ORIGINAL ARTICLE
The significance of serum total immunoglobulin E for in vitro diagnosis
of allergic rhinitis
Daniel Chung, MA1 , K.T. Park, MD, MSc2 , Bharat Yarlagadda, MD3 , Elizabeth Mahoney Davis, MD1 and
Michael Platt, MD, MSc1
Background: Allergic rhinitis is diagnosed by clinical pa-
rameters with no widely accepted screening test. Measure-
ment of total serum immunoglobulin E (IgE) has limited use
in the general population due to a low negative predictive
value. The value of total IgE level in select populations un-
dergoing in vitro allergy testing remains unknown. The aim
of this study is to determine the utility of total serum IgE in
the in vitro diagnosis of allergic rhinitis.
Methods: A retrospective chart review of patients under-
going testing for allergic rhinitis was performed. Clinical
parameters, total IgE level, and enzyme-linked immunosor-
bent assay (ELISA) for serum-specific IgE levels were ana-
lyzed with multivariate logistic regression. The positive and
negative predictive values and a receiver operating charac-
teristic (ROC) curve were used to assess the utility of total
IgE in predicting serum-specific IgE test results.
Results: Records from 1073 patients were reviewed. ROC
curve for total IgE >150 IU/mL ( 0.88) indicates good dis-
crimination in identifying patients with sensitization by in
vitro testing, whereas low total IgE level had strong nega-
A llergic rhinitis (AR) is a common inflammatory dis-
ease that is defined by an immunoglobulin E (IgE)-
mediated triggering of nasal congestion, rhinorrhea, sneez-
ing, and itching in response to specific environmental trig-
gers. AR affects 10% to 30% of Americans and up to 40%
of children.1 The gold standard for diagnosis of AR is a
1 Department of Otolaryngology–Head & Neck Surgery, Boston
University School of Medicine, Boston, MA; 2 Division of
Gastroenterology, Lucile Packard Children’s Hospital, Stanford
University, Palo Alto, CA; 3 Department of Otolaryngology,
Massachusetts Eye & Ear Infirmary, Boston, MA
Correspondence to: Michael Platt, MD, Department of
Otolaryngology–Head and Neck Surgery, 820 Harrison Avenue, 4th Floor,
Boston, MA 02118; e-mail: miplatt@bu.edu
Potential conflict of interest: None provided.
Presented orally at the Annual ARS Meeting on September 8, 2012,
Washington, DC.
Received: 11 August 2013; Accepted: 17 September 2013
DOI: 10.1002/alr.21240
View this article online at wileyonlinelibrary.com.
tive predictive value (0.87, IgE <10) in identifying negative
specific IgE testing. Multivariate logistic regression showed
that differences in covariables did not significantly change
the odds of a positive in vitro allergy test panel.
Conclusion: Serum total IgE level is useful in the in vitro
diagnosis of allergic rhinitis. In vitro testing for specific IgE
may be unnecessary in patients with low serum total IgE,
whereas high total IgE level suggests that in vitro testing
would confirm specific sensitizations in patients with aller-
gic rhinitis. 
C 2013 ARS-AAOA, LLC.
Key Words:
allergic rhinitis; immunoglobulin E; in vitro testing; atopy;
allergy
How to Cite this Article:
Chung D, Park KT, Yarlagadda B, Davis E, Pla M. The
significance of serum total immunoglobulin E for in vitro
diagnosis of allergic rhinitis. Int Forum Allergy Rhinol.
2014;4:56–60.
clinical summary of history, physical exam findings, and
measurement of specific IgE reactivity. A challenge remains
in correctly identifying AR in the absence of absolute objec-
tive measures and limitations in current testing strategies.
Symptoms of AR cause a significant impact on quality of
life; AR is associated with loss of productivity and a finan-
cial expenditure ranging in the billions of dollars every year
through direct and indirect medical costs.2
The expense of allergy testing is affected by the method
of testing and number of tests performed. There are mul-
tiple allergy testing methods that have individual advan-
tages and disadvantages. One simple test that has been
viewed as a potential cost-saving measure is the use of
total serum immunoglobulin E (tIgE) levels to rule out
or assist in identifying sensitization to specific allergens.
With an increasing prevalence of AR coupled with the
costs of diagnosis and treatment, and improved under-
standing of the value of the available testing methods
would lead to greater efficiency in the use of healthcare
expenditures.
International Forum of Allergy & Rhinology, Vol. 4, No. 1, January 2014 56
The significance of serum total IgE

