| 1. |
- Bensing, Sophie
(författare)
-
Pituitary autoantibodies in endocrine disorders
- 2005
-
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.
|
|
| 2. |
- Dalin, Frida, 1984-
(författare)
-
Model diseases for studies of autoimmunity.
- 2015
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The events triggering autoimmune diseases are to large extent unknown and model diseases are an important tool in studies aiming to elucidate molecular mechanisms in autoimmunity. Autoimmune Addison’s disease (AAD) is a rare disease characterized by autoimmune destruction of adrenal glands and most patients with AAD have autoantibodies against the enzyme 21‑hydroxylase in the adrenal cortex. The autoimmune destruction in AAD is however suspected to be initiated by T cells. One of the most important investigations in this thesis was to characterize the T cell response in AAD. It could be concluded the T cells in AAD patients respond to three immunodominant epitopes on the 21-hydroxylase.In addition, this thesis aims to gain updated data on comorbidities, replacement therapy, autoantibody profiles, and metabolic factors in AAD. A cohort of 660 AAD patients was studied and it was found that AAD patients are prone to develop other autoimmune conditions. AAD is one of three main disease components Autoimmune Polyendocrine Syndrome type 1 (APS-1), a rare disorder caused by mutations in the AutoImmune REgulator gene (AIRE) that can be potentially fatal without timely diagnosis. Screening for autoantibodies against interferon-ω, interferon-α4, and interleukin-22 revealed four new APS-1 patients among the AAD cohort, confirmed by the presence of disease causing mutations in the AIRE gene.Cancer Associated Retinopathy (CAR) is a paraneoplastic phenomenon arising as a consequence to an autoimmune response triggered by a malignant neoplasm present in the body. This disease is devastating and it is valuable to identify new biomarkers associated with CAR, not least from a tumor diagnostic perspective. In this thesis, a patient with osteosarcoma and CAR was studied and by screening of a proteom array, and the novel CAR autoantigen Aryl hydrocarbon receptor interacting protein-like 1 (AIPL1) was identified.In conclusion, this thesis covers studies on T cell and B cell responses in AAD. Moreover, it includes an update on clinical and immunological characterisation of AAD patients. Finally, a novel autoantigen in CAR was identified and proposed as a diagnostic marker for the paraneoplastic syndrome.
|
|
