Single-cycle rituximab-induced immunologic changes in children Enhanced in neuroimmunologic disease?

被引:12
作者
Deya-Martinez, Angela [1 ,2 ,3 ,4 ]
Gordon, Yadira [2 ,3 ]
Molina-Anguita, Cristina [3 ,4 ,7 ]
Vlagea, Alexandru [4 ,6 ]
Piquer, Monica [2 ,3 ,4 ]
Juan, Manel [4 ,5 ,6 ]
Esteve-Sole, Ana [1 ,2 ,3 ,4 ]
Anton, Jordi [3 ,5 ,9 ]
Madrid, Alvaro [10 ]
Garcia-Garcia, Ana [1 ,2 ,3 ,4 ]
Plaza, Ana M. [2 ]
Armangue, Thais [7 ,8 ]
Alsina, Laia [1 ,2 ,3 ,4 ,5 ]
机构
[1] Hosp St Joan Deu, Clin Immunol & Primary Immunodeficiencies Unit, Barcelona, Spain
[2] Hosp St Joan Deu, Pediat Allergy & Clin Immunol Dept, Barcelona, Spain
[3] Inst Recerca St Joan Deu, Barcelona, Spain
[4] Hosp St Joan Deu, Clin Immunol Unit, Hosp Clin, Barcelona, Spain
[5] Univ Barcelona, Barcelona, Spain
[6] Hosp Clin IDIBAPS, Biomed Diagnost Ctr, Immunol Dept, Barcelona, Spain
[7] Univ Barcelona, Hosp St Joan Deu, Neurol Dept, Pediat Neuroimmunol Unit, Barcelona, Spain
[8] Univ Barcelona, Hosp Clin, Inst Invest Biomed IDIBAPS, Neuroimmunol Program, Barcelona, Spain
[9] Hosp St Joan Deu, Pediat Rheumatol Div, Barcelona, Spain
[10] Hosp St Joan Deu, Pediat Nephrol Dept, Barcelona, Spain
关键词
AUTOIMMUNE; SAFETY; HYPOGAMMAGLOBULINEMIA; CHILDHOOD;
D O I
10.1212/NXI.0000000000000724
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Objective To investigate the immunologic impact of a single cycle of rituximab (RTX) in children and adolescents with immune-mediated disorders, we evaluated B cells and immunoglobulin levels of 20 patients with neuroimmunologic, nephrologic, dermatologic, and rheumatologic disorders treated under recommended guidelines. Methods Retrospective study of immunologic changes in children (aged <= 18 years) diagnosed with immune-mediated disorders in which RTX was prescribed between June 2014 and February 2019. Patients were excluded if they had prior diagnosis of malignant disease or primary immunodeficiency. Patients were clinically and immunologically followed up every 3 months. Only patients having received a single cycle of RTX and with a follow-up greater than 12 months were included in the analysis of persistent dysgammaglobulinemia. Results Twenty children were included. Median age at RTX treatment was 12.8 years (interquartile range [IQR] 6.6-15.5 years). Median follow-up was 12.6 months (IQR 10.2-24 months). Of the 14 patients eligible for persistent dysgammaglobulinemia analysis (3 had received RTX retreatment, 2 had <12 months post-RTX follow-up, and in 1 data for this time point was missing), 2/14 (14%) remained with complete B-cell depletion, and 5/14 (36%) had dysgammaglobulinemia. Patients with dysgammaglobulinemia were younger (7.8 vs 15.6 years,p= 0.072), had more underlying neuroimmunologic diseases (5/5 vs 0/9,p< 0.001), and had received more frequently concentrated doses of RTX (3/5 vs 1/9,p= 0.05) than patients without dysgammaglobulinemia. Kinetics of immunoglobulins in the 20 patients revealed a decrease as early as 3 months after RTX in patients with neuroimmunologic disorders. Conclusion In our cohort, single-cycle RTX-induced dysgammaglobulinemia was enhanced in patients with neuroimmunologic diseases. Further studies are needed to confirm this observation.
引用
收藏
页数:8
相关论文
共 31 条
[1]   Association of Immunoglobulin Levels, Infectious Risk, and Mortality With Rituximab and Hypogammaglobulinemia [J].
