Elsevier

Vaccine

Volume 24, Issue 16, 12 April 2006, Pages 3217-3223
Vaccine

Influenza vaccine administration in patients with systemic lupus erythematosus and rheumatoid arthritis: Safety and immunogenicity

https://doi.org/10.1016/j.vaccine.2006.01.028Get rights and content

Abstract

Objective

To evaluate immunological safety and immunogenicity of influenza vaccine administration in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).

Patients and methods

Twenty-four patients with low and/or stable disease activity 14 with SLE (mean age 43.42 ± 12.18 years; 13 women) and 10 with RA (mean age 51 ± 14.57 years; 9 women), diagnosed on the basis of the American College of Rheumatology criteria, have been immunized with trivalent split influenza vaccine without adjuvant. Further 24 non-vaccinated patients, 14 with SLE and 10 with RA, and 10 vaccinated healthy subjects, all age- and sex-matched, were used as controls. The patients underwent clinical and laboratory (specific anti-influenzavirus antibodies, auto-antibodies, peripheral blood lymphocyte subpopulations) evaluation before and 30 days after vaccination; auto-antibodies were also assessed at 90 days and disease activity at 90 and 180 days.

Results

The specific antibody response towards the three used antigens (A/New Caledonia/20/99, A/Moscow/10/99, and B/Shangdong/7/97) significantly increased in both patients and healthy controls, without any significant difference between them. No significant difference could instead be observed on the clinical activity, auto-antibodies, and peripheral blood lymphocyte subpopulations before and after vaccination, and between patients and controls.

Conclusions

Trivalent split influenza vaccine without adjuvant seems to be safe and immunogenic in patients with SLE and RA, provided that only patients with low and/or stable disease activity are selected.

Introduction

Vaccines represent a very important tool for the prevention of infectious diseases, whose morbidity and mortality have been significantly reduced by mass vaccination programs. The use of vaccines in subjects with autoimmune diseases, however, should be carefully evaluated. In these patients, in fact, vaccines may theoretically prevent infectious complications and flares, but the possible risk of side effects deriving from stimulation of a disregulated immune system should not be forgotten [1], [2]. Infectious agents and vaccines, indeed, have been implicated in inducing or worsening several autoimmune diseases, even though it has been demonstrated that the risk related to infections was higher than the one associated with immunization [1], [2], [3]. In genetically predisposed subjects, infections may trigger autoimmunity by several mechanisms such as molecular mimicry, polyclonal activation, release of previously sequestered self-antigens and stimulus on innate immune response [1], [2]. Impairment of the network responsible for the maintenance of the immune homeostasis and tolerance to self-antigens is also required [1], [2]. The same mechanisms may be applied to autoimmunity induced by vaccination. More rarely, flares can also occur after vaccination, mainly in patients with active disease [4].

In subjects with autoimmune diseases, infections represent a major cause of morbidity and mortality [5], being the infectious risk and its related complications worsened by the immune system disregulation and immunosuppressive therapy [6]. Among the several infectious diseases, prevention of influenza should receive particular attention, considering the danger coming from the annual possible stimulation of a disregulated immune system, the high attack rate in epidemic periods as well as the potentially severe complications [7]. In the past years studies on the effect of influenza vaccine in patients with systemic lupus erythematosus (SLE) [8], [9], [10], [11], [12], [13], [14], [15], [16] and rheumatoid arthritis (RA) [8], [17], [18], [19], [20] have been performed, generally suggesting safety of vaccination, but reduced immunogenicity, this latter mainly ascribed to the consequences of immunosuppressive therapy. In the above reported studies safety and immunogenicity have been mostly evaluated by measuring disease activity, number and severity of flares and specific antibody response, but regulatory CD4+/CD25+ T cells (Tregs) have not been analysed. Tregs are involved in the maintenance of immune homeostasis and tolerance to self-antigens [21], moreover they modulate the immune-response against infectious agents and down-regulate exuberant inflammatory reactions [22], [23]. Hence Tregs may be considered as immunological substitute for safety. The aim of this study was therefore the evaluation of immunological safety and immunogenicity of influenza vaccine in patients with SLE and RA.

Section snippets

Study design

Twenty-four patients selected during the winter 2003–2004 among those attending our outpatient clinic, 14 diagnosed as SLE and 10 as RA, according to the American College of Rheumatology criteria, [24], [25], were vaccinated against influenza after informed consent. All patients with low (systemic lupus erythematosus disease activity index [SLEDAI] <12 [26] and disease activity score28 [DAS28] <4 [27], [28]) and/or stable disease activity [stable disease activity is defined as the disease not

Demographics

Demographic features of the patients are shown in Table 1. The patients included in the current study generally presented DAS <3.2, whereas three stable patients presented DAS ranging between 3.2 and 4. SLEDAI, instead, was generally <8, although in two stable patients it was ranging between 8 and 12.

Safety

No systemic adverse reactions were observed in vaccinated patients and healthy controls, thus they did not undergo physical examination or blood sample collection during the first week of

Discussion

The possible induction of autoimmunity in vaccine recipients has been hypothesized since 1948, when three cases of SLE following typhoid–paratyphoid parenteral vaccine and scarlet fever streptococcus toxin administration were described [38]. In the succeeding years a wide variety of autoimmune phenomena, ranging from the sole development of auto-antibodies to the clinical evidence of systemic autoimmune diseases [4] has been reported, thus suggesting that immunization may induce autoimmunity in

Acknowledgments

The authors wish to thank Dr. Rachele Amodeo and Mrs. Laura Calzoletti for their helpful scientific and technical support.

Dr. Flavia Del Porto has received an “Assegno di Ricerca” from the University “La Sapienza,” Second School of Medicine, for a research entitled “Aspetti immunologici delle malattie autoimmuni sistemiche.”

The study was financially supported by two grants, the first one (C26F938154) from the University “La Sapienza,” Second School of Medicine, for a research entitled

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