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Rad. Medical Sciences, Zagreb, 2008., str. 117-128

S. Dodig: Current laboratory diagnosis of allergy
Slavica Dodig
Srebrn|ak Children's HospiLal, Reference CenLer for Clinical IediaLric Allergology of
Lhe MinisLry of HealLh and Social Welfare, Zagreb, CroaLia
1ho roquosts or laboratory dlagnosls o allorglc dlsoasos roor to a battory o tosts that
should rovldo tho ollowlng. 1) dotormlno tho tyo o allorglc roactlon by dotoctlng
humoral (total lgL) and collular (ooslnohlllc and basohlllc granulocyto count, ooslnohll
catlonlc rotoln) modlators o allorglc roactlon, 2) ldontly trlggors o allorglc roactlon
(socllc lgL to artlcular causatlvo allorgons, tosts or basohlllc granulocyto e\ v|vo actlva-
tlon, loukotrlonos, CD63, hlstamlno), 3) assoss tho cllnlcal courso o allorglc roactlon
(trytaso or lmmodlato roactlon, ooslnohll catlonlc rotoln or dolayod roactlon), 4)
onablo socllc lmmunothoray monltorlng (total and socllc lgL, socllc lgC4 and lgC1,
lgC4/lgC1 ratlo, roallorglc and rolnlammatory cytoklnos), and 5) ostlmato dlagnostlc
olcloncy o dotormlnatlon o artlcular humoral or collular modlators o allorglc roactlon
(l.o., sonsltlvlty, socllclty, osltlvo and nogatlvo rodlctlvo valuo).
Althouh laboratory lnvostlgatlons aro a usoul tool ln tho dlagnosls and managomont
o allorglc dlsoasos many robloms romaln unsolvod. 1hoso robloms can bo grouod lnto
throo catogorlos. roanalytlcal (soclmon colloctlon), analytlcal and ost-analytlcal (lntor-
rotatlon, ollow-u, rotostlng) hasos o laboratory tostlng.
Kcywords. allorgy, lgL, basohlls, loukotrlono, lmmunothoray
The requesLs made Lo clinical biochemisLs for laboraLory diagnosis of allergic diseas-
es refer Lo a baLLery of LesLs LhaL should provide Lhe folloving: 1) deLermine Lhe Lype of
allergic reacLion by deLecLing humoral and cellular mediaLors of allergic reacLion, 2)
idenLify Lriggers of allergic reacLion, 3) assess Lhe clinical course of allergic reacLion
(immediaLe, delayed, or prolonged), 4) enable specific immunoLherapy moniLoring,
UDK 616-022.8/.9-07
Received: 14 December 2007
Accepted: 20 February 2008
Correspondence Lo: Doc. dr. sc. Slavica Dodig, Ih. D., Srebrn|ak Children HospiLal, Srebrn|ak 100,
10000 Zagreb, L-mail: slavica_dodig.neL
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S. Dodig: Current laboratory diagnosis of allergy
and 5) esLimaLe diagnosLic efficiency of deLerminaLion of parLicular humoral or cellular
mediaLors of allergic reacLion. The LesLs currenLly used and Lheir diagnosLic value in Lhe
deLecLion and LherapeuLic moniLoring of allergic diseases are briefly described.
IdenLificaLion of Lhe Lype of allergic reacLion implies deLerminaLion of humoral and
cellular allergic reacLion mediaLors, including LoLal immunoglobulin L (IgL) concenLra-
Lion, eosinophilic and basophilic granulocyLe counL |1], eosinophil caLionic proLein
(LCI) concenLraLion |2], idenLificaLion of membrane markers of basophil acLivaLion (CD63),
and hisLamine release from basophilic granulocyLes |3].
1. 1. Determination of totaI IgE concentration
As a simple and auLomaLed meLhod, deLerminaLion of LoLal IgL concenLraLion in
serum is included in Lhe screening vork-up for aLopy |4]. Serum concenLraLion of IgL
anLibodies varies from very lov levels in infancy Lhrough several-fold levels from Lhe
age of nine years (Table 1). None of oLher immunoglobulins undergoes such an increase
viLhin Lhe normal range during lifeLime.
