Diabetologia 9 Springer-Veriag 1988

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1 Diabetlgia (1988) 31: Diabetlgia 9 Springer-Veriag 1988 Antibdies t a Mr-64 islet cell prtein in Swedish children with newly diagnsed Type 1 (insulin-dependent) diabetes M. ChristiC, M. Landin-lssn 2, G. Sundkvist 2, G. Dahlquist 3, A. Lernmark 1'2 and S. B~ekkeskv 1 lhagedrn Research Labratry, Gentfte, Denmark, 2Department f Medicine, University f Lurid, Maim6 General Hspital, Malrn6 and 3Department f Paediatrics, Karlinska Institute, Sachs Childrens Hspital, Stckhlm, Sweden Summary. Sera frm 4 Swedish children diagnsed as having Type 1 (insulin-dependent) diabetes mellitus during a ne year perid alng with 4 age and gegraphically matched cntrl subjects were tested fr antibdies t a Mr- 64 islet prtein by immunprecipitatin f 35S-methinine-labelled rat islet amphiphilic prteins. f the 4 diabetic patients, 29 (73%) were fund t be psitive whereas all 4 cntrl subjects were negative. Samples were als tested fr titres f islet cell cytplasmic antibdies by indirect immunflurescence n frzen sectins f human pancreas. In the diabetic grup, 3 f the 4 patients (75%) were psitive fr islet cell cytplasmic antibdies cmpared with 2 f the 4 cntrl subjects (5%). A cmparisn f levels f antibdies t the Mr-64 prtein with islet cell cytplasmic antibdies revealed a weak (rs =.46), but significant (p<.1) crrelatin between the tw tests. There was n effect f age r sex n levels f antibdies t the Mr-64 prtein. These results in ppulatin-based diabetic children and cntrl subjects demnstrate a high frequency f antibdies t the Mr-64 prtein at the time f clinical nset. Key wrds: Type 1 (insulin-dependent) diabetes mellitus, islets f Langerhans, autantibdies, antantigens, autimmune disease. Humral autimmunity t pancreatic islet cell antigens is a cmmn feature assciated with the nset f Type 1 (insulin-dependent) diabetes. The appearance f islet cell antibdies in the perid preceding the clinical nset f the disease has arused cnsiderable interest as autantibdies culd ptentially serve as markers f early phase B-cell destructin [1]. Substrates cmmnly used in the detectin f islet cell antibdies include frzen sectins f pancreas (typically islet cell cytplasmic antibdies, ICA) [2, 3] r suspensins f islet cells (islet cell surface antibdies, ICSA) [4]. These assays suffer frm the ptential f antisera t bind t bth specific and nn-specific islet cell cmpnents. The identificatin f individual islet cell antigens will allw the develpment f accurate tests fr islet cell antibdies. Characterisatin f these antigens and the antibdy respnses t them shuld prvide a clearer understanding f the relevance f B-cell autimmunity in the pathgenesis f Type I diabetes. A human islet cell prtein f Mr-64 (64k antigen) has been identified as ne t which antibdies are frequently fund in Type I diabetes [51. In the riginal study, 8/1 recently diagnsed diabetic patients were fund t be psitive fr antibdies t the 64k antigen, and in a subsequent study [6], antibdies were detected up t 91 mnths befre the clinical nset f Type I diabetes in 11/14 individuals. Upn testing cntrl grups f 21 healthy individuals and 41 patients with ther autimmune disrders, antibdies t the 64k antigen were nly detected in ne individual, a healthy sibling t a diabetic patient [6]. Thus, these studies prvided evidence fr a humral respnse t the 64k antigen that may be specific fr Type I diabetes. Hwever, the frequency f antibdies t the prtein in Type I diabetes cannt be unambiguusly assessed frm these studies since the sample sizes were small and were nt drawn frm well-defined ppulatins. In the present study, we have tested a representative sample f children develping diabetes in Sweden tgether with apprpriate cntrl subjects t estimate the frequency f antibdies t the 64k antigen in children at clinical nset f Type I diabetes. In additin, we have examined a pssible crrelatin between autantibdies t the 64k antigen with thse measured as ICA and have assessed pssible patterns in 64k autantibdy levels with regard t age, sex and gegraphical rigin f the diabetic patients.

