Increased B cell-activating factor (BAFF) level in the sputum of children with asthma

Abstract

PurposeB cell-activating factor (BAFF) is a tumor-necrosis factor (TNF) superfamily member best known for its role in the survival and maturation of B cells. BAFF activity is observed in naïve cells as well as in effector/memory T cells. We aimed to explore whether BAFF in sputum is expressed at elevated levels in asthmatic airways and associated with eosinophilic inflammation, pulmonary function, and bronchial hyperresponsiveness in children.MethodsOne hundred and fifty-four asthmatic children and 98 healthy children were enrolled in the study. Sputum supernatants were collected and sputum BAFF and eosinophil cationic protein (ECP) levels were measured. We performed pulmonary function tests and methacholine challenge tests, while measuring total eosinophil count, total serum IgE, and serum ECP in all subjects.ResultsAsthmatic children had significantly higher levels of BAFF in induced sputum [26.50 (10.50-100.27) pg/mL] compared to healthy children [18.32 (7.68-44.63) pg/mL; P=0.011]. Sputum BAFF positively correlated with sputum eosinophils (γ=0.406, P<0.001) and sputum ECP (γ=0.789, P<0.001). Significant negative correlations were found between sputum BAFF and FEV1 (γ=-0.291, P<0.001) or post-bronchodilator FEV1 (γ=-0.334, P<0.001), whereas nonsignificant correlations were found between sputum BAFF and bronchial hyperresponsiveness, serum eosinophil count, and serum ECP.ConclusionThese findings suggest that BAFF may play a role in childhood asthma, and BAFF levels in sputum could be a supportive marker that represents airway inflammation, especially eosinophilic inflammation.

ORMDL3 Facilitates the Survival of Splenic B Cells via an ATF6α–Endoplasmic Reticulum Stress–Beclin1 Autophagy Regulatory Pathway

“…Loss of BAFF impairs B cell development at the transitional stage from T1 B to T2 B cells, thereby decreasing the number of mature B cells and hence Ig level and autoantibodies (34). The expression of BAFF is elevated in patients with autoimmune diseases such as rheumatic arthritis, multiple sclerosis, SLE, and asthma, and belimumab, which is known as a mAb targeting human BAFF, has become the first approved targeted therapy for SLE (35)(36)(37). As a consequence, the way to inhibit BAFF has generated great potential to alleviate the phenotype of SLE.…”

Role of Autophagy in Lung Inflammation

“…For example, specific phenotypes of disease, such as B cell activating factor from the TNF family (BAFF) induced inflammatory diseases could be targeted through regulation of intracellular Ca 2+ level or CaMKII, AKT, or mTOR ultimately regulating autophagy and attenuating disease (155). Increased levels of BAFF have been observed in child asthma patients compared to healthy children (156). A variety of cytokines have been found to effect autophagy in B cells including IFN-α (153) and IL-4 (152).…”

IRF‐1 SNPs influence the risk for childhood allergic asthma: A critical role for pro‐inflammatory immune regulation

“…Increased Fc receptor‐like 5 ( FCRL5 ) expression in AA carrying the risk gene variants may point to reduced B‐cell regulation as this gene encodes for a membrane receptor found to bind IgG, thus negatively regulating B‐cell stimulation. Yet, this is surprising as B‐cell activation factor was previously upregulated in serum and sputum of asthma patients . As we could not additionally assess B cells in depth, we cannot conclude a direct influence of FCRL5 expression on B‐cell regulation in this cohort.…”