Article Text
Abstract
Objectives Vaccination of patients with rheumatic disease has been reported to result in lower antibody titres than in healthy individuals. However, studies primarily include patients on immunosuppressive therapy. Here, we investigated the immune response of treatment-naïve patients diagnosed with primary Sjögren’s syndrome (pSS) to an H1N1 influenza vaccine.
Methods Patients with Sjögren’s syndrome without immunomodulatory treatment and age-matched and gender-matched healthy controls were immunised with an H1N1 influenza vaccine and monitored for serological and cellular immune responses. Clinical symptoms were monitored with a standardised form. IgG class switch and plasma cell differentiation were induced in vitro in purified naïve B cells of untreated and hydroxychloroquine-treated patients and healthy controls. Gene expression was assessed by NanoString technology.
Results Surprisingly, treatment-naïve patients with Sjögren’s syndrome developed higher H1N1 IgG titres of greater avidity than healthy controls on vaccination. Notably, off-target B cells were also triggered resulting in increased anti-EBV and autoantibody titres. Endosomal toll-like receptor activation of naïve B cells in vitro revealed a greater propensity of patient-derived cells to differentiate into plasmablasts and higher production of class switched IgG. The amplified plasma cell differentiation and class switch could be induced in cells from healthy donors by preincubation with type 1 interferon, but was abolished in hydroxychloroquine-treated patients and after in vitro exposure of naïve B cells to chloroquine.
Conclusions This comprehensive analysis of the immune response in autoimmune patients to exogenous stimulation identifies a mechanistic basis for the B cell hyperactivity in Sjögren’s syndrome, and suggests that caution is warranted when considering vaccination in non-treated autoimmune patients.
- Sjögren’s syndrome
- B-cells
- autoantibodies
- vaccination
- INFα
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Footnotes
Contributors SB and MWH conceived the study and designed the experiments with input from VM, CT, LK and VKK; SB, SM, SP, MF-M, KAB and MWH performed the experiments, SB, LF, SP, JM, LW, CT, VM, VKK and MWH analysed the data, MK and GN managed study participant recruitment and clinical data analysis, SB, AA, VKK and MWH wrote the manuscript and all authors participated in revision until its final form.
Funding This study was supported by grants from the Swedish Research Council, the Heart-Lung Foundation, the Stockholm County Council, the Karolinska Institute, the Swedish Rheumatism Association, King Gustaf the V:th 80-year Foundation, and the Torsten and Ragnar Söderberg Foundation.
Competing interests None declared.
Patient consent Detail has been removed from this case description to ensure anonymity. The editors and reviewers have seen the detailed information available and are satisfied that the information backs up the case the authors are making.
Ethics approval Ethics Committee Stockholm North.
Provenance and peer review Not commissioned; externally peer reviewed.