HLA genetics of LADA.pdf — page 2

ceptibility (±10%) conferred by the variable
number of tandem repeats located upstream of
the INS/IGF2 genes (IDDM2) cannot be distin-
guished from that observed in type 1 diabetes
[6]. A previous genetic study also found similar
HLA susceptibility genes in type 1 diabetes and
LADA [7].Thus, the similarity of the genetic
predisposition associated with the two major sus-
ceptibility loci of type 1 diabetes strongly sug-
gests that adult-onset autoimmune diabetes is
just an age-related extension of the same patho-
genic process responsible for type 1 diabetes in
children. However, a series of other extra-HLA
genes linked to type 1 diabetes (CTLA4,
PTPN22, IL2RA, IL10) have not yet been inves-
tigated in LADA.
There remains a very important question
about the pathogenesis of LADA: either it
involves long-standing cell-specific autoimmu-
nity with slow β-cell destruction over many
years, or it corresponds to the onset of islet
autoimmunity in adulthood with a short pre-
clinical phase. At present, no one is able to
answer this important question, although some
arguments support the idea that type 1 diabetes
could be a relapsing-remitting autoimmune dis-
ease, at least in some cases (like multiple sclero-
sis) [8]. If such a view were proved correct,
LADA might in fact simply correspond to a late-
stage form of type 1 diabetes.Therefore other
studies are clearly needed to firmly demonstrate
that LADA is a clinical entity different from clas-
sical type 1 diabetes. Nevertheless, as recently
stated [9], if β-cell destruction is slowly progres-
sive in LADA, this implies a wider therapeutic
window for preventive strategies including
immune-based therapies.
References
1. Tuomi T, Groop LC, Zimmet PZ et al. Antibodies to
glutamic acid decarboxylase reveal latent autoimmune
diabetes mellitus in adults with a non-insulin-dependent
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2. Gale EAM. Latent autoimmune diabetes in adults: a
guide for the perplexed. Diabetologia 2005; 48: 2195–9.
3. Groop L,Tuomi T, Rowley M et al. Latent autoimmune
diabetes in adults (LADA) — more than a name.
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4. Karjalainen J, Salmela P, Ilonen J et al. A comparison of
childhood and adult type 1 diabetes mellitus. N Engl J
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5. Caillat-Zucman S, Garchon HJ,Timsit J et al. Age-
dependent HLA genetic heterogeneity of type 1 insulin-
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6. Desai M, Zeggini E, Horton VA et al.The variable num-
ber of tandem repeats upstream of the insulin gene is a
susceptibility locus for latent autoimmune diabetes in
adults. Diabetes 2006; 55: 1890–4.
7. Hosszufalusi N,Vatay A, Rajczy K et al. Similar genetic
features and different islet cell autoantibody pattern of
latent autoimmune diabetes in adults (LADA) com-
pared with adult-onset type 1 diabetes with rapid pro-
gression. Diabetes Care 2003; 26: 452–7.
8. von Herrath M, Sanda S, Herold K.Type 1 diabetes as
a relapsing-remitting disease? Nat Rev Immunol 2007; 7:
988–94.
9. Fourlanos S, Dotta F, Greenbaum CJ et al. Latent
autoimmune diabetes in adults (LADA) should be less
latent. Diabetologia 2005; 48: 2206–12.
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International Diabetes Monitor
Volume 20, Number 3, 2008
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