Analysis of Peripheral Blood Basophils in Pediatric Systemic Lupus Erythematosus

Abstract

Basophils are the least abundant circulating leukocytes, and their immunological role has not yet been completely elucidated. There is evidence supporting their immunomodulatory role in several pathological settings; recently, studies in both experimental models and humans suggested that basophil homeostasis may be altered in systemic lupus erythematosus (SLE). Here, we first assessed circulating basophils in children affected with pediatric SLE (pSLE). In this cross-sectional study, circulating basophils were enumerated by fluorescence-based flow cytometry analysis in children affected with pSLE, in addition to children suffering from juvenile idiopathic arthritis (JIA) or non-inflammatory/non-rheumatic conditions. This study included 52 pediatric patients distributed in these three groups. We observed a statistically significant reduction of peripherally circulating basophils in children with pSLE compared to the other two groups of patients. This preliminary study is consistent with the available studies in adult patients with SLE showing a reduced number of circulating basophils. However, further research is needed to draw final conclusions on basophils’ homeostasis in pSLE, in addition to their correlation with the disease activity and concomitant therapies.

Double-Negative T (DNT) Cells in Patients with Systemic Lupus Erythematosus

“…Therefore, the presence of differences in DNT cells between SLE patients and other rheumatic patients might further support a specific immunopathological role of DNT cells in SLE, compared to the contrary hypothesis that these alterations could be an unspecific epiphenomenon of autoimmunity. Indeed, in our previous flow cytometry-based studies, we also confirmed another interesting peculiarity of immune cell homeostasis in SLE children, namely a reduction in basophils in their peripheral blood (compared to both controls and patients affected with juvenile idiopathic arthritis) [64,65], as previously shown mainly in adult SLE patients [66,67]. This additional example of peculiar alterations of specific immune cells (like basophils) compared to another rheumatic disorder led us to speculate about the immunopathological relevance of these changes, also considering the respective potential contribution of both basophils and DNT cells in the promotion of Th2skewed immune response (also by producing IL-4) [68,69] and autoantibody production (by supporting B cells) [23,34], according to both general and specific evidence in mice.…”

Blood Composite Scores in Patients with Systemic Lupus Erythematosus

“…Some evidence exists regarding their role in SLE. For example, basophil count has been described to be lower in SLE children compared to controls [18]. Similarly, the absolute counts and frequencies of natural killer T-like cells were described to be downregulated in SLE patients significantly, which correlated to disease activities and could recover to normal after treatment [19].…”

PD-L1- and IL-4-expressing basophils promote pathogenic accumulation of T follicular helper cells in lupus

“…We and others reported that peripheral basopenia and activation of blood basophils correlate with disease activity in SLE patients 14 , 15 , 20 , 22 , 27 . Our current SLE patient cohort further confirmed this blood basophil phenotype as evidenced by basopenia and overexpression of the activation marker CD203c, the chemokine receptor CXCR4, and the L-selectin CD62L, all of them being associated with disease activity (Supplementary Fig.…”

“…In agreement, constitutive basophil deficiency prevents lupus-like disease onset in the pristane-induced lupus-like disease model 16 . Autoreactive IgE titers in SLE patients are associated with disease activity, increased basophil activation (CD203c), basophil migration abilities (increased CD62L, PTGDR-2, and CXCR4 expressions), and basopenia that reflects their accumulation into SLO 14 , 15 , 17 – 22 . The latter is driven through a prostaglandin D2 (PGD 2 )-induced CXCR4 externalization on basophil surface, making them sensitive to SLO-derived CXCL12 gradient 15 .…”