2 598 M. Christie et al.: Antibdies t an islet prtein in Swedish children Subjects and methds Serum samples In Sweden, all children with diabetes are referred t paediatric departments and are hspitalised fr a perid after diagnsis. This system allws the identificatin f virtually all children with newly diagnsed diabetes. The Swedish Childhd Diabetes Study, with all 44paediatric departments in Sweden cllabrating, is a casecntrl study designed by Dahlquist and c-wrkers [7]. As part f this investigatin [8] serum samples have been btained within 2 weeks f diagnsis frm 389 f the 45 incident cases (aged -14 years) f Type 1 diabetes in Sweden during the perid 1 September 1985 t 31 August In additin, sera frm 321 age, sex and gegraphically matched cntrl subjects were cllected in parallel. Frm these ppulatins study grups f 4diabetic and 4 cntrl individuals were selected fr measurement f antibdies t the Mr-64 prtein. In view f seasnal variatins in incidence rate f diabetes, we have selected every tenth individual develping diabetes t btain an even distributin f patients thrughut the study perid. The mean delay after diagnsis f diabetes in the incident cases and sampling the reference subjects was mnths. Details f the ttal ppulatin and study grups are given in Table 1. Sera frm a recently diagnsed diabetic patient previusly shwn t be strngly psitive fr antibdies against the Mr-64 prtein (patient 3, reference 5), and frm a nrmal, healthy bld dnr were included in each analysis f antibdies against the Mr-64 prtein. The study was apprved by the thics Cmmittee f the Karlinska Institute, Stckhlm, Sweden. Measurement f islet cell cytplasmic antibdies nd pint titres f ICA were determined using a tw clurimmunflurescence test [9, 1] n serial dilutins (1:2, 1:4, 1:8, etc.) f the 8 serum samples. T facilitate interlabratry cmparisn, titres have been cnverted t Juvenile Diabetes Fundatin (JDF) units by cmparisn with a standard curve cnstructed with a standard reference serum as previusly described [11]. Measurement f antibdies t the Mr-64 islet prtein Levels f antibdies t the Mr-64 islet cell prtein were measured by immunprecipitatin f rat islet cell extracts using a mdificatin f methds previusly described [6]. Islets were islated frm 5-7-day ld Wistar rats by cllagenase digestin f pancreata [12]. Islets were individually selected under the dissecting micrscpe and maintained in tissue culture fr 1-3 days in RPMI-164 medium cntaining 4.2 mml/l NaHC3, 2 mml/1 Hepes, 1% (w/v) newbrn calf serum, 1 U/ml penicillin and 1 gtg/ml streptmycin. After washing twice by centrifugatin (lmin, 2g) in methinine-free RPMI-164 cntaining 16mml/1 glucse, 4.2mml/1 NaHC3, 2mml/l Hepes, 2% (v/v) Nuserum (Teknunc, Rskilde, Denmark), 1 U/ml penicillin and 1 txg/ml streptmycin, islets (batches f 2) were incubated fr 5 h in 4 ml f the same medium supplemented with 2 mci f 35Smethinine (Amersham Internatinal, Amersham, UK; >5Ci retl- ~). After labelling, islets were washed twice in 5 ml f Hanks Slutin cntaining 2% (v/v) Nuserum and.1 mml/1 methinine and nce in 15retl/1 NaC1, 1mml/l Hepes (ph7.4),.5 mml/1 methinine and 1 mml/1 benzamidine. The labelled islets were hmgenised fr 3s in 3~tl f.25 mml/l sucrse, 1 mml/1 Hepes (ph 7.4),.5 mml/1 methinine, 1 mml/1 benzamidine,.1 mml/1 p-chlrmercuribenzenesulphnic acid and.5% (w/v) Trasyll (Nv, Bagsv~erd, Denmark) using a Plytrn hmgeniser. The hmgenate was cen- trifuged at 36, g fr 3 rain at 4 ~ C. The pellet was resuspended in 15 ~tl f 2% Tritn X-114 in Hepes buffer (1 mml/1 Hepes (ph 