# Prevalence of Various Systemic and Organ-Specific Autoimmune Markers in Addison’s Disease Patients Compared to Healthy Controls

**Authors:** Aylin Feyzullova, Georgi Kirilov, Atanaska Elenkova, Dobromir Tanev, Krassimir Kalinov, Sabina Zacharieva, Ralitsa Robeva

PMC · DOI: 10.3390/jcm14113951 · 2025-06-03

## TL;DR

This study finds higher rates of certain autoimmune markers in Addison’s disease patients compared to healthy individuals, suggesting a link between Addison’s disease and other autoimmune conditions.

## Contribution

The study is among the first to systematically compare multiple autoimmune markers in Addison’s disease patients versus controls.

## Key findings

- Addison’s disease patients showed significantly higher prevalence of rheumatoid factor and ANA antibodies compared to controls.
- A positive correlation was found between 21-hydroxylase antibodies and rheumatoid factor antibodies in Addison’s disease patients.
- ZnT8Ab positivity was not typical in adult Addison’s disease patients, while GADAbs were linked to autoimmune diabetes.

## Abstract

Background: Addison’s disease (AD) is a rare disorder that often develops in the context of autoimmune polyglandular syndromes. However, the prevalence of rheumatological autoimmune diseases and corresponding autoimmune markers in AD is poorly investigated. Therefore, the present study aims to explore systemic and organ-specific immune markers in a cohort of AD patients from a single tertiary endocrine center. Material and methods: In total, 43 adult AD patients and 31 controls were included in the study. 21-hydroxylase autoantibodies (21OHAb), glutamic acid decarboxylase autoantibodies (GADAbs), zinc transporter-8 autoantibodies (ZnT8Abs), antibodies against nuclear antigens (ANAs), autoantibodies against cyclic citrullinated peptides (CCPAbs), rheumatoid factors (RFs), IgG autoantibodies against cardiolipin (ACLAbs), and autoantibodies against beta-2-Glycoprotein I (β2-GPIAbs) were measured in all participants. Results: An increased prevalence of antibodies against RFs (27.91% vs. 0%, p < 0.001) and ANAs (13.95% vs. 0%, p = 0.037) was found in AD patients compared to controls. Moreover, the titers of 21-hydroxylase and RF antibodies correlated positively (r = +0.269, p = 0.020). The AD patients tended to show an increased prevalence of subthreshold ACL antibody reactivity compared to controls. All patients diagnosed with type 1 diabetes mellitus were GADAb- but not ZnT8Ab-positive. Conclusions: The results show an increased prevalence of ANA and RF positivity in AD patients compared to controls and a significant association between 21-OHAb and RF positivity. ZnT8Ab positivity was not typical for adult AD patients from our ethnic group, while GADAbs were an essential marker for autoimmune diabetes mellitus. Extensive studies in different ethnic groups are needed to establish the clinical significance of various immunological markers for AD comorbidity and the appropriate follow-up protocols for patients with different antibody positivity.

## Linked entities

- **Diseases:** Addison’s disease (MONDO:0100480), type 1 diabetes mellitus (MONDO:0005147), autoimmune polyglandular syndromes (MONDO:0017278)

## Full-text entities

- **Genes:** SLC30A8 (solute carrier family 30 member 8) [NCBI Gene 169026] {aka ZNT8, ZnT-8}
- **Diseases:** autoimmune polyglandular syndromes (MESH:D016884), rheumatological autoimmune diseases (MESH:D001327), AD (MESH:D000224), type 1 diabetes mellitus (MESH:D003922), autoimmune diabetes mellitus (MESH:C565730)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12155909/full.md

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Source: https://tomesphere.com/paper/PMC12155909