NAA and Adrenalitis
Overview of Adrenalitis
The adrenal glands develop from the mesenchyme the outer part (cortex) from the mesoderm and the central part (medulla) from the neuroectoderm, which comprises part of the chromaffin system. The adult adrenal gland has a pyramidal configuration that lies immediately over the kidney on its posteromedial surface. Autoimmune Addison's Disease (AAD) depends on a combination of genetic, environmental, and endogenous factors able to both induce a break of immune tolerance and initiate an autoimmune attack on the adrenal cortex, as for other autoimmune diseases.
Identification of Autoantigens of Adrenal Cortex Autoantibodies
21-OH is an adrenal-specific enzyme of the cytochrome P450 family and plays a key role in the synthesis of the cortical hormones. 21-OH is encoded by the CYP21B gene, whereas the CYP21A gene is inactive. 21-OH catalyzes the conversion of progesterone and 17-hydroxyprogesterone into 11-deoxycorticosterone and 11-deoxycortisol. It is a 55 kDa microsomal protein containing a heme group, located in the active site of the C-terminal end of the molecule, which is important for autoantibody binding and in oxidation-reduction reactions. Analysis of autoantibody-binding sites on 21-OH indicated that the epitopes on 21-OH were conformational and confirmed the participation of both the central and C-terminal parts of the molecule.
Fig.1 Main steps of the pathway of adrenal cortex hormone synthesis and the respective enzymes.1
Techniques for Identification of Autoantibodies to 21-Hydroxylase
Following the discovery that 21-OH is the major adrenal cortex autoantigen, a specific and sensitive technique was described, by labeling the protein with 35S-methionine in an in vitro transcription-translation system and using a radioimmunoprecipitation assay (RIA), for the detection of antibodies. Thereafter, because of certain limitations of this technique, a more convenient assay to measure 21-OHAbs was developed based on the use of 125I-labeled recombinant human 21-OH and the precipitation of the immunocomplexes using solid-phase protein A (RIA).
Services at Creative Biolabs
Autoantibody has become an important part of adrenalitis diagnosis, therapy development, and has great potential in clinical application. As a professional explorer in autoantibody research, Creative Biolabs has accumulated rich experience from step-by-step practice. Based on our accumulation, we have developed a comprehensive technology platform providing a variety of autoantibody related services and products:
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If you are also focusing on autoantibody research, or you have any other questions about our services, please feel free to contact us for more information.
Reference
- Wolff, Anette SB, Isil Kucuka, and Bergithe E. Oftedal. "Autoimmune primary adrenal insufficiency-current diagnostic approaches and future perspectives." Frontiers in Endocrinology 14 (2023): 1285901.