Faculdade de Medicina da Universidade de São Paulo, Disciplina de Reumatologia, Av. Dr. Arnaldo 455, Cerqueira César, Sao Paulo, SP, Brazil 01246-903.
J Rheumatol. 2012 Jan;39(1):167-73. doi: 10.3899/jrheum.110721. Epub 2011 Nov 15.
To assess the immunogenicity and safety of non-adjuvanted influenza A H1N1/2009 vaccine in patients with juvenile autoimmune rheumatic disease (ARD) and healthy controls, because data are limited to the adult rheumatologic population.
A total of 237 patients with juvenile ARD [juvenile systemic lupus erythematosus (JSLE), juvenile idiopathic arthritis (JIA), juvenile dermatomyositis (JDM), juvenile scleroderma, and vasculitis] and 91 healthy controls were vaccinated. Serology for anti-H1N1 was performed by hemagglutination inhibition assay. Seroprotection rate, seroconversion rate, and factor-increase in geometric mean titer (GMT) were calculated. Adverse events were evaluated.
Age was comparable in patients and controls (14.8 ± 3.0 vs 14.6 ± 3.7 years, respectively; p = 0.47). Three weeks after immunization, seroprotection rate (81.4% vs 95.6%; p = 0.0007), seroconversion rate (74.3 vs 95.6%; p < 0.0001), and the factor-increase in GMT (12.9 vs 20.3; p = 0.012) were significantly lower in patients with juvenile ARD versus controls. Subgroup analysis revealed reduced seroconversion rates in JSLE (p < 0.0001), JIA (p = 0.008), JDM (p = 0.025), and vasculitis (p = 0.017). Seroprotection (p < 0.0001) and GMT (p < 0.0001) were decreased only in JSLE. Glucocorticoid use and lymphopenia were associated with lower seroconversion rates (60.4 vs 82.9%; p = 0.0001; and 55.6 vs 77.2%; p = 0.012). Multivariate logistic regression including diseases, lymphopenia, glucocorticoid, and immunosuppressants demonstrated that only glucocorticoid use (p = 0.012) remained significant.
This is the largest study to demonstrate a reduced but adequate immune response to H1N1 vaccine in patients with juvenile ARD. It identified current glucocorticoid use as the major factor for decreased antibody production. The short-term safety results support its routine recommendation for patients with juvenile ARD. ClinicalTrials.gov; NCT01151644.
评估无佐剂流感 A H1N1/2009 疫苗在青少年自身免疫性风湿病（ARD）患者和健康对照者中的免疫原性和安全性，因为数据仅限于成年风湿病患者。
共纳入 237 例青少年 ARD [青少年系统性红斑狼疮（JSLE）、青少年特发性关节炎（JIA）、青少年皮肌炎（JDM）、青少年硬皮病和血管炎]患者和 91 名健康对照者进行疫苗接种。采用血凝抑制试验检测抗-H1N1 抗体。计算血清保护率、血清转化率和几何平均滴度（GMT）的增长率。评估不良事件。
患者和对照组的年龄相当（14.8±3.0 岁 vs 14.6±3.7 岁；p=0.47）。免疫接种 3 周后，青少年 ARD 患者的血清保护率（81.4% vs 95.6%；p=0.0007）、血清转化率（74.3% vs 95.6%；p<0.0001）和 GMT 的增长率（12.9 倍 vs 20.3 倍；p=0.012）均显著低于对照组。亚组分析显示，JSLE（p<0.0001）、JIA（p=0.008）、JDM（p=0.025）和血管炎（p=0.017）患者的血清转化率降低。仅在 JSLE 患者中观察到血清保护率（p<0.0001）和 GMT（p<0.0001）降低。糖皮质激素的使用和淋巴细胞减少与血清转化率降低相关（60.4% vs 82.9%；p=0.0001；55.6% vs 77.2%；p=0.012）。包括疾病、淋巴细胞减少、糖皮质激素和免疫抑制剂在内的多变量逻辑回归分析表明，只有糖皮质激素的使用（p=0.012）仍然具有统计学意义。
这是最大规模的研究，证明青少年 ARD 患者对 H1N1 疫苗的免疫反应虽降低但仍足够。该研究确定了目前糖皮质激素的使用是抗体产生减少的主要因素。短期安全性结果支持常规推荐该疫苗用于青少年 ARD 患者。ClinicalTrials.gov；NCT01151644。
