Editorial: Community Series in Primary Immunodeficiencies Worldwide: Volume II

Antonio Condino-Neto ^1* Anne-Sophie Korganow ² Hirokazu Kanegane ³

• ¹ Immunology, University of São Paulo, São Paulo, SP, Brazil
• ² Centre National de Référence, Hôpitaux Universitaires de Strasbourg, Strasbourg, Alsace, France
• ³ Department of Child Health and Development, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan

Research continues to uncover the genetic basis of PIDs, shedding light on their clinical variability. A case report by Chen et al (1). illustrates how mutations in the recombination-activating gene 1 (RAG1) can present atypically as autoimmune hemolytic anemia. By leveraging next-generation sequencing and lymphocyte subset analysis, the case underscores the need for genetic tools to identify atypical PID presentations.Similarly, Jiang et al. ( 2) report a novel mutation in the IL2RG gene linked to X-linked severe combined immunodeficiency (X-SCID). Despite intensive anti-infection treatment, the patient succumbed to disseminated BCG disease. This case highlights the critical role of early diagnosis and timely allogeneic hematopoietic cell transplantation (HCT), emphasizing the importance of newborn screening (NBS) to improve outcomes for rare PIDs like X-SCID. The phenotypic variability of PIDs presents diagnostic challenges. Al-Saud et al. (9) describe a mild case of STK4 mutation-related immunodeficiency with severe T-cell lymphopenia, showcasing how functional analyses can delineate disease severity.Similarly, Fink et al. (10) report severe aplastic anemia associated with STAT1 gain-offunction mutations, broadening understanding of immune dysregulation's impact on hematologic health.The articles collectively highlight progress in PID research, particularly in genetic diagnostics, NBS, and cost-effective tools like calculated globulin and FCM. They also underscore the need to manage immune dysregulation and malignancies in conditions such as AT and Nijmegen breakage syndrome. Expanding NBS programs to underserved regions is crucial for reducing diagnostic delays. Moreover, advancements in gene therapy and targeted biologics hold promise for transforming PID management. International collaboration will be vital in fostering equitable access to these innovations. For example, Sartorelli de Toledo Piza et al. (5) illustrate how calculated globulin complements traditional IgG assessments, and Tahiat et al. ( 6) demonstrate FCM's diagnostic versatility.The articles in this volume highlight the complexity and diversity of PIDs, emphasizing the importance of early diagnosis, innovative diagnostic tools, and targeted therapies.By fostering global collaboration and sharing advancements, the PID community can advance understanding and care for these conditions, ultimately improving outcomes for patients worldwide.