Primary immunodeficiency disease: A retrospective study of 112 Chinese children in a single tertiary care center

Abstract

Background:
Primary immunodeficiency disease (PID) is a disorder caused by an inherited flaw in the immune system that increases the susceptibility to infections.

Methods:
In this study, 112 children with PID were diagnosed and classified based on the 2017 criteria presented by the International Union of Immunological Societies (IUIC) in a single tertiary care center from January 2013 to November 2018. We retrospectively studied the clinical features of those PID children and followed-up them as well.

Results:
It was revealed that male/female ratio was 6:1. The most frequent diagnosed PID was severe combined immunodeficiency (SCID) (28.6%) and hyper-IgM (HIGM) syndrome (24.1%), followed by predominantly antibody deficiencies (17.8%). Combined immunodeficiencies with associated or syndromic features (12.5%) and congenital defects of phagocyte number, function, or both (10.7%) were less common in our center compared with SCID and HIGM syndrome. Besides, we found that 20 children (17.8%) had a positive family history of PID, and almost all cases (97.3%) had a history of recurrent infection. Recurrent respiratory tract infection was among the most common symptoms, followed by the bacterial infection of the skin and mucous membranes and diarrhea. Additionally, adverse event following immunization (AEFI) was found in 20.5% of the patients, and immune disorder was commonly observed in PID patients. In the present study, 47 patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), and 2-year overall survival (OS) rate for these patients was 78.7% (37/47). It is noteworthy that OS widely differed among PID patients with different phenotypes who underwent allo-HSCT. The 2-year OS rate for SCID, HIGM syndrome, and the remaining of PID patients who underwent allo-HSCT was 14.3, 83.3, and 100%, respectively.

Conclusions:
PID typically emerges at early age. Recurrent infection and serious infection were the most common clinical manifestations. Allo-HSCT is a relatively effective therapeutic strategy for PID patients.

Full text

R E S E A R C H A R T I C L E Open Access
Primary immunodeficiency disease: a
retrospective study of 112 Chinese children
in a single tertiary care center
Jinhong Wu, Wenwei Zhong, Yong Yin and Hao Zhang
*
Abstract
Background: Primary immunodeficiency disease (PID) is a disorder caused by an inherited flaw in the immune
system that increases the susceptibility to infections.
Methods: In this study, 112 children with PID were diagnosed and classified based on the 2017 criteria presented by
the International Union of Immunological Societies (IUIC) in a single tertiary care center from January 2013 to
November 2018. We retrospectively studied the clinical features of those PID children and followed-up them as well.
Results: It was revealed that male/female ratio was 6:1. The most frequent diagnosed PID was severe combined
immunodeficiency (SCID) (28.6%) and hyper-IgM (HIGM) syndrome (24.1%), followed by predominantly antibody
deficiencies (17.8%). Combined immunodeficiencies with associated or syndromic features (12.5%) and congenital
defects of phagocyte number, function, or both (10.7%) were less common in our center compared with SCID and
HIGM syndrome. Besides, we found that 20 children (17.8%) had a positive family history of PID, and almost all cases
(97.3%) had a history of recurrent infection. Recurrent respiratory tract infection was among the most common
symptoms, followed by the bacterial infection of the skin and mucous membranes and diarrhea. Additionally, adverse
event following immunization (AEFI) was found in 20.5% of the patients, and immune disorder was commonly
observed in PID patients. In the present study, 47 patients underwent allogeneic hematopoietic stem cell transplantation
(allo-HSCT), and 2-year overall survival (OS) rate for these patients was 78.7% (37/47). It is noteworthy that OS widely
differed among PID patients with different phenotypes who underwent allo-HSCT. The 2-year OS rate for SCID, HIGM
syndrome, and the remaining of PID patients who underwent allo-HSCT was 14.3, 83.3, and 100%, respectively.
Conclusions: PID typically emerges at early age. Recurrent infection and serious infection were the most common
clinical manifestations. Allo-HSCT is a relatively effective therapeutic strategy for PID patients.
Keywords: Primary immunodeficiency disease, Clinical features, Demographic characteristics, Children, China
Background
Primary immunodeficiency disease (PID) refers to a het-
erogeneous group of over 130 disorders that result from
defects in immune system development and/or function.
