J ALLERGY CLIN IMMUNOL
VOLUME 135, NUMBER 2
5. Liu L, Okada S, Kong XF, Kreins AY, Cypowyj S, Abhyankar A, et al. Gain-of-
function human STAT1 mutations impair IL-17 immunity and underlie chronic
mucocutaneous candidiasis. J Exp Med 2011;208:1635-48.
6. Harrison C, Kiladjian JJ, Al-Ali HK, Gisslinger H, Waltzman R, Stalbovskaya V,
et al. JAK inhibition with ruxolitinib versus best available therapy for myelofi-
brosis. N Engl J Med 2012;366:787-98.
7. Soltesz B, Toth B, Shabashova N, Bondarenko A, Okada S, Cypowyj S, et al. New
and recurrent gain-of-function STAT1 mutations in patients with chronic mucocu-
taneous candidiasis from Eastern and Central Europe. J Med Genet 2013;50:
567-78.
8. Sharfe N, Nahum A, Newell A, Dadi H, Ngan B, Pereira SL, et al. Fatal combined
immunodeficiency associated with heterozygous mutation in STAT1. J Allergy
Clin Immunol 2014;133:807-17.
9. Puel A, Cypowyj S, Marodi L, Abel L, Picard C, Casanova JL. Inborn errors of
human IL-17 immunity underlie chronic mucocutaneous candidiasis. Curr Opin
Allergy Clin Immunol 2012;12:616-22.
10. Ng WF, von Delwig A, Carmichael AJ, Arkwright PD, Abinun M, Cant AJ, et al.
Impaired T(H)17 responses in patients with chronic mucocutaneous candidiasis
with and without autoimmune polyendocrinopathy-candidiasis-ectodermal dystro-
phy. J Allergy Clin Immunol 2010;126:1006-15, e1-4.
11. Romberg N, Morbach H, Lawrence MG, Kim S, Kang I, Holland SM, et al.
Gain-of-function STAT1 mutations are associated with PD-L1 overexpression
and a defect in B-cell survival. J Allergy Clin Immunol 2013;131:1691-3.
http://dx.doi.org/10.1016/j.jaci.2014.12.1867
Humanized antiIFN-g (HuZAF) in the treatment
of psoriasis
To the Editor:
Psoriasis is a chronic inflammatory skin disease in which
epidermal hyperplasia occurs because of skin infiltration of
activated immune cells. TH1 cells, defined by their ability to
produce IFN-g, are increased in the peripheral circulation and
in skin lesions of patients with psoriasis.1,2 IFN-g has been
postulated to be a key cytokine in psoriasis due to several
important observations. The number of TH1 cells in skin lesions
is strongly associated with disease activity,1 IFN-g mRNA is
elevated in skin lesions,3 IFN-g is increased in serum from
individuals with psoriasis,4 and large-scale gene expression
studies identify increased expression of IFN-gregulated genes
in lesions.1 Because of the appreciation of increased IFN-g in
psoriasis, 2 small pilot studies were conducted between 2001
and 2003 using a neutralizing humanized antiIFN-g antibody,
HuZAF (Fontolizumab; Protein Design Laboratory, Fremont,
Calif). It was hypothesized that blockade of IFN-g with HuZAF
could reverse the expression of inflammatory gene products in
psoriatic lesions and decrease disease activity.
In this letter, we present the results of both single-dose and
multidose HuZAF injections in psoriasis treatment (see additional
information in this articles Online Repository at www.jacionline.
org). To test the safety and activity of HuZAF in patients with
psoriasis, a single-infusion tolerability study was conducted in
2001. Thirteen men and 7 women (age range, 21-73 years) with
moderate-severe stable plaque psoriasis participated in this trial.
Cohorts of 4 patients received ascending doses of HuZAF: 0.1,
1, 3, and 10 mg/kg or placebo. Across all dose levels, infusions
were well tolerated with only mild/moderate adverse effects noted
(transient headache and chills were the most common adverse
effects, occurring in 25% and 18% of HuZAF-treated patients,
respectively). No severe or serious adverse events were noted.
