Augmented ILT3/LILRB4 Expression of Peripheral Blood Antibody Secreting Cells in the Acute Phase of Kawasaki Disease

Abstract

Background: Kawasaki disease (KD) is an acute, systemic vasculitis syndrome that occurs in children. The clinical symptoms and epidemiologic features of KD strongly suggest that KD is triggered by unidentified infectious agents in genetically predisposed patients. In addition, a number of studies have described the role of B cells in the development of KD. To obtain a mechanistic insight into the humoral immune response of B-lineage cells in KD patients, we examined peripheral blood antibody secreting cells (ASCs) and inhibitory immunoreceptors, immunoglobulin-like transcript (ILT)/leukocyte immunoglobulin-like receptor (LILR), on each B cell subpopulation. Methods: Eighteen Japanese KD patients and thirteen healthy control subjects were recruited for this study. Their peripheral blood mononuclear cells were examined by flow cytometry for the number of CD19+ B cells, the size of each B cell subset and the expression of the inhibitory isoforms of ILT/LILR on the B cell subset. Results: The frequency of CD19+CD27high ASCs was significantly increased in the acute phase of KD and reduced after high-dose intravenous immunoglobulin (IVIG) treatment. Interestingly, while ILT2/LILRB1 expression was ubiquitously observed on every B cell/ASCs subset and the level was not significantly different after IVIG, ILT3/LILRB4 (B4) was uniquely expressed on only ASCs, and its expression was significantly decreased after IVIG. Conclusions: In the acute phase of KD, the frequency of ASCs is high with augmented B4 expression, whereas it is lower with decreased B4 expression after IVIG. Further studies of B4 expression on ASCs in autoimmune and infectious diseases will be needed to confirm the significance of our findings.

Impaired Circulating Antibody-Secreting Cells Generation Predicts the Dismal Outcome in the Elderly Septic Shock Patients

“…26 A study demonstrated the frequency of CD19 + CD27 hi ASCs was dramatically increased in acute phase of Kawasaki disease (KD). 27 Ashenafi et al also revealed a greater proportion of circulating plasmablasts (PB), which is CD3 − CD19 + CD20 − CD27 hi CD38 hi , was found in adult participants with active TB. 28 In contrast, Sealy et al showed that ASCs were fractionally reduced, but nonetheless observed in respiratory tract tissues in the absence of eosinophils by evaluating virus-specific responses 1 month and 4 months following an intranasal virus infection of eosinophil-null mice.…”

Disruption of Circadian Clock Induces Abnormal Mammary Morphology and Aggressive Basal Tumorigenesis by Enhancing LILRB4 Signaling

“…Together, these findings reveal that LILRB4 creates an immunosuppressive microenvironment, thereby decreasing its antitumor efficacy. LILRB4 expression is upregulated under pathological conditions, such as Kawasaki disease, systemic lupus erythematosus, sepsis, and mental illness, in addition to tumors ( 71 ). CRD alters several cell-autonomous mechanisms to induce tumorigenesis.…”

Molecular regulatory mechanism of LILRB4 in the immune response

“…Jensen et al revealed that ILT3 loss of function polymorphism was associated with the increase of inflammatory cytokine level in SLE [42]. In addition to SLE, LILRB4 is also associated with a variety of immune diseases, such as Kawasaki disease [43] and allergic diseases [18]. LILRB4 is also closely related to diseases of other systems.…”