Measurement of tIgE has been used in clinical practice TABLE 1. Allergens tested for specific IgE by ImmunoCapa
and investigated for its diagnostic role for allergic disor-
ders such as rhinitis3 and asthma.4 However, secondary Months in season
factors such as environment,5 location,6, 7 age,8 sex,6, 8, 9 (for statistical
and smoking6 have also been implicated in affecting base- Allergen class Allergen tested analysis)

line tIgE levels. Furthermore, the true value measurement of Grasses Bahia May-July
tIgE levels is currently inconclusive because studies report
Bermuda
considerable overlap of values between sensitized and non-
sensitized individuals, whereas others report specific refer- Johnson
ence and/or diagnostic predictive values.8–12 These limita- Rye
tions have led the American Academy of Allergy, Asthma,
and Immunology to publish a guideline suggesting that Timothy
measurement of tIgE not be routinely performed (page 47).1 Trees Birch March-May
The primary purpose of this study was to assess the value
Alder
of tIgE levels as a diagnostic tool for allergic rhinitis and its
predictive value in identifying elevated specific IgE (sIgE) Box elder
values for patients undergoing in vitro allergy testing. Oak
Pine
Patients and methods Elm
Subjects
Weeds Common ragweed August-October
A retrospective chart review was performed for patients
who were evaluated at an outpatient otolaryngology clinic Lambs quarter
at a single urban academic medical center between 2006 Russian thistle
and 2010 and were found to have symptoms and findings
Mugwort
consistent with allergic disease in the head and neck. Pa-
tients of all ages and ethnicities who had both sIgE and English plantain
tIgE levels drawn as part of their diagnostic workup were Epidermals/danders Dermatophagoides farinae All
included in this study.
Dermatophagoides
Clinical data obtained included patient age, gender, race,
pteryonyssinus
comorbid conditions, month when tested, and symptoms.
Primary diagnoses were obtained from chart review. Rhini- Cat epithelium
tis was defined as having 1 of the following symptoms: rhi- Dog epithelium
norrhea, itchiness, sneezing, or congestion/obstruction not
Cockroach
solely due to anatomical factors. A diagnosis of sinusitis
was made based on patient history, endoscopic findings, Molds Alternaria alternata All
and imaging results in accordance with contemporary defi- Aspergillus fumigatus
nitions of the condition.13 Otologic findings included clin-
ical diagnoses of chronic otitis media or Eustachian tube Cladosporium herbarum
dysfunction. Diagnosis of chronic laryngitis was made by Helminthosporium
history and fiber-optic laryngoscopy.
Mucor racemosus
Comorbid conditions included asthma, either confirmed
by the patient or another provider, and a documented Penicillum notatum
episode of anaphylaxis with or without angioedema. A a
The months “in season” for each class of allergen were used to determine if
single episode of nonanaphylactic allergy reported by the there were differences in total IgE level sensitivities when subjects were tested
“in season.”
patient, such as isolated facial edema or skin rash, was
not recorded as an anaphylactic history. The finding of
nasal polyps was noted by anterior rhinoscopy or nasal
endoscopy performed as part of the clinical scenario. Measurement of tIgE and sIgE
Patients with nonspecific tIgE reporting (value <25 com- Results of sIgE testing by enzyme-linked immunosorbent
pared to <10), incomplete medical record data regarding assay (ELISA) (ImmunoCap; Phadia, Uppsala, Sweden), for
the history of present illness, use of oral steroids on the day 27 inhalant allergens were obtained (Table 1). Specific IgE
of testing, and alternate cause for elevated IgE (ie, hyper- class results were presented in terms of “low,” “moderate,”
IgE syndrome or parasitic infection), and measurement of “high,” and “very high” were assigned a value of 2, 3,
less than 12 allergens by sIgE were excluded. Approval 5, and 6, respectively. The patient was considered to be
from the Institutional Review Board was obtained prior to sensitized to an allergen if the sIgE testing resulted in a
commencing this study. value of ≥0.35 IU/mL.

57 International Forum of Allergy & Rhinology, Vol. 4, No. 1, January 2014

Chung et al.

