Suppressed plasmablast responses in febrile infants, including children with Kawasaki disease

Abstract

BackgroundKawasaki disease (KD), the leading cause of acquired heart disease in children, primarily affects infants and toddlers. Investigations on immune responses during KD are hampered by a limited understanding of normal immune responses in these ages. It’s well known that Infants have poorer vaccine responses and difficulty with maintaining prolonged serum immunity, but there are few studies on human infants detailing immune deficiencies. Limited studies propose an inability to maintain life-long bone marrow plasma cells. Plasmablasts are a transitional cell form of B cells that lead to long-term Plasma cells. Plasmablasts levels rise in the peripheral blood after exposure to a foreign antigen. In adult studies, these responses are both temporally and functionally well characterized. To date, there have been few studies on plasmablasts in the predominant age range of KD.MethodsChildren presenting to an urban pediatric emergency room undergoing laboratory evaluation, who had concern of KD or had fever and symptoms overlapping those of KD, were recruited. Peripheral blood mononuclear cells were isolated and evaluated utilizing flow cytometry with specific B cell markers from 18 KD subjects and 69 febrile controls.ResultsPlasmablast numbers and temporal formation are similar between infectious disease controls and KD subjects. In both groups, infants have diminished plasmablast responses compared to older children.ConclusionIn this single-time point survey, infants have a blunted peripheral plasmablast response. Overall, similar plasmablast responses in KD and controls support an infectious disease relationship to KD. Future time-course studies of plasmablasts in infants are warranted as this phenomenon may contribute to observed immune responses in this age group.

Antibodies and Immunity During Kawasaki Disease

“…We postulated if KD is caused by an infection, we should see a predictable rise of PBs in the peripheral blood. On single timepoint collection, we showed 15 of 18 KD samples had elevation of their PBs, and overall this response was similar to the range of data shown in our 69 infected controls (45). Results of this study are consistent with the majority of the literature that show B cell stimulation and increasing peripheral B cell numbers during KD (6,9,71,190).…”

“…Rare but more significant pulmonary disease has also been reported (43). Notably, however, concomitant respiratory viruses are near 10% of cases (44,45). A persistent infection has been theorized (46).…”

“…In the few published studies on peripheral cell subsets during acute KD, circulating B cells are generally elevated ( 6 , 9 , 45 , 71 , 190 ). Lack of changes in acute and convalescent B cells subgroups and increases in CD69+ natural killer and γδ T cells supported a role for the innate immune system ( 71 ).…”

An Angiotensinogen Gene Polymorphism (rs5050) Is Associated with the Risk of Coronary Artery Aneurysm in Southern Chinese Children with Kawasaki Disease

“…KD mainly occurs between 6 months and 5 years of age, and a major complication of KD is CAA [4, 5]. Recently, the disease has become among the most common causes of acquired heart disease in children [6]. The results of a genome-wide association study (GWAS) showed that single-nucleotide polymorphisms (SNPs) in the genes nebulette (NEBL) (rs16921209), inositol 1,4,5-trisphosphate 3-kinase C (ITPKS) (19q23), transforming growth factor- β (TGF- β ) (19q13.1), and potassium calcium-activated channel subfamily N member 2 (KCNN2) (5q22.3) were closely related to coronary artery lesions in KD [7–10].…”

How Should We Classify Kawasaki Disease?

“…Plasmablasts are B cells (CD19+ CD20- CD27+ CD38+) transitioning to plasma cells that circulate in the peripheral blood cell compartment. KD patients showed a plasmablast response similar to children with infectious diseases, thus suggesting that circulating plasmablasts during KD produce antibodies that specifically target the agent responsible for the KD (17). Moreover, electron microscopy studies on bronchial epithelium of KD showed intracytoplasmic inclusion bodies (18) and oligoclonal IgA antibodies (19) suggesting a response to a pathogen entering through the upper respiratory tract.…”