No significant clinical or histological changes were observed in
cohorts receiving less than 10 mg/kg (data not shown). In
the highest dose group, 3 of 4 patients showed histologic
improvements in index psoriasis lesions from baseline to 29
LETTERS TO THE EDITOR 553
days of treatment (representative responding patient shown in
Fig 1, A), including reversal of acanthosis (epidermal thickening),
and restoration of the granular layer (Fig 1, A and D). In addition,
keratin 16 (K16) immunoreactivity (a marker of keratinocyte
hyperproliferation) was reversed in day 29 posttreatment
biopsies in 2 of 4 cases (representative responding patient shown
in Fig 1, B); K16 mRNA was also reduced in these patients (data
not shown). The Psoriasis Area and Severity Index (PASI) score
was decreased in 1 of 2 patients (Fig 1, C) receiving 10 mg/kg
(the PASI score was not available for 2 patients).
Inflammatory parameters were also modified by a single dose
of 10 mg/kg of HuZAF. CD31 T-cell counts were reduced in 2 of
4 cases (Fig 1, E). On average, the expression of inflammation-
related genes such as CXCL9, IL12p40, and iNOS was reduced
at day 29 versus baseline in 3 of 4 cases (Fig 1, F). Pooled data
and statistics of Fig 1, D to F, are found in Fig E1 in this articles
Online Repository available at www.jacionline.org. Using an
antibody specific for the therapeutic antibody (AF2id),5 HuZAF
was detected in skin lesions of both a responding patient and a
nonresponding patient after treatment with 10 mg/kg. These
data showed that short-term HuZAF (at the 10-mg/kg dose) was
well tolerated and detectable in lesional skin, with the potential
to improve inflammatory parameters and disease-related gene
expression.
Based on results above from this single 10-mg/kg dose of
HuZAF, a small follow-up pilot study was performed to determine
the efficacy of multidose HuZAF; 3 patients were studied at our
institution and 7 at a second site. Results from patients at our
institution are provided in Fig 2. HuZAF was administered at
10 mg/kg, 4 times within a 10-week period (at weeks 0, 2, 6,
and 10) (Fig 2, A). Nonlesional and lesional skin biopsies from
the same index plaque were taken at baseline, as well as at weeks
2, 6, and 12. Reduction in the PASI score was observed in 1 patient
(blue), a mild transient reduction in the PASI score was observed
in 1 patient (red), and a worsening of the PASI score was observed
in 1 patient, who then stopped the study (green) (Fig 2, A).
Quantitative RT-PCR was used to determine changes in the
expression of K16, IL23/p19, CXCL9, IL12/23/p40, and iNOS
(Fig 2, B and C). On average, the expression of these inflamma-
tory markers declined at week 2 postinitiation of HuZAF as
was previously observed with a single dose. However, results
between patients were highly variable and not sustained. The
patient who had the greatest reduction in the PASI score (blue)
also demonstrated the greatest reduction in K16, p19, CXCL9,
IL12/23/p40, and iNOS. However, in 2 of 3 patients, additional
doses of HuZAF did not improve outcome, and after multiple
doses of HuZAF, increased expression of p19, CXCL9, IL12/23/
p40, and iNOS was noted. Statistical analysis of inflammatory
gene expression in all 10 patients from both sites is provided
in Fig E2 in this articles Online Repository available at
www.jacionline.org. HuZAF failed to significantly reduce the
expression of K16, p19, and IL12/23p40. The expression of
iNOS was transiently reduced, and the expression of only
CXCL9 was significantly suppressed by HuZAF through week
12. This finding is interesting because CXCL9 is heavily regulated
by IFN-g, demonstrating that IFN-g was successfully blocked in
these patients despite lack of clinical efficacy. Of all 10
patients treated 4 times with 10 mg/kg of HuZAF, only 1 patient
(10%) achieved a significant clinical response. In comparison,
treatments such as briakinumab, inflizimab, and ustekinumab
achieve PASI75 in 60% to 90% of all patients.6
554 LETTERS TO THE EDITOR J ALLERGY CLIN IMMUNOL
FEBRUARY 2015

FIG 1. Effect of a single dose of HuZAF (10 mg/kg) for treatment of psoriasis. H&E (A) and K16 (B) staining of
a responding patient. C, PASI scores for 2 patients. D, Epidermal thickness in baseline nonlesional (NL)
and lesional skin (LS), as well as day 29 posttreatment. E, CD31 T cells quantified by immunohistology.