Although this group of 27 inhalant allergens comprises TABLE 2. Statistical outcomes for multivariate analysis of
a usual sIgE panel, miscellaneous inhalant allergens are oc- serum total IgE as a predictor of specific IgE in patients
casionally tested outside of the panel for more uncommon with rhinitis
allergens, and were included within the total number of
sIgE tests to meet the minimum inclusion criteria of 12 al- Covariable n % Odds ratio (95% CI) p
lergens per patient. These miscellaneous allergen were not Gender
included for multivariate analysis.
Male 431 40.2 1.26 (0.58–2.76) 0.563
Female 642 59.8
Statistical analysis
Statistical analysis was performed using Excel (Microsoft Age
Corp, Redmond, WA) and Stata 12 (StataCorp LP, College Mean 36.9 0.97 (0.94–0.99) 0.01
Station, TX) software. Multiple logistic regression analy-
Range 1–91
ses were performed to determine association between sIgE,
tIgE, and covariates. The positive and negative predictive Medications
values (PPV and NPV), sensitivity, and specificity for sub- Antihistamines 194 18.1 2.54 (0.84–7.63) 0.098
sequent positive sIgE results were calculated for various
cutoff values of tIgE. Nasal steroids 317 29.5 0.62 (0.22–1.71) 0.356
To show whether a given level of tIgE can be used to Primary symptoms
discriminate between positive or negative sIgE results in Rhinitis 753 70.2
the same patient, receiver operating characteristic (ROC)
curve analyses were performed. ROC curves show the rela- Sinusitis 203 18.9 3.48 (0.85–14.3) 0.083
tionship between the true positive rate (ie, sensitivity) and Other 57 5.3 0 0.991
the false positive rate (ie, 1 − specificity) for a given cutoff
Laryngitis 27 2.5 0 0.992
value of tIgE.
Angioedema 16 1.5 N/A
Otitis media 15 1.4 0 0.991
Results
Rash 2 0.2 N/A
The records of 1232 patients were reviewed. One hundred
and fifty-nine subjects were excluded due to a less-specific Ethnicity
reported total IgE level (IgE <25 kU/L, 5 patients), insuffi- White 296 27.6 2.45 (0.51–11.7) 0.261
cient documentation of patient history preceding in vitro Black 330 30.8 1.00 (0.22–4.54) 0.996
testing (39 patients), use of oral steroids during day of
radioallergosorbent test (RAST) testing (22 patients), and Hispanic 245 22.8 1.31 (0.27–6.21) 0.737
less than 12 allergens tested by ELISA (93 patients). An Asian 72 6.7 2.29 (0.29–18.2) 0.432
average of 22.2 sIgE tests were obtained (range, 12–30;
Other 79 7.4 0.94 (0.13–6.75) 0.953
Table 2). Primary symptoms reported by patient history
were rhinitis (70.2%), sinusitis (18.9%), laryngitis (2.5%), Uncertain 51 4.8
angioedema (1.5%), otitis media (1.4%), rash (0.2%), and CI = confidence interval; IgE = immunoglobulin E; N/A = not applicable.
other (5.3%).
For the 1073 subjects fulfilling the inclusion criteria, 431
change the likelihood of a positive in vitro allergy test-
were male and 642 were female. The average age at the
ing panel (Table 2). However, total serum IgE correlated
time of testing was 36.9 years of age, with a range of
with clinical and statistical significance to the PPVs and
1 to 91 years. The patients’ ethnicities were as follows:
NPVs for identifying patients with positive in vitro allergy
296 white, 330 black, 245 Hispanic, 72 Asian, 51 unde-
tests. The ROC curve using a cutoff value of 150 IU/mL
termined, 79 other. Comorbid conditions included asthma
had an area under the curve of 0.88, indicating a good
in 263 patients, history of anaphylaxis in 36 patients, and
level of discrimination in determining patients with allergen
sinus polyps in 119 patients.
sensitization diagnosed by in vitro testing (Fig. 1). For pa-
There were 632 positive sIgE tests and 441 negative sIgE
tients with low levels of tIgE, there was a favorable negative
tests. For patients with negative sIgE tests, the mean tIgE
predictive value for IgE <10 (89.6%; Fig. 2). For patients
level was 69.9 and 356.9 for patients with positive sIgE
with high total IgE levels, there was a progressive favorable
testing.
positive predictive value (IgE >150, 89.6%, Fig. 3).
Multivariate logistic regression analysis showed that dif-
ferences in age, gender, ethnicity, use of medications, the
month or season of allergy testing panel, allergen class, and Discussion
the presence of comorbid conditions including asthma, his- Contrary to published recommendation against use of tIgE
tory of anaphylaxis, and nasal polyps did not significantly in the diagnosis of AR,1 we demonstrated that tIgE level

