Utility of the monocyte CD64/neutrophil CD64 ratio in autoimmune and autoinflammatory diseases: A retrospective...

Distinguishing superimposed infection from disease flare in systemic autoimmune and autoinflammatory diseases remains challenging, because neutrophil CD64 (nCD64) is sensitive for infection but may have reduced specificity in this setting. We evaluated the monocyte-to-neutrophil CD64 ratio (mCD64/nCD64 ratio) as an adjunctive biomarker in a single-center retrospective study of 408 patients with inflammatory conditions (infection, n = 242; non-infectious inflammation, n = 166). Diagnostic performance of nCD64 and the ratio was assessed by receiver operating characteristic analysis and net reclassification improvement (NRI), including a prespecified subgroup of 86 patients with systemic autoimmune and autoinflammatory diseases to distinguish flares (n = 60) from superimposed infections (n = 26). In the overall cohort, nCD64 showed high accuracy for infection (AUC 0.791), similar to the ratio (AUC 0.764). In the autoimmune/autoinflammatory subgroup, the ratio outperformed nCD64 (AUC 0.926 vs 0.870; p = 0.030) with high sensitivity (96.2%), and improved reclassification (total NRI 0.76; p < 0.001), driven mainly by correct identification of non-infected patients (NRI non-events 0.53). These findings suggest that the mCD64/nCD64 ratio may better distinguish flares from superimposed infections than nCD64 alone in autoimmune/autoinflammatory disease, supporting rule-out decisions when immunosuppressive therapy is being considered.