The process begins with adults who have suspected inborn errors of immunity. The flowchart splits into two main paths: Classical AID (MEFV, NLRP3) and Atypical RMD or ID-like cases. For Classical AID, rheumatologists order a KDRI panel and directly interpret the results. For Atypical RMD or ID-like cases, the case is reviewed in a multidisciplinary conference involving rheumatologists, pediatric immunologists, clinical geneticists, and genetic counselors. They discuss the likelihood of IEI and potential diagnostic or therapeutic implications. Based on this review, the appropriate testing modality is selected, which can be an in-house panel, KDRI/PIDJ-400 expanded panel, or whole-exome sequencing (IRUD). After genetic testing, a joint post-genetic testing review is conducted by the same multidisciplinary team. The final step is the integrated final diagnosis and treatment plans.
Clinical workflow for multidisciplinary genomic evaluation in adults with suspected IEI. Patients with clinically apparent classical autoinflammatory diseases (e.g., MEFV- or NLRP3-associated disorders) were initially evaluated by rheumatologists, who ordered targeted testing through the KDRI and directly interpreted the results when the phenotype was concordant. In contrast, patients with atypical rheumatic manifestations or ID-like features were systematically reviewed in multidisciplinary conferences involving rheumatologists, pediatric immunologists, clinical geneticists, and genetic counselors. These discussions addressed IEI likelihood and the potential diagnostic or therapeutic implications of genetic findings. Based on this review, the appropriate testing modality was selected—ranging from in-house targeted panels to KDRI/PIDJ-400 expanded panels or WES through the Initiative on IRUD program. All pathogenic or likely pathogenic variants identified through genetic testing were subsequently interpreted jointly across specialties, and final clinical interpretation was performed in the context of clinical phenotypes and disease course.