Pre-Type 1 (insulin-dependent) diabetes: common endocrinological course despite immunological and immunogenetic heterogeneity

Srikanta, S.; Ganda, Om P; Jackson, Richard A.; Brink, Stuart; Fleischnick, E.; Yunis, Edmond J.; Alper, Chester A.; Soeldner, J S; Eisenbarth, George S.

doi:10.1007/bf00275674

Cited by 46 publications

(25 citation statements)

References 7 publications

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“…The gels were stained with Coomassie Brilliant Blue and processed for fluorography using Enlightning (New England Nuclear) and Kodak X-omat AR film. Mr standards (Pharmacia Fine Chemicals) used were phosphorylase b (94,000), bovine serum albumin (67,000), catalase (60,000), ovalbumin (43,000), carbonic anhydrase (30,000), trypsin inhibitor (20,100), and lactalbumin (14,400).…”

Section: Methodsmentioning

confidence: 99%

“…Sera were obtained from 14 IDDM patients (Table I) who had been carefully studied before the clinical onset by being monozygotic twins or a monozygotic triplet (patients 1,3,6,11,12,14, and 5, respectively) (10,11,17), or healthy siblings to IDDM patients (patients 2,8,9) (15 Furthermore sera were tested from one patient with atoxic diffuse and one patient with toxic adenom of the thyroid.…”

Section: Methodsmentioning

confidence: 99%

“…Fig. 2 shows the immunoprecipitation ofcrude islet cell lysates using sera from IDDM patients 6, 7, 9, 13, and 14 (Fig. 2, lane K, Fig.…”

Section: Methodsmentioning

confidence: 99%

“…IDDM in man seems to develop after a long latency period, which is reflected both in a decreased first-phase insulin release after intravenously administered glucose (10)(11)(12)(13) and in the appearance of ICCA (14)(15)(16), which precedes the clinical onset of IDDM up to several years. Our hypothesis is that the 64,000 Mr protein is a primary target autoantigen.…”

Section: Introductionmentioning

confidence: 99%

“…Our hypothesis is that the 64,000 Mr protein is a primary target autoantigen. In this study we have therefore tested whether carefully documented individuals followed before their clinical onset of IDDM (10)(11)(12)(13)(14)(15)17) and first degree relatives with signs ofimpaired (3-cell function, had 64,000…”

Section: Introductionmentioning

confidence: 99%

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Antibodies to a 64,000 Mr human islet cell antigen precede the clinical onset of insulin-dependent diabetes.

Bækkeskov¹,

Landin²,

Kristensen³

et al. 1987

J. Clin. Invest.

316

164

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Antibodies in sera from newly diagnosed insulin-dependent diabetes mellitus (IDDM) patients are directed to a human islet cell protein of relative molecular mass (Mr) 64,000. Since Il)DM seems to develop after a prodromal period of,8-cell autoimmunity, this study has examined whether 64,000 Mr antibodies could be detected in 14 individuals who subsequently developed IDDM and five first degree relatives who have indications of altered (3-cell function. Sera were screened by immunoprecipitation on total detergent lysates of human islets and positive sera retested on membrane protein preparations. Antibodies to the 64,000 Mr membrane protein were consistently detected in 11/14 IDDM patients, and in all 5 first degree relatives. 10 IDDM patients were already positive in the first samples, obtained 4-91 mo before the clinical onset of IDIM, whereas 1 patient progressed to a high 64,000 M, immunoreactivity, at a time where a commencement of a decline in (3-cell function was detected. 64,000 M, antibodies were detected before islet cell cytoplasmic antibodies (ICCA) in two patients. In the control groups of 21 healthy individuals, 36 patients with diseases of the thyroid and 5 SLE patients, the 64,000 Mr antibodies were detected in only one individual, who was a healthy sibling to an IDDM patient. These results suggest that antibodies against the Mr 64,000 human islet protein are an early marker of (-cell autoimmunity and may be useful to predict a later development of IDDM.

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Section: Methodsmentioning

confidence: 99%