H1N1 Vaccination Triggers TLR Activation and Autoantibody Production in DMARD-naïve pSS Save

Increased morbidity and mortality from infectious causes in patients with autoimmune disorders has led to the overall consensus that vaccination of such patients is important and should be widely promoted in clinical practice. However, the autoimmune-biased immune system of the patient with rheumatic disease and use of immunosuppressive drugs tend to affect response to vaccination.

Published studies have shown reduced immunization responses with decreased protective antibody titers in such patients. As H1N1-related mortality amongst a younger population increased, it has become a common practice to provide protective immunization to all.

This Swedish study was designed to assess immune response to the vaccine of DMARD naïve primary Sjogren’s (pSS) patients. Primary SS patient with +SSA and SSB antibodies and matched healthy controls were vaccinated twice with adjuvanted inactivated H1N1 vaccine. Blood samples were collected and clinical parameters assess prior to, at week 1 and week 3 after each vaccination.

Researchers observed markedly higher levels of H1N1 influenza-specific IgG antibodies in patients, mainly of the IgG1 subclass, compared with controls. Furthermore, H1N1 antibodies developed by the patients had higher avidity than those of controls. Similar response was observed with influenza A and B strains.

Further investigation of antibodies to non-influenza pathogen Epstein-Barr virus (EBV) showed that antibody titers to EBV increased in patients following vaccination, but not incontrols. In terms of clinical response, increased frequency of fever, fatigue, myalgia and arthralgia were observed during the vaccination period.

H1N1 vaccination in pSS induced higher specific antibody responses in untreated autoimmune patients with pSS, and drove polyclonal B cell activation, including that of autoreactive cells, leading to an increase in autoantibody titers. High basal serum levels of the pro-inflammatory cytokines IFN-α, BAFF and TNF-α were observed in untreated patients with pSS during vaccination period. Researchers speculated that such response is possibly due to endosomal TLR stimulation (TLR7 and TLR9 in particular).

That would also explain the fact that such stimulatory effect was abolished in patient treated with hydroxychloroquine (HCQ). It is known that HCQ acts by inhibiting endosomal TLR signaling and subsequent B cell class switch and cytokine production.