1ab/e 1. Uor llmlts o lgL concontratlon ln 95 o chlldron accordlng to ago
Ago (yoars) lgL, 95
contllo (klU/L)
<1 20.2
1 30.4
2 38.6
3 57.0
4 57.2
5 65.4
6 73.0
7 82.6
8 76.4
9 98.4
10 102.6
11 104.8
12 101.4
13 97.4
14 94.2
15 105.2
16 100.0
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S. Dodig: Current laboratory diagnosis of allergy
The upper reference limiLs of LoLal IgL concenLraLion in children are consisLenL viLh
cuL-off values beLveen aLopic (n~4520) and nonaLopic (n~3355) sub|ecLs. The values
vere deLermined aL DeparLmenL of Clinical LaboraLory Diagnosis, Srebrn|ak Children's
HospiLal in Zagreb (blood sampling vas performed during Lhe 2001-2004 period) |5].
In addiLion Lo iLs role in deLecLing aLopic disease, deLerminaLion of IgL concenLra-
Lion appears Lo poinL Lo Lhe disease severiLy, in children belov 16 years of age in parLic-
ular |6,7], hovever, some auLhors vould noL agree viLh Lhe laLLer |8,9].
1. 2. Losinophilic and basophilic granulocq!c coun!
AlLhough numerous cell Lypes (lymphocyLes, eosinophilic granulocyLes, masLocyLes,
basophilic granulocyLes, endoLhelial cells, epiLhelial cells of Lhe respiraLory sysLem, neu-
Lrophilic granulocyLes, anLigen-presenLing cells) are involved in allergic reacLion, eosi-
nophilic granulocyLe counL in Lhe blood and nasal svab is mosLly deLermined in daily
rouLine. The advenL of blood counLers offering auLomaLed deLerminaLion of basophilic
granulocyLe counL has enabled Lhe use of Lhis ad|uncL parameLer in Lhe assessmenL of
allergic disease.
Cllnlcal symtoms o allorgy
LCl <15 mg/L
(chlldron <20 mg/L)
doos not olnt to
allorglc lnlammatlon,
contlnuo tostlng
LCl <15 mg/L
(chlldron <20 mg/L)
olnts to allorglc
antl-lnlammatory thoray
LCl <15 mg/L
(LCl <20 mg/L)
dlscontlnuo thoray
LCl <25 mg/L
(20<LCl<30 mg/L)
contlnuo thoray
LCl <25 mg/L
(LCl <30 mg/L)
lncroaso drug dosago

lig. 1. Assossmont o LCl valuo ln monltorlng/troatmont o allorglc lnlammatlon.

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S. Dodig: Current laboratory diagnosis of allergy
1. 3. EosinophiI cationic protein (ECP) concentration
In daily rouLine, deLerminaLion of Lhe concenLraLion of LCI released from eosino-
philic granulocyLe granules allovs for Lhe course of allergic reacLion Lo moniLor, since
an increased LCI concenLraLion (like eosinophilic granulocyLe counL) poinLs Lo acuLe
allergen exposure and Lhus Lo Lhe severiLy of allergic inflammaLion |10,11]. Thus, iL can
be used as a marker in LherapeuLic moniLoring in asLhmaLic paLienLs. The upper refer-
ence limiL is 15 g/L for adulLs and 20 g/L for children, and levels exceeding Lhese cuL-off
values poinL Lo allergic inflammaLion (Iig. 1).
A - Increased serum LCI concenLraLion (>15g/L in adulLs and > 20 g/L in chil-
dren, respeciLvely) provides an addiLional informaLion Lo complemenL Lhe clinical eval-
uaLion of allergic inflammaLion. - Since Lherapy viLh corLicosLeroids can reduce aller-
gic inflammaLion, LCI measuremenL can Lherefore be used for guiding Lhe anLi-inflam-
maLory response. The advice is Lo check LCI before considering changing Lhe LreaLmenL
dose. CorLicosLeroid LreaLmenL may be reduced if Lhe paLienL's clinical siLuaLion is sLable
and Lhe LCI level is normal.
lood concenLraLion of specific IgL Lo parLicular causaLive allergens deLecLed by
cuLaneous LesLing is deLermined Lo idenLify Lhe Lrigger of allergic reacLion. In early child-
hood vhen cuLaneous LesLs are less reliable, deLerminaLion of IgL Lo a group of causaLive
allergens (inhalanL or nuLriLional, IhadiaLop Yes or No LesL for IgL, 93% sensiLiviLy and
89% specificiLy) is recommended in screening for causaLive allergens, as an alLernaLive Lo
cuLaneous LesLing |12]. If hypersensiLiviLy is noL demonsLraLed by Lhis procedure, no
furLher LesLing is required (99% negaLive predicLive value), hovever, vhen hypersensi-
LiviLy Lo a group of allergens is proven (89% posiLive predicLive value), Lhe procedure
should be folloved by deLerminaLion of parLicular specific IgL in Lhe same serum sam-
ple. IL should be noLed LhaL Lhe values obLained by IhadiaLop meLhod are expressed in
arbiLrary uniLs seL by Lhe manufacLurer.
