HLA-DR antigen association with proliferative diabetic retinopathy

Middleton, Derek; Johnston, Patrick B.; Gillespie, Effie L.

doi:10.1007/bf00136459

Cited by 7 publications

(3 citation statements)

References 6 publications

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“…The HLA gene complex has been repeatedly studied for its association with DR for the past 30 years with both negative [29], [30], [31], [32], [33], [34], [35], [36] and positive findings [37], [38], [39], [40], [41], [42], [43], [44], [45], [46], [47], [48], [49]. Two separate properties of the HLA complex make it difficult to study.…”

Section: Introductionmentioning

confidence: 99%

HLA Genes, Islet Autoantibodies and Residual C-Peptide at the Clinical Onset of Type 1 Diabetes Mellitus and the Risk of Retinopathy 15 Years Later

et al. 2011

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Aims/HypothesisHLA genes, islet autoantibodies and residual C-peptide were studied to determine the independent association of each exposure with diabetic retinopathy (DR), 15 years after the clinical onset of type 1 diabetes in 15–34 year old individuals.MethodsThe cohort was identified in 1992 and 1993 by the Diabetes Incidence Study in Sweden (DISS), which investigates incident cases of diabetes for patients between 15 and 34 years of age. Blood samples at diagnosis were analyzed to determine HLA genotype, islet autoantibodies and serum C-peptide. In 2009, fundus photographs were obtained from patient records. Study measures were supplemented with data from the Swedish National Diabetes Registry.ResultsThe prevalence of DR was 60.2% (148/246). Autoantibodies against the 65 kD isoform of glutamate decarboxylase (GADA) at the onset of clinical diabetes increased the risk of DR 15 years later, relative risk 1.12 for each 100 WHO units/ml, [95% CI 1.02 to 1.23]. This equates to risk estimates of 1.27, [95% CI 1.04 to 1.62] and 1.43, [95% CI 1.06 to 1.94] for participants in the highest 25th (GADA>233 WHO units/ml) and 5th percentile (GADA>319 WHO units/ml) of GADA, respectively. These were adjusted for duration of diabetes, HbA1c, treated hypertension, sex, age at diagnosis, HLA and C-peptide. Islet cell autoantibodies, insulinoma-antigen 2 autoantibodies, residual C-peptide and the type 1 diabetes associated haplotypes DQ2, DQ8 and DQ6 were not associated with DR.ConclusionsIncreased levels of GADA at the onset of type 1 diabetes were associated with DR 15 years later. These results, if confirmed, could provide additional insights into the pathogenesis of the most common microvascular complication of diabetes and lead to better risk stratification for both patient screenings and DR treatment trials.

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Section: Introductionmentioning

confidence: 99%

HLA Genes, Islet Autoantibodies and Residual C-Peptide at the Clinical Onset of Type 1 Diabetes Mellitus and the Risk of Retinopathy 15 Years Later

et al. 2011

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“…An HLA association for capillary basement membrane thickening has been suggested by one study (19). Some studies support an association between HLA and retinopathy, although this is controversial (20,21).…”

Section: Discussionmentioning

confidence: 93%

Aggregation of Subclinical Autonomic Nervous System Dysfunction and Autoantibodies in Families With Type I Diabetes

Brown

Watts²,

Rabinowe³

1991

Diabetes

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The purpose of our study was to evaluate the occurrence of autonomic nervous system autoantibodies (ANS) in the nondiabetic family members of insulin-dependent (type I) diabetic subjects. We studied 24 families, including 45 nondiabetic parents and 53 nondiabetic siblings of a type I diabetic proband. One hundred one nondiabetic population control subjects were also studied. Stored sera from nondiabetic family members and control subjects were evaluated for the presence of complement-fixing (CF) adrenal medullary antibodies (CF-ADM), sympathetic ganglia antibodies (CF-SG), and vagus nerve antibodies (CF-V) by indirect immunofluorescence. HLA-DR3 and -DR4 typing was performed on 42 nondiabetic family members and 104 diabetic subjects. One or more CF-ANS were in 45 of 93 (40%) nondiabetic family members compared to 2 of 70 (2.8%) control subjects. CF-SG were in 28 of 92 (30%) family members compared to 0 of 101 control subjects (P = 0.0001). CF-V were in 25 of 95 (26%) family members compared to 0 of 76 control subjects (P = 0.0001). CF-ADM were in 10 of 83 (12%) family members compared to 2 of 70 (2.8%) control subjects (P = 0.056). There was no HLA-DR3 or HLA-DR4 association with ANS. Subclinical autonomic dysfunction was demonstrated in 3 of 4 family members with autoantibodies compared to 0 of 4 family members without autoantibodies.

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“…Falck et al (15) studied 103 Finnish adolescents with type 1 diabetes mellitus and found significantly higher prevalence of HLA-DR1 in patients with retinopathy. However, some authors have found no difference in the frequencies of HLA antigens between diabetics with and without proliferative retinopathy (16)(17)(18).…”

Section: Discussionmentioning

confidence: 99%