7.4) supplemented with 15 mml/1 NaC1,.5 rnml/1 methinine, 1 mml/1 benzamidine and.5% (w/v) Trasyll). Prteins were extracted n ice fr 2 h. Clumps f particulate matter were disrupted by repetitive pipetting and insluble matter after extractin remved by centrifugatin at 16, g fr 2 min at 4 ~ C. Detergent extracts (15 gl) were verlaid nt 225 ~tl f a cushin f 6% (w/v) sucrse in Hepes buffer in a silicnised test tube. The tube was incubated at 3 ~ C fr 3 rain fllwed by centrifugatin at 3 g fr 3 min t sediment aggregated detergent micelles. The upper, aqueus phase was remved, Tritn X-114 added t a cncentratin f l% (v/v) and incubated fr 1 rain n ice. The re-extracted aqueus phase was again verlaid nt the sucrse cushin and the phase separatin perfrmed as befre. The upper phases were discarded and the detergent phase suspended in 1 ml f Hepes buffer with a final Tritn X-114 cncentratin f 1% (v/v). xtracts representing detergent-phase purified amphiphilic prteins frm 2 islets were used fr each sample. The preparatins were initially precleared by incubatin fr 7 h at 4 ~ C with a pl f nrmal human serum (25 ~tl per sample) and binding t preswllen prtein A-Sepharse (t~tl per sample; Pharmacia, Uppsala, Sweden). After centrifugatin (3 s, 1 g), the supernatant was dispensed in 1 ~tl aliquts and incubated with 25 ~tl f test serum (unless therwise indicated) fr 18 h at 4 ~ C. Immune cmplexes were islated by incubatin with pre-swllen prtein A-Sepharse (1 ~tl per sample) fr 2h at 4~ with cntinuus shaking. Immunprecipitates were washed 5 times with 1.6 ml f 1 mml/l Hepes (ph7.4) supplemented with 5% (v/v) Tritn X-114, 15 mml/l NaC1,.5 retl/1 methinine, 1 mml/1 benzamidine and.5 mg/ml bvine serum albumin and nce with 1.6 ml f water. Prteins were eluted frm the immunsrbent as previusly described [6], and run n 1% sdium ddecyl sulphate-plyacrylamide gels accrding t Laemmli [13]. Gels were prcessed fr autradigraphy as previusly described [6]. Analysis f autradigrams All autradigrams were analysed independently by tw bservers withut knwledge f sample identity. Samples were ranked psitive r negative after cmparisn with the psitive and negative cntrls run with every experiment. A quantitative estimate f Mr-64 prtein antibdy psitivity in samples was btained by densitmetric scanning f bands crrespnding t the prtein n autradigrams using an LKB Ultrscan densitmeter. The mean frm 2-3 independent experiments was calculated fr each sample. Peak height was taken as a measure f band density and results are expressed as a prprtin f the height f peaks crrespnding t the psitive cntrls in each experiment. Statistical analysis The significance f crrelatins between bservatins were tested by the Spearman Rh test f rank crrelatin with crrectin, where apprpriate, fr large values f n. The significance f differences between grups was tested by the Mann-Whitney test. All tests were tw-tailed. A p value f <.5 was cnsidered significant. Results Immunprecipitatin f the Mr-64 prtein by a standard diabetic serum Serum frm a diabetic patient f recent nset previusly shwn [5] t have high titres f antibdies t the M~-64 prtein was used as a psitive cntrl in

