Abstract
Oral problems significantly affect individuals with inborn errors of immunity (IEI),
compromising their quality of life. Our study aimed to explore the genetic, microbiological, and
proteomic aspects of IEI patients' oral health. We recruited 30 participants, including 10 IEI
patients, 10 with periodontitis, and 10 healthy individuals. Through various analyses, we identified
genetic variants in genes like ELANE, STAT3, and BTK, associated with conditions such as severe
congenital/cyclic neutropenia, hyper IgE syndrome, and X-linked agammaglobulinemia.
Metagenomic analysis revealed altered oral microbe composition in XLA patients, with 23
microbial species significantly increased in the XLA group compared to controls, while
Granulicatella adiacens was significantly decreased. Proteomic analysis showed upregulated
proteins such as S100A9, LCP1, and UBA1 in the periodontitis group, with LENG9 downregulated
compared to controls. Furthermore, comparison between IEI and control groups identified 10
proteins, including S100A9, CAMP, and DEFA1, that were upregulated in IEI patients, while CST1,
IGHA1, and IGHA2 were downregulated. Univariate and multivariate logistic regression analysis
highlighted gingivitis, calculus, caries, and mucosal ulcers as the most common oral findings in IEI
patients. Furthermore, antibiotics were found to elevate the risk of caries by 5 times, daily
Granulocyte-Colony Stimulating Factor increased periodontal destruction by 27 times, and lowincome children showed a 9-fold increase in calculus accumulation. This project highlights the
intricate relationship between genetics, the oral microbiome, and proteomics in IEI and
periodontitis patients, aiding diagnosis and treatment. It underscores the need for greater
awareness of dental healthcare among these patients and the lack of tailored national policies.
Thus, we propose implementing policies to improve access to dental services, enhance
awareness, and support effective management and prevention of oral diseases in these high-risk groups.
