:
Prof.dr. H.F.J. Savelkoul
Prof.dr. J.M.W. Hazes
Dr.ir. A.Burdorf

Copromotor:
Dr. R. Gerth van Wijk

Financial assist for the printing of this thesis from the following companies is gratefully
acknowledged:
ACM Ooms Allergie BV, ALK Abelló BV, DPC Nederland BV, HAL Allergy BV, Koppert BV,
Mead Johnson, Pharmacia Diagnostics AB, Precision bijscholingen BV, Schering- Plough BV
Aan mijn ouders

Table of contents

Part one: General introduction

Chapter 1 1

Part two: Occupational pollen allergy

Chapter 2 Prevalence of occupational allergy to chrysanthemum pollen in 13
Greenhouses in the Netherlands.
Allergy 2002;57:835-40

Chapter 3 Occupational allergy caused by flowers. 25
Allergy 1998;53:204-9.

Part three: Occupational latex allergy

Chapter 4 Prevalence of natural rubber latex allergy (Type I and Type IV) in laboratory 33
workers in the Netherlands.
Contact Dermatitis 1998;38:159-163

Part four: Food allergy

Chapter 5 Reproducibility and stability of ‘in house manufactured’ extracts used in the 43
diagnosis of IgE mediated Allergy.
Submitted

Chapter 6 Birch pollinosis and atopy caused by apple, peach, and hazelnut; comparison 55
of three extraction procedures with two apple strains. Adapted from:
Allergy 1996;51:712-8.

Part five: Cross-reactivity

Chapter 7 Immunoblot and RAST-inhibition studies of allergenic cross-reactivity of the 65
predatory mite Amblyseius cucumeris.
Ann. Allergy Asthma Immunol. 2004;93:281-7

Part six: Intervention

Chapter 8 Honeybees as an aid in reducing occupational pollen allergy complaints in 79
sweet bell pepper (Capsicum annuum) greenhouses.
Submitted

Chapter 9 Allergy to bumblebee venom. III. Immunotherapy follow-up study 91
(safety and efficacy) in patients with occupational bumblebee-venom
anaphylaxis.
Allergy 1999;54:980-4.

Part seven: General discussion and summary

Chapter 10 General discussion and summary 97
Samenvatting 111
Dankwoord 113
Curriculum Vitae 115
Publications 116
Abbreviations used

Ac Amblyseius cucumeris
As Acarus siro
BBP bell pepper pollen
CCD crossreactive carbohydrate determinants
CI confidence interval
CH case history
CV coefficient of variation
DBPCFC double-blind, placebo-controlled food challenge
Dp Dermatophagoides pteronyssinus
FEV1 forced expiratory volume in 1 second
FS field sting
FVC forced vital capacity
HC hospital sting challenge
HBV honeybee (Apis mellifera) venom
HEIC histamine equivalent intracutaneous test
HEP histamine equivalent prick test
HMW high molecular weight
IHR in house reference
ICT intracutaneous test
ICC intra class correlation
IL interleukin
IQR inter Quartile Range
LAS work-related lower airway symptoms
Ld Lepidoglyphus Destructor (Ld)
LMW low molecular weight
LR local reaction
ND not done
NRL natural rubber latex
OAS oral allergy syndrome
PBS phosphate buffered saline (pH 7.4, 0.03% human serum albumin, 0.5% phenol)
PBS – A phosphate buffered saline, with 10 mM EDTA and 0.3% BSA
PBS – T phosphate buffered saline, with 0.1 % NaN3, 0.2% Tween
PBS – AT phosphate buffered saline, with 0.1 % NaN3, 0.2% Tween, 0.3% BSA
PEF peak expiratory flow
PR pathogenesis related
PRR prevalence rate ratio
QOL quality of life
RAST radio allergo sorbent test
RIA radioimmunoassay
SE standard error
SD standard deviation
SPT: skin prick test
SDS PAGE sodium dodecyl sulfate polyacrylamide gel electrophoresis
SR systemic reaction
Th T-helper
Tp Tyrophagus putrescentiae
UAS work related upper airway symptoms
UV-B ultraviolet B light
VAS visual analogue scale
VIT venom immunotherapy
YJV yellow jacket (Vespula germanica) venom
Preface
Allergic disorders are common in the northern part of Europe. Besides the well known house dust
mite, grass and tree pollen as causative agents many other allergens such as insects, foods, biological
agents, and latex, can elicit allergic symptoms as well. An increase in prevalence of allergic
disorders has also been observed. An increasingly accepted explanation for this is provided by the
hygiene hypothesis (Smith et al. 2004) This hypothesis suggests that the increasing prevalence of
allergy is due to a diminished exposure to immune stimulants such as viruses, bacteria and endotoxins,
in particular in the early childhood. As an underlying mechanism for this hypothesis, it is proposed
that due to the lack of microbial stimulation either a misbalance in T helper type responses or a
misbalance in regulatory mechanisms develop.

