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- Erichsen, Martina M, et al.
(författare)
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Clinical, Immunological, and Genetic Features of Autoimmune Primary Adrenal Insufficiency: Observations from a Norwegian Registry.
- 2009
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 94, s. 4882-4890
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Primary adrenal insufficiency [Addison's disease (AD)] is rare, and systematic studies are few, mostly conducted on small patient samples. We aimed to determine the clinical, immunological, and genetic features of a national registry-based cohort. Design: Patients with AD identified through a nationwide search of diagnosis registries were invited to participate in a survey of clinical features, health-related quality of life (HRQoL), autoantibody assays, and human leukocyte antigen (HLA) class II typing. Results: Of 664 registered patients, 64% participated in the study. The prevalence of autoimmune or idiopathic AD in Norway was 144 per million, and the incidence was 0.44 per 100,000 per year (1993-2007). Familial disease was reported by 10% and autoimmune comorbidity by 66%. Thyroid disease was most common (47%), followed by type 1 diabetes (12%), vitiligo (11%), vitamin B12 deficiency (10%), and premature ovarian insufficiency (6.6% of women). The mean daily treatment for AD was 40.5 mg cortisone acetate and 0.1 mg fludrocortisone. The mean Short Form 36 vitality scores were significantly diminished from the norm (51 vs. 60), especially among those with diabetes. Concomitant thyroid autoimmunity did not lower scores. Anti-21-hydroxylase antibodies were found in 86%. Particularly strong susceptibility for AD was found for the DR3-DQ2/ DRB1*0404-DQ8 genotype (odds ratio, 32; P = 4 x 10(-17)), which predicted early onset. Conclusions: AD is almost exclusively autoimmune, with high autoimmune comorbidity. Both anti-21-hydroxylase antibodies and HLA class II can be clinically relevant predictors of AD. HRQoL is reduced, especially among diabetes patients, whereas thyroid disease did not have an impact on HRQoL. Treatment modalities that improve HRQoL are needed.
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| 2. |
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| 3. |
- Krogvold, Lars, et al.
(författare)
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Detection of a low-grade enteroviral infection in the islets of Langerhans of living patients newly diagnosed with type 1 diabetes
- 2015
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 64:5, s. 1682-1687
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Tidskriftsartikel (refereegranskat)abstract
- The Diabetes Virus Detection study (DiViD) is the first to examine fresh pancreatic tissue at the diagnosis of type 1 diabetes for the presence of viruses. Minimal pancreatic tail resection was performed 3-9 weeks after onset of type 1 diabetes in 6 adult patients (age 24-35 years). The presence of enteroviral capsid protein 1 (VP1) and the expression of class I HLA were investigated by immunohistochemistry. Enterovirus RNA was analyzed from isolated pancreatic islets and from fresh frozen whole pancreatic tissue using PCR and sequencing. Non-diabetic organ donors served as controls. VP1 was detected in the islets of all type 1 diabetes patients (2 of 9 controls). Hyperexpression of class I HLA molecules was found in the islets of all patients (1 of 9 controls). Enterovirus specific RNA sequences were detected in 4 of 6 cases (0 of 6 controls). The results were confirmed in different laboratories. Only 1.7 % of the islets contained VP1 positive cells and the amount of enterovirus RNA was low. The results provides evidence for the presence of enterovirus in pancreatic islets of type 1 diabetic patients, being consistent with the possibility that a low grade enteroviral infection in the pancreatic islets contribute to disease progression in humans.
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| 4. |
- Skinningsrud, Beate, et al.
(författare)
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Multiple Loci in the HLA Complex Are Associated with Addison's Disease.
- 2011
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 96, s. 1703-1708
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Tidskriftsartikel (refereegranskat)abstract
- Context: A strong association between autoimmune Addison's disease (AAD) and major histocompatibility complex class II-encoded HLA-DRB1-DQA1-DQB1 haplotypes is well known. Recent evidence from other autoimmune diseases has suggested that class I-encoded HLA-A and HLA-B gene variants confer HLA-DRB1-DQA1-DQB1-independent effects on disease. Objective: We aimed to explore AAD predisposing effects of HLA-A and -B and further investigate the role of MICA and HLA-DRB1-DQA1-DQB1 in a much larger material than has previously been studied. Design: HLA-A, -B, -DRB1, and -DQB1 and a microsatellite in MICA were genotyped in 414 AAD patients and 684 controls of Norwegian origin. Results: The strongest association was observed for the DRB1 locus, in which the DRB1*03:01 and DRB1*04:04 conferred increased risk of AAD, particularly in a heterozygous combination [odds ratio 22.13; 95% confidence interval (11.39-43.98); P = 6 × 10(-20)]. After conditioning on DRB1, association with AAD was still present for HLA-B and MICA, suggesting the presence of additional risk factors. Conclusions: The major histocompatibility complex harbors multiple risk loci for AAD, in which DRB1 appears to represent the main risk factor.
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