Barmettler, Sara ;
Ong, Mei-Sing ;
Farmer, Jocelyn R. ;
Choi, Hyon ;
Walter, Jolan .
JAMA NETWORK OPEN, 2018, 1 (07)
[2]   Prospective phase 1/2 study of rituximab in childhood and adolescent chronic immune thrombocytopenic purpura [J].
Bennett, CM ;
Rogers, ZR ;
Kinnamon, DD ;
Bussel, JB ;
Mahoney, DH ;
Abshire, TC ;
Sawaf, H ;
Moore, TB ;
Loh, ML ;
Glader, BE ;
McCarthy, MC ;
Mueller, BU ;
Olson, TA ;
Lorenzana, AN ;
Mentzer, WC ;
Buchanan, GR ;
Feldman, HA ;
Neufeld, EJ .
BLOOD, 2006, 107 (07) :2639-2642
[3]   The shaving reaction: Rituximab/CD20 complexes are removed from mantle cell lymphoma and chronic lymphocytic leukemia cells by THP-1 monocytes [J].
Beum, PV ;
Kennedy, AD ;
Williams, ME ;
Lindorfer, MA ;
Taylor, RP .
JOURNAL OF IMMUNOLOGY, 2006, 176 (04) :2600-2609
[4]   Risk factors predisposing to the development of hypogammaglobulinemia and infections post-Rituximab [J].
Christou, Evangelos A. A. ;
Giardino, Giuliana ;
Worth, Austen ;
Ladomenou, Fani .
INTERNATIONAL REVIEWS OF IMMUNOLOGY, 2017, 36 (06) :352-359
[5]   Utility and safety of rituximab in pediatric autoimmune and inflammatory CNS disease [J].
Dale, Russell C. ;
Brilot, Fabienne ;
Duffy, Lisa V. ;
Twilt, Marinka ;
Waldman, Amy T. ;
Narula, Sona ;
Muscal, Eyal ;
Deiva, Kumaran ;
Andersen, Erik ;
Eyre, Michael R. ;
Eleftheriou, Despina ;
Brogan, Paul A. ;
Kneen, Rachel ;
Alper, Gulay ;
Anlar, Banu ;
Wassmer, Evangeline ;
Heineman, Kirsten ;
Hemingway, Cheryl ;
Riney, Catherine J. ;
Kornberg, Andrew ;
Tardieu, Marc ;
Stocco, Amber ;
Banwell, Brenda ;
Gorman, Mark P. ;
Benseler, Susanne M. ;
Lim, Ming .
NEUROLOGY, 2014, 83 (02) :142-150
[6]   Development of immunity in early life [J].
Goenka, Anu ;
Kollmann, Tobias R. .
JOURNAL OF INFECTION, 2015, 71 :S112-S120
[7]   Suppression of normal immune responses after treatment with rituximab [J].
Kado, Ruba ;
Sanders, Georgiana ;
McCune, W. Joseph .
CURRENT OPINION IN RHEUMATOLOGY, 2016, 28 (03) :251-258
[8]   Single dose of rituximab for refractory steroid-dependent nephrotic syndrome in children [J].
Kamei, Koichi ;
Ito, Shuichi ;
Nozu, Kandai ;
Fujinaga, Shuichiro ;
Nakayama, Makiko ;
Sako, Mayumi ;
Saito, Mari ;
Yoneko, Maki ;
Iijima, Kazumoto .
PEDIATRIC NEPHROLOGY, 2009, 24 (07) :1321-1328
[9]   Leveraging Administrative Data to Monitor Rituximab Use in 2875 Patients at 42 Freestanding Children's Hospitals across the United States [J].
Kavcic, Marko ;
Fisher, Brian T. ;
Seif, Alix E. ;
Li, Yimei ;
Huang, Yuan-Shung ;
Walker, Dana ;
Aplenc, Richard .
JOURNAL OF PEDIATRICS, 2013, 162 (06) :1252-U226
[10]  
KDIGO, 2012, CLIN PRACT GUID GLOM