Diagnostic Microbiology and Infectious Disease xxx (2015) xxx–xxx

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Diagnostic Microbiology and Infectious Disease

journal homepage: www.elsevier.com/locate/diagmicrobio

Drug-induced lymphocyte stimulation test in the prediction of

drug-induced hypersensitivity to antituberculosis drugs
Qin Sun a, Wei Sha a,⁎, Xu-Wei Gui a, Yang-Jiong Xiao b, Wei-Hong Zeng b, Wen-Wen Sun a,
He-Ping Xiao a, Wei-Yi Ye b
a
Clinic and Research Center of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China
b
Shanghai Institute of Immunology, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China

a r t i c l e i n f o a b s t r a c t

Article history: Antituberculosis (TB) chemotherapeutic drugs may cause a variety of adverse drug reactions (ADRs). To assess
Received 15 December 2014 the potential of drug-induced lymphocyte stimulation test (DLST) in screening ADRs in patients treated with
Received in revised form 3 March 2015 anti-TB drugs, we performed DLST in 272 TB patients (176 cases with ADRs and 96 controls without ADRs)
Accepted 8 March 2015
treated with anti-TB drugs isoniazid (INH), rifampicin (RFP), ethambutol (EMB), and pyrazinamide (PZA). The
Available online xxxx
ADRs were diagnosed by drug provocation test based on clinical and laboratory examinations. The sensitivities
Keywords:
of DLST in the diagnosis of INH-, RFP-, EMB-, or PZA-induced ADRs were 57.8%, 37.1%, 42.4%, and 23.1%,
Adverse drug reaction respectively, with the corresponding specificities being 93.4%, 94.0%, 97.5%, and 98.8%. DLST has high specificity
Drug-induced hypersensitivity and limited sensitivity in the diagnosis of anti-TB drug-induced ADRs. In combination with clinical observation
Drug-induced lymphocyte stimulation test and drug use history, DLST could have a predictive validity of ADRs, especially when a positive result is obtained.
Tuberculosis © 2015 Elsevier Inc. All rights reserved.

1. Introduction or other diseases, where exposure may provoke a situation beyond

Tuberculosis (TB) is 1 of the leading infectious diseases in the world,
with worldwide incidence of 9.4 million in 2009, resulting in an
estimated 1.7 million deaths per year (Lawn and Zumla, 2011).
Currently, the standard treatment regimens consist of isoniazid (INH),
rifampicin (RFP), ethambutol (EMB), and pyrazinamide (PZA), effective
in treating most patients with previously untreated TB. However, those
chemotherapeutic drugs can cause a variety of adverse drug reactions
(ADRs). Hypersensitivity or drug allergy is one of the most common
adverse reactions in the clinic, often impacting on the quality of life in
affected patients. In severe cases, drug hypersensitivity results in
reduced adherence to treatment regimens and even discontinuation of
the medication. The irregular and low-dose use of the TB medication
may lead to therapeutic failure, disease recurrence, and drug-resistant
Mycobacterium tuberculosis (Nanashima et al., 2012).
Currently, the drug provocation test (DPT) is considered the “gold
standard” for identification of drug hypersensitivity (Aberer et al.,
2003). Labor and time consuming, small doses of anti-TB drugs are
applied one by one to the patient with hypersensitivity, and the
offending drug can be identified when same adverse reactions occur.
However, when DPT is conducted, severe and even life-threatening
allergic reactions may occur, even at low dosages. In addition, DPT is
not recommended for use in pregnant women or patients at increased
risk due to comorbidities such as acute infections, uncontrolled asthma,
⁎ Corresponding author. Tel.: +86-13671758200; fax: +86-21-55660989.
E-mail address: shfksw@126.com (W. Sha).
medical control (Aberer et al., 2003).
The T-cell–mediated delayed hypersensitivity is responsible for the
pathogenesis of severe ADRs (Chung et al., 2008; Hanafusa et al.,
2012; Nishio et al., 2007; Takahashi et al., 2006). The in vitro drug-
induced lymphocyte stimulation test (DLST) has been extensively
used to diagnose immunity-mediated drug hypersensitivity (Hanafusa
et al., 2012; Matsuno, 2012; Nyfeler and Pichler, 1997). DLST is a
laboratory-based in vitro method that measures the uptake of a DNA
precursor, tritiated [ 3H] thymidine, by lymphocytes after exposure to
an antigen in vitro. DLST has certain advantages over DPT, with less pa-
tient risk. A single blood sample can be used to test for multiple drugs
simultaneously. In Japan, DLST has been widely used to examine drug-
induced pneumonitis and liver injury (Ikegame et al., 2011; Kawakami
et al., 2007; Matsuno et al., 2007). However, the use of DLST in detection
of hypersensitivity of anti-TB drugs remains controversial and has only
been reported in a few studies to date (Ikegame et al., 2011; Matsuno
et al., 2007; Miwa et al., 2012; Nyfeler and Pichler, 1997; Suzuki et al.,
2008). In the present study, we assessed the potential of DLST for deter-
mining drug-induced ADRs in a large number of Chinese patients with
newly diagnosed TB by comparing the results between DLST and DPT.
2. Study population and methods
This prospective study was reviewed and approved by the Ethics
Committee of Shanghai Pulmonary Hospital in accordance with the
Declaration of Helsinki, and informed consent was obtained from each
patient. The methods were carried out in accordance with the approved
American Thoracic Society guidelines (Blumberg et al., 2003).