3 M.Christie et al.: Antibdies t an islet prtein in Swedish children all experiments. Dilutins f this serum were perfrmed t characterise the immunprecipitatin reactin (Fig. 1). The quantity f prtein immunprecipitated, as assessed by the density f the crrespnding band n autradigrams, was dependent n the vlume f serum used with half-maximal recvery f prtein using 2.7 gl f serum and maximum recvery at 2-25 [xl. In rder t maximise detectin f antibdies t the prtein in lw titre sera, subsequent experiments n the frequency f antibdies were perfrmed using 25 p.1 f test serum. This standardisatin prvides fr an accurate and reliable assay with which t evaluate the presence f 64k antibdies in randm serum samples G Frequency f antibdies t the Mr-64 prtein in diabetic and cntrl children 9 ~ ' -,e-,, L Vl Serum (.IJ[) Fig. 1. Cncentratin dependence f immunprecipitatin f an Mr- 64 prtein by serum frm a diabetic patient. Precleared detergent phase purified islet amphiphilic prteins (1 p J) were incubated with 1-2 gl f serum frm a diabetic patient fr 18 h at 4 ~ C. Immune cmplexes were purified n prtein A-Sepharse, eluted and separated by SDS plyacrylamide gel electrphresis. Islet prteins immunprecipitated were detected by autradigraphy. The quantity f Mr-64 prtein immunprecipitated was assessed by densitmetric scanning f autradigraphs expressing results as a prprtin f the maximum band density crrespnding t the Mr-64 prtein seen in each experiment. Results shwn are the mean f three independent experiments A representative autradigram shwing plypeptides immunprecipitated by sera frm 8 diabetic patients (even numbers n gel) tgether with their age, sex and gegraphically matched cntrl subjects (dd numbers) is shwn in Figure 2. The Mr-64 prtein was the nlyamphiphilic islet cell membrane prtein t be specifically immunprecipitated by the majrity f diabetic sera. n this gel samples 2, 4, 6, 1, 12 and 16 were fund t be psitive fr antibdies t the 64k antigen whereas samples 8 and 14 were negative. All 8 cntrl subjects included in this analysis were negative. The entire sample f 8 individuals was tested n Fig. 2. lmmunpreeipitatin f &let prteins by sera frm diabetic and cntrl children. Precleared detergent phase purified islet amphiphilic prteins (aliquts f 1 gl) were incubated with 25 ~tl f serum frm diabetic patients r their matched cntrl subjects fr 18 h at 4 ~ C, Immune cmplexes were purified n prtein A-Sepharse, eluted and separated n SDS plyacrylamide gels. The figure shws a representative autradigram shwing peptides immunprecipitated by sera frm 8 diabetic patients (even numbered lanes n gel) tgether with their apprpriate cntrl subjects (adjacent left hand lane)

4 6 M. Christie et al.: Antibdies t an islet prtein in Swedish children Table 1. Descriptin f study grups Number f individuals Male/female Median (range) age (years) at sampling ICA psitive ICA levels (range) a Type I (insulin-dependent) diabetic patients Ttal Sample a ICA values f psitive samples nly are expressed in JDF units [11] /186 21/19 9 (-14) 8 (1-13) 316 (81%) 3 (75%) 7 (3-82) 7 (6-29) Cntrl subjects Ttal /151 l (-15) 9 (3%) 27 (17-12) Sample 4 24/16 8 (1-14) 2 (5%) 17, C 6 "~. 9 {3. } 2~ ~3 4 2 ~ Ne 3 9 ~ 'S_ i 9 I ~ ~ g ~ 9 I 9 ~ I ~. Nrthern Swede n ICA titre (JDFunits) 4 Age ( years ) 5 9 = 9 ".J.- {3- g 8 6, ~. 4 8,, ; ) $ 9! 9 9 Central Sweden &~ Suthern Sweden Fig.3. Cmparisn f levels f antibdies t the Mr64 prtein with levels f lca. Antibdies t the Mr-64 prtein in sera frm diabetic patients were detected as described in the legend t Figure 2. Antibdy levels were quantified by densitmetric scanning f autradigrams, expressing data as a prprtin f the prtein immunprecipitated by 25 Ixl f a psitive cntrl serum run in each experiment. The data are presented as a scatter plt relative t units f [CA, measured by indirect immunflurescence n frzen sectins f human pancreas. Clsed circles (e) are bys, pen