ABSTRACT
RESUMEN El síndrome tirogástrico autoinmune es la asociación entre dos patologías de origen autoinmune: la anemia perniciosa y la tiroiditis autoinmune, generalmente de presentación en adultos mayores. Se presenta caso de una mujer de 34 años que acude por derrame pericárdico asociado a una pancitopenia por déficit de vitamina B12 debida a una gastritis atrófica de origen autoinmunitaria. Se diagnostica una tiroiditis autoinmune. Recibe tratamiento con complejo B y levotiroxina, con mejoría del derrame. Es importante que ante patologías autoinmunitarias se realice la búsqueda sistemática de otras enfermedades de la misma estirpe para el mejor manejo clínico.
ABSTRACT Autoimmune thyrogastric syndrome is the association between two pathologies of autoimmune origin: pernicious anemia and autoimmune thyroiditis, which usually presents in older adults. We present the case of a 34-year-old woman who consult about pericardial effusion associated with pancytopenia caused by vitamin B12 deficiency due to autoimmune atrophic gastritis. Autoimmune thyroiditis is diagnosed. She receives treatment with complex B and levothyroxine, with improvement of the effusion. It is important that in the case of autoimmune pathologies, a systematic search for other diseases of the same lineage is carried out for the best clinical management.
ABSTRACT
Autoimmune polyendocrine syndrome (APS) is assumed to involve an immune system malfunction and entails several autoimmune diseases co-occurring in different tissues of the same patient; however, they are orphans of its accurate diagnosis, as its genetic basis and pathogenic mechanism are not understood. Our previous studies uncovered alterations in the ATPase H+/K+ Transporting Subunit Alpha (ATP4A) proton pump that triggered an internal cell acid-base imbalance, offering an autoimmune scenario for atrophic gastritis and gastric neuroendocrine tumors with secondary autoimmune pathologies. Here, we propose the genetic exploration of APS involving gastric disease to understand the underlying pathogenic mechanism of the polyautoimmune scenario. The whole exome sequencing (WES) study of five autoimmune thyrogastric families uncovered different pathogenic variants in SLC4A2, SLC26A7 and SLC26A9, which cotransport together with ATP4A. Exploratory in vitro studies suggested that the uncovered genes were involved in a pathogenic mechanism based on the alteration of the acid-base balance. Thus, we built a custom gene panel with 12 genes based on the suggested mechanism to evaluate a new series of 69 APS patients. In total, 64 filtered putatively damaging variants in the 12 genes of the panel were found in 54.17% of the studied patients and none of the healthy controls. Our studies reveal a constellation of solute carriers that co-express in the tissues affected with different autoimmune diseases, proposing a unique genetic origin for co-occurring pathologies. These results settle a new-fangled genetics-based mechanism for polyautoimmunity that explains not only gastric disease, but also thyrogastric pathology and disease co-occurrence in APS that are different from clinical incidental findings. This opens a new window leading to the prediction and diagnosis of co-occurring autoimmune diseases and clinical management of patients.