With the development and use of flow cytometry and
genetic technology for clinical diagnosis, diagnostic rate
of PID has been markedly increased in China. To date,
354 distinct disorders with 344 different gene defects
have been identified in patients with PID [1]. PID is
characterized by diverse clinical manifestations, such as
recurrent or prolonged serious infections, autoimmune/
inflammatory disease, allergy, or malignancy. In addition,
physicians or general practitioners may not able to
recognize PID because of rarity of those diseases, particu-
larly in developing countries (e.g., China) [2,3]. As a result,
delayed diagnosis or misdiagnosis are quite common in
clinical practice, which may lead to the poor outcomes for
children with PID. In the present study, we retrospectively
analyzed the clinical features and prognosis of 112 PID
children over a 6-year period in a single tertiary care center
to strengthen our understanding about PID.
© The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
* Correspondence: zhang123hao2004@163.com
Department of Pulmonary, Shanghai Children’s Medical Center Affiliated to
Shanghai Jiaotong University School of Medicine, Shanghai 200127, China
Wu et al. BMC Pediatrics (2019) 19:410
https://doi.org/10.1186/s12887-019-1729-7
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Methods
Classification and diagnosis
A single-center retrospective study was carried out at
Shanghai Children’s Medical Center Affiliated to Shanghai
Jiao Tong University (Shanghai, China) from January 2013
to November 2018. A total of 112 patients were in-
cluded for investigation and classified according to the
2017 criteria presented by the International Union of
Immunological Societies (IUIS) classification system
[1]. In addition, PID was grouped as follows: immuno-
deficiencies affecting cellular and humoral immunity;
predominantly antibody-deficiency diseases; combined
immunodeficiencies with associated or syndromic features;
diseases of immune dysregulation; congenital defects of
phagocyte number or function; defects in intrinsic and
innate immunity; autoinflammatory disorders; and comple-
ment deficiencies [4,5]. Because the clinical features and
prognosis of hyper-IgM (HIGM) syndrome are different
from those associated with severe combined immunodefi-
ciency (SCID), patients with HIGM syndrome were not
herein included in the group of immunodeficiencies in-
fluencing cellular and humoral immunity. All patients
were diagnosed according to the diagnostic criteria and
confirmed by genetic phenotyping. Immunodeficiencies
secondary to other conditions (e.g., human immunodefi-
ciency virus (HIV) infection) were excluded as well.
Data collection
All clinical data were collected from the hospital medical
records. Sex, family history, age of the first hospitalization,
clinical features, onset of symptoms, signs, age of onset,
age at diagnosis, auxiliary examination, and disease pro-
gress were included in this study.
Specimen collection and sequencing analysis of relevant
genes
Patients’specimens were collected during hospitalization
from January 2013 to November 2018. For comparative
purposes, we also collected specimens from the parents.
Anticoagulant venous blood was collected and was further
centrifuged at 3500 rpm for 10 min. Peripheral blood cells
were stored at −80 °C and used for DNA extraction and
gene sequencing using next-generation sequencing (NGS)
technique, which were further performed based on the
clinical features and auxiliary examination results.
Statistical analysis
Data were analyzed by using SPSS 17.0 software (IBM,
Armonk, NY, USA). The differences between the groups
were compared by the Student’st-test. Pvalues < 0.05
were considered statistically significant.
Results
Demographic features of PID patients
Frequency and distribution of PID
Diagnosis was based on clinical, immunological, and
genetic testing, and 112 patients were diagnosed with
PID in our hospital from January 2013 to November
2018. There were 18 PIDs diagnosised in 112 patients
with pathogenic mutations which grouped into 7 main
categories (Table 1). As shown in Table 1, SCID was
found in 32 patients (28.6%), HIGM syndrome in 27
(24.1%), combined immunodeficiencies with associated
or syndromic features 14 (12.5%), predominantly anti-
body deficiencies in 20 (17.8%), diseases related to immune
dysregulation in 4 (3.6%), congenital defects of phagocyte
number or function, or both in 12 (10.7%), defects in
intrinsic and innate immunity in 2(1.8%), and complement
deficiencies in 1 (0.9%) (Table 1). None of the patients
were diagnosed with phenocopies of PID or defects in
autoinflammatory disorders. Combination of T- and B-cell
immunodeficiencies was the most common (n= 32) among
all the patients with PID, followed by HIGM syndrome
(n= 27). Wiskott–Aldrich syndrome (WAS) was the most
common PID in combined immunodeficiencies with asso-
ciated or syndromic features group (n=9), followed by
dyskeratosis congenita (n= 2). Predominantly antibody
deficiencies were the most common PIDs in patients with
severe serum immunologlobulin isotypes reduction and B
cells decreased or absent(n= 16), followed by common
variable immunodeficiency disorders (n= 3). There were 7
and 5 patients who diagnosed with chronic granulomatous
disease and congenital neutropenias, respectively. Those
patients showed congenital defects in phagocyte number,
function or both.