circles () are girls Fig.4. Relatinship f levels f antibdies t the Mr-64 prtein with age at nset f diabetes. Levels f antibdies t the Mr-64 prtein were analysed in sera frm diabetic patients as described in the legend t Figure 3. Results are shwn as a scatter plt relative t the age f nset f each individual. Clsed circles (e) are bys, pen circles () are girls Fig.5. Gegraphical variatin in the levels f antibdies t the Mr-64 prtein. Levels f antibdies t the Mr-64 prtein in sera frm diabetic patients were determined as described in the legend t Figure 3. Data were gruped accrding t the regin f rigin f each diabetic patient. Nrthern Sweden was defined as the area nrth f, and including the cunties f Kppaberg and G~ivlebrg. Suthern Sweden was defined as the area suth f and including sterg6tland, J6nkping and Halland. Central Sweden was defined as the intermediate regin. The median f antibdy levels in Suthern Sweden (15%) was significantly lwer than that in Central Sweden (47%; p<.1, Mann Whitney test) at least tw separate islet preparatins. Where there was a dubt as t a psitive identificatin samples were tested an additinal time. f the 4 diabetic patients, 29 (73%) were psitive fr antibdies t the 64k antigen. All 4 cntrl samples were negative in tw repetitins f the assay. Crrelatin f levels f antibdies t the Mr-64 prtein with titres f islet cell cytplasmic antibdies The cllectin f diabetic and cntrl sera were examined fr ICA by indirect immunflurescence n pancreatic sectins. In this assay 3 f the 4 (75%) diabetic patients were fund psitive fr ICA. The median level f ICA, determined by end pint titratin, was 7JDF units and the range 6-29JDF units (Table 1). Amng the cntrl subjects tw (5%) were ICA psitive; their levels f ICA were 17 and 43 JDF units respectively. A quantitative estimate f levels f antibdies t the Mr-64 prtein was btained by densitmetric scanning f the apprpriate bands n autradigrams, expressing results relative t the psitive cntrl. This analysis allwed a cmparisn between levels f 64k antibdies and ICA (Fig.3) t demnstrate a weak crrelatin between the tw tests (r=.46, p<.a; Spearman's Rh test). Thus, 24/4 (6%) f the patients had serum autantibdies capable f bth detecting ICA in pancreatic sectins and immunprecipitaring the 64k prtein. ffects f age and sex n levels f antibdies t the Mr-64 prtein The effect f age at nset f diabetes n antibdy levels shwed a slight tendency fr higher levels f antibdies t the 64k antigen t be assciated with children develping diabetes at a later age (Fig.4). This

5 M.Christie et al.: Antibdies t an islet prtein in Swedish children 61 was nt, hwever, statistically significant. N significant differences were bserved between bys and girls in the frequencies r levels f antibdies t the 64k antigen. Thus 13/21 (62%) f bys and 16/19 (84%) girls were fund t be psitive fr antibdies t the 64k antigen with median antibdy levels f 21% and f 29% respectively. Reginal variatins in levels f antibdies t the Mr-64 prtein T analyse pssible reginal variatins in antibdy levels, Sweden was divided int three regins: Nrthern Sweden was defined by the area nrth f and including the cunties f Kppaberg and Gavlebrg; Suthem Sweden was defined by the area suth f and including the cunties f IJsterg6tland, J6nk6ping and Halland; and Central Sweden was cnsidered t be the regin between these tw. In the study grup nly 7 diabetic children inhabited the sparcely ppulated Nrthern regin f Sweden making it difficult t analyse pssible reginal differences with respect t this