莱姆病疫苗接种后发生关节炎的人群中 HLA 类型及对伯氏疏螺旋体外膜蛋白 a 的免疫反应
HLA type and immune response to Borrelia burgdorferi outer surface protein a in people in whom arthritis developed after Lyme disease vaccination.
作者信息
Ball Robert, Shadomy Sean V, Meyer Abbie, Huber Brigitte T, Leffell Mary S, Zachary Andrea, Belotto Michael, Hilton Eileen, Bryant-Genevier Marthe, Schriefer Martin E, Miller Frederick W, Braun M Miles
机构信息
Center for Biologics Evaluation and Research, FDA, Rockville, Maryland, USA.
出版信息
Arthritis Rheum. 2009 Apr;60(4):1179-86. doi: 10.1002/art.24418.
OBJECTIVE
To investigate whether persons with treatment-resistant Lyme arthritis-associated HLA alleles might develop arthritis as a result of an autoimmune reaction triggered by Borrelia burgdorferi outer surface protein A (OspA), the Lyme disease vaccine antigen.
METHODS
Persons in whom inflammatory arthritis had developed after Lyme disease vaccine (cases) were compared with 3 control groups: 1) inflammatory arthritis but not Lyme disease vaccine (arthritis controls), 2) Lyme disease vaccine but not inflammatory arthritis (vaccine controls), and 3) neither Lyme disease vaccine nor inflammatory arthritis (normal controls). HLA-DRB1 allele typing, Western blotting for Lyme antigen, and T cell reactivity testing were performed.
RESULTS
Twenty-seven cases were matched with 162 controls (54 in each control group). Odds ratios (ORs) for the presence of 1 or 2 treatment-resistant Lyme arthritis alleles were 0.8 (95% confidence interval [95% CI] 0.3-2.1), 1.6 (95% CI 0.5-4.4), and 1.75 (95% CI 0.6-5.3) in cases versus arthritis controls, vaccine controls, and normal controls, respectively. There were no significant differences in the frequency of DRB1 alleles. T cell response to OspA was similar between cases and vaccine controls, as measured using the stimulation index (OR 1.6 [95% CI 0.5-5.1]) or change in uptake of tritiated thymidine (counts per minute) (OR 0.7 [95% CI 0.2-2.3]), but cases were less likely to have IgG antibodies to OspA (OR 0.3 [95% CI 0.1-0.8]). Cases were sampled closer to the time of vaccination (median 3.59 years versus 5.48 years), and fewer cases had received 3 doses of vaccine (37% versus 93%).
CONCLUSION
Treatment-resistant Lyme arthritis alleles were not found more commonly in persons who developed arthritis after Lyme disease vaccination, and immune responses to OspA were not significantly more common in arthritis cases. These results suggest that Lyme disease vaccine is not a major factor in the development of arthritis in these cases.
目的
研究携带与治疗抵抗性莱姆关节炎相关的人类白细胞抗原（HLA）等位基因的个体，是否会因莱姆病疫苗抗原——伯氏疏螺旋体外膜蛋白A（OspA）引发的自身免疫反应而患上关节炎。
方法
将接种莱姆病疫苗后发生炎性关节炎的个体（病例组）与3个对照组进行比较：1）患炎性关节炎但未接种莱姆病疫苗的个体（关节炎对照组），2）接种莱姆病疫苗但未患炎性关节炎的个体（疫苗对照组），3）既未接种莱姆病疫苗也未患炎性关节炎的个体（正常对照组）。进行HLA - DRB1等位基因分型、莱姆抗原的蛋白质印迹分析以及T细胞反应性检测。
结果
27例病例与162名对照匹配（每个对照组54名）。病例组与关节炎对照组、疫苗对照组和正常对照组相比，携带1个或2个治疗抵抗性莱姆关节炎等位基因的比值比（OR）分别为0.8（95%置信区间[95%CI]0.3 - 2.1）、1.6（95%CI 0.5 - 4.4）和1.75（95%CI 0.6 - 5.3）。DRB1等位基因频率无显著差异。使用刺激指数（OR 1.6[95%CI 0.5 - 5.1]）或氚标记胸腺嘧啶摄取量变化（每分钟计数）（OR 0.7[95%CI 0.2 - 2.3]）测量时，病例组与疫苗对照组对OspA的T细胞反应相似，但病例组产生抗OspA IgG抗体的可能性较小（OR 0.3[95%CI 0.1 - 0.8]）。病例组在更接近接种疫苗的时间进行采样（中位数3.59年对5.48年），且接种3剂疫苗的病例较少（37%对93%）。
结论
在接种莱姆病疫苗后发生关节炎的个体中，未更常见地发现治疗抵抗性莱姆关节炎等位基因，且关节炎病例中对OspA的免疫反应也未更常见。这些结果表明，莱姆病疫苗不是这些病例中关节炎发生的主要因素。
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