Abstract Objectives Two different European Reference Networks cover CTDs with paediatric onset, the European Reference Network on Rare and Complex Connective Tissue Diseases (ERN ReCONNET) and the European Reference Network on Rare Immunological Disorders (ERN RITA). The transition of care is a significant focus, with ReCONNET centres actively addressing this through updated programs. Despite these efforts, challenges persist. We aimed to inventory transitional care programs for rare CTDs across Europe. Methods In April 2023, the ERN ReCONNET Transition of Care Task Force, consisting of expert clinicians, patient advocates and coordination team members, created a survey to assess transitional care practices. The survey was distributed to ERN ReCONNET and ERN RITA centres and responses received by 15 March 2024 were analysed. Results A total of 67 responses from 59 centres across 20 European countries were collected. Paediatric rheumatologists typically initiated the transition process (49% of centres). Twenty centres had joint clinics. Despite positive self-assessments of transitional programs, significant limitations were noted. Transition policies varied, with only 40% of centres having a formal standardized policy and less than half of the centres adhering to available transition of care guidelines. Transfer readiness was evaluated using validated questionnaires in 13% of centres, while 29% transitioned patients based solely on age without any readiness assessments. The main challenges included finding adult-oriented centres and the lack of guidelines or engagement from adult centres. Adult healthcare providers also noted a lack of training in adolescent medicine. Conclusion The survey highlighted diverse transition practices and resources across centres, with challenges in readiness evaluation and the use of guidelines. Despite these obstacles, respondents rated ongoing transition processes positively. Enhancing patient perspectives in the transition process is crucial to meet their needs during this critical phase.

Simple Summary Patients with chronic lymphocytic leukemia (CLL) are more susceptible to infections, which are also the most common cause of death in these patients. Previous studies in patients with CLL described elevated levels of FOXP3+ regulatory T cells (Tregs), which also correlated with decreased T cell responses to microbial antigens. As the activation of the STAT5 transcription factor induces the expression of FOXP3 and human CD4+FOXP3+ T cells that also contain nonsuppressive T cells, we analyzed STAT5 phosphorylation (pSTAT5) and suppressive subpopulations, including activated Tregs (aTregs). We found a significantly increased frequency of aTregs in patients with advanced stages, which significantly correlated with the total tumor mass score. aTreg expansion in vitro was associated with significantly higher aTreg pSTAT5 responses to SARS-CoV-2 antigen-specific stimulation in vitro. Finally, a subgroup of patients characterised by an increased aTreg percentage among CD4+FOXP3+ T cells experienced a more severe disease course with serious grade ≥3 infections during follow-up. Abstract Introduction: Advanced chronic lymphocytic leukemia (CLL) is accompanied by increased circulating regulatory T cells (Tregs) and increased susceptibility to severe infections, which were also shown to entail a striking induction of FOXP3 expression in Tregs. As homeostasis of the most suppressive CD45RA−FOXP3high activated Treg (aTreg) subset differs, it is critical to analyse homeostatic signalling in Treg subsets. Materials and Methods: In this study, by using conventional and imaging flow cytometry, we monitored STAT5 signalling/phosphorylation (pSTAT5) and investigated Treg subsets in relation to the Binet stage, the total tumor mass score (TTM) and the disease course during a follow-up of 37 patients with CLL. Results: The aTreg percentage was significantly increased among CD4+ T cells from patients with advanced disease and significantly correlated with the TTM. A subgroup of patients with higher aTreg percentages among CD4+FOXP3+ T cells at the start of therapy was characterised by more frequent episodes of severe infections during follow-up. Conclusions: The results suggesting that an aTreg fraction could represent a possible marker of a severe disease course with infectious complications. Augmented homeostatic STAT5 signalling could support aTreg expansion, as higher pSTAT5 levels were significantly correlated with an increased aTreg frequency among CD4+FOXP3+ T cells during the follow-up of patients on therapy, as well as following SARS-CoV-2 antigen-specific stimulation in vitro.