Università Vita-Salute San Raffaele and Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS San Raffaele Scientific Institute, Milan, Italy.
Unit of Immunohaematology and Transfusion Medicine, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Clin Exp Rheumatol. 2019 May-Jun;37 Suppl 118(3):159-166. Epub 2019 Jan 11.
Glucocorticoids induce prompt clinical improvement in patients with IgG4-related disease (IgG4-RD) but their mechanisms of action in this specific condition are not fully understood. B lymphocytes appear central to IgG4-RD pathogenesis because B-cell depletion with rituximab leads to swift clinical responses. In the present work we aim to assess the effects of glucocorticoids on B-cell subpopulations in patients with IgG4-RD.
Fifty patients with active untreated IgG4-RD and 20 healthy controls were enrolled in the present study. Flow cytometry analysis for total circulating CD19+ and CD20+ cells, naïve B cells, memory B cells, plasmablasts, and plasma cells was performed at baseline in all patients, and after 6 months of glucocorticoid treatment in 30 patients. Correlation studies with biomarkers of disease activity were also performed.
At baseline, patients with IgG4-RD showed reduced CD19+ and CD20+ B cells compared to healthy controls, but increased circulating plasmablasts and plasma cells. Circulating plasmablasts and plasma cells correlated with clinical and serological biomarkers of IgG4-RD activity. Glucocorticoid-induced disease remission was accompanied by a reduction of naïve B cell count, an increase of memory B cells, and by a depletion of circulating plasmablasts and plasma cells. CD19+ and CD20+ B cells, were not affected by glucocorticoids.
The efficacy of glucocorticoids in IgG4-RD is associated with selective effects on different B-cell subpopulations. Further studies are warranted to fully understand possible perturbations of the naïve and memory B-cell compartments in patients with IgG4-RD.
糖皮质激素可使 IgG4 相关疾病（IgG4-RD）患者的临床症状迅速改善，但目前尚不完全了解其在该疾病中的作用机制。B 细胞似乎在 IgG4-RD 的发病机制中起核心作用，因为利妥昔单抗可清除 B 细胞，从而迅速缓解临床症状。本研究旨在评估糖皮质激素对 IgG4-RD 患者 B 细胞亚群的影响。
本研究纳入了 50 例未经治疗的活动性 IgG4-RD 患者和 20 例健康对照者。所有患者在基线时及 30 例患者接受糖皮质激素治疗 6 个月后进行流式细胞术检测外周血循环 CD19+和 CD20+B 细胞、初始 B 细胞、记忆 B 细胞、浆母细胞和浆细胞。同时还进行了与疾病活动标志物的相关性研究。
与健康对照者相比，基线时 IgG4-RD 患者的 CD19+和 CD20+B 细胞减少，但循环浆母细胞和浆细胞增加。循环浆母细胞和浆细胞与 IgG4-RD 活动的临床和血清学标志物相关。糖皮质激素诱导的疾病缓解与初始 B 细胞计数减少、记忆 B 细胞增加以及循环浆母细胞和浆细胞耗竭有关。糖皮质激素对 CD19+和 CD20+B 细胞无影响。
糖皮质激素治疗 IgG4-RD 的疗效与对不同 B 细胞亚群的选择性作用有关。需要进一步研究以充分了解 IgG4-RD 患者中初始和记忆 B 细胞亚群可能受到的影响。