http://dx.doi.org/10.1016/j.diagmicrobio.2015.03.008
0732-8893/© 2015 Elsevier Inc. All rights reserved.

Please cite this article as: Sun Q, et al, Drug-induced lymphocyte stimulation test in the prediction of drug-induced hypersensitivity to
antituberculosis drugs, Diagn Microbiol Infect Dis (2015), http://dx.doi.org/10.1016/j.diagmicrobio.2015.03.008
2 Q. Sun et al. / Diagnostic Microbiology and Infectious Disease xxx (2015) xxx–xxx

2.1. Study population Table 2

Adverse reactions of 176 patients of case group dosed with anti-TB drugs.

We enrolled patients with previously untreated pulmonary TB who Events Number (n) Percentage (%) Time of onset (day)a
were admitted to Shanghai Pulmonary Hospital for TB treatment Eruption 57 28.1 20.5 ± 19.2
between February 2010 and January 2013. The patients who developed Liver injury 104 51.2 28.3 ± 16.1
ADRs were selected as case group, and the patients without ADRs during Fever 42 20.7 24.2 ± 18.4
the treatment were selected as control group. a
Mean ± SE.
Inclusion criteria were 1) being ≥18 years of age; 2) being positive
for sputum culture for M. tuberculosis for at least 2 times; 3) having ini-
tially received first-line standard anti-TB therapy, including INH Society guidelines (Blumberg et al., 2003). For patients with rash and
(5 mg/kg), RFP (10 mg/kg), EMB (15 mg/kg), and PZA (25 mg/kg); drug fever, RFP was the first drug for test. We used a low dosage of
4) manifesting hypersensitivity after anti-TB therapy in case group. 150 mg (1 capsule) per day as a starting dose and gradually increased
The adverse events were categorized as reported previously (Miwa the dosage to 300 mg, 450 mg and 600 mg per day at intervals of
et al., 2012; Suzuki et al., 2008: A) Drug eruption: generalized 2–3 days. If there was symptom provoked, the test was stopped and
measles-like rash with itching following anti-TB therapy. Other possible interpreted as positive. After all symptoms had resolved, INH (100 mg,
causes were excluded and rash disappeared after withdrawal of thera- 200 mg, and 300 mg per day), EMB (250 mg, 500 mg, and 750 mg),
py. B) Drug-induced liver injury: alanine aminotransferase (ALT) and and PZA (250 mg, 500 mg, 1000 mg, and 1500 mg) were then tested
total bilirubin (TBIL) levels more than 3 times of the normal limits in sequentially. For patients with liver injury, a test plan with longer
2 months after anti-TB therapy, regardless the presence of symptoms observation duration of at least 1 week was scheduled. ALT and TBIL
such as nausea, vomiting, and abdominal pain. Liver injury caused by levels were strictly monitored.
other possible causes including viral hepatitis, cirrhosis, liver cancer,
and other drug-induced injury were excluded. C) Drug fever: recurrence
of fever (N39.0 °C) despite microbiological and radiographic improve- 2.3. Identification of drug allergy with DLST in case and control groups
ment by anti-TB therapy for several weeks. Fever due to infection,
including TB, was excluded. Drug-related fever spontaneously resolved DLST was performed in patients within 2 weeks after the presenta-
after withdrawal of drugs. The patients of control group showed none of tion of ADRs. None of the patients were treated with glucocorticoids
the above ADRs throughout anti-TB treatment and had no history of before completion of DLST. DLST was performed, as previously de-
hypersensitivity to any other drug. scribed (Lopez et al., 2009; Martin et al., 2010; Nyfeler and Pichler,
Exclusion criteria were 1) being HIV positive; 2) having autoimmune 1997). Twenty milliliters of heparinized peripheral venous blood were