area. Hwever, patients frm the Suthern area f Sweden had significantly lwer median antibdy levels than patients frm the central regin (Fig.5, p_<.1; Mann Whitney test). Discussin arlier studies n the diabetes-assciated Mr-64 islet cell antigen have emplyed human islets as the surce f antigen [5, 6]. Where islets frm rdents have been used, detectin f the prtein has been hampered by a heavy backgrund n autradigrams f nn-specifically bund prtein [14]. In the present wrk we have used a preparatin f amphiphilic membrane prteins frm rat islets as surce f antigen. The prcedure described remves much f the backgrund, thus reducing the pssibility f assigning false psitive values t test samples. The ability t detect the Mr- 64 prtein in the mre readily available rat islet shuld facilitate studies n the pssible rle f the prtein in the pathgenesis f Type 1 diabetes. Here, in an extensin t previus wrk and using a semiquantitative test, we have tried t btain an estimate f the frequency and levels f antibdies t the prtein in children with recently diagnsed Type 1 diabetes. A cntrl grup f age and gegraphically matched healthy individuals was available fr cmparisn [7, 8]. The assay emplyed invlves immunprecipitatin f metablically radilabelled endgenus prteins frm purified islet preparatins fllwed by electrphresis and autradigraphy. This prcedure has the advantage f high specificity with regard t the islet antigen that is nt encuntered with ther detectin methds such as radiidinatin and autradigraphy r immunflurescence where exgenus antigen structures may be recgnised [15]. Hwever, there are clearly limitatins t the prcedure. The assay is nt a high capacity assay. The labrius nature f islet islatin and immunprecipitatin tgether with the expense f radilabelling islets at the high specific activity required fr antigen detectin precluded a study n mre than 8 f the 71 samples available. In rder t maximise the sensitivity f the test, we have used a serum dilutin f I : 5. With this dilutin, as illustrated by the experiments with the psitive cntrl, samples with high titres f antibdies t the prtein will immunprecipitate virtually all f the prtein in the islet extract. Thus, the antibdy levels f high respnders may be underestimated in this test. Furthermre, in rder t be detected in this assay the 64k antibdies have t be immunprecipitating, bind t prtein A (i. e. IgG and nt IgM) and in the present study crssreact with the rat prtein. False negative sera culd cntain antibdies failing t meet ne r mre f thse criteria. Subject t such limitatins, the results presented here prvide nvel infrmatin cncerning humral autimmunity against islet cell antigens in a lcalised and carefully matched ppulatin [16]. f the 4 diabetic patients selected, 29 (73%) were psitive fr antibdies t the Mr-64 prtein. This figure is cnsistent with earlier studies using human islets where antibdies were detected in 8% (8/1) [5] r 78% (11/14) [6] f the diabetic patients tested. Antibdies were nt detected in any f the 4 cntrl individuals. It is clear, therefre, that humral autimmunity t the 64k prtein is a frequent phenmenn in Type 1 diabetes. The semi-quantitative nature f the assay has enabled us t investigate pssible crrelatins with ICA. ICA were detected in 3 (75%) f the diabetic patients and in 2 (5%) f the 4 cntrl subjects. The frequency f antibdies t the Mr-64 prtein in the diabetic patients was thus appraching that f ICA. In the 4 diabetic patients there was a significant but weak crrelatin between levels f antibdies t the Mr- 64 