Patients’demographic characteristics
There were 96 males and 16 females in the present
study. The male/female ratio was 6:1, and there were
different ratios among subgroups of PIDs (Table 2). All
patients with PID related to X-linked recessive inheritance
were male (e.g., Bruton tyrosine kinase (BTK)-deficiency,
WAS, and HIGM syndrome).
Distribution of age in patients with PID
The average onset age of all patients with PID was 13
months (range, 2 days-117 months). The onset age of 68
children (60.7%) was younger than 6 months, there were
28 (25%) patients aged between 6 months and 3 years,
and 16 (14.3%) patients were older than 3 years as well.
The average time to the first diagnosis as PID was 24
months (range, 1-130 months). Besides, 38 (33.9%) chil-
dren were diagnosed with PID who were younger than
6 months, 45 (40.2%) children aged between 6 months
and 3 years, and 29 (25.9%) children were older than 3
years (Table 2). There were statistically significant
Wu et al. BMC Pediatrics (2019) 19:410 Page 2 of 7
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difference among subgroups of PID according to the age
of onset and age at the time of diagnosis (Table 2). Our
study indicated that symptoms were notably observed
earlier in WAS and SCID patients compared with other
subgroups with the median onset age of 1 and 4 months,
respectively; meanwhile, the time of the first diagnosis
was shorter in WAS and SCID patients with the median
diagnosis time of 7.22 and 5.94 months, respectively.
Compared with WAS and SCID patients, patients with
primary antibody deficiency displayed symptoms re-
markably later with the median age of 26.5 months, in
which the mean time to diagnosis was 41.8 months.
Main clinical manifestations
In our study population, 20 patients (17.8%) had a positive
family history of PID (Table 2). Additionally, patients with
PID presented various clinical manifestations during diagno-
sis (Table 3). A previous history of recurrent infection was
found in almost all the patients (n= 109, 97.3%). The main
pathogen of infection was bacterial infection (n= 108), and
fungal infection (n= 18) ranked in the second place,
followed by viral infection in the third place (n=7).Respira-
tory infection was the most common complication (n= 89,
79.5%), including sinusitis, acute otitis, bronchitis, bronchi-
ectasis, and pneumonia. The second common complications
were infections of skin and mucous membranes. There were
38 cases of skin and mucous membrane infection (33.9%),
including 11 cases of mouth ulcers, 9 cases of perianal
abscess, 7 cases of mycotic stomatitis, 7 cases of skin pus-
tules and nodules, and 4 case of eczema. The third common
complication was digestive tract infection, of which diarrhea
was found in 26 cases (23.2%). However, diarrhea not only is
caused by infection, but also caused by immune disorder. In
addition, we found 7 cases with infection of central nervous
system (CNS). It should be noted that 23 children (20.5%)
had adverse event following immunization (AEFI), involving
Bacillus Calmette-Guérin (BCG)-osis, local skin infection,
and fever. Furthermore, 21 patients (17%) had BCG-osis
Table 1 Distribution of PIDs according to the International Union of Immunological Societies criteria
Type No. of Cases (%)
Immunodeficiencies affecting cellular and humoral immunity 59 (28.6)
SCID 32
HIGM 27
Combined immunodeficiencies with associated or syndromic features 14 (12.5)
WAS 9
DKC 2
DGS 1
EDA-ID 1
HIES 1
Predominantly antibody deficiencies 20 (17.8)
Severe reduction in all serum immunologlobulin isotypes with profoundly decreased or absent B cells 16
CVID 3
APDS 1
Diseases of immune dysregulation 4 (3.6)
IPEX syndrome 2
Immune dysregulation with colitis 1
CHS 1
Congenital defects of phagocyte number or function 12 (10.7)
