| 1. |
- Bensing, Sophie, et al.
(författare)
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Increased death risk and altered cancer incidence pattern in patients with isolated or combined autoimmune primary adrenocortical insufficiency
- 2008
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Ingår i: Clinical Endocrinology. - : Wiley. - 0300-0664 .- 1365-2265. ; 69:5, s. 697-704
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Primary adrenocortical insufficiency is mostly caused by an autoimmune destruction of the adrenal cortex. The disease may appear isolated or as a part of an autoimmune polyendocrine syndrome (APS). APS1 is a rare hereditary disorder with a broad spectrum of clinical manifestations. In APS2, primary adrenocortical insufficiency is often combined with autoimmune thyroid disease and/or type 1 diabetes. We analysed mortality and cancer incidence in primary adrenocortical insufficiency patients during 40 years. Data were compared with the general Swedish population. DESIGN AND PATIENTS: A population based cohort study including all patients with autoimmune primary adrenocortical insufficiency (3299) admitted to Swedish hospitals 1964-2004. MEASUREMENTS: Mortality risk was calculated as the standardized mortality ratio (SMR) and cancer incidence as the standardized incidence ratio (SIR). RESULTS: A more than 2-fold increased mortality risk was observed in both women (SMR 2.9, 95% CI 2.7-3.0) and men (SMR 2.5, 95% CI 2.3-2.7). Highest risks were observed in patients diagnosed in childhood. SMR was higher in APS1 patients (SMR 4.6, 95% CI 3.5-6.0) compared with patients with APS2 (SMR 2.1, 95% CI 1.9-2.4). Cancer incidence was increased (SIR 1.3, 95% CI 1.2-1.5). When tumours observed during the first year of follow-up were excluded, only the cancer risk among APS1 patients remained increased. Cause-specific cancer incidence analysis revealed significantly higher incidences of oral cancer, nonmelanoma skin cancer, and male genital system cancer among patients. Breast cancer incidence was lower than in the general population. CONCLUSIONS: Our study shows a reduced life expectancy and altered cancer incidence pattern in patients with autoimmune primary adrenocortical insufficiency.
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| 2. |
- Bensing, Sophie, et al.
(författare)
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Lymphocytic hypophysitis : report of two biopsy-proven cases and one suspected case with pituitary autoantibodies
- 2007
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Ingår i: Journal of Endocrinological Investigation. - 0391-4097 .- 1720-8386. ; 30:2, s. 153-162
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Tidskriftsartikel (refereegranskat)abstract
- Lymphocytic hypophysitis (LyH) is a rare inflammatory disease, considered to be autoimmune. LyH has mainly been reported in females and in relation to pregnancy or the post-partum period. We describe a 73-yr-old woman and a 63-yr-old male who were evaluated at our clinic because of pituitary hormone deficits. Both patients had pituitary masses suggestive of a pituitary adenoma on magnetic resonance imaging (MRI). Transsphenoidal pituitary surgery was performed and histopathological examinations revealed LyH in both cases. Clinical, laboratory, radiological and the histopathological findings in these two patients are discussed in detail. In addition, we report on a 79-yr-old man with partial hypopituitarism and empty sella. Screening of a human pituitary cDNA library with his serum revealed autoantibodies against secretogranin II. This is a protein commonly present in human gonadotrophs, thyreotrophs and corticotrophs. Since the patient selectively showed the corresponding pituitary insufficiencies, we speculate on an autoimmune background. Further studies may ascertain the importance of secretogranin II autoantibodies as markers for LyH.
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| 3. |
- Bensing, Sophie, et al.
(författare)
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Pituitary autoantibodies in autoimmune polyendocrine syndrome type 1
- 2007
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 104:3, s. 949-954
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Tidskriftsartikel (refereegranskat)abstract
- Autoimmune polyendocrine syndrome type 1 (APS1) is a rare autosomal recessive disorder caused by mutations in the autoimmune regulator (AIRE) gene. High titer autoantibodies (Aabs) toward intracellular enzymes are a hallmark for APS1 and serve as diagnostic markers and predictors for disease manifestations. In this study, we aimed to identify pituitary autoantigens in patients with APS1. A pituitary cDNA expression library was screened with APS1 sera and a tudor domain containing protein 6 (TDRD6) cDNA clone was isolated. Positive immunoreactivity against in vitro translated TDRD6 fragments was shown in 42/86 (49%) APS1 patients but not in patients with other autoimmune diseases or in healthy controls. By using immunohistochemistry, sera from 3/6 APS1 patients with growth hormone (GH) deficiency showed immunostaining of a small number of guinea pig anterior pituitary cells, and 40-50% of these cells were GH-positive. No such immunostaining was seen with sera from healthy controls. The APS1 Aab-positive, GH-negative cells may represent a novel subpopulation of anterior pituitary cells. In addition, 4/6 patient sera showed staining of a fiber-plexus in the pituitary intermediate lobe recognizing enzymes of monoamine and GABA synthesis. Thus, we have identified TDRD6 as a major autoantigen in APS1 patients and shown that several sera from GH-deficient patients stain specific cell populations and nerves in the pituitary gland.