prtein and ICA. This culd be interpreted in tw ways. The immunflurescence detected n frzen sectins f pancreas in the ICA assay culd, in part, be due t a reactin with the Mr-64 prtein. Hwever, recent studies have indicated that the antigen recgnised n frzen sectins f pancreas by diabetic sera may have the prperties f a sialglyccnjugate [17]. Treatment f sectins with the prtease, prnase, did nt reduce ICA irnmunflurescence. Thus, unless resistant t prnase treatment, the Mr- 64 antigen may nt cntribute significantly t antigens detected by indirect immunflurescence. Quantities f purified Mr-64 prtein are required fr absrptin studies t clarify this pint. The lw r-value fund by Spearman's Rh test is, rather, an indicatin f an indirect than direct crrelatin between the tw tests. An alternative explanatin fr crrelatin between the tw antibdy tests may be that certain indi-

6 62 viduals have enhanced humral autimmunity t a number f islet cell cmpnents. This may be related t the severity f autimmune aggressin against islet cells and pssibly t the severity f the disease. High titres f ICA have indeed been assciated with a mre rapid lss f endgenus C-peptide after diagnsis [18]. Whether this als hlds fr antibdies t the 64k antigen remains t be established. It is ntewrthy that 5 patients (13%) did nt shw detectable levels f either ICA r antibdies t the 64k antigen at diagnsis (Fig. 3). This lack f a humral respnse t islet cell antigens might be related t a cnsiderable lss f B-cell mass and thus f stimulating antigen. Hwever, in previus studies [6, 19], individuals have been identified with weak r n antibdy respnses t islet antigens in the prediabetic perid. It can be speculated that thse patients may have been psitive nly befre the bservatin perid r that humral autimmunity t islet cell antigens is nt invlved in the develpment f diabetes in sme patients. The number f samples tested was t small t examine seasnal effects n antibdy levels. The data did prvide sme evidence fr reginal variatin in 64k antibdy levels suggesting that patients frm the suthern part f Sweden had significantly lwer levels f antibdies than thse living in the central regin. Much cautin must be taken in the interpretatin f data frm such a small sample in a study perfrmed ver a shrt perid. Hwever, these results call fr further investigatin int pssible reginal hetergenity in immune respnses t islet cell antigens and t identify factrs that may influence such differences. In cnclusin, the high frequency f antibdies t the Mr-64 prtein and the crrelatin with ICA pint t the Mr-64 prtein being a likely candidate antigen t cmplement r perhaps supersede indirect immunflurescence n pancreatic sectins in the assessment f anti-islet autimmunity in Type 1 diabetes. Acknwledgements. We thank Ms. H.Richter-lesen and Ms. B. Delgad-Frhm fr excellent technical assistance, Mr. H. Wedsted Wenghlt fr statistical analysis, Dr. D. Hanahan fr critical reading f the manuscript and Ms. I. Drhse fr help in preparing the manuscript. S.B~ekkeskv was supprted by a Career Develpment Award frm the Juvenile Diabetes Fundatin. The study was supprted by grants frm the Natinal Institutes f Health (DK 2619, DK33873), The Juvenile Diabetes Fundatin, the Swedish Medical Cuncil (757, 7531), and the fundatin Nrdisk Insulinlabratrium. References 1. Baekkeskv S, Christie M, Lernmark A (1986) Islet Cell Antibdies. In: MacGregr AM (ed) Immunlgy f endcrine diseases. MTP Press, Lancaster, pp Bttazz GF, Flrin-Christensen A, Dniach D (1974) Islet cell antibdies in diabetes