When antigens enter the body, the immune system produces T-helper (Th) cells. These lymphocytes
produce high levels of cytokines in order to protect the body against the antigens. Based on their
unique cytokine production profiles these Th cells can be classified into subsets with different
functional properties: Th1 and Th2 cells. Th1 cells play an important role in the protecting against
inter cellular infections, e.g. viruses, whereas Th2 cells are essential in the clearance of extra cellular
parasites e.g. bacteria. A dysregulation of the immune system can cause an increased production of
Th1 or Th2 cells as a result of the absence of a network of anti-inflammatory regulatory cells (Tr-
cells). An increased production of Th1 cells is seen in type I, e.g. diabetes mellitus and, rheumatoid
arthritis. Characteristic of allergic patients is the excessive and persistent maturation of T-cell immune
response into Th2 direction. The Th2 cells produce high levels of cytokines e.g. interleukin (IL) 4 and
IL 13, which favours the production of specific IgE by B-cells. This specific IgE binds to mast cells
and basophils, leading to mediator release after contact with an allergen.

Allergic reactions can be distinguished in four different types: IgE mediated (Type I) and non-IgE
mediated (Type II, III and IV). Type I is the immediate type (reactions within 15 minutes), and type
IV is called the delayed (reactions after 48-72 hours) type.

Antibody or
Type of Lymphocytes Clinical
Reaction induced Manifestations
I IgE Urticaria, rhinitis, conjunctivitis, asthma,
Anaphylaxis, oral symptoms,
Gastrointestinal symptoms
II IgM, IgG Haemolytic anaemia
Blood transfusion reactions
III IgG Serum sickness,
Glomerulonephritis
IV Th cells Contact dermatitis

The diagnosis of IgE mediated allergy (Type I) largely depends on the clinical history (CH).
Consequently, the clinical history needs to be confirmed by other methods. The skin prick test (SPT)
or the intracutanous test (ICT) with an extract of the suspected allergen is the first diagnostic
procedure to be applied. The Radioallergosorbent test (RAST) is used for the detection of allergen
specific IgE. This determination of IgE is now widely performed and generally correlates with other
diagnostic procedures. Furthermore, an allergen provocation with the responsible allergen is possible.
In the case of a food allergy, the double blind placebo controlled food challenge (DBPCFC) is
considered to be ‘the golden standard’. In case of inhalant allergies a lung provocation or nose
provocation is possible.
The most common inhalant allergen extracts for SPT, ICT and RAST are commercially available and
standardised. On the contrary, the diagnostic work up of the uncommon allergies caused by relatively
new allergens, e.g. certain food allergens, occupational allergens, is more difficult. Commercial
extracts are not generally available, the allergens are often unknown and in vitro assays often give
unpredictable responses. Consequently, the need for good standardised extracts to confirm these
uncommon allergies is increasing.

Not only the prevalence of allergic diseases is increasing; also the spectrum of sensitivities in allergic
subjects seems to extend. There is an increasing awareness that patients may be sensitised to a series
of related allergens. Likewise, pollen allergic patients are frequently co-sensitised to different plant
foods. This phenomenon is not limited to plant foods. Many examples are described and can be
explained by cross-reactive IgE antibodies directed to homologous allergens. In the diagnosis of the
allergic subjects, physicians should pay attention to these co-sensitisations. Again, standardised
extracts being not available, makes it difficult to examine co-sensitisation.

The treatment of allergic disorders comprises allergen avoidance, pharmacotherapy, and -in selected
cases only- immunotherapy. In case of food allergy, avoidance of the offending food is warranted. In
case of occupational allergy, change of profession might be the only solution.

This thesis presents the results of some diagnostic and therapeutic studies, on occupational - and food
allergies. Furthermore, research has been done on cross-reactivity between inhalation mutual and
between inhalation and food allergens. Because standardised commercially available extracts were not
available, ‘in house manufactured’ extracts have been used in most studies. Finally we examined the
quality of ‘in house manufactured’ extracts.