2. 1. Determination of aIIergen-specific IgE concentrations
Upon deLecLion of causaLive allergens by Lhe skin prick LesL, Lhe presence of specific
IgL againsL Lhese allergens and Lheir main epiLopes is deLermined in serum of paLienLs
viLh a clinical picLure of allergic disease. DeLerminaLion of specific IgL in serum indi-
caLes currenL immune acLiviLy, vhile skin LesLing reveals IgL local bioacLiviLy mediaLed
by long-living cells |13]. If Lhe concenLraLion of specific IgL is deLermined by Lhe sLan-
dardized meLhod |14] (according Lo Lhe World HealLh rganizaLion Second InLernaLion-
09 Dodig.p65 04.02.2008., 11:20 120
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S. Dodig: Current laboratory diagnosis of allergy
1ab/e 2. Sorum lovols o socllc lgL antlbodlos (CAl rocoduro) |15}
Socllc lgL (kU
/L) Class kosult lntorrotatlon
<0.35 0 Unmoasurablo concontratlon o socllc lgL
0.36-0.7 1 Lowost concontratlon o socllc lgL
0.71-3.5 2 Low concontratlon o socllc lgL
3.6-17.5 3 Modorato concontratlon o socllc lgL
17.6-50.0 4 Hlgh concontratlon o socllc lgL
51.0-100.0 5 Vory hlgh concontratlon o socllc lgL
>100.0 6 Lxtromoly hlgh concontratlon o socllc lgL
1ab/e 3. lntorrotatlon o |o v|t|o rocoduros
1otal lgL (klU/L) Socllc lgL (klU
<0.35 0.36-0.7 0.71-3.5 3.6-17.5 17.6-50.0 51.0-100.0 >100.0
lorhas not losslblo losslblo losslblo losslblo losslblo
slgnllcant, lndlvldual lndlvldual lndlvldual multllo multllo
Vory low No atoy roqulros hyor- hyor- hyor- hyor- hyor-
rooat sonsltlvlty, sonsltlvlty sonsltlvlty sonsltlvlty sonsltlvlty
tostlng' rooat
lorhas not Cut-o losslblo losslblo losslblo lrobably
slgnllcant, valuo, lndlvldual lndlvldual multllo multllo
Normal No atoy roqulros rooat hyor- hyor- hyor- hyor-
rooat tostlng' sonsltlvlty sonsltlvlty sonsltlvlty sonsltlvlty
Atoy not Atoy not Atoy not lrobably Multllo lrobably lrobably
oxcludod, oxcludod, oxcludod, multllo hyor- multllo multllo
lncroasod oxand oxand oxand hyor- sonsltlvlty hyor- hyor-
socllc lgL socllc lgL socllc lgL sonsltlvlty sonsltlvlty sonsltlvlty
soctrum soctrum soctrum, hlstory

'thoso lndlngs may bo duo to tho atlonts ollon hyorsonsltlvlty, thorooro rooat tostlng uon comlotlon o olllnatlon may rovo usoul
al Reference IreparaLion for Human IgL, WH 2
IRI 75/502), resulLs can be quanLiLa-
Lively expressed viLhin a range from 0.36 Lo 100 kU
/L, excepL for IgL classes 1-6 (Table 2).
Table 3 shovs correlaLion of Lhe resulLs obLained by deLerminaLion of LoLal and spe-
cific IgL in serum and can be used a guide in inLerpreLaLion of resulLs.