mellitus with autimmune plyendcrine defiencies. Lancet II: MacCuich AC, lrvine JW, Barnes W, Duncan LJP (1974) Antibdies t pancreatic islet cells in insulin dependent diabetics with cexistant autimmune disease. Lancet II: M. Christie et al.: Antibdies t an islet prtein in Swedish children 4. Lernmark A, Freedman ZR, Hfman C, Rubenstein AH, Steiner DF, Jacksn RL, Winter RJ, Traisman HA (1978) Islet cell surface antibdies in juvenile diabetes mellitus. N ngl J Med 33 : B~ekkeskv S, Nielsen JH, Marner B, Bilde T, Ludvigssn J, Lernmark A_ (1982) Autantibdies in newly diagnsed diabetic children immunprecipitate human pancreatic islet cell prteins. Nature (Lnd.) 298: B~ekkeskv S, Landin M, Kristensen JK, Srikanta S, Bruining GJ, Mandrup-Pulsen T, de Beaufrt C, Seldner JS, isenbarth G, Lindgren F, Sundquist G, Lernmark A (1987) Antibdies t a 64 Mr human islet cell prtein.precede the clinical nset f insulin-dependent diabetes. J Clin Invest 79: Blm L, Dahlquist G, Nystrrm L, Sandstr~Sm A, Wall S (1987) The Swedish childhd diabetes registry - familial disease pattern. Diabetlgia 3: 51A 8. Landin lssn M, Blm L, Dahlquist G, Lernmark A, Sundkvist G (1987) Islet cell antibdies in newly diagnsed Type 1 (insulindependent) children - a case-reference study in Sweden during ne year. Diabetlgia 3: 546A 9. Madsen D, Landin lssn M, Bille G, Sundkvist G, Lernmark Dahlkvist G, Ludvigssn J (1986) A tw-clur immunflurescence test with a mnclnal human prinsulin antibdy imprves the assay fr islet cell antibdies. Diabetlgia 29: Landin-lssn M, Sundkvist G, Lernmark.~. (1987) Prlnged incubatin in the tw-clur immunflurescence test increases the prevalence and titres f islet cell antibdies in Type 1 (insulin-dependent) diabetes meuitus. Diabetlgia 3: Bnifaci, Lernmark A, Dawkins RL and c-authrs (1987) Serum exchange and use f dilutins have imprved precisin f measurement f islet cell antibdies. J Immunl Methds 16: Brnnstedt J, Nielsen JH, Lernmark,~, Hagedrn Study Grup (1984) Islatin f islets frm mice and rats. In: Lamer J, Phl SL (eds) Methds in diabetes research, VlI. Labratry methds, part C.Jhn Wiley and Sns, New Yrk, pp Laemmli UK (197) Cleavage f structural prteins during the assembly f the head f bacteriphage T4. Nature (Lnd.) 227: Kanatsuna T, B~ekkeskv S, Lernmark A, Ludvigssn J (1983) Immunglbulin frm insulin-dependent diabetic children inhibits glucse-induced insulin release. Diabetes 32: Clman PG, Campbell IL, Kay TWH, Harrisn LC (1987) 64,-Mr autanfigen in Type i diabetes. vidence against its surface lcatin n human islets. Diabetes 36: Dahlquist G, Blm L, Hlmgren G, H~iggl6f B, Larssn Y, Sterky G, Wall S (1985) The epidemilgy f diabetes in Swedish children -14 years - a six year prspective study. Diabetlgia 28: Nayak RC, mar MAK, Rabizadeh A, Srikanta S, isenbarth GS (1985) "Cytplasmic" islet cell antibdies: evidence that the target antigen is a Sialglyccnjugate. Diabetes 34: Marner B, Agner T, Binder C, Lernmark,h~ Nernp J, Mandrup- Pulsen T, Walldrf S (1985) Increased reductin in fasting C- peptide is assciated with islet cell antibdies in type 1 (insulindependent) diabetic patients. Diabetlgia 28: Grsuch AN, Spencer KM, Lister J, McNally JM, Dean BM, Bttazz GF Cudwrth AG (1981) The natural histry f Type 1 (insulin-dependent) diabetes mellitus: evidence fr a lng prediabetic perid. Lancet II: Received: 31 December 1987 and in revised frm: 16 May 1988 Dr. M. Christie Charles H. Best Institute 112 Cllege Street Trnt, ntari, M5G IL6 Canada

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