F, Inflammatory gene expression as determined by quantitative RT-PCR. G, Staining of HuZAF using
AF2id. All histology images shown at same magnification; bar 5 10 mm. Each colored line represents a
single patient. H&E, Hematoxylin and eosin.

Although these studies were limited due to small patient explored after the discovery of TH17 cells in psoriasis.6 It is
sample size, the results fall short compared with the highly possible that IFN-g is important for the initiation of lesions
successful therapies targeting the IL-17 axis, which were whereas IL-17 is critical for the chronic nature of psoriasis.
J ALLERGY CLIN IMMUNOL
VOLUME 135, NUMBER 2
FIG 2. Results of a multiple-dose regimen of HuZAF in the treatment of psoriasis. A, PASI scores in patients
receiving 4 HuZAF infusions (arrows indicate the administration of treatment). B and C, Inflammatory gene
expression as determined by quantitative RT-PCR, for each patient in nonlesional (NL), lesional (LS), and
posttreatment LS skin. Each colored line represents a single patient.
Successful resolution of psoriasis after etanercept (antiTNF-a)
correlated more significantly with reduction in IL-17responsive
genes than in IFN-gresponsive genes.7 A recently published
study using the IL-23specific, antip19-targeting mAb
(guselkumab) demonstrated outstanding clinical efficacy (at the
highest dose, all patients achieved PASI75), but without
significant reduction in the IFN-g gene signature.8 In addition,
antiIFN-g antibody (HuZAF) was found to be present in skin
lesions of both responders and nonresponders (Fig 1, G), demon-
strating that blocking IFN-g did not lead to disease amelioration.
These findings suggest that specific targeting and reduction of
IL-17 and IL-17responsive genes is more therapeutic than
targeting and reduction of IFN-g and IFN-g responsive genes.
This may allude to the initiating and pathogenic importance of
IFN-g in psoriasis, but reduction is not required for the resolution
of chronic psoriatic inflammation. IFN-g may certainly contribute
to inflammation in psoriasis; however, the IL-17 axis appears to
be the major driver of this disease. Currently, HuZAF is undergo-
ing clinical trials as treatment in Crohn disease, and is showing
promise for this particular inflammatory disease.9
In conclusion, we have reported here that antiIFN-g
(HuZAF), while safe and tolerable in patients with psoriasis,
had minimal efficacy in the treatment of psoriasis. This suggests
that IFN-g is not a major pathogenic cytokine in chronic psoriasis
lesions, leading to the need to redraw the current pathogenic
models of this disease.
We acknowledge the contributions of Drs Diane Baker, Ken Gordon,
D. ONeill, and Elizabeth Layug to this work.
Jamie L. Harden, PhDa
Leanne M. Johnson-Huang, PhDa
Maria Francesca Chamian, MDa
Edmund Lee, MDa
Tillman Pearce, MDb
Craig L. Leonardi, MDc
Asifa Haider, PhDa
Michelle A. Lowes, MD, PhDa
James G. Krueger, MD, PhDa
LETTERS TO THE EDITOR 555
From athe Laboratory for Investigative Dermatology, The Rockefeller University, New
York, NY; bthe Protein Design Laboratory, Fremont, Calif; and cthe Department of
Dermatology, St Louis University, St Louis, Mo. E-mail: jgk@rockefeller.edu.