International Forum of Allergy & Rhinology, Vol. 4, No. 1, January 2014 58

The significance of serum total IgE
FIGURE 1. ROC curve for patients with a total IgE >150 that demonstrates
the ratio between the sensitivity and specificity. An area under the curve of
0.88 represents a very favorable clinical value for a diagnostic test. ROC =
receiver operating characteristic; IgE = immunoglobulin E.
FIGURE 2. The negative predictive value of total IgE in identifying pa-
tients with negative in vitro ELISA testing. The highest negative predictive
value is for those patients with total IgE levels <10. ELISA = enzyme-linked
immunosorbent assay; IgE = immunoglobulin E.
has good PPVs and NPVs in the in vitro diagnosis of AR in
patients presenting to a specialty clinic for symptoms of AR.
With 10% to 30% of the U.S. population affected by AR
with an increasing prevalence1 of atopic disease, improved
diagnostic methods can lead to increased efficiency for the
management of AR. Allergy testing offers diagnostic confir-
mation, implementation of avoidance measures for specific
allergens, and option of immune desensitization to the spe-
cific allergens. tIgE level is a simple, low-cost, and rapid test
that has been used in the diagnosis of AR. With expanding
use of in vitro allergy testing for patients with suspected
AR, the clinical use of tIgE level may have an important
value for selected groups of patients.
In this study, tIgE level provided clinical value at both the
high and low ends of the range for patients with otolaryngic
allergy symptoms who were evaluated at a specialty clinic.
59 International Forum of Allergy & Rhinology, Vol. 4, No. 1, January 2014
FIGURE 3. The positive predictive value of total IgE in identifying patients
with positive in vitro ELISA testing. The highest positive predictive values
are seen at total IgE levels >150. ELISA = enzyme-linked immunosorbent
assay; IgE = immunoglobulin E.
A low tIgE level suggests that further in vitro testing has a
low chance of identifying sensitization to allergens causing
rhinitis. A high tIgE level is very likely to be associated with
AR and further in vitro testing should be able to identify
specific allergens. Factors that can affect IgE levels, includ-
ing the environment,5 location,6, 7 age,8 and sex,6, 8, 9 did
not affect our results. The number and type of allergens in
symptomatic patients were not found to affect tIgE levels
in this study as opposed to other reports.17, 18
Prior studies have examined the value of tIgE levels, with
varying results showing overlap of values between sensi-
tized and nonsensitized individuals,14 and others reporting
specific reference and/or diagnostic predictive values.8–12 In
a general population sample (n = 2,327) comparing skin
tests, tIgE, and sIgE tests, there was overlap in tIgE levels in
patients with and without allergy-related diseases. tIgE was
not useful to rule out sensitization to common allergens in
this general population.15 A limitation in this study was that
only 5 allergens were analyzed by in vitro testing, which is
a much lower number than is usually tested for in allergy
testing panels. In the current study, tIgE level was able to
predict a larger panel of in vitro allergy tests for patients
seeing a specialist for symptoms suggestive of allergy.
Confounding variables in the study of tIgE levels are the
presence of asthma and patient age. Burrows reported that
asthma was more closely correlated with tIgE and positive
skin testing; however, tIgE levels did have significant cor-
relation with diagnosis of rhinitis.4 Sinclair measured tIgE
and sIgE levels in 301 patients under the age of 16 years
and concluded that allergy testing should not proceed if
total IgE <10 kU/L and symptoms are nonspecific. In a pe-
diatric population, there was good correlation between the
number and strength of sIgE and tIgE levels, with low tIgE
(<10 kU/L) having good NPV for predicting sIgE testing.11
Chung et al.

tIgE was found to have an NPV of 100% and 95%, in
males and females, respectively, at a value less than 5 kU/L
in adults age 45 to 70 years, whereas a younger group 20
to 44 years old was found to have 96% PPV of tIgE for
at least 1 allergy test.15 The number of positive Immuno-
Cap sIgE tested significantly increased when using total IgE
≥200 kU/L as a cutoff value16 and these patients had a
higher number of positive ImmunoCap results compared
to skin testing results.
AR remains a clinical diagnosis with testing for sIgE as
an adjunct to confirming the diagnosis and identifying spe-
cific antigens. The benefits and limitations vary for differ-
ent allergy testing methods, which often include in vitro
testing for specific serum antibodies by ELISA, skin prick
testing, or intradermal skin testing. The differing opinions
regarding preferred testing method can be seen within the
medical community where clinicians may use 1 or more
of these methods as the primary modality used to iden-
tify sensitization to allergens. In vitro testing has bene-
fits of decreased risk of adverse reaction, ease of testing
with a single blood draw, improved patient comfort, and
improved specificity compared to skin testing.16 Increased
costs and decreased sensitivity for in vitro tests are recog-
nized as limitations in clinical practice. For primary care
physicians, skin testing is not readily available, whereas in
vitro testing can be ordered through a clinical phlebotomy
laboratory.
For patients who are unable to have skin testing due
to skin diseases such as dermatographism, use of medica-
tions that preclude testing (antihistamines, beta-blockers),
or concern about risks of allergic reaction, in vitro testing is
a widely accepted method of testing. Given the widespread
use of in vitro testing for sIgE antibodies in patients who
cannot undergo skin testing or for those practitioners that
routinely use in vitro testing as the primary modality, the
value of a simple screening test such as tIgE level can have
significant impact on the costs associated with in vitro
testing.
Conclusion
Serum tIgE level has value in the in vitro diagnosis of AR
for patients being evaluated in a specialty clinic who have
head and neck symptoms of allergic disease. tIgE is in-
dependent of multiple demographic, seasonal, and clinical
factors. Further in vitro testing may be unnecessary in pa-
tients with low serum tIgE, whereas high tIgE level can
forecast positive sIgE testing in patients with AR.

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