diseases such as systemic lupus erythematosus, Sjogren's syndrome, obtained from each patient and centrifuged to obtain autologous plas-
and Rheumatoid arthritis; 3) having long-term use of hormones and/ ma. The lymphocytes were isolated via density gradient centrifugation
or immunosuppressive agents; 4) having diabetes mellitus; 5) use of and resuspended to a cell density of 106 cells/mL in RPMI 1640 medium
nonstandard treatment regimens; and 6) no positive drug being (Gibco, Carlsbad, CA, USA), in the presence of 20% autologous plasma
identified with DPT test. and penicillin (10,000 units/mL)–streptomycin (10 mg/mL). The
lymphocytes were seeded in 96-well dishes (200 μL per well) and
2.2. Identification of drug allergy with DPT in case group cultured with each anti-TB drug (INH, RFP, EMB, and PZA), at concentra-
tions of 1 μg/mL, 10 μg/mL, and 100 μg/mL. The positive control was
When ADRs were observed, all drugs were temporarily stopped. phytohemagglutinin, and the negative control was vehicle. After
After all symptoms resolved and the laboratory parameters became 5 days of incubation at 5% CO2, [ 3H] thymidine was added for an addi-
normal, DPT was performed with careful observation. The anti-TB tional 18 h. The lymphocytes were harvested, and mitogenic activity
drugs were restarted one by one, starting with low dosage, and gradual- was quantified by [ 3H] thymidine incorporation using a scintillation
ly increasing to the usual dosage in accordance with American Thoracic counter (SN-6930, Shanghai Nucleus Research Institute, Shanghai,
China). Experiments were performed in triplicate. The stimulation
Table 1 index (S.I.) is defined as count per minute (cpm) of the stimulation/
Clinical characteristics of the subjects enrolled in the present study. cpm of the negative control. The DLST negative controls (cpm) are
Characteristics Case group Control group
367 ± 84 and 356 ± 72, for the case group and control group, respec-
tively. DLST findings were considered positive if the S.I. was N1.8.
Total number 176 96
Male/female 109:67 61:35
Mean age (year) with range 45 ± 17 (21–71) 47 ± 15(19–73) Table 3
Complicated with Comparison of S.I. between DPT-positive and DPT-negative cases with anti-TB drugs.
Lymph node TB 23 12
Events Drug DPT-positive DPT-negative U value P value
Miliary TB 5 1
S.I. value S.I. value
Endobronchial TB 26 18
Pulmonary TB only 122 65 Total, n = 176 INH 3.13 ± 2.33 1.28 ± 0.73 −5.740 0.001
Drug sensitive test RFP 2.24 ± 1.85 1.32 ± 0.66 −2.039 0.041
Sensitive to 4 drugs 164 89 EMB 2.12 ± 1.37 1.16 ± 0.45 −3.357 0.001
Resistant to anti-TB drugs, not MDR 12 7 PZA 1.59 ± 1.07 1.12 ± 0.36 −1.561 0.118
MDR or XDR 0 0 Drug eruption, INH 3.71 ± 2.57 1.29 ± 0.77 −3.655- 0.001
History of other diseases n = 57 RFP 2.47 ± 2.12 1.35 ± 0.88 −1.918 0.055
Chronic respiratory disease 11 4 EMB 2.26 ± 1.48 1.19 ± 0.34 −2.212 0.027
Hypertension 24 14 PZA
Cardiovascular disease 8 5 Drug-induced liver INH 2.61 ± 2.08 1.24 ± 0.82 −3.752 0.001
Duodenal/gastric disease 14 6 injury, n = 104 RFP 2.09 ± 1.68 1.29 ± 0.86 −2.165 0.030
Hyperthyroidism 2 0 EMB 2.00 ± 1.24 1.16 ± 0.59 −2.917 0.004
None 117 67 PZA 1.70 ± 0.91 1.14 ± 0.32 −1.047 0.295
Outcomes Fever, n = 42 INH 3.61 ± 2.56 1.36 ± 0.74 −2.446 0.014
Survival 176 96 RFP 2.34 ± 1.76 1.41 ± 0.78 −0.302 0.762
Death 0 0 EMB 2.82 ± 1.46 1.12 ± 0.23 −2.515 0.012
PZA 1.55 ± 0.91 1.06 ± 0.22 −0.1.474 0.141
MDR = multidrug-resistant tuberculosis; XDR = extensively drug-resistant tuberculosis.