CGD 7
Congenital neutropenias 5
Defects in intrinsic and innate immunity 2 (1.8)
IFN-γreceptor deficiency 1
Predisposition to invasive fungal diseases (CARD9 deficiency) 1
Complement deficiencies 1 (0.9)
Complement deficiencies 1
Abbreviations: APDS activated PI3Kδsyndrome immunodeficiency, CGD chronic granulomatous disease, CHS Chediak-Higashi syndrome, CVID common variable
immunodeficiency disorders, DGS DiGeorge syndrome, DKC dyskeratosis congenital, EDA-ID anhidrotic ectodermodysplasia with immunodeficiency, HIGM hyper-
IgM syndrome, HIES Hyper-IgE syndromes, IPEX immunodysregulation, polyendocrinopathy, enterop athy X-linked syndrome, SCID severe combined immune
deficiency, WAS Wiskott–Aldrich syndrome, XLA X-linked agammaglobulinemia
Wu et al. BMC Pediatrics (2019) 19:410 Page 3 of 7
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after BCG vaccination, and BCG-osis was mainly observed
in patients with SCID (9 cases), chronic granulomatous dis-
ease (7 cases), idiopathic primary hypogammaglobulinemia
(4 cases), and interferon-gamma receptor deficiency (1 case).
Thus, AEFI may lead to the consideration of the possibility
of PID. Additionally, a variety of clinical manifestations, such
as leukopenia, anemia, thrombocytopenia, seizure, rash, and
lymphoma, were rarely observed in the patients with PID in
our study.
Outcomes
Of the 112 patients, 43 (33 males and 10 females, 38.4%)
died due to recurrent and severe infections during the
follow-up. The mean age of death for SCID patients was 7
months, while patients with HIGM syndrome and predom-
inantly antibody deficiencies had the mean age of death
equal to 88.5 and 46 months, respectively (Table 2). Of
these, 38 died during hospitalization, and 5 died after
discontinuing treatment (all with SCID). In addition, 65
patients survived, and 4 patients were lost follow-up during
the follow-up period. Respiratory failure after pneumonia,
sepsis, complications after allogeneic hematopoietic stem
cell transplantation (allo-HSCT), disseminated BCG, and
pericardial effusion were the most common causes of death
as well. It is noteworthy that 93.8% (30/32) of the SCID pa-
tients died (including 6 cases who underwent allo-HSCT)
except for 1 case who underwent allo-HSCT and the other
who is currently alive and preparing to undergo allo-
HSCT. In the present study, a total of 47 cases underwent
allo-HSCT, and the 2-year overall survival (OS) rate was
78.7%. The OS widely differed among PID patients with
different phenotypes who underwent allo-HSCT (Table 4).
Among 7 patients with SCID who underwent allo-HSCT,
3 patients died of sepsis, 2 patients died of graft-versus-
host-disease (GVHD), and 1 patient died of pretreatment
before allo-HSCT, while only 1 case was survived. Among
24 patients with HIGM syndrome who underwent allo-
HSCT, 3 patients died of sepsis, 1 patient died of GVHD,
Table 2 General characteristics of patients with primary immunodeficiency diseases
Category No. of
Cases
Gender
Ratio (F/M)
No. of
Death
Age at death
(mo)
No. of
HSCT
Age at
onset (mo)
Age at
diagnosis
(mo)
Family
history
SCID 32 22/10 30 7.03 ± 1.25
(1-28)
7 4.03 ± 0.88
(0.5-23)
5.94 ± 1.06
(1-28)
7
HIGM 27 27/0 4 88.50 ± 44.66
(16-205)
24 9.536 ± 2.23
(1-60)
31.25 ± 6.23
(3-120)
4
WAS 9 9/0 0 9 1.00 ± 0.14
(0.5-2)
7.22 ± 1.98
(2-22)
0
DGS 1 1/0 0.5 0.5 0
DKC 2 2/0 1 26 1 37.00 ±
23.00
44.00 ± 20.00 1
EDA-ID 1 1/0 1 4 0.5 3 1
HIES 1 1/0 1 133 60 60 0
Severe reduction in all serum immunologlobulin
isotypes with profoundly decreased or absent B cells
16 15/1 3 46.00 ± 23.29
(3-83)
26.50 ± 6.89
(2-60)
41.80 ± 10.44
(3-120)
3
CVID 3 3/0 0 29.33 ±
13.13 (4-48)
46.33 ± 26.21
(7-96)
0
APDS 1 1/0 0 96 96 0
IPEX syndrome 2 2/0 0 2 6, 28 6, 28 0
Immune dysregulation with colitis 1 0/1 1 13 1 4 0
