Department of Rheumatology, University Medical Centre Ljubljana, Ljubljana, 1000, Slovenia.
Faculty of Mathematics, Natural Science and Information Technologies, University of Primorska, 6000, Koper, Slovenia.
Clin Rheumatol. 2019 May;38(5):1277-1292. doi: 10.1007/s10067-019-04439-y. Epub 2019 Feb 14.
Influenza may cause severe complications in patients with autoimmune inflammatory rheumatic disease (AIRD), to whom vaccinations are especially recommended. However, AIRD patients require cautious scrutiny of immunogenicity as they might exhibit poor antibody response to vaccination, especially when taking immunomodulatory medications.
The aim was to determine immunogenicity of seasonal and pandemic influenza vaccine in AIRD patients, its timeline/persistence, and influence of medications on immune response.
One hundred and thirty-seven AIRD and 54 healthy controls were vaccinated with trivalent seasonal influenza. After 3-5 weeks, 15 healthy controls and 93 AIRD were vaccinated with pandemic influenza vaccine, and 63 of patients were vaccinated a second time after 3-5 weeks. Sera were collected before vaccination, 18-90 days after each vaccination, and more than 180 days after the last vaccination. The immune response was measured using hemagglutination inhibition (HI) assay and IgG/IgA antibodies against influenza A/B with ELISA.
Our findings indicate that following vaccination with seasonal influenza vaccine, seroprotection, seroresponse, and change in geometric mean titers (GMT) in AIRD patients was not compromised compared to healthy. Similarly, we report for pandemic influenza vaccination little added benefit of the second dose. We confirm lowest increase in HI titer in rituximab-treated AIRD compared to other medications. Vaccination largely tilts the balance from negative ELISA A IgG and IgA titers to positive titers in seasonal H1N1 seroresponsive AIRD patients and controls. A significant decrease in HI GMT and seroprotection was observed only in AIRD at > 180 days after vaccination highlighting an absent persistence of immunogenic response in AIRD patients. Due to high initial HI titers for influenza vaccine, we foresee their benefit in personalized medicine in the future.
Influenza vaccination is immunologically active for AIRD, with little value of the second dose of the pandemic vaccine and further scrutiny on persistence of immune response to vaccine in AIRD is needed.
流感可能会给自身免疫性炎症性风湿病（AIRD）患者带来严重的并发症，因此特别建议他们接种疫苗。然而，由于 AIRD 患者可能对疫苗的免疫原性反应较差，尤其是在服用免疫调节药物时，因此需要谨慎地检查他们的免疫原性。
本研究旨在确定季节性和大流行性流感疫苗在 AIRD 患者中的免疫原性、时间/持久性，以及药物对免疫反应的影响。
137 名 AIRD 患者和 54 名健康对照者接种了三价季节性流感疫苗。3-5 周后，15 名健康对照者和 93 名 AIRD 患者接种了大流行性流感疫苗，其中 63 名患者在 3-5 周后再次接种。在接种前、接种后 18-90 天和最后一次接种后 180 天以上采集血清。使用血凝抑制（HI）试验和 ELISA 检测流感 A/B 型的 IgG/IgA 抗体来测量免疫反应。
我们的研究结果表明，与健康对照组相比，接种季节性流感疫苗后，AIRD 患者的血清保护率、血清反应和几何平均滴度（GMT）变化并未受到影响。同样，我们也报告了第二次大流行性流感疫苗接种的获益很小。我们证实，与其他药物相比，利妥昔单抗治疗的 AIRD 患者的 HI 滴度增加最低。接种疫苗在很大程度上使季节性 H1N1 血清反应性 AIRD 患者和对照组的 ELISA A IgG 和 IgA 滴度从阴性转为阳性。仅在 AIRD 患者中观察到接种后 >180 天 HI GMT 和血清保护率显著下降，这表明 AIRD 患者的免疫反应持久性缺失。由于流感疫苗的初始 HI 滴度较高，我们预计未来在个体化医学中它们将具有一定的益处。
流感疫苗对 AIRD 具有免疫活性，大流行性流感疫苗的第二次接种获益较小，需要进一步研究 AIRD 患者对疫苗免疫反应的持久性。