Please cite this article as: Sun Q, et al, Drug-induced lymphocyte stimulation test in the prediction of drug-induced hypersensitivity to
antituberculosis drugs, Diagn Microbiol Infect Dis (2015), http://dx.doi.org/10.1016/j.diagmicrobio.2015.03.008
 Q. Sun et al. / Diagnostic Microbiology and Infectious Disease xxx (2015) xxx–xxx 3

3.2. Adverse drug reactions

Among the 203 ADRs to anti-TB drugs from the 176 patients in the
case group (Table 2), 57 (28.1%) were drug eruption, 104 (51.2%)
were drug-induced liver injury, and 42 (20.7%) were drug-induced
fever. The average time of onset was 20.5 ± 19.2 days for drug eruption,
28.3 ± 16.1 days for drug-induced liver injury, and 24.2 ± 18.4 days for
drug-induced fever. Drug eruption and liver injury simultaneously oc-
curred in 15 (8.5%) patients; drug eruption and fever occurred in 6
(3.4%) patients; and drug-induced liver injury and fever occurred in 6
(3.4%) patients. None of the patient had more than 2 ADRs.

3.3. Comparison of DLST and DPT results

Fig. 1. Analysis of differences in S.I. between DPT-positive and DPT-negative cases. The box
plots show 90th percentile (bars); 75th, 25th percentiles (box); and median (bar in box),
outliers (circle); and extrema (asterisk).
2.4. Statistical analysis
Statistical analysis was performed using statistics software SPSS 16.0
(SPSS, Chicago, IL, USA). Continuous variables were expressed as
mean ± SEM. Paired t-test was conducted for variables obtained prior
and post DLST. All paired variables were used in the analyses. The values
of the S.I. of DLST were analyzed by Mann–Whitney U test; P values
b0.05 were considered statistically significant.
3. Results
3.1. Characteristics of the study population
Study subjects were selected according to the inclusion and exclu-
sion criteria from a total of 1806 non-HIV patients with previously un-
treated TB, admitted to Shanghai Pulmonary Hospital from February
2010 to January 2013. Out of 644 excluded patients, 117 patients were
excluded due to age (b18 years old); 284, due to diabetes; 136, due to
having autoimmune diseases and long-term use of hormones and/or
immunosuppressive agents; and the rest were excluded due to the
use of nonstandard treatment regimens. Of the 1162 patients selected
(mean age, 48 ± 19 years; range, 18–84 years; 743 males and 419 fe-
males), 198 patients (17.0%) developed certain ADRs to anti-TB drugs
during treatment. DPT was performed for all 198 patients to identify
the causative drug. Of the 198 patients with ADRs, 22 patients (11.1%)
were negative for DPT test and were consequently excluded from the
case group. Therefore, the case group included a total of 176 patients.
A control group of 96 patients was randomly selected from the 964
patients without ADRs. The clinical characteristics of the case group
and control group are shown in Table 1. DPT was performed when the
patients were hospitalized and under a physician's observation. All the
patients survived, and no death resulted from ADRs of the anti-TB drugs.
DLST was performed for each of the 4 anti-TB drugs (INH, RFP, EMB,
and PZA) in all 176 patients with ADRs and 96 control patients. The S.I.
values of DLST for each drug were compared between DPT-positive and
DPT-negative patients in the case group (Table 3 and Fig. 1). For the
drugs INH and EMB, the S.I. values in DPT-positive cases were signifi-
cantly higher than those in DPT-negative cases of all 3 ADRs
(P b 0.05). For RFP, there was no significant difference between DPT-
positive and DPT-negative cases of drug eruption and fever. The S.I.
values for PZA showed no significant changes between DPT positive
and negative cases of liver injury and fever (P N 0.05).
As shown in Table 4, DPT identified 193 positive cases out of 176 pa-
tients in the case group. Among those patients, 7 were both RFP and INH
positive, 5 were both RFP and EMB positive, 3 were both INH and EMB
positive, 2 were both RFP and PZA positive, and none was positive for
more than 2 drugs. However, none of the patients (both case and con-
trol groups) were identified as positive for more than 1 drug using
DLST. Results from DLST in case group showed that 94 out of 176
(53.4%) patients showed hypersensitivity reactions to 1 of the 4 drugs.
Of those 94 patients, 33 (18.8%) were positive for INH, 39 (22.2%)
were positive for RFP, 16 (9.1%) were positive for EMB, and 6 (3.4%)
were positive for PZA. In the control group, 20 out of 96 (20.8%) patients
were positive for DLST, which were considered as false positive. Among
them 8 (8.3%) patients were false positive for INH; 5 (5.2%), for RFP; 4
(4.2%), for EMB; and 3 (3.1%), for PZA. Notably, false positivity for
DLST test was shown in 15 patients from case group as well, of which
7 out of 131 DPT-negative patients (5.3%) were false positive for INH,
6 out of 87 (6.9%) for RFP, and 2 out of 143 (1.4%) for EMB.
3.4. Diagnostic values of DLST
As shown in Table 5, the sensitivity of DLST for INH, RFP, EMB, and
PZA was 57.8%, 37.1%, 42.4%, and 23.1%, respectively. The specificity of
DLST was 93.4%, 94.0%, 97.5%, and 98.8%, respectively. The diagnostic
sensitivity of DLST for drug-induced eruption, liver injury, and fever in
patients taking INH was 64.7%, 44.4%, and 63.6%, with the specificity
being 92.6%, 93.1%, and 92.9%, respectively. The sensitivity for RFP was
43.3%, 32.7%, and 40.0%, with the specificity being 94.3%, 94.6%, and
94.9%, respectively. The sensitivity for EMB was 43.8%, 33.3%, and
57.1%, with the specificity being 97.1%, 96.7%, and 96.9%, respectively.
The sensitivity for liver injury and fever in patients taking PZA was

