Antibodies to tissue transglutaminase C in newly diagnosed and long-standing Type I diabetes mellitus
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Yours faithfully, M. Iwatani, T. Wasada, K. Katsumori
,
C. Watanabe-Takahashi, N. Kamatani, Y. Iwamoto
Fig. 1. Change in serum uric acid concentrations after treatment with troglitazone in 95 Type II diabetic patients ance in Type II diabetic and in non-diabetic subjects. These findings again support the close association between hyperuricaemia and insulin resistance or hyperinsulinaemia or both.
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Dear Sir,
We read with interest the recent paper by Lampasona et al. [1]
about the detection of autoantibodies to tissue
transglutaminase C (tTGA) in patients with newly diagnosed Type I
(insulin-dependent) diabetes mellitus to determine the extent of
gluten-associated autoimmunity. Tissue transglutaminase C
has been recently identified as an autoantigen target of
antiendomysium antibodies (EMA), known as the serological
marker of coeliac disease (CD) [2]. The authors found a
prevalence of IgA antibodies to transglutaminase C [1] in about 8 %
and a low level of IgG autoantibodies to transglutaminase C in
a further 32 % of newly diagnosed Type I diabetic patients.
This suggests that the high prevalence of autoimmunity to
transglutaminase C could be due to an involvement of the gut
in the pathogenesis of Type I diabetes or to a release of
transglutaminase C from destroyed pancreatic beta cells.
We report our results about the detection of specific IgA to
tTG and IgA antiendomysium (EMA) in 68 patients with
Type I diabetes (36 males and 32 females, aged between 1 and
25.7 years). Amongst patients, 31 were newly diagnosed and
37 had long-standing diabetes, with a disease duration ranging
between 1.1 and 16 years. Antibodies to protein tyrosine
phosphatase (IA-2A) and to glutamic acid decarboxylase (GADA)
were also detected in all patients. We measured tTG-IgA by
an immunoenzymatic method (Genesis Diagnostics,
Cambridgeshire, UK); both intra-assay and inter-assay coefficients
of variation of this test were less than 12 %. We detected EMA
by immunofluorescence (Bios Labordiagnostik, Grafelfing,
Germany), IA-2A and GADA by radioimmunoassay (CIS
Bio International ORIS Group Cedex, F and Medipan
Diagnostica, Solchow, Germany, respectively). We defined
tTGIgA values higher than 14 U/ml (mean + 3SD of 56 age and
sex-matched healthy control subjects) as positive. Out of 68
patients 18 (26.4 %), in particular 6 newly diagnosed (19.3 %) and
12 with long-standing diabetes (32.4 %), were positive for
tTGIgA, with a higher frequency than control subjects (0/56)
(Yates corrected c2 = 15.27; p = 0.000 093). The high frequency
of tTG-IgA found in our newly diagnosed patients is different
from the results in other reports [1, 4]. This could be due to the
different method used for tTG-IgA detection
(radioimmunoassay instead of enzyme-linked immunoassay) [1, 4]. Amongst 31
newly diagnosed patients, 6 (19.3 %) were positive for tTGA,
and 2 of them for both tTGA and EMA. Jejunal biopsy in these
2 patients with both tTGA and EMA showed coeliac disease.
Amongst 37 patients with long-standing diabetes, 12 (32.4 %)
were positive for tTG-IgA and 10 of them for both tTG-IgA
and EMA. Jejunal biopsy in these 10 patients showed total
villous atrophy compatible with coeliac disease in 9 and partial
villous atrophy compatible with latent coeliac disease in 1.
Immunological markers of Type I diabetes showed a
significant association between GADA positivity and antibodies
associated with coeliac disease in long-standing patients
(p = 0.0006, c2 test), not found in newly diagnosed patients
(NS, Fisher exact test) (Table 1). It has been reported [5] that
GADA detection in patients with long-standing diabetes could
be due to a persistence of some residual beta cells or specific
environmental factors or both, capable of sustaining the
auNewly diagnosed
diabetic patients
(n = 31)
aAbnormal biopsies
a Only EMA positive p (...truncated)