M.A.L. and J.L.H. were supported by the National Institutes of Health (grant no.
1R01AR060222). L.M.J.-H. was supported by the Linda and Leonard Berkowitz
Postdoctoral Fellowship.
Disclosure of potential conflict of interest: J. L. Harden and M. A. Lowes have received
research support from the National Institutes of Health/National Institute of Arthritis,
Musculoskeletal and Skin Diseases (grant no. 1R01AR060222). L. M. Johnson-
Huang has received research support from the Linda and Leonard Berkowitz
Foundation. M. F. Chamian is employed at a private dermatological practice.
T. Pearce is employed by PDF Biopharma and has received stock options as part of
his compensation. C. L. Leonardi has received a fee for service as an investigator
for PDL, Addvie, Amgen, Anacor, Celgene, Galderma, Janssen, Maruho, Merck,
Novartis, Eli Lilly, Leo, Pfizer, Stiefel, and Tolmar; has consultant arrangements
with Abbvie, Amgen, Dermira, Eli Lilly, Leo Pharmaceuticals, Pfizer, Sandoz, and
UCB; and has received payment for lectures from Abbvie. J. G. Krueger has received
research support, consulting fees, and provision of drug for the study from Protein
Design Laboratory; has consultant arrangements with Abbvie, Akros, Amgen,
Astellas, Boehringer, Biogen-Idec, Janssen, Dermira, Eli Lilly, Genzyme-Sanofi,
Leo Pharmaceutical, Merck, Novartis, and Pfizer; and has received research support
from Akros, Amgen, Astellas, Boehringer, Biogen Idec, Centocor/Janssen, Dermira,
Lilly, Genzyme-Sanofi, Merck, Novartis, and Pfizer. The rest of the authors declare
that they have no relevant conflicts of interest.
REFERENCES
1. Lew W, Bowcock AM, Krueger JG. Psoriasis vulgaris: cutaneous lymphoid tissue
supports T-cell activation and type 1 inflammatory gene expression. Trends
Immunol 2004;25:295-305.
2. Austin LM, Ozawa M, Kikuchi T, Walters IB, Krueger JG. The majority of
epidermal T cells in Psoriasis vulgaris lesions can produce type 1 cytokines,
interferon-gamma, interleukin-2, and tumor necrosis factor-alpha, defining TC1
(cytotoxic T lymphocyte) and TH1 effector populations: a type 1 differentiation
bias is also measured in circulating blood T cells in psoriatic patients. J Invest
Dermatol 1999;113:752-9.
3. Uyemura K, Yamamura M, Fivenson DF, Modlin RL, Nickoloff BJ. The cytokine
network in lesional and lesion-free psoriatic skin is characterized by a T-helper
type 1 cell-mediated response. J Invest Dermatol 1993;101:701-5.
4. Chodorowska G. Plasma concentrations of IFN-gamma and TNF-alpha in psoriatic
patients before and after local treatment with dithranol ointment. J Eur Acad
Dermatol Venereol 1998;10:147-51.
5. Thakur AB, Landolfi NF. A potent neutralizing monoclonal antibody can
discriminate amongst IFNgamma from various primates with greater specificity
than can the human IFNgamma receptor complex. Mol Immunol 1999;36:1107-15.
556 LETTERS TO THE EDITOR
6. Johnson-Huang LM, Lowes MA, Krueger JG. Putting together the psoriasis puzzle:
an update on developing targeted therapies. Dis Model Mech 2012;5:423-33.
7. Zaba LC, Suarez-Farinas M, Fuentes-Duculan J, Nograles KE, Guttman-Yassky E,
Cardinale I, et al. Effective treatment of psoriasis with etanercept is linked to
suppression of IL-17 signaling, not immediate response TNF genes. J Allergy
Clin Immunol 2009;124:1022-10.e1-395.
