Infection is one of the major causes of mortality in patients with systemic lupus erythematosus (SLE). We previously found that CD38, an ectoenzyme that regulates the production of NAD + , is up-regulated in CD8 + T cells of SLE patients and correlates with the risk of infection. Here, we report that CD38 reduces CD8 + T cell function by negatively affecting mitochondrial fitness through the inhibition of multiple steps of mitophagy, a process that is critical for mitochondria quality control. Using a murine lupus model, we found that administration of a CD38 inhibitor in a CD8 + T cell–targeted manner reinvigorated their effector function, reversed the defects in autophagy and mitochondria, and improved viral clearance. We conclude that CD38 represents a target to mitigate infection rates in people with SLE.

Originally developed as research tools, different classification criteria sets for systemic lupus erythematosus (SLE) are also used to diagnose SLE in routine clinical care. The recently developed European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) 2019 criteria set is noted to perform better than previous SLE classification criteria. This study applied the new criteria schema to a tertiary center SLE cohort, ascertained its performance, and identified the clinical characteristics of patients who did not fulfill these criteria. From the 217 patients who were included, 11 (5%) did not meet the new criteria, mainly because of the antinuclear antibody entry criterion, resulting in a diagnostic sensitivity of 94%. Within this group, we found that constitutional and renal manifestations were unusual. Additionally, specific SLE antibodies as well as hypocomplementemia were less likely to be present. We did not observe a statistically significant difference in outcomes between the two groups of patients (fulfilling vs. unfulfilling the new criteria). We conclude that the EULAR/ACR criteria may misclassify a small subset of SLE patients with milder disease. It is important to be cognizant of key clinical and serologic features of these patients and treat them accordingly to prevent further irreversible damage.

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