2. 2. Activation of basophiIic granuIocytes
This group of LesLs also includes deLerminaLion of Lhe concenLraLions of released
hisLamine (radioimmunology, LLISA), leukoLrienes (LLISA) |16,17] and surface CD mark-
ers (flov cyLomeLry) folloving basophilic granulocyLe acLivaLion by Lhe causaLive aller-
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S. Dodig: Current laboratory diagnosis of allergy
gen cx titc (Iig. 2) |18]. Cellular in tiirc diagnosis has greaLly improved viLh Lhe inLro-
ducLion of Lhe meLhod of flov cyLomeLry. In allergic diseases, Lhe diagnosis based on
flov cyLomeLry is for Lhe Lime being mosLly employed in research sLudies |19]. The role
of LesLs for basophilic granulocyLe acLivaLion in Lhe diagnosis of allergies remains Lo be
LvaluaLion of Lhe clinical course of allergic reacLion, i.e. immediaLe, delayed or pro-
longed hypersensiLiviLy, can LheoreLically be done by deLerminaLion of Lhe exisLing me-
diaLors such as LrypLase (a marker of anaphylaxis, immediaLe reacLion) or LCI (delayed
reacLion), or by deLerminaLion of synLhesized mediaLors of allergic reacLion such as leu-
koLrienes folloving basophilic granulocyLe exposure Lo causaLive allergens. Ior Lhe Lime
being, Lhese LesLs are only performed in research. TrypLase is a serine proLease LhaL is
released, along viLh hisLamine, from masLocyLes upon Lhe allergen-IgL complex forma-
Lion, and represenLs a marker of anaphylacLic reacLion |20]. As hisLamine concenLraLion
rises viLhin 15-30 minuLes and reLurns Lo normal values viLhin one hour, iL is quiLe
difficulL Lo measure. Therefore, Lhe measuremenL of LrypLase is used as a more reliable
laboraLory parameLer. Increased LrypLase concenLraLion (>13.5 g/L) can be demonsLraL-
ed viLhin 3-6 hours of anaphylacLic reacLion, Lhen iL reLurns Lo cuL-off values in Lhe nexL
12-14 hours.
lig. 2. 1ho rlncllo o mothods o basohlllc granulocyto actlvatlon. asohlllc granulocytos
dorlvod rom atlont blood aro actlvatod by tho causatlvo allorgon e\ v|vo, thon varlous markors o
tholr actlvatlon can bo dotormlnod (CAS1 ~ Collular Allorgon Stlmulatlon 1ost).
09 Dodig.p65 04.02.2008., 11:20 122
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S. Dodig: Current laboratory diagnosis of allergy
Specific immunoLherapy (SIT) in tiirc moniLoring is burdened viLh a number of
problems, from Lhose relaLed Lo Lhe paLienL himself and Lhe immune paLhomechanisms
LhaL have led Lo Lhe developmenL of allergic disease, coadminisLraLion of sympLomaLic
and anLi-inflammaLory Lherapy, long-Lerm SIT (currenLly, no parameLers are available Lo
predicL viLh cerLainLy in Lhe early sLage of disease vheLher Lherapy vill evenLually
prove useful for Lhe paLienL), choice of biomarkers and defining Lheir cuL-off values
above or belov vhich Lhere is or Lhere is no proLecLive acLion of an immune sysLem
segmenL, Lhrough laboraLory procedures LhaL undergo rapid modificaLions and advanc-
es, Lhus Lhe resulLs obLained aL Lhe beginning of some longiLudinal sLudies cannoL be
reliably compared viLh Lhe resulLs recorded aL Lhe end of Lhe same sLudies or viLh Lhe
resulLs reporLed from oLher sLudies, in addiLion, many of Lhe laboraLory procedures LhaL
could be used Lo deLermine some key biomarkers (e.g., immunoglobulin subclasses, cell
subpopulaLions, cyLokines, eLc.) cannoL be employed in daily rouLine buL remain re-
served for scienLific research. esides clinical sympLoms, some sLudies also moniLored
resulLs of in titc (cuLaneous LesLing) and in tiirc LesLs |21,22], e.g., deLerminaLion of Lhe
concenLraLion of LoLal IgL and specific IgL |23], specific IgC |24,25], specific IgC4 and
IgC1 (IgC4/IgC1 raLio) |26], IgC2, lymphocyLe T subpopulaLion |27], proallergic cyLok-
ines (IL-4, IL-13 and IL-5), proinflammaLory cyLokines (IIN-, IL-2 and IL-12) |28], and
leukoLrienes |29]. IL should noL be forgoLLen LhaL moniLoring of Lhe severiLy of clinical
sympLoms in each individual paLienL is of paramounL imporLance in Lhe overall immu-
noLherapy moniLoring in paLienLs viLh allergic diseases.
LaLely, recombinanL allergens have been used vorldvide in Lhe diagnosis and in
SIT, enabling deLerminaLion of paLienL profile and use of individualized SIT, i.e. only
Lhose allergen deLerminanLs (epiLopes) Lo vhich hypersensiLiviLy has developed in Lhe
respecLive paLienL. AssessmenL of specific IgL and specific IgC4 concenLraLions during
immunoLherapy yields beLLer resulLs viLh Lhe use of recombinanL allergens Lhan viLh
Lhe usual allergen preparaLions |30].
lig. 3. Antl-lgL (a-lgL) blnds roo lgL.