8. Sofen H, Smith S, Matheson RT, Leonardi CL, Calderon C, Brodmerkel C, et al.
Guselkumab (an IL-23-specific mAb) demonstrates clinical and molecular
response in patients with moderate-to-severe psoriasis. J Allergy Clin Immunol
2014;133:1032-40.
9. Hommes DW, Mikhajlova TL, Stoinov S, Stimac D, Vucelic B, Lonovics J, et al.
Fontolizumab, a humanised anti-interferon gamma antibody, demonstrates
safety and clinical activity in patients with moderate to severe Crohns disease.
Gut 2006;55:1131-7.
Available online July 29, 2014.
http://dx.doi.org/10.1016/j.jaci.2014.05.046
Genetic variants of inducible costimulator are
associated with allergic asthma susceptibility
To the Editor:
The prevalence of allergic diseases has increased worldwide
over the past decades, with 300 million people now affected by
asthma and an estimated 400 million more suffering from allergic
rhinitis.1 These allergic phenotypes result from a complex inter-
play between genetic and environmental risk factors that remain
incompletely defined. Previous genetic studies associating induc-
ible costimulator (ICOS) promoter polymorphisms with allergic
sensitization2 and IgE3 were not consistently reproduced.4,5
Thus, the role of ICOS polymorphisms in allergy and asthma
risk remained unclear. Here we investigate the association of
polymorphisms in the ICOS gene with the risk of developing
allergic asthma, and report for the first time a significant associa-
tion between single nucleotide polymorphisms (SNPs) of ICOS
and asthma. Furthermore, we demonstrate that the minor allele
of the tagSNP rs4675374 is associated with increased expression
of ICOS on T lymphocytes including regulatory T (Treg) cells and
lower risk of atopy and asthma.
Our association analysis included an adult Singapore Chinese
cohort and an independent Dutch Caucasian cohort.6 (For more
information, see this articles Methods section and for demo-
graphic characteristics, see Tables E1 and E2 in the Online Repos-
itory at www.jacionline.org.) We identified the T allele of the
tagSNP rs4675374 as having the most significant association
with allergic asthma in the Singapore Chinese cohort, with
an odds ratio of 0.69 (95% CI, 0.59-0.80) and a P value of
9.77 3 1027 (see Table E3 in this articles Online Repository at
www.jacionline.org). This SNP was also significantly associated
with allergic asthma (P 5 .017) in the Dutch Caucasian cohort,
with the same direction of effect (see Table E4 in this articles On-
line Repository at www.jacionline.org). In a meta-analysis using
data from the Singapore Chinese and Dutch allergic asthma co-
horts, the T allele (minor) was significantly associated with
allergic asthma (Pmeta 5 7.16 3 1028 and an odds ratio of 0.72;
Table I). To test whether our findings on ICOS variants and asthma
risk could be reproduced in an unrelated and independent cohort,
we analyzed data from a recently published meta-analysis of
asthma in North American populations.7 We used association
summary statistics including risk and alternative alleles, z score,
and P value from the study data to ask whether ICOS genetic var-
iants were associated with asthma in this population (see Table E5
in this articles Online Repository at www.jacionline.org). We
J ALLERGY CLIN IMMUNOL
FEBRUARY 2015
found that the most significantly associated SNP in the Singapore
Chinese population, rs4675374, was also the most significantly
associated SNP in the North American populations (Pmeta 5
.006). In addition, in a Singaporean population of ethnic Chinese
from the Singapore Cohort study Of the Risk factors for Myopia
study,8 we observed that the allele frequency of the T genotype of
rs4675374 SNP was higher in controls (40%) than in asthmatic
cases (36%). In conclusion, the association of the T allele of
rs4675374 ICOS SNP with lower asthma risk was validated in
several independent cohorts of diverse ethnic origin.