Table 4
Comparison of DLST and DPT results between case and control groups.

Drug Case group, Drug eruption, Drug-induced liver Fever, Control group,
n = 176 n = 57 injury, n = 104 n = 42 n = 96

DLST positive, DPT positive, DLST positive, DPT positive, DLST positive, DPT positive, DLST positive, DPT positive, DLST positive,
n (%) n (%) n (%) n (%) n (%) n (%) n (%) n (%) n (%)

INH 33 (18.8) 45 (23.3) 13 (22.8) 17 (27.0) 16 (15.4) 27 (23.3) 8 (19.0) 11 (23.9) 8 (8.3)
RFP 39 (22.2) 89 (46.1) 15 (26.3) 30 (47.6) 20 (19.2) 52 (44.8) 9 (21.4) 20 (43.5) 5 (5.2)
EMB 16 (9.1) 33 (17.1) 7 (12.3) 16 (28.1) 8 (7.7) 18 (15.5) 4 (9.5) 7 (15.2) 4 (4.2)
PZA 6 (3.4) 26 (13.5) 0 0 5 (4.8) 19 (16.4) 2 (4.8) 8 (17.4) 3 (3.1)

Please cite this article as: Sun Q, et al, Drug-induced lymphocyte stimulation test in the prediction of drug-induced hypersensitivity to
antituberculosis drugs, Diagn Microbiol Infect Dis (2015), http://dx.doi.org/10.1016/j.diagmicrobio.2015.03.008
4 Q. Sun et al. / Diagnostic Microbiology and Infectious Disease xxx (2015) xxx–xxx

Table 5
Diagnostic value of DLST for hypersensitivity to anti-TB drugs.

Events Drug Sensitivity (%) Specificity (%) False positive (%) False negative (%) PPV (%) NPV (%) PLR NLR

Total, n = 272 INH 57.8 93.4 6.6 42.2 63.4 91.8 8.89 0.45
RFP 37.1 94.0 6.0 62.9 75.0 75.4 6.18 0.67
EMB 42.4 97.5 2.5 57.6 70.0 92.5 16.96 0.59
PZA 23.1 98.8 1.2 76.9 66.7 92.4 19.25 0.78
Drug eruption, n = 57 INH 64.7 92.6 7.4 35.3 52.4 95.5 8.74 0.38
RFP 43.3 94.3 5.7 56.7 65.0 87.2 7.60 0.60
EMB 43.8 97.1 2.9 56.2 63.6 93.7 15.10 0.58
PZA − − − − − − − −
Drug-induced liver injury, n = 104 INH 44.4 93.1 6.9 55.6 50.0 91.5 6.43 0.60
RFP 32.7 94.6 5.4 67.3 68.0 80.0 6.06 0.71
EMB 33.3 96.7 3.3 66.7 50.0 93.6 10.09 0.69
PZA 26.3 98.3 1.7 73.7 62.5 92.7 15.48 0.75
Fever, n = 42 INH 63.6 92.9 7.1 37.4 43.8 96.7 8.96 0.39
RFP 40.0 94.9 5.1 60.0 57.1 90.3 7.84 0.63
EMB 57.1 96.9 3.1 42.9 50.0 97.7 18.41 0.44
PZA 25.0 97.7 2.3 75.0 40.0 95.5 10.87 0.77

PPV = positive predictive value; NPV = negative predictive value; PLR = positive likelihood ratio; NLR = negative likelihood ratio.

