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Ann Rheum Dis. 2017 Jul 31. pii: annrheumdis-2016-210509. doi: 10.1136/annrheumdis-2016-210509. [Epub ahead of print]
H1N1 vaccination in Sj?gren's syndrome triggers polyclonal B cell activation and promotes autoantibody production.
Brauner S1, Folkersen L1, Kvarnstr?m M1, Meisgen S1, Petersen S1, Franz?n-Malmros M1, Mofors J1, Brokstad KA2, Klareskog L1, Jonsson R2, Westerberg LS3, Trollmo C1, Malmstr?m V1, Ambrosi A1, Kuchroo VK4, Nordmark G5, Wahren-Herlenius M1.
Author information
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-na?ve patients diagnosed with primary Sj?gren's syndrome (pSS) to an H1N1 influenza vaccine.
METHODS:
Patients with Sj?gren'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 na?ve B cells of untreated and hydroxychloroquine-treated patients and healthy controls. Gene expression was assessed by NanoString technology.
RESULTS:
Surprisingly, treatment-na?ve patients with Sj?gren'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 na?ve 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 na?ve 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 Sj?gren's syndrome, and suggests that caution is warranted when considering vaccination in non-treated autoimmune patients.
? Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
KEYWORDS:
B-cells; INFα; Sjögren’s syndrome; autoantibodies; vaccination
PMID: 28760805 DOI: 10.1136/annrheumdis-2016-210509
H1N1 vaccination in Sj?gren's syndrome triggers polyclonal B cell activation and promotes autoantibody production.
Brauner S1, Folkersen L1, Kvarnstr?m M1, Meisgen S1, Petersen S1, Franz?n-Malmros M1, Mofors J1, Brokstad KA2, Klareskog L1, Jonsson R2, Westerberg LS3, Trollmo C1, Malmstr?m V1, Ambrosi A1, Kuchroo VK4, Nordmark G5, Wahren-Herlenius M1.
Author information
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-na?ve patients diagnosed with primary Sj?gren's syndrome (pSS) to an H1N1 influenza vaccine.
METHODS:
Patients with Sj?gren'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 na?ve B cells of untreated and hydroxychloroquine-treated patients and healthy controls. Gene expression was assessed by NanoString technology.
RESULTS:
Surprisingly, treatment-na?ve patients with Sj?gren'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 na?ve 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 na?ve 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 Sj?gren's syndrome, and suggests that caution is warranted when considering vaccination in non-treated autoimmune patients.
? Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
KEYWORDS:
B-cells; INFα; Sjögren’s syndrome; autoantibodies; vaccination
PMID: 28760805 DOI: 10.1136/annrheumdis-2016-210509