IgE levels are a strong indicator of allergic disease and hence
we next tested whether rs4675374 was also associated with serum
IgE levels. Analysis of samples from 182 individuals within the
adult Singaporean Chinese cohort revealed that the presence of
the T allele, which is associated with a lower risk of allergic
asthma, was also associated with lower total IgE and house dust
mite-specific IgE levels in serum (see Fig E1, A and B, in this ar-
ticles Online Repository at www.jacionline.org). When we tested
the same hypothesis in a cohort of Korean asthmatic patients, we
found that individuals with the TT allele had significantly lower
total IgE levels (mean, 397 U/mL) than did those with the CC
or CT genotypes (mean, 305 U/mL), which was consistent with
findings in the Singapore Chinese cohort (see Fig E1, C).
The genetic associations described above for the rs4675374
ICOS SNP were indeed significant but it was not clear whether
this SNP drove a measurable biological phenotype or function.
To address this question, we used a large expression quantitative
trait locus meta-analysis data set of European origin that
comprised 9 different whole-blood expression data sets with cor-
responding whole genome SNP information.9 Fig 1 demonstrates
a strong association of rs4675374 with ICOS mRNA levels in
whole blood in this independent population of unrelated individ-
uals from Europe. Individuals with the T allele had a significantly
higher ICOS gene expression level than did those with the C
allele. The direction of the effect was identical for 7 of the 8
data sets, with a meta P value that indicated significance (false-
discovery rate, <0.05) with P 5 1.5 3 1027 (z score of 5.25 for
all the cohorts combined). Thus, having the low asthma-risk T
allele for the tagSNP rs4675374 is associated with higher ICOS
mRNA levels in an independent population of unrelated individ-
uals of European ethnicity.
To evaluate whether the difference in gene expression translated
into a higher ICOS protein level, we selected a group of 40
individuals from the Singaporean Chinese adult cohort carrying
the CC or TT rs4675374 genotype and determined the expression
of ICOS protein on peripheral blood T cells. Of the group of 40
individuals, 16 were homozygous for the minor T allele of
rs4675374. The expression of ICOS on unstimulated CD31 T cells
from PBMCs was relatively low (see Fig E2, A, in this articles On-
line Repository at www.jacionline.org) but increased after activa-
tion with anti-CD3 and anti-CD28 antibodies, as previously
described2 (see Fig E2, B). Surface expression of ICOS in acti-
vated total CD31 T cells, as well as in the CD41 and CD81 subsets
(see Fig E2, B, C, and D, respectively), was significantly higher in
samples from individuals carrying the rs4675374 TT genotype
associated with a lower risk for asthma (P value .014 for CD31
cells, .047 for CD41 cells, and .032 for CD81 cells).
The effect of the rs4675374 tagSNP genotype on ICOS
expression level was also assessed in various peripheral blood
CD41 T helper cell subpopulations (TH1, TH2, TH17, and Tfh) in
the absence of stimulation (see Fig E3 in this articles Online
556.e1 LETTERS TO THE EDITOR J ALLERGY CLIN IMMUNOL
FEBRUARY 2015

METHODS tuberculosis or other mycobacterial infection, and patients with guttate

psoriasis, pustular psoriasis, or whole-body erythroderma.
Study design
The following studies were Rockefeller University Institutional Review
Boardapproved protocols. Infusions were intravenous administration over 30
minutes. No significant adverse events were reported for either the single-dose
Immunohistochemistry
Frozen tissue sections were stained with hematoxylin (Fisher Scientific,
or the multidose HuZAF study.