CHS 1 0/1 0 1 2 68 0
Congenital neutropenias 5 4/1 0 1 2
CGD 7 6/1 1 12 1 2.17 ± 1.17
(1-8)
5.00 ± 2.11
(1-15)
2
IFN-γreceptor deficiency 1 0/1 0 1 2 60 0
Predisposition to invasive fungal diseases
(CARD9 deficiency)
1 1/0 0 117 130 0
Complement deficiencies 1 1/0 0 48 60 0
Abbreviations: APDS activated PI3Kδsyndrome immunodeficiency, CGD chronic granulomatous disease, CHS Chediak-Higashi syndrome, CVID common variable
immunodeficiency disorders, DGS DiGeorge syndrome, DKC dyskeratosis congenital, EDA-ID anhidrotic ectodermodysplasia with immunodeficiency, HIGM hyper-
IgM syndrome, HIES Hyper-IgE syndromes, IPEX immunodysregulation, polyendocrinopathy, enterop athy X-linked syndrome, SCID severe combined immune
deficiency, WAS Wiskott–Aldrich syndrome, XLA X-linked agammaglobulinemia
Wu et al. BMC Pediatrics (2019) 19:410 Page 4 of 7
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and 20 cases were survived. The remaining cases were all
survived and exhibited complete immune reconstitution.
The 2-year OS rate for patients with SCID, HIGM syn-
drome, and the remaining patients with PID who received
allo-HSCT was 14.3, 83.3, and 100%, respectively (Table 4).
Discussion
PIDs are rare inherited diseases involved the immune
system, typically associating with recurrent and severe
infection, autoimmune disease and increased incidences of
malignancies. At present, fast diagnosis of PID in non-
specialized hospitals or clinics across China accompanies
with great challenges. Delayed diagnosis and misdiagnosis
commonly occur, mainly leading to poor clinical progno-
sis. In the current research, we studied 112 patients with
PID during 6 years in our hospital based on their clinical,
immunological, and molecular characteristics, aiming to
provide a reference for perfect diagnosis of PID.
In the present research study, the most common PID was
combined immunodeficiencies (28.6%), followed by HIGM
syndrome (24.1%), predominantly antibody-deficiency dis-
eases (17.8%), combined immunodeficiencies with associ-
ated or syndromic features (12.5%), congenital defects of
phagocyte number or function (10.7%), diseases of immune
dysregulation (3.6%), defects in intrinsic and innate immun-
ity (1.8%), and complement deficiencies accounted for
about 0.9% of cases, which were found to be different from
those previously reported [6–8] probably because our
hospital is a tertiary referral center and our cases were in-
patients and a number of them were admitted from else-
where. Therefore, the proportion of patients with PID, who
are prone to have severe complications and difficult to diag-
nose, significantly increased. In addition, our hospital is one
of the main referral centers for allo-HSCT in China, and
some of the PID patients in our study were previously diag-
nosed with PID in other hospitals who needed to receive
Table 3 Clinical manifestations and complications of patients with primary immunodeficiency diseases
Type Respiratory
infections
Repeated
Diarrhea
Bacterial Infection Of Skin
and Mucous Membrane
Fungal
Infection
Meningitis BCG-osis
SCID 19 13 8 6 4 9
HIGM 26 6 10 7 0 4
WAS 5 2 4 0 0 0
DGS 1 0 0 0 0 0
DKC 2 1 1 0 0 0
EDA-ID 1 0 0 0 0 0
HIES 1 0 0 0 0 0
Severe reduction in all serum immunologlobulin isotypes
with profoundly decreased or absent B cells
14 1 2 1 2 0
CVID 3 0 0 0 1 0
APDS 1 0 0 0 0 0
IPEX syndrome 1 2 1 1 0 0
Immune dysregulation with colitis 0 1 1 0 0 0
CHS 0 0 1 0 0 0
Congenital neutropenias 7 0 1 2 1 0
CGD 6 1 6 0 0 7
IFN-γreceptor deficiency 1 0 1 0 0 1
CARD9 deficiency 0 0 1 1 1 0
Complement deficiencie 1 0 1 0 1 0
Total (%) 89 (79.5) 26 (23.2) 38 (33.9) 18 (16.1) 10 (8.9) 21 (18.8)
Table 4 The overall survival of PIDs patients after allogeneic
HSCT
Type No. of Cases No. of Survival No. of Death