09 Dodig.p65 04.02.2008., 11:20 123
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S. Dodig: Current laboratory diagnosis of allergy
The adminisLraLion of monoclonal anLi-IgL (omalizumab) resulLs in free IgL block-
ing, Lhus reducing Lhe level of free IgL capable of binding Lo masLocyLes and basophilic
granulocyLes (Iig. 3) |31]. Therefore, deLerminaLion of LoLal IgL concenLraLion on Lhe
very firsL day of omalizumab adminisLraLion is useful Lo moniLor free IgL concenLraLion.
DiagnosLic procedures are expecLed Lo be accuraLe, precise, sensiLive, specific, reli-
able, reproducible, and viLh minimal inLerfering facLors |32,33]. A prerequisiLe for Lhe
mosL efficienL use of diagnosLic LesLs is Lo knov Lheir limiLaLions, Lheir analyLical, prean-
alyLical and posLanalyLical inLerferences, and Lheir diagnosLic efficiency (i.e. sensiLiviLy,
specificiLy, posiLive and negaLive predicLive value, Lable 4). Lach healLhcare insLiLuLion
should deLermine diagnosLic value of every diagnosLic procedure in titc or in tiirc.
1ab/e 4. Dlagnostlc olcloncy o total and socllc lgL (lncludlng lhadlato) and LCl dotormlna-
tlon (adatod rom 34, 35)
Analyto Sonsltlvlty Socllclty losltlvo Nogatlvo
() () rodlctlvo rodlctlvo
valuo () valuo ()
1otal lgL 97.1 93.3 94.5 96.6
lhadlato - adults 70.8 90.7 72.6 89.9
lhadlato - lnants 65.0 100.0 100.0 93.0
Socllc lgL, asthmatlc chlldron
(De|nato|ago|oes te|oojss|ous) 100.0 96.7 97.3 100.0
LCl, asthmatlc chlldron 97.4 100.0 100.0 96.8
AlLhouh laboraLory invesLigaLions are a useful Lool in Lhe diagnosis and manage-
menL of allergic diseases many problems remain unsolved. Those problems can be
grouped inLo Lhree caLegories: preanalyLical (specimen collecLion), analyLical (LesLing)
and posL-analyLical (inLerpreLaLion, follov-up, reLesLing) phases of laboraLory LesLing.
6. 1. PreanaIyticaI probIems
Time of blood collecLion for deLerminaLion of LoLal IgL, specific IgL, LCI and eosi-
nophil counL, respecLively, could be imporLanL in cases of hypersensiLiviLy Lo:
seasonal allergens (level of selecLed analyLes is greaLer in pollen season),
insecL sLing allergens (vaning of allergen-specific IgL viLh Lime folloving expo-
sure), and
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S. Dodig: Current laboratory diagnosis of allergy
drug allergens (long Lime elapsed beLveen Lhe adminisLraLion of Lhe drug and
specific IgL deLerminaLion vill resulL viLh negaLive specific IgL).
The eosiniphil release of LCI in viLro during cloLLing is Lime- and LemperaLure-
dependenL. LCI levels in serum increase viLh Lime as Lhe LCI release from Lhe
eosinophils vill conLinue unLil serum is separaLed from Lhe cells. Therefore Lhe
blood collecLion Lube, coagulaLion Lime and LemperaLure musL be kepL viLhin spec-
ified limiLs during cloLLing.
Increased concenLraLion of LoLal LrypLase acLiviLy can be deLecLed up Lo Lhree Lo six
hours afLer Lhe anaphylacLic reacLion. IL reLurns Lo normal value viLhin 12-14 hours
afLer release. Samples should preferably be collecLed beLveen 15 minuLes and 3
hours afLer Lhe suspecLed evenL causing masL cell acLivaLion |20].
6. 2. AnaIyticaI probIems
ToLal and specific IgL anLibody deLerminaLion in serum can produce differenL re-
sulLs depending on Lhe meLhod. Therefore sLandardized meLhods should be used.
6. 3. Post-anaIyticaI probIems
CorrelaLion of in tiirc LesLing viLh in titc LesLing as vell as viLh clinical finding is
Lhe mosL imporLanL for diagnosis and moniLoring of allergic disease |8,15]. Some prob-
lems can be specialized:
Under ideal condiLions, specific IgL deLerminaLion should provide resulLs concor-
danL viLh skin prick LesLing. Hovever, common allergen exLracLs are noL used in
Lhese Lvo meLhods.
In spiLe of Lhe facL LhaL reference inLervals for LoLal IgL are defined, 5 % of non-aLopic
sub|ecLs have increased LoLal IgL concenLraLion, and up Lo 10% of aLopic sub|ecLe
mighL have IgL concenLraLion inside Lhe reference inLervals |5].
