Department of Rheumatology and Clinical Immunology, University Hospital Freiburg, Freiburg, Germany.
PLoS One. 2012;7(5):e37626. doi: 10.1371/journal.pone.0037626. Epub 2012 May 21.
To assess the impact of immunosuppressive therapy with cyclophosphamide (CYC) and rituximab (RTX) on serum immunoglobulin (Ig) concentrations and B lymphocyte counts in patients with ANCA-associated vasculitides (AAVs).
Retrospective analysis of Ig concentrations and peripheral B cell counts in 55 AAV patients.
CYC treatment resulted in a decrease in Ig levels (median; interquartile range IQR) from IgG 12.8 g/L (8.15-15.45) to 9.17 g/L (8.04-9.90) (p = 0.002), IgM 1.05 g/L (0.70-1.41) to 0.83 g/L (0.60-1.17) (p = 0.046) and IgA 2.58 g/L (1.71-3.48) to 1.58 g/L (1-31-2.39) (p = 0.056) at a median follow-up time of 4 months. IgG remained significantly below the initial value at 14.5 months and 30 months analyses. Subsequent RTX treatment in patients that had previously received CYC resulted in a further decline in Ig levels from pre RTX IgG 9.84 g/L (8.71-11.60) to 7.11 g/L (5.75-8.77; p = 0.007), from pre RTX IgM 0.84 g/L (0.63-1.18) to 0.35 g/L (0.23-0.48; p<0.001) and from pre RTX IgA 2.03 g/L (1.37-2.50) to IgA 1.62 g/L (IQR 0.84-2.43; p = 0.365) 14 months after RTX. Treatment with RTX induced a complete depletion of B cells in all patients. After a median observation time of 20 months median B lymphocyte counts remained severely suppressed (4 B-cells/µl, 1.25-9.5, p<0.001). Seven patients (21%) that had been treated with CYC followed by RTX were started on Ig replacement because of severe bronchopulmonary infections and serum IgG concentrations below 5 g/L.
In patients with AAVs, treatment with CYC leads to a decline in immunoglobulin concentrations. A subsequent RTX therapy aggravates the decline in serum immunoglobulin concentrations and results in a profoundly delayed B cell repopulation. Surveying patients with AAVs post CYC and RTX treatment for serum immunoglobulin concentrations and persisting hypogammaglobulinemia is warranted.
评估环磷酰胺（CYC）和利妥昔单抗（RTX）免疫抑制治疗对anca 相关性血管炎（AAV）患者血清免疫球蛋白（Ig）浓度和 B 淋巴细胞计数的影响。
对 55 例 AAV 患者的 Ig 浓度和外周 B 细胞计数进行回顾性分析。
在中位随访时间为 4 个月时，CYC 治疗导致 IgG 从 12.8 g/L（8.15-15.45）降至 9.17 g/L（8.04-9.90）（p=0.002），IgM 从 1.05 g/L（0.70-1.41）降至 0.83 g/L（0.60-1.17）（p=0.046），IgA 从 2.58 g/L（1.71-3.48）降至 1.58 g/L（1-31-2.39）（p=0.056）。在中位随访时间为 14.5 个月和 30 个月的分析中，IgG 仍明显低于初始值。先前接受 CYC 治疗的患者随后接受 RTX 治疗，导致 IgG 水平进一步下降，从 RTX 前 IgG 9.84 g/L（8.71-11.60）降至 7.11 g/L（5.75-8.77；p=0.007），IgM 从 RTX 前 0.84 g/L（0.63-1.18）降至 0.35 g/L（0.23-0.48；p<0.001），IgA 从 RTX 前 2.03 g/L（1.37-2.50）降至 IgA 1.62 g/L（IQR 0.84-2.43；p=0.365）。RTX 治疗后 14 个月，所有患者的 B 细胞均被完全耗尽。中位观察时间为 20 个月时，中位 B 淋巴细胞计数仍严重抑制（4 个/μl，1.25-9.5，p<0.001）。由于严重的支气管肺部感染和血清 IgG 浓度低于 5 g/L，7 名（21%）接受 CYC 序贯 RTX 治疗的患者开始接受免疫球蛋白替代治疗。
在 AAV 患者中，CYC 治疗可导致免疫球蛋白浓度下降。随后的 RTX 治疗加重了血清免疫球蛋白浓度的下降，并导致 B 细胞重建明显延迟。对接受 CYC 和 RTX 治疗后的 AAV 患者进行血清免疫球蛋白浓度和持续低丙种球蛋白血症的监测是必要的。
