McCoy Allison N, Kim Denise S, Gillespie Erin F, Atkins Stephen J, Smith Terry J, Douglas Raymond S
Department of Ophthalmology and Visual Sciences (A.N.M., D.S.K., E.F.G., S.J.A., T.J.S., R.S.D.), Kellogg Eye Center, University of Michigan, Department of Internal Medicine (T.J.S.), University of Michigan Medical School, and Veterans Affairs Medical Center (R.S.D.), Ann Arbor, Michigan 48105.
J Clin Endocrinol Metab. 2014 Jul;99(7):E1294-9. doi: 10.1210/jc.2013-3207. Epub 2014 Mar 26.
Rituximab depletes CD20(+) B cells and has shown potential benefit in thyroid-associated ophthalmopathy (TAO). The impact of rituximab on T cell phenotype in TAO is unexplored.
The objective of the study was to quantify the abundance of IGF-I receptor-positive (IGF-1R(+)) CD4 and CD8 T cells in active TAO before and after treatment with rituximab.
This was a retrospective case series assessing IGF-1R(+) T cells before and after treatment with rituximab with an 18-month follow-up.
The study was conducted at a tertiary care medical center.
Study participants included eight patients with severe TAO.
Two infusions of rituximab (1 g or 500 mg each) were administered 2 weeks apart.
Quantification of IGF-1R(+) T cells using flow cytometry was measured.
Eight patients with moderate to severe TAO [mean pretreatment clinical activity score (CAS) 5.1 ± 0.2 (SEM)] were treated. Four to 6 weeks after treatment, CAS improved to 1.5 ± 0.3, whereas the proportion of IGF-1R(+) CD3(+) T cells declined from 41.9% to 28.3% (P = .004). The proportion of IGF-1R(+) CD4(+) and IGF-1R(+) CD8(+) T cells declined 4-6 weeks after treatment (from 45.6% to 21.5% and from 32.0% to 15.8%, P = .003 and P = .001, respectively). In two patients, IGF-1R(+) CD4(+) and IGF-1R(+) CD8(+) subsets approximated pretreatment levels after 16 weeks.
Frequency of IGF-1R(+) T cells in patients with TAO declines within 4-6 weeks after rituximab treatment. This phenotypic shift coincides with clinical improvement. Thus, assessment of the abundance of IGF-1R(+) T cells in response to rituximab may provide a biomarker of clinical response. Our current findings further implicate the IGF-1R pathway in the pathogenesis of TAO.
利妥昔单抗可清除CD20(+) B细胞，并且已显示出在甲状腺相关眼病（TAO）中具有潜在益处。利妥昔单抗对TAO中T细胞表型的影响尚未得到研究。
本研究的目的是量化利妥昔单抗治疗前后活动性TAO中IGF-I受体阳性（IGF-1R(+)）CD4和CD8 T细胞的丰度。
这是一项回顾性病例系列研究，评估利妥昔单抗治疗前后的IGF-1R(+) T细胞，并进行18个月的随访。
该研究在一家三级医疗中心进行。
研究参与者包括8例重度TAO患者。
相隔2周给予两次利妥昔单抗输注（每次1 g或500 mg）。
使用流式细胞术对IGF-1R(+) T细胞进行定量测定。
治疗了8例中度至重度TAO患者[治疗前平均临床活动评分（CAS）为5.1±0.2（SEM）]。治疗后4至6周，CAS改善至1.5±0.3，而IGF-1R(+) CD3(+) T细胞的比例从41.9%降至28.3%（P = 0.004）。治疗后4至6周，IGF-1R(+) CD4(+)和IGF-1R(+) CD8(+) T细胞的比例下降（分别从45.6%降至21.5%和从32.0%降至15.8%，P分别为0.003和0.001）。在两名患者中，16周后IGF-1R(+) CD4(+)和IGF-1R(+) CD8(+)亚群接近治疗前水平。
TAO患者中IGF-1R(+) T细胞的频率在利妥昔单抗治疗后4至6周内下降。这种表型转变与临床改善相一致。因此，评估对利妥昔单抗反应的IGF-1R(+) T细胞丰度可能提供临床反应的生物标志物。我们目前的发现进一步表明IGF-1R途径在TAO的发病机制中起作用。
