Immature granulocyte (IG) percentage may help distinguish active systemic lupus erythematosus from remission in pediatric patients, with diagnostic performance comparable to erythrocyte sedimentation rate (ESR).
In a prospective, single-center study, researchers included 74 pediatric patients with childhood-onset systemic lupus erythematosus (SLE), including 43 with active disease and 31 in remission, along with 112 age-matched healthy controls. They incorporated cross-sectional comparisons and longitudinal assessments. The patients with active disease were evaluated at enrollment, 4 to 6 weeks later, and upon achieving inactive disease. The researchers measured white blood cell inflammatory parameters (WBC-IP) using a Sysmex XN-9000 automated hematology analyzerand assessed associations between WBC-IP and disease activity using the SLE Disease Activity Index 2000 (SLEDAI-2K), clinical SLEDAI-2K, and physician global assessment (PGA). They also evaluated the ability of these parameters to distinguish active disease from remission, compared their performance with conventional inflammatory markers, and examined longitudinal changes during treatment.
Among the WBC-IP evaluated, IG percentage (IG%) demonstrated the highest discriminatory performance, with an area under the receiver operating characteristic curve (AUC) of 0.90 for distinguishing active disease from remission. This was comparable to the AUC of 0.92 observed for ESR, with no statistically significant difference between their discriminatory performance. At an IG% cutoff greater than 0.35%, sensitivity was 81%, specificity was 87%, and overall diagnostic accuracy was 84%.
Median IG% was 0.9% among patients with active disease vs. 0.2% among those in remission and 0.2% among healthy controls. IG% demonstrated moderate correlations with SLEDAI-2K, clinical SLEDAI-2K, and PGA. Although IG% showed the strongest associations among the WBC-IP, conventional inflammatory markers demonstrated stronger correlations with disease activity. Complement C3 showed the strongest inverse correlations, while procalcitonin and ESR were also associated with disease activity.
Other WBC-IP demonstrated varying discriminatory performance. The lymphocyte fluorescence dispersion index had an AUC of 0.83, followed by the lymphocyte size dispersion index at 0.76 and lymphocyte complexity dispersion index at 0.75. The neutrophil fluorescence intensity index demonstrated an AUC of 0.73. These findings indicated that several automated measurements reflecting changes in leukocyte characteristics differed between active disease and remission, although IG% showed the strongest overall performance among the new parameters.
Longitudinal analyses demonstrated changes in WBC-IP alongside improvements in clinical disease activity. Median SLEDAI-2K scores decreased from 14 at enrollment to 8 after 4 to 6 weeks and 2 upon achieving inactive disease. However, IG% increased from 0.9% at enrollment to 2.3% after 4 to 6 weeks before declining to 0.5% during inactive disease. After adjustment for multiple comparisons, IG%, neutrophil granularity intensity, and lymphocyte size dispersion remained among the parameters demonstrating statistically significant longitudinal changes.
The researchers noted that the transient increase in IG% during follow-up may have reflected treatment-related changes rather than persistent disease activity. Glucocorticoids can influence circulating IG, while other immunosuppressive therapies may alter leukocyte populations. Consequently, treatment exposure may complicate interpretation of WBC-IP during longitudinal monitoring.
The findings reinforced the importance of conventional laboratory assessments. ESR demonstrated slightly higher discriminatory performance than IG%, while complement C3 showed stronger correlations with disease activity. The researchers emphasized that WBC-IP may provide complementary information rather than replace established laboratory markers or clinical assessments.
The study was limited by its small sample size, single-center design, and lack of independent validation. The optimal IG% cutoff was derived and evaluated within the same cohort, potentially overestimating its diagnostic performance. Treatment-related hematologic changes may have influenced longitudinal measurements, and subclinical infections could not be completely excluded. The absence of established pediatric reference ranges for WBC-IP limited interpretation. Larger multicenter studies are needed to validate the findings and clarify the effects of treatment on these parameters.
“Our findings suggest that WBC-IP, particularly IG%, may serve as complementary biomarkers for assessing disease activity in children with [childhood-onset] SLE,” wrote lead study author ButsabongLerkvaleekul, MD, of the Faculty of Medicine Ramathibodi Hospital atMahidol University in Thailand, and colleagues.
Full disclosures of the study authors can be found in the study.
Source: ACR Open Rheumatology