26.3% and 25.0%, respectively, with the specificity being 98.3% and
97.7%, respectively. None of the patients with drug-induced eruption
was positive for PZA by DPT or DLST.
4. Discussion
In the present study, the diagnostic value of DLST on anti-TB
drug-induced ADRs was investigated in 272 TB patients treated with
the first-line anti-TB drugs, INH, RFP, EMB, and PZA. The sensitivity of
DLST in the diagnosis of ADRs associated with the 4 drugs varied from
23.1% to 57.8%, and the specificity varied from 93.4% to 98.8%. Notably,
a low probability of false positives from 1.2% to 6.6% was obtained for
DLST. Our results showed that DLST had very high diagnostic specificity
for each of the tested drugs (INH, RFP, EMB, and PZA) with very low
probability of false positivity, suggesting a diagnostic role of DLST in
determining drug-induced hypersensitivity. Therefore, a patient should
be considered at a high risk for a hypersensitivity reaction if an anti-TB
drug is DLST positive.
In contrast to the high specificity, the sensitivity of DLST was
relatively low. Yet, our results were apparently higher than those from
previous studies (Miwa et al., 2012; Suzuki et al., 2008). Suzuki et al.
(2008) reported a lower sensitivity of DLST in the diagnosis of ADRs
caused by the same drugs (INH, 14.3%; RFP, 13.6%; EMB, 14.3%; PZA,
0%). Therefore, the group concluded that DLST had a very low value in
diagnosis of anti-TB drug-induced ADRs (Anon, 1999). Several factors
may result in discrepancies between our results and Suzuki's results
(deShazo and Kemp, 1997). First, in present study, 22 patients (11.1%)
with negative DPT results were excluded. Some of these DPT-negative
patients may have developed ADRs due to sensitivities to unidentified
foods or drugs other than the tested anti-TB drugs. Potential complicat-
ed drug interactions due to the combination usage of anti-TB drugs may
also cause ADRs. However, these ADRs will not be detected by DPT, in
which each drug was tested separately. Moreover, a spontaneous
desensitization to the drugs tested by DPT may also have been induced
in some patients, since DPT was performed after the patients had devel-
oped ADRs. In contrast, a considerable proportion (23.4%) of the
patients were negative for DPT and were not excluded in the study
from Suzuki et al. (2008), which may negatively skewed sensitivity of
DLST. Second, we excluded patients with suppressed immunity
resulting from conditions such as diabetes mellitus, autoimmune
diseases, and long-term use of hormones and/or immunosuppressive
agents. In contrast, a sizable proportion of patients (7.2%) with diabetes
were included in the Suzuki et al. (2008), which may have impaired T
lymphocyte function, influencing the DLST results. Third, our study
featured a relatively large sample size, compared to only 31 patients
in Suzuki's study (Miwa et al., 2012).
Our study has some limitations. For example, among the 3 different
types of hypersensitivity, sensitivity for drug-induced liver injury was
relatively low. This finding may be explained by the fact that, in addition
to immune-mediated hypersensitivity, anti-TB drug-induced liver
injury can also be caused by toxicity from drug metabolites. Generally,
it is clinically difficult to distinguish between immune-mediated ADRs
and hepatotoxicity from drug metabolites (Park et al., 2005; Walgren
et al., 2005; Yasuda et al., 2012).
Funding source
This study was supported by Research Project of Shanghai Municipal
Health Bureau (No. 20124Y024).
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antituberculosis drugs, Diagn Microbiol Infect Dis (2015), http://dx.doi.org/10.1016/j.diagmicrobio.2015.03.008
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Please cite this article as: Sun Q, et al, Drug-induced lymphocyte stimulation test in the prediction of drug-induced hypersensitivity to
antituberculosis drugs, Diagn Microbiol Infect Dis (2015), http://dx.doi.org/10.1016/j.diagmicrobio.2015.03.008