Therefore, a sudden and rapid reduction of the circulating sUA levels by high-dose urate-lowering medications may disrupt the immune balance by rapidly releasing CD38 activity before MSU crystal dissolution (Figure 4—figure supplement 6), resulting in the increased risk of gout attack in the initiation of therapy (Becker et al., 2005; Wen et al., 2024), a well-known paradox in gout therapy. Here, CD38 is linked to gout.