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Titolo:
ANALYSIS OF ANTIBODY MARKERS, DRB1, DRB5, DQA1 AND DQB1 GENES AND MODELING OF DR2 MOLECULES IN DR2-POSITIVE PATIENTS WITH INSULIN-DEPENDENTDIABETES-MELLITUS
Autore:
SANJEEVI CB; LYBRAND TP; LANDINOLSSON M; KOCKUM I; DAHLQUIST G; HAGOPIAN WA; PALMER JP; LERNMARK A;
Indirizzi:
KAROLINSKA INST,KAROLINSKA HOSP,DEPT ENDOCRINOL,BOX 60500 S-10401 STOCKHOLM SWEDEN UNIV WASHINGTON,CTR BIOENGN SEATTLE WA 98195 UNIV LUND HOSP,DEPT MED S-22185 LUND SWEDEN UMEA UNIV,DEPT PEDIAT UMEA SWEDEN UMEA UNIV,DEPT EPIDEMIOL & PUBL HLTH UMEA SWEDEN UNIV WASHINGTON,DEPT MED SEATTLE WA 00000
Titolo Testata:
Tissue antigens
fascicolo: 2, volume: 44, anno: 1994,
pagine: 110 - 119
SICI:
0001-2815(1994)44:2<110:AOAMDD>2.0.ZU;2-I
Fonte:
ISI
Lingua:
ENG
Soggetto:
GLUTAMIC-ACID DECARBOXYLASE; HLA-DQ; ISLET-CELL; SUSCEPTIBILITY; AUTOANTIBODIES; POPULATION; SYSTEM; ASSAY; IDDM; PROTECTION;
Keywords:
GAD65; HLA-DR; HLA-DQ; ICA; IAA; IDDM; MOLECULAR MODELING; PCR; RFLP;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
44
Recensione:
Indirizzi per estratti:
Citazione:
C.B. Sanjeevi et al., "ANALYSIS OF ANTIBODY MARKERS, DRB1, DRB5, DQA1 AND DQB1 GENES AND MODELING OF DR2 MOLECULES IN DR2-POSITIVE PATIENTS WITH INSULIN-DEPENDENTDIABETES-MELLITUS", Tissue antigens, 44(2), 1994, pp. 110-119

Abstract

HLA-DR2 is negatively associated with insulin-dependent diabetes mellitus (IDDM). The aim of the present study was to analyze DR2-positive patients among 425 consecutively diagnosed unrelated Swedish children with IDDM and in 367 matched controls. HLA-DRB, -DQA and -DQB were determined by Tag I restriction fragment length polymorphism analysis. Amplification by polymerase chain reaction (PCR) and hybridization with sequence-specific oligonucleotide probes was done for DQA1, DQB1 and DRB1 and DRB5. DR2 was positive in 11/425 patients (3%) and 101/367 (28%) controls (OR 0.07, p<0.0001). Of the 11 DR2-positive patients, PCR was done in 10, of whom 8 were positive for DRB1()1601-DRB5(*)0201 compared to 4/96 (4%) controls (OR 92.0; p<0.001) while the remaining 2 were positive for DRB1()1501-DRB5(*)0101 compared to 92/96 (96%, OR 0.01; p<0.001). In 2 patients, a recombination between the haplotypes DQB1()0502-DQA1(*)0102 (DQ5)-DRB1(*)1601-DRB5(*)0201 (DR16 Dw21) and DQB1()0301-DQA1(*)0501 (DQ7)-DRB1(*)1602-DRB5(*)0202 (DR16 Dw22) was observed resulting in the DQB1()0301-DQA1(*)0501 (DQ7) DRB1(*)1601-DRB5()0201 (DR16 Dw22) haplotypes. The second haplotype was DR3 DQ2 in 6/11 and DR4 DQ8 in 2/11 DR2-positive patients. In all 3 DQB1()0602-DQA10102-DR15-positive patients the second haplotype was DR3-positive. In order to test whether physicochemical properties of the DR2 molecules were associated with IDDM, we constructed three-dimentional models of the peptide binding and T-cell recognition sites (alpha 1 and beta 1 domains) of five subtypes of DR2-DRB1, based on the published DR1 crystal structure. No correlations were observed for DR molecule physicochemical properties and diabetes susceptibility. Islet cell antibodies, insulin autoantibodies and GAD65 antibodies, were measured in DR2-positive patients (n = 11) and controls (n = 101). Despite the presence of the DR2 haplotype the antibody markers were significantly elevated in the patients compared to the controls (GAD65 3/10 patients and 2/101 controls; ICA 7/11 patients and 1/101 controls and IAA 3/11 patientsand 0/101 controls). In conclusion, of the five subtypes of DR2, onlyone, the DRB1()1501, DRB5*0101, DQB1(*)0602-DQA1(*)0102 haplotype, was negatively associated with IDDM. DQ may therefore confer more protection from the disease than DR.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/12/20 alle ore 01:08:59