Adult reference intervals for IgG subclasses with Siemens immunonephelometric assays in Chinese population
Li et al.
Allergy Asthma Clin Immunol
Adult reference intervals for IgG subclasses with Siemens immunonephelometric assays in Chinese population
Ping Li 0
Zhongjuan Liu 1
Ziyan Wu 0
Xiaoting Wen 0
Liubing Li 0
Shulan Zhang 0
Yingchun Xu 1
Yongzhe Li 0
0 Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education , Beijing 100730 , China
1 Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences , Beijing 100730 , China
Objective: To determine the adult reference intervals for the Siemens IgG subclass reagents. Methods: 636 blood samples of healthy adults were analyzed to determine the level of IgG subclass using the reagents of Siemens immunonephelometric assay with molecular biology kits. Results: IgGSc reference intervals were as follows: IgG1 4.45-9.76 g/L, IgG2 2.07-8.57 g/L, IgG3 0.08-0.80 g/L and IgG4 0.05-1.54 g/L. There was an excellent correlation between the total IgG and the sum of the IgG subclasses. No significant gender and age differences were observed. Conclusions: Our data provide the missing reference intervals and enable the use of the nephelometric IgG subclass reagents in Chinese. The study can offer reference on clinic diagnose.
Immunoglobulin subclasses; Immunonephelometric assays; Chinese population
Background
Four distinct heavy chain subgroups of human IgG were
first demonstrated in the 1960s by using polyclonal
antisera prepared in animals immunized with human
myeloma proteins [
1, 2
]. Since then, determination of
selective immunoglobulin subclasses (IgGSc) has become
an established tool in the diagnosis of many diseases,
such as immunologic deficiencies and adult IgG4-related
disease (IgG4-RD) [
3, 4
].
Recurrent respiratory tract infections that are poorly
responsive to antibiotics are common presentations of
immunoglobulin (Ig) deficiency in adults and children.
There is a group of patients with similar clinical
presentation, but who have serum IgG levels within or close
to the bottom of the normal range and in whom one
or more of the IgG subclasses 1–4 is entirely lacking or
present in greatly reduced amounts [
5, 6
]. IgG4-RD is a
recently recognized fibroinflammatory condition that
has tumefactive lesions, a dense lymphoplasmacytic
infiltrate rich in IgG4-positive plasma cells, and this
disease is typically associated to an increase of serum IgG4
level. Serum IgG4 elevation becomes from this date a
biological marker of IgG4-RD, and serum IgG4 elevation
(> 1.35 g/L) is considered as a diagnosis criteria for
IgG4RD [
7, 8
].
The immunonephelometric determination of IgG
subclasses in serum is based upon the specific reaction of the
respective human IgG subclass with a polyclonal (mono)
specific, highly avid anti-IgG subclass antiserum.
Immunonephelometric assays were designed for fast, fully
automated and specific quantification of human IgG
subclasses profile (IgG1, IgG2, IgG3 and IgG4).
Although more and more serum IgG subclasses assays
were performed by the Dade Behring IgG subclass
reagents (Siemens Healthcare Diagnostics Products GmbH
BN™) in China, a limitation of IgGSc is the lack of larger
cohorts providing populational serum concentration
measurements in order to establish normal reference
values, and published reference intervals are limited to a
certain geographical area. Therefore, the purpose of this
study was to assess IgGSc reference intervals in healthy,
mostly Chinese adults, using fully automated and
reproducible immunonephelometric assays. We performed the
whole experiment process according to the test method
recommended by Clinical and Laboratory Standards
Institute (CLSI) [
9
].
Methods
Information of the recruited subjects
The study population included 636 clinically healthy
adults (309 males and 327 females) from 18 to 85 years
of age who were admitted to Peking Union Medical
College Hospital for health physical examination. Good
health was confirmed by a clinical questionnaire and
blood parameters within reference intervals. The serum
was frozen within less than 4 h in sterile at −80 °C until
measurement. All specimens included for analysis were
the first received on each patient during the period,
duplicates being excluded. The study was approved by
the ethics committee of the Peking Union Medical
College hospital and all subjects gave informed consent.
Measurements of reference intervals
All IgGSc were measured by nephelometry
according to the manufacturer’s instructions (BN2
nephelometer, Dade Behring GmbH, Marburg, Germany). The
inter-assay coefficients of variation (CV) are 1.9–5.3%
with total CV of 2.6–6.2%. We used the following
concentrations for the CVs: Level SL-H: IgG1 = 7.33 g/L,
IgG2 = 3.87 g/L, IgG3 = 0.482 g/L, IgG4 = 0.779 g/L;
for Level SL-L: IgG1 = 3.78 g/L, IgG2 = 1.94 (...truncated)