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| 4. |
- Bensing, Sophie
(författare)
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Pituitary autoantibodies in endocrine disorders
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Autoimmune endocrine disorders are characterised by the development of autoantibodies to specific autoantigens in the target organs. Lymphocytic hypophysitis (LyH) is a disease characterised by inflammation of the pituitary gland, often resulting in hypopituitarism. The aetiology of LyH is considered to be autoimmune. However, only a few pituitary autoantigens have so far been identified. Reliable autoantibody markers are requested in the diagnostic procedure of LyH to avoid unnecessary surgical intervention. The aim of this study was to evaluate the occurrence of pituitary autoantibodies in patients with nonadenomatous pituitary disease and also to identify novel pituitary autoantigens. Autoantibodies to human pituitary cytosolic proteins were determined by immunoblotting. Reactivity to a M, 49 000 pituitary autoantigen was significantly more frequent in patients with idiopathic pituitary hormone deficiency (6/21 (28%) p< 0.05) as well as their relatives (10/35 (28%) p<0.02) compared to control subjects (3/44 (6.8%)). The importance of these pituitary autoantibodies as markers for LyH remains to be confirmed. Autoantibodies against human pituitary cytosol and ten additional organspecific autoantigens were measured in sera from 30 patients with empty sella syndrome (ESS). None of the autoantibodies tested was more frequently found in ESS patients compared to healthy controls. Thus, by analysing autoantibodies we did not find evidence of ESS being associated with any autoimmune disease. Autoantibodies to a novel 36-kDa pituitary cytosolic autoantigen were more common in patients with ACTH-deficiency (12/65 (18.5%) compared to control subjects (2/57 3.5%) (p<0.0214). In addition, autoantibodies to thyroglobulin (M) were positively correlated to immunoreactivity against the 36-kDa pituitary autoantigen. A human pituitary cDNA expression library was successfully constructed. Immunoscreening identified secretogranin II as a pituitary autoantigen in a patient with partial pituitary insufficiency and empty sella. By immunohistochemistry, autoantibodies against ACTH and gonadotrophs were detected in sera from patients with autoimmune polyendocrine syndrome type 1 (APS1) and GHdeficiency. Sera from these patients also showed staining of monoamine and GABA nerve terminals in the pituitary intermediate lobe, in agreement with immunoreactivity towards enzymes involved in the biosynthesis of neurotransmittors. By screening of the human pituitary cDNA expression library we identified TDR136 as a major autoantigen in APS 1.
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| 5. |
- Crock, PA, et al.
(författare)
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Autoimmune Hypophysitis
- 2007
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Ingår i: Autoimmune Diseases in Endocrinology. - : Humana Press, Totawa, USA.
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Bokkapitel (populärvet., debatt m.m.)
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| 6. |
- Fetissov, Sergueï O, et al.
(författare)
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Autoantibodies in autoimmune polyglandular syndrome type I patients react with major brain neurotransmitter systems.
- 2009
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Ingår i: The Journal of comparative neurology. - : Wiley. - 1096-9861 .- 0021-9967. ; 513:1, s. 1-20
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Tidskriftsartikel (refereegranskat)abstract
- Patients with autoimmune polyglandular syndrome type I (APS1) often display high titers of autoantibodies (autoAbs) directed against aromatic L-amino acid decarboxylase (AADC), tyrosine hydroxylase (TH), tryptophan hydroxylase (TPH), and glutamic acid decarboxylase (GAD). Neurological symptoms, including stiff-man syndrome and cerebellar ataxia, can occur in subjects with high levels of GAD autoAbs, particularly when patient sera can immunohistochemically stain gamma-aminobutyric acid (GABA) neurons. However, it was not known if APS1 sera can also stain major monoamine systems in the brain. Therefore, in this work we applied sera from 17 APS1 patients known to contain autoAbs against AADC, TH, TPH, and/or GAD to rat brain sections and processed the sections according to the sensitive immunohistochemical tyramide signal amplification method. We found that autoAbs in sera from 11 patients were able to stain AADC-containing dopaminergic, serotonergic, and noradrenergic as well as AADC only (D-group) neurons and fibers in the rat brain, in several cases with a remarkably high quality and sensitivity (dilution up to 1:1,000,000); and, since they are human antibodies, they offer a good opportunity for performing multiple-labeling experiments using antibodies from other species. Six APS1 sera also stained GABAergic neuronal circuitries. Similar results were obtained in the mouse and primate brain. Our data demonstrate that many APS1 sera can immunostain the major monoamine and GABA systems in the brain. Only in a few cases, however, there was evidence that these autoAbs can be associated with neurological manifestations in APS1 patients, as, e.g., shown in previous studies in stiff-man syndrome.
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