Abstract Body

In line with historically confirmed concepts of disturbed immunosurveillance as a hallmark of cancer, the increased risk of malignancies in patients with long-term pharmacological immunosuppression or acquired immunodeficiency, and the success of immunotherapeutical approaches against various types of malignancies, the risk of malignancies is substantially increased in inborn errors of immunity (IEI). Therefore, it is not surprising, that, after autoimmunity and autoinflammation, malignancies have stepped into the limelight as a prime feature of IEI.

The observed distribution of different types of cancer among the subtypes of IEI, together with recent advances of large-scale analyses of the mutational landscapes of germline mutations in cancer patient cohorts, formed the basis of an attempt to classify the typical mechanisms of the increased risk of malignancies in IEI, and to draw a structured 4D-map of IEI to look for in certain types of malignancies.

Similar to other cancer predisposition syndromes, the approach to establish the diagnosis of IEI, as well as subsequent patient management and screening, nowadays, needs to incorporate counseling for the risk of malignancies and timing appropriate diagnostic measures. In addition to basic scientific studies on molecular underpinnings, not least, awareness is key to improve the diagnosis of an IEI-associated malignancy in order to tailor and optimize treatment.

Abstract Body

Inborn errors of immunity with immune dysregulation, many of which belonging to the subclass of combined immunodeficiencies, often present with variable severity even within one family. Predictors of the clinical course are difficult to identify, and the benefit-risk ratio of hematopoietic stem cell transplantation needs to be weighed against the risks of a chronic disease burden and lifelong immunosuppressive therapy. Therefore, we aimed to develop a disease activity score using a retrospecitvely collected dataset of patients with LRBA deficiency. The score was named IDDA score and aims to take into account all known phenotypical features of this severely compromising inborn error of immunity with autoimmunity, grading their severity, and it is multiplied by physician-reported outcome measures such as hospitalization days, requirement and intensity of supportive care, and performance scores. The usefulness of the IDDA score to monitor disease activity longitudinally, and ideally, also cross-sectionally (intra- and interindividually, respectively), and to improve the risk-benefit assessment of various treatment options in LRBA deficiency is being calculated and will be open for discussion. If successful, the IDDA score might be applied in patients with similar disorders to facilitate their management.