Division of Medical Genetics, Department of Pediatrics, Duke University Health System, Durham, NC, USA.
Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, USA.
Genet Med. 2019 Apr;21(4):887-895. doi: 10.1038/s41436-018-0270-7. Epub 2018 Sep 14.
To investigate immune tolerance induction with transient low-dose methotrexate (TLD-MTX) initiated with recombinant human acid α-glucosidase (rhGAA), in treatment-naïve cross-reactive immunologic material (CRIM)-positive infantile-onset Pompe disease (IOPD) patients.
Newly diagnosed IOPD patients received subcutaneous or oral 0.4 mg/kg TLD-MTX for 3 cycles (3 doses/cycle) with the first 3 rhGAA infusions. Anti-rhGAA IgG titers, classified as high-sustained (HSAT; ≥51,200, ≥2 times after 6 months), sustained intermediate (SIT; ≥12,800 and <51,200 within 12 months), or low (LT; ≤6400 within 12 months), were compared with those of 37 CRIM-positive IOPD historic comparators receiving rhGAA alone.
Fourteen IOPD TLD-MTX recipients at the median age of 3.8 months (range, 0.7-13.5 months) had a median last titer of 150 (range, 0-51,200) at median rhGAA duration ~83 weeks (range, 36-122 weeks). One IOPD patient (7.1%) developed titers in the SIT range and one patient (7.1%) developed titers in the HSAT range. Twelve of the 14 patients (85.7%) that received TLD-MTX remained LT, versus 5/37 HSAT (peak 51,200-409,600), 7/37 SIT (12,800-51,000), and 23/37 LT (200-12,800) among comparators.
Results of TLD-MTX coinitiated with rhGAA are encouraging and merit a larger longitudinal study.
研究与重组人酸性α-葡萄糖苷酶（rhGAA）联合使用的短暂低剂量甲氨蝶呤（TLD-MTX）在初治交叉反应免疫物质（CRIM）阳性婴儿期发病庞贝病（IOPD）患者中的免疫耐受诱导作用。
新诊断的 IOPD 患者接受皮下或口服 0.4mg/kg 的 TLD-MTX，共 3 个周期（每个周期 3 个剂量），与前 3 次 rhGAA 输注同时进行。抗 rhGAA IgG 滴度分为高持续（HSAT；≥51,200，6 个月后≥2 倍）、持续中等（SIT；≥12,800 且＜51,200 在 12 个月内）或低（LT；≤6400 在 12 个月内），与 37 例接受 rhGAA 单药治疗的 CRIM 阳性 IOPD 历史对照者的滴度进行比较。
14 例 IOPD TLD-MTX 接受者的中位年龄为 3.8 个月（范围为 0.7-13.5 个月），中位 rhGAA 持续时间约 83 周（范围为 36-122 周）时的中位最后滴度为 150（范围为 0-51,200）。1 例（7.1%）患者出现 SIT 范围内的滴度，1 例（7.1%）患者出现 HSAT 范围内的滴度。14 例患者中有 12 例（85.7%）接受 TLD-MTX 治疗后仍为 LT，而对照组中有 5/37 例为 HSAT（峰值 51,200-409,600）、7/37 例为 SIT（12,800-51,000）和 23/37 例为 LT（200-12,800）。
TLD-MTX 与 rhGAA 联合应用的结果令人鼓舞，值得进行更大规模的纵向研究。