Fair Lawn, NJ) and eosin (Shandon, Pittsburgh, Pa), and with murine mAbs to
For single-dose HuZAF studies, 13 men and 7 women (age range, 21-73
K16 (Sigma Aldrich, St Louis, Mo) and CD3 (BD, Franklin Lakes, NJ) as
years) with moderate-severe stable plaque psoriasis participated in this trial in
previously described.E1 AF2id, an anti-idiotypic antibody against the HuZAF
2001. Four cohorts of patients received ascending doses of HuZAF
murine parent antibody AF2 (PDL, 10 ug/mL), was used to evaluate the
(fontolizumab): 0.1, 1, 3, and 10 mg/kg; for each cohort, 1 patient (n 5 1
presence of the therapeutic antibody in skin.E2 Epidermal thickness
out of a cohort of 4-5) was randomly assigned to receive a placebo infusion.
measurements and CD31 T-cell counts were determined through National
Nonlesional and lesional skin biopsies were taken at baseline, as well as on
Institutes of Health software (NIH Image-J 6.1).
days 8 and 29 from the same index plaque posttreatment.
For multidose HuZAF studies, male and female patients 18 years or older
with moderate to severe psoriasis vulgaris could enroll (PASI score > 12). Four
doses of 10 mg/kg HuZAF were administered at study days 0, 14 (week 2), 42
RT-PCR
Quantative RT-PCR was performed on RNAs isolated from skin biopsy
(week 6), and 70 (week 10). Nonlesional and lesional skin biopsies were taken
samples as previously described.E3 Genes of interest were normalized to
at baseline, as well as on week 2, week 6, and week 12 from the same index
human acidic ribosomal protein, a housekeeping gene.
plaque posttreatment.
For both studies, patients must have adequate organ function, have not
received standard systemic therapies other than biologics (methotrexate, REFERENCES
cyclosporine A, retinoids, psoralen with ultraviolet A) within 30 days, and E1. Vallat VP, Gilleaudeau P, Battat L, Wolfe J, Nabeya R, Heftler N, et al. PUVA
have not received antibody or investigational therapies (such as alefacept, bath therapy strongly suppresses immunological and epidermal activation in pso-
infliximab, etanercept, and efalizumab) within 60 days. Patients must test riasis: a possible cellular basis for remittive therapy. J Exp Med 1994;180:283-96.
negative in urine pregnancy tests within 48 hours before the first study drug E2. Thakur AB, Landolfi NF. A potent neutralizing monoclonal antibody can
discriminate amongst IFNgamma from various primates with greater specificity
administration. Exclusion criteria include malignancy within 5 years or
than can the human IFNgamma receptor complex. Mol Immunol 1999;36:
current malignancies, pregnant or nursing mothers, patients with evidence of 1107-15.
infection with HIV, hepatitis B virus, or hepatitis C virus, hematologic E3. Johnson-Huang LM, Suarez-Farinas M, Sullivan-Whalen M, Gilleaudeau P,
abnormalities, previous HuZAF treatment, history of immune deficiency or Krueger JG, Lowes MA. Effective narrow-band UVB radiation therapy
autoimmune disorders other than psoriasis or psoriatic arthritis, serious suppresses the IL-23/IL-17 axis in normalized psoriasis plaques. J Invest
infection, hypersensitivity to glycine, histidine, or Polysorbate 80, Dermatol 2010;130:2654-63.
J ALLERGY CLIN IMMUNOL LETTERS TO THE EDITOR 556.e2
VOLUME 135, NUMBER 2

FIG E1. Gene expression of single dose HuZAF (10 mg/kg) study. Data from individiual patients are pooled
and displayed here. Error bars 5 SE. Data analyzed using paired t test. *P < .05.
556.e3 LETTERS TO THE EDITOR J ALLERGY CLIN IMMUNOL
FEBRUARY 2015

FIG E2. Gene expression of multi-dose HuZAF trial. Inflammatory gene expression determined in biopsies of
basline NL and LS, as well as post-treatment. Data from 10 individual patients (A) and combined data (mean)
from all 10 patients (B); error bars 5 SE. Data analyzed using paired t test. *P < .05, **P < .01, and ***P < .001.