Total 47 37 10
SCID 7 1 6
HIGM 24 20 4
WAS 9 9 0
DKC 1 1 0
IPEX syndrome 2 2 0
CHS 1 1 0
Congenital neutropenias 1 1 0
CGD 1 1 0
IFN-γreceptor deficiency 1 1 0
Wu et al. BMC Pediatrics (2019) 19:410 Page 5 of 7
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allo-HSCT. Furthermore, we cannot ignore a possibility
that a number of differences were based on race and rela-
tive incidence of disease in ourpopulation.Ourdatafurther
showed that the male/female ratio was 6.0:1, and 60.7% of
the cases presented symptoms less than 6 months. Be-
sides, 17.8% of the patients in our study had family
history of PID, which was found similar to a previous
study [8].
Repeated and chronic infections, particularly pulmon-
ary infections, are a main feature of PID. Large sample
cohort studies on PID indicated that almost all patients
with PID had a history of recurrent infection before
diagnosis was finalized [9–11]. In agreement with those
reports, the present study revealed that 97.3% of PID
patients presented recurrent infections before diagnosis.
The most common occurrences were respiratory tract
infection, followed by bacterial infection of the skin and
mucous membranes in 38 cases (33.9%). Of note, gastro-
intestinal disorders are frequent in patients with PID
[12,13]. Moreover, 26 (112, 23.2%) patients with infec-
tious or noninfectious diarrhea showed a poor growth as
well. Besides, PID-related gastrointestinal diseases not
only are caused by infection, but also by autoimmunity,
an inflammatory response, or malignancy. Recurrent
gastrointestinal symptom could be the first presentation
of PID, thus physicians should be aware of the possibility
of PID in patient with intractable diarrhea, malabsorption,
and failure to thrive, especially those cases who failed to
respond to conventional treatment strategies [14,15].
Sarmiento et al. reported 7.65% of AEFI in patients
with PID [16]. The majority of cases of AEFI have
occurred in patients with CGD, SCID, and idiopathic
primary hypogammaglobulinemia. It was reported that
BCG is a vaccine, mainly associating with AEFI in pa-
tients with PID [17]. In the current study, AEFI was
found in 20.5% of patients with PID after vaccination,
especially with BCG vaccine, and included extra regional
lymph nodes, skin, or lungs as the most common clinical
presentations. For patients with CGD and SCID, the
percentage of BCG-osis was 100 and 28.1%, respectively,
which found to be in line with previously reported find-
ings [18–20]. Notably, 17.8% of the cases included family
history of PID. Because BCG vaccination is routinely
carried out at birth in China, PID patients who receive
BCG vaccination before immune deficiency are highly
suspected. BCG vaccination should be avoided if any
family history or clinical or laboratory evidence concerns
a neonate’s immune competency. Moreover, dissemi-
nated BCG infection should be suspected in any vacci-
nated infants who accompany with a persistent fever or
comparable disease of unknown etiology.
In addition to recurrent and severe infections, immun-
ity disorder is commonly observed in PID patients, espe-
cially in patients who accompany with predominantly
antibody deficiencies [21,22]. A recent study, that involved
an Iranian cohort of 471 patients, reported inflammatory
manifestations in 26.5% of patients. Furthermore, the
prevalence of immunity disorder appeared to increase with
age in PID cohorts, influencing a significant proportion of
patients [23]. In this study, we also found that not only
autoimmune gastrointestinal disease, but also autoimmune
cytopenias were the common autoimmune manifestations
in patients with PID. When a child associates with auto-
immune manifestations, the possibility of incidence of PID
should be highly taken into account.
