| Summary: | Abstract Objectives The present phenotype‐based disease classification causes ambiguity in diagnosing and determining timely, effective treatment options for primary immunodeficiency (PID). In this study, we aimed to examine the characteristics of early‐onset PID and proposed a JAK‐STATopathy subgroup based on their molecular defects. Methods We reviewed 72 patients (< 100 days) retrospectively. These patients exhibited various immune‐related phenotypes and received a definitive molecular diagnosis by next‐generation sequencing (NGS)‐based tests. We evaluated the PID‐causing genes and clinical parameters. We assessed the genes that shared the JAK‐STAT signalling pathway. We also examined the potential high risks related to the 180‐day death rate. Results We identified PID disorders in 25 patients (34.72%, 25/72). The 180‐day mortality was 26.39% (19/72). Early onset of disease (cut‐off value of 3.5 days of age) was associated with a high 180‐day death rate (P = 0.009). Combined immunodeficiency with associated or syndromic features comprised the most common PID class (60.00%, 15/25). Patients who presented life‐threatening infections were most likely to exhibit PID (odds ratio [OR] = 2.864; 95% confidence interval [CI]: 1.047‐7.836). Twelve out of 72 patients shared JAK‐STAT pathway defects. Seven JAK‐STATopathy patients were categorised as PID. They were admitted to NICUs as immunological emergencies. Most of them experienced severe infections and thrombocytopenia, with 4 succumbing to an early death. Conclusions This study confirmed that NGS can be utilised as an aetiological diagnostic method of complex immune‐related conditions in early life. Through the classification of PID as pathway‐based subtypes, we see an opportunity to dissect the heterogeneity and to direct targeted therapies.
|
|---|