SensiLisaLion alone does noL indicaLe clinically significanL hypersensiLiviLy. Con-
versely, a negaLive resulL does noL necessarily exclude clinically significanL allergy.
No single Lype of in tiirc LesL should be used as Lhe only diagnosLic LesL for food
No biomarker can assess clinical course of allergic disease.
AlLhough effecLive SIT is accompanied by increase of allergen specific IgC/IgC4
anLibodies and decrease of LoLal/specific IgL anLibodies |24-26], as yeL, no early mark-
er can predicL Lhe final ouLcome of SIT.
In conclusion, iL should be noLed LhaL clinical biochemisLry laboraLories in CroaLia
included in Lhe CroaLian InsLiLuLe of HealLh Insurance sysLem perform mosL diagnosLic
procedures in Lhe field of allergology (e.g., eosinophilic granulocyLe counL, LoLal and
specific IgL concenLraLion, LCI, LrypLase) by use of sLandardized meLhods, Lhus making
09 Dodig.p65 04.02.2008., 11:20 125
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S. Dodig: Current laboratory diagnosis of allergy
Lhe values obLained aL differenL laboraLories comparable. In addiLion, Lhese clinical bio-
chemisLry laboraLories are included in inLernaLional performance qualiLy assessmenL,
e.g., QualiLy Club (Iharmacia DiagnosLics), Lhus receiving reporLs on performance qual-
iLy in each individual laboraLory for parLicular analyLes on a monLhly basis.
|1] Prussin C, Mcisc|jc DD. IgL, masL cells, basophils, and eosinophils. } Allergy Clin
Immunol 2006,117:S450-6.
|2] Njc I, |c|sun! OD, Ccr|scn K-H. Losinophil caLionic proLein (LCI) in schoolchildren
living in a mounLainous area of Norvay: a populaLion-based sLudy of LCI as a Lool
for diagnosing asLhma in children viLh reference values. Allergy 2001,56:138-43.
|3] Szcgc!i A, |rini 8, Gc| M, Hunc!i j, Dcn|c K, Kiss |, Sip|c S, Szcgc!i G, Gimcsi |.
SignificanL correlaLion beLveen Lhe CD63 assay and Lhe hisLamine release assay in
chronic urLicaria. r } DermaLol 2006,155:67-75.
|4] P|ciis-Mi||s 1A|. The role of immunoglobulin L in allergy and asLhma. Am } Respir
CriL Care Med 2001,164:1-5.
|5] Dc!ig S, |ic|icr D, 8cn|c 8, Zitcic j, |ccs M, Ncgc|c 8, Ccpc|c| |, Dc!ig M. CuL-off
values of LoLal serum IgL beLveen nonaLopic and aLopic children in norLh-vesL
CroaLia. Clin Chem Lab Med 2006,44:639-47.
|6] Sircux V, Orszczn MP, Pci |, Kcujjmcn I, Piscn C, Vcrt|cci D, Pin |. RelaLionships
of allergic sensiLizaLion, LoLal immunoglobulin L and blood eosinophils Lo asLhma
severiLy in children of Lhe LCLA SLudy. Clin Lxp Allergy 2003,33:746-51.
|7] Kctcc K, Dc!ig S, 1jcsic-Drin|ctic D, |ccs M. CorrelaLion beLveen asLhma severiLy
and serum IgL in asLhmaLic children sensiLized Lo Dcrmcicp|cgci!cs picrcnssinus.
Arch Med Res 2007,38:99-105.
|8] Ducnc IS, Sicin |, Hc|cncn M, Hc||crg Cj, \rig|i A, Mcriincz ID. ToLal serum IgL and
iLs associaLion viLh asLhma sympLoms and allergic sensiLizaLion among children. }
Allergy Clin Immunol 1999,104:28-36.
|9] Ics|c N, Niggcmcnn 8. Does Lhe severiLy of aLopic dermaLiLis correlaLe viLh serum
IgL levels` IediaLr Allergy Immunol 2004,15:86-8.
|10] Prc|n A, Scgcr |A, Ic|cr j, 1crrcscni 1, Mc|incri I, Gcr|cr A, Scn|cuscr IH. The rela-
Lionship of serum-eosinophil caLionic proLein and eosinophil counL Lo disease ac-
LiviLy in children viLh bronchial asLhma. IediaLr Allergy Immunol 1998,9:197-203.