Immunoglobulin replacement therapy and allo-HSCT
are effective therapeutic strategies for patients with PID.
On the basis of previous reports, immunoglobulin replace-
ment therapy was found to be effective for 83% of children
with hypogammaglobulinemia [24,25]. At present, the
majority of patients with PID only receive symptomatic
treatment. Allo-HSCT, which has been used as an effect-
ive treatment for PID [26,27], isn’tfrequentinChina.The
2-year OS rate in the SCID patients was 90% during 25
months of follow-up [28]. A total of 47 cases underwent
allo-HSCT and the OS rate was 78.7% (37/47) in the
present study, which was in agreement with those findings
previously reported [27]. However, the OS widely differed
among PID patients with different phenotypes who under-
went allo-HSCT. The 2-year OS rate for SCID, HIGM
syndrome, and the remaining of PID patients who under-
went allo-HSCT was 14.3, 83.3, and 100%, respectively.
The OS of SCID is mainly poor because SCID patients are
often severely infected, and bone marrow transplantation
of severely infected SCID children has a poor prognosis.
Compared with patients with active infection and older
age who underwent allo-HSCT, OS was better in those
patients who received a transplant when they were youn-
ger and free from infection. Thus, allo-HSCT is more
effective in younger PID children, and allo-HSCT is often
helpful when an appropriate donor is available.
However, the present study contains some limitations,
including its retrospective nature, small sample size, and
all the cases were recruited at a single center. A possible
selection bias also might be present because the clinical
data were taken from hospitalized children with PID.
Further researches involving more PID patients and
multiple centers are required in the future study.
Conclusions
Our study indicated that PID typically emerges at early
age. Recurrent infection and serious infection were the
most common clinical manifestations. Delayed diagnosis
or misdiagnosis may lead to poor clinical prognosis as
well. Allo-HSCT is a relatively effective therapeutic strat-
egy for PID patients. Our study may provide a reliable
reference for pediatricians to diagnosis children with PID.
Wu et al. BMC Pediatrics (2019) 19:410 Page 6 of 7
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Abbreviations
AEFI: adverse events following immunization; Allo-HSCT: allogeneic
hematopoietic stem cell transplantation; APDS: activated PI3Kδsyndrome
immunodeficiency; BCG: Bacillus Calmette–Guérin; CGD: chronic
granulomatous disease; CHS: Chediak-Higashi syndrome; CVID: common
variable immunodeficiency disorders; DGS: DiGeorge syndrome;
DKC: dyskeratosis congenital; EDA-ID: anhidrotic ectodermodysplasia with
immunodeficiency; GVHD: graft versus host disease; HIES: Hyper-IgE
syndromes; HIGM: hyper-IgM syndrome; IPEX: immunodysregulation,
polyendocrinopathy, enteropathy X-linked syndrome; IUIS: International
Union of Immunological Societies; OS: overall survival; PIDs: primary
immunodeficiency diseases; SCID: severe combined immune deficiency;
WAS: Wiskott–Aldrich syndrome; XLA: X-linked agammaglobulinemia
Acknowledgments
None.
Authors’contributions
JH-W designed the study, wrote the first and final drafts, and revised the
manuscript. WW-Z and YY analyzed the data and conducted statistical
analyses. WW-Z and JH-W prepared Figs. HZ provided critical feedback. All
authors read and approved the final manuscript.
Funding
This work was supported by grants from the National Natural Science
Foundation of China (81400019, to Jinhong Wu), the Science and
Technology Commission Foundation of Shanghai Pudong New Area (No.
PKJ2013-Y65, to Jinhong Wu) and the Shanghai Science and Technology
Commission Biomedicine Department key Science and Technology Projects
(16411950800, to Hao Zhang).
Availability of data and materials
The datasets used in the current study are available from the corresponding
author upon reasonable request.
Ethics approval and consent to participate
The Ethics Committee of the Shanghai Children’s Medical Center Affiliated to
Shanghai Jiaotong University School of Medicine approved the study, and
each patient provided written informed consent.
Consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing interests.
Received: 24 March 2019 Accepted: 20 September 2019
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