SA JOURNAL OF DIABETES & VASCULAR DISEASE
RESEARCH ARTICLE
VOLUME 7 NUMBER 4 • NOVEMBER 2010
149
Comparison of HLA class II antigens between three type 1
diabetes groups in the central region of Algeria
R RAACHE, A BENYAHIA, H AMROUN, N ATTAL, W HAMIANE, M AZZOUZ, L LACET, S HAWORTH,
A BOUDIBA, MC ABBADI
Abstract
I
n human type 1 diabetes (T1D), both genetic and
environmental factors are involved in the pathogenesis of
the disease. The strongest genetic contribution has been
mapped to the major histocompatibility complex (MHC) on
the short arm of chromosome 6, which encodes the human
leukocyte antigens (HLA). It is estimated that HLA class
II gene polymorphisms account for 20 to 50% of familial
aggregation of type 1 diabetes. Several studies have clearly
demonstrated that there are susceptibility and protective
markers at HLA-DR and -DQ.
In this study, HLA class II antigens were investigated using
a serological method in 210 T1D patients from the central
region of Algeria, and compared to 140 healthy controls.
Marker frequencies were compared between three groups
of diabetics: children, juveniles and adults with latent
autoimmune diabetes (LADA), and the control group.
The frequency was calculated for HLA-DR and -DQ.
Significant differences were detected between T1D patient
and the control groups for the frequencies of HLA-DR3, -DR4,
-DQ2 and -DQ8 (DQ3) but therewereno significant differences
in these antigen frequencies between the three T1D groups
versus the controls, with the respective frequencies of HLA-
DR3 (71.76, 66.67, 70% vs 31.43%), HLA-DR4 (64.71, 48.89,
52.50% vs 26.43%), HLA-DQ2 (76.47, 66.67, 75% vs 39.29%)
and HLA-DQ8 (3) (64.71, 46.67, 47.50% vs 19.29%).
Mantel-Haenszel tests were used to calculate the odds
ratio for the presence of type 1 diabetes in association with
HLA-DR3, -DR4, -DQ2 and -DQ8 (3). The values for each
respective HLA antigen were as follows: for the T1D children
(OR: 5.54; 5.1; 5.02; 7.67) for the juveniles (OR: 4.36; 2.66;
3.09; 3.66) and for LADA (OR: 5.09; 3.08; 4.64; 3.79). The
heterozygous phenotype HLA-DR3/DR4 increased the risk
(conferred the highest susceptibility) (OR: 8.79, 2.68, 4.23 for
children, juveniles and the LADA group, respectively).
These results confirm the positive association between
T1D and HLA class II antigens, as previously reported in other
populations in the central region of Algeria.
Keywords:
Algerian, HLA class II antigens, LADA, type 1 diabetes
Introduction
Type 1 diabetes (T1D) is an autoimmune disease characterised by
T-cell-mediated destruction of the insulin-producing beta-cells in
the islets of Langerhans. CD8 T-cells recognising auto-antigens such
as islet-specific glucose-6-phosphatase catalytic subunit-related
protein, insulin, or glutamic acide decarboxylase (GAD) are believed
to play important roles in the early and late phase of beta-cell
destruction via mechanisms such as Fas/FasL, perforin/granzyme,
reactive oxygen and nitrogen species and pro-inflammatory
cytokines.
1-3
Although T1D is a complex phenotype influenced
by multiple genetic and environmental factors, human leucocyte
antigen (HLA) accounts for about half of the genetic susceptibility,
through a large number of protective and predisposing haplotypes,
and therefore HLAs play a significant role.
4,5
The generation of the T-cell repertoire and its autoimmune
potential is controlled directly by HLA class II molecule-mediated
editing of thymocyte antigen receptor specificities and affinities
for class II peptides. Class II molecules also regulate target antigen
presentation at the sites of inflammation. At the peptide-binding
sites of HLA-DR and -DQ molecules, the presence or absence of
critical residues, e.g. residue 57 of the -DQ
β
-chain and its charged/
non-charged amino acid dimorphism correlate well, though not
completely, with T1D resistance and susceptibility.
6,7
Latent autoimmune diabetes in adults (LADA) is a disorder in
which, despite the presence of islet antibodies at diagnosis of
diabetes, the progression of autoimmune
b
-cell failure is slow.
LADA patients are therefore not insulin requiring, or at least not
during the first six months following diagnosis of diabetes.
8-12
Methods
This was a randomised, retrospective study and the study population
consisted of 210 unrelated patients with T1D, and 140 unrelated,
healthy controls. The patients were divided into three groups: group
1: 85 children (1–15 years), group 2: 45 juveniles (16–25 years),
and group 3: 80 LADA
(>
25 years). Individuals within the control
group had the same ethnic background as the patient groups and
none had a first-degree relative affected with diabetes.
Patients were randomly selected from the Centre Hospitalier
Correspondence to: R Raache
Université des Sciences et de la Technologie Houarie Boumediene (USTHB),
Alger, Algérie
Service d’Immunologie, Institut Pasteur d’Algérie (IPA), Alger, Algérie
e-mail:
H Amroun, N Attal, W. Hamiane, MC Abbadi
Service d’Immunologie, Institut Pasteur d’Algérie (IPA), Alger, Algérie
A Benyahia
Laboratoire Central de biologie, CHU N’Fissa Hamoud, Hussein Dey, Alger,
Algérie
M Azzouz, A Boudiba
Service de Diabétologie, CHU Mustapha, Alger, Algérie
L Lacet
Service de Pédiatrie CHU N’Fissa Hamoud, Hussein Dey, Alger, Algérie
S Haworth
Fondazione IRCCS, Ospedale Maggiore Poloclinico, Milano, Italy
S Afr J Diabetes Vasc Dis
2010;
7
: 149–153.