|11] Vcngc P. Serum measuremenLs of eosinophil caLionic proLein (LCI) in bronchial
asLhma.Clin Lxp Allergy 1993:23(Suppl 2):3-7.
|12] 8c||cr!ini N, Ni|sscn C, Ni|sscn M, Ii|jc G. ImmunoCAI IhadiaLop InfanL a nev
blood LesL for deLecLing IgL sensiLisaLion in children aL 2 years of age. Allergy
09 Dodig.p65 04.02.2008., 11:20 126
Rad. Medical Sciences, Zagreb, 2008., str. 117-128
S. Dodig: Current laboratory diagnosis of allergy
|13] A||sic!i S. UndersLanding Lhe usefulness of specific IgL LesLs in allergy. Clin Lxp
Allergy 2002,32:11-6.
|14] jc|cnsscn SGO. ImmunoCAI. Specific IgL LesL: an ob|ecLive Lool for research and
rouLine allergy diagnosis. LxperL Rev Mol Diagn 2004,4:273-9.
|15] P|c|cni M. Clinical evaluaLion and cosL-benefiL analysis of a nev sysLem (Iharmacia
CAI sysLem) for Lhe idenLificaLion of specific IgL. Uppsala: Iharmacia DiagnosLics
A, 52-5103-40/01, 1991.
|16] !c \cc| AI, Scnz MI. Cellular Allergen SLimulaLion TesL (CAST) 2003, a reviev. }
InvesL Allergol Clin Immunol 2004,14:253-73.
|17] |u!c|j M, Mi|ctcc-Purciic V, Iipczcncic j, Mc|cnicc 8. Clinical usefulness of cellular
anLigen sLimulaLion LesL in deLecLion of aspirin allergy. AcLa DermaLovenerol CroaL
|18] Dcmc| P, Ic|c| 8, Arncux 8. Allergy reviev series X: Irogress in diagnosis of allergy
in tiirc allergen induced mediaLor release LesLs. Allergy 2003,58:553-8.
|19] Dc|cris D. |n tiirc di|agnosLika celularnih imunoreakci|a u alergi|skim bolesLima
disnog susLava. Medicus 1997,6:45-53.
|20] |!sicn |, tcn Hcgc-Hcmsicn M, jc|cnsscn SG. TrypLase aL lasL a useful diagnosLic
marker for anaphylacLic deaLh. Allergy 1996,51:443-4.
|21] 8cusuci j, Cc|tcrcc P, Gucrin 8 eL al. ImmunoLherapy viLh sLandardized Dcrmcicp|-
cgci!cs picrcnssinus exLracL. I. |n titc and in tiirc parameLers afLer a shorL course of
LreaLmenL. } Allergy Clin Immunol 1985,76:734-44.
|22] Crcmcri |. Allergy diagnosis, allergen reperLoires, and Lheir implicaLions for aller-
gen-specific immunoLherapy. Immunol Allergy Clin NorLh Am 2006,26:179-89.
|23] |ccs M, Dc!ig S, Kcncu| |, 1rcsccc A. Iracen|e ucinkoviLosLi imunoLerapi|e asLme u
d|ece u in titc i in tiirc LesLu. IaediaLr CroaL 1993,37:71-3.
|24] |incrsscn |, Drc|crg S, Hcmmcrsircm I, Icj|tisi 1, Smii| S|, Stcnsscn G. MoniLoring
of miLe Dcrmcicp|cgci!cs jcrincc allergen-specific IgC and IgC subclass disLribuLion
in paLienLs on immunoLherapy. Allergy 1992,47:76-82.
|25] A|!is M, A|!is CA. Mechanisms of allergen-specific immunoLherapy. } Allergy Clin
Immunol 2007,119:780-91.
|26] Gc|||cr K, Sc||cc| M, 8cc|cr \M, 8ujc A. MoniLoring allergen immunoLherapy of
pollen-allergic specific IgC4 Lo IgC1 correlaLes viLh clinical ouLcome. Clin Lxp
Allergy 1999,29:497-506.
|27] cnjcpcnpiic| S, Orc A, Mcguirc P, Mcrin|ctic| V, Dc Krujj |H, Umcisu D1. The
kineLics of change in cyLokine producLion by CD4 T cells during convenLional
allergen immunoLherapy. } Allergy Clin Immunol 1999,103:468-75.
|28] Ncuri-Aric K1, \cc||c|z PA, Ircncis jN, jccc|scn M|, \c||cr SM, \i|ccc| IK, Sicp|c SQ,
Ac||crsc |C, 1i|| Sj, Dur|cm S|. Crass pollen immunoLherapy induces mucosal and
peripheral IL-10 responses and blocking IgC acLiviLy. } Immunol 2004,172:3252-9.
