A Taiwanese team of researchers discovered that the prescription of proton pump inhibitors (PPIs) is associated with a higher risk of developing autoimmune disease, including cold agglutin disease (CAD), according to a study published in Frontiers in Immunology. 

The team hypothesized that PPIs disrupt host immunity and increase the risk of autoimmune diseases.

PPIs are drugs used to treat gastroesophageal reflux and peptic ulcers. PPIs change gastrointestinal microbiota, which influences immune function. The microbiota consists of millions of organisms within the human body that contribute to either health or pathology.

Continue Reading

The researchers conducted their retrospective study using data sourced from the Taiwan National Health Insurance Research Database between 2002 and 2015. They identified patients who received PPI prescriptions and tracked their progress until the development of autoimmune disease, death, or the conclusion of the study period. 

Read more about CAD etiology

There were 297,099 patients on PPIs and they were identified through the database. The results of this study demonstrated that the incidence rate of overall autoimmune diseases was 3.9 times higher in the PPI cohort compared to the non-PPI control. After adjustment for age, sex, and comorbidity, the hazard ratio was 3.32.

The group of autoimmune diseases that were looked at consisted of autoimmune hemolytic anemia (of which CAD is a subgroup), Graves disease, myasthenia gravis, rheumatoid arthritis, psoriasis, and more. The researchers also discovered that PPI users reported an increased risk of organ-specific and systemic autoimmune diseases.

“Therefore, it is recommended that awareness of the increased risk of autoimmune diseases in patients with PPI treatment is very important for clinicians. Furthermore, the mechanism of PPIs inducing autoimmune diseases needs further research to elucidate,” Lin et al concluded.


Lin SH, Chang YS, Lin TM, et al. Proton pump inhibitors increase the risk of autoimmune diseases: a nationwide cohort study. Front Immunol. Published online September 30, 2021. doi:10.3389/fimmu.2021.736036