The GAIN Registry — a New Prospective Study for Patients with Multi-organ Autoimmunity and Autoinflammation

Abstract

Patient registries are a very important and essential tool for investigating rare diseases, as most physicians only see a limited number of cases during their career. Diseases of multi-organ autoimmunity and autoinflammation are especially challenging, as they are characterized by diverse clinical phenotypes and highly variable expressivity. The GAIN consortium (German multi-organ Auto Immunity Network) developed a dataset addressing these challenges. ICD-11, HPO, and ATC codes were incorporated to document various clinical manifestations and medications with a defined terminology. The GAIN dataset comprises detailed information on genetics, phenotypes, medication, and laboratory values. Between November 2019 and July 2022, twelve centers from Europe have registered 419 patients with multi-organ autoimmunity or autoinflammation. The median age at onset of symptoms was 13 years (IQR 3–28) and the median delay from onset to diagnosis was 5 years (IQR 1–14). Of 354 (84.5%) patients who were genetically tested, 248 (59.2%) had a defined monogenetic cause. For 87 (20.8%) patients, no mutation was found and for 19 (4.5%), the result was pending. The most common gene affected was NFkB1 (48, 11.5%), and the second common was CTLA4 (40, 9.5%), both genetic patient groups being fostered by specific research projects within GAIN. The GAIN registry may serve as a valuable resource for research in the inborn error of immunity community by providing a platform for etiological and diagnostic research projects, as well as observational trials on treatment options.

Transition database for rare diseases and its use for clinical documentation

“…This in turn forms the basis for research on quality-assured data and enables access to improved care. Examples of the successful implementation of registries include the German registry for Cystic Fibrosis (https://www.muko.info/), LORIS MyeliNeuroGene rare disease database 34 , the United Kingdom Primary Immune Deficiency registry 36 as well as the GAIN Registry 37 . In addition, registry software tools can also use the described approach to update the underlying terminologies.…”

Too much of a good thing: a review of primary immune regulatory disorders

“…Whilst timeand resource-consuming, these collaborations are necessary to further our understanding of these diseases, particularly for studies with a longitudinal component, such as assessing treatment efficacy or natural history. Setup and maintenance of prospective disease registries, including adaptations of existing projects such as addition of the IDDA2.1 score to the ESID registry, or formation of the German multi-organ AutoImmunity Network, www.g-a-i-n.de), will provide databases to be interrogated for future studies (27,183).…”