09 Dodig.p65 04.02.2008., 11:20 127
Rad. Medical Sciences, Zagreb, 2008., str. 117-128
S. Dodig: Current laboratory diagnosis of allergy
|29] Kcpp MV, Mccicpc| |, |ngc|s |, 8rcu|urgcr j, |ic!ingcr I, ||crsi G, \c|n U, Kuc|r j.
Urinary leukoLriene L4 levels in children viLh allergic rhiniLis LreaLed viLh specif-
ic immunoLherapy and anLi-IgL (malizumab). IediaLr Allergy Immunol
|30] Mci|cs N, Vc|cnic |, Spiizcucr S. Allergy LesLing: Lhe role of recombinanL allergens.
Clin Chem Lab Med 2006,44:125-32.
|31] 8cc| KM, 8cicr j, 8u|| |. Saisonale Schvankungen des Serum-IgL-Spiegels und
deren mgliche edeuLung fur die erechnung der LherapeuLischen Dosis von
malizumab (rhuMab-L25, anLi-IgL). Ineumologie 2004,58:546-51.
|32] \i||icms P8, 8crncs jH, Szcin|cc| SI, Su||itcn 1j. AnalyLic precision and accuracy of
commercial immunoassays for specific IgL: esLablishing a sLandard. } Allergy Clin
Immunol 2000,105(6 IL 1):1221-30.
|33] Dc|cn \K. IgL anLibody in Lhe serum deLecLion and diagnosLic significance. Al-
lergy 2003,58:717-23.
|34] Vi!c| C, Gu!c I, 8cucic O, Icrncn!cz-Mcrinc MC, Mciji!c IM, |c j, Icjc S, Gcnzc|cs-
Quinic|c A. LvaluaLion of Lhe IhadiaLop LesL in Lhe diagnosis of allergic sensiLiza-
Lion in a general adulL populaLion. } InvesL Allergol Clin Immunol 2005,15:124-30.
|35] Ncgc|c 8. IspiLivan|e di|agnosLicke os|eLl|ivosLi, specificnosLi i d|eloLvornosLi LesLo-
va in titc i in tiirc u d|ece preos|eLl|ive na inhalaci|ske alergene. MS Lhesis. Zagreb:
Zagreb UniversiLy School of Medicine, 2005.
Suvrcmcna Iaboratorijska dijagnostika aIcrgijc
Zaht|ovl laboratorl|sko dl|agnostlko alorgl|sklh bolostl odnoso so na odablr anallza ko|o bl
trobalo. 1. odrodltl vrstu alorgl|sko roakcl|o otkrlvan|om humoralnlh (ukunl lgL) l stanlcnlh (bro|
oozlnollnlh odnosno bazollnlh granuloclta, oozlnollnl katlonskl rotoln), 2. otkrltl okrotaco
alorgl|sko roakcl|o (socllcnl lgL na o|odlnacno uzrocno alorgono, tostovl e\ v|vo aktlvacl|o bazo-
llnlh granuloclta loukotrl|onl, CD63, hlstamln), 3. rocl|onltl kllnlckl tl|ok roakcl|o (trltaza za
ranu roakcl|u, oozlnollnl katlonskl rotoln za kasnu roakcl|u), 4. omogucltl racon|o us|osnostl
socllcno lmunotoral|o (ukunl l socllcnl lgL, socllcnl lgC4 l lgC1, om|or lgC4/lgC1, roal-
orgl|skl l roualnl cltoklnl), 5. odrodltl dl|agnostlcku d|olotvornost odrodlvan|a o|odlnlh hu-
moralnlh lll stanlcnlh osrodnlka alorgl|sko roakcl|o (os|otl|lvost, socllcnost, ozltlvna l nogatlv-
na, rodvldl|lva vrl|odnost).
lako su laboratorl|ska lstrazlvan|a korlsna u dl|agnozl l ll|ocon|u alorgl|sklh bolostl, bro|nl
robloml |os su norl|osonl. 1l so robloml mogu svrstatl u trl glavno katogorl|o. roanalltlcka
(uzorkovan|o), analltlcka l osll|oanalltlcka (tumacon|o, racon|o, onavl|no tostlran|o) aza labo-
ratorl|skog odrodlvan|a.
KIjucnc rijcci. alorgl|a, lgL, bazollnl granulocltl, loukotrl|onl, lmunotoral|a
09 Dodig.p65 04.02.2008., 11:20 128