Elsevier

Vaccine

Volume 29, Issue 3, 10 January 2011, Pages 444-450
Vaccine

A/H1N1 influenza vaccination in patients with systemic lupus erythematosus: Safety and immunity

https://doi.org/10.1016/j.vaccine.2010.10.081Get rights and content

Abstract

Objectives

To determine the safety of and immunogenicity induced by A/H1N1 influenza vaccination in patients with systemic lupus erythematosus (SLE).

Research design and methods

The study population comprised 21 SLE patients and 15 healthy control subjects who underwent split-virion, inactivated monovalent A/H1N1 vaccination between December 2009 and January 2010. Sera were obtained before, three weeks after, and six months after vaccination. SLE disease activity index (SLEDAI) scores and autoantibodies were measured at every visit in SLE patients. Haemagglutination inhibition and the serum immunoglobulin G (IgG) level were calculated using the World Health Organization (WHO) procedure to evaluate the antibody responses. We also recorded current medications and past seasonal influenza vaccinations to analyse the interactions between vaccinations and the autoimmunity of SLE patients.

Results

The mean age of the enrolled population was 34.3 years for SLE patients and 39.4 years for control subjects. The average SLEDAI score for SLE patients was 4.1 at vaccination, 4.5 at three weeks, and 4.3 at six months. The seroprotection rate at three weeks was 76.2% in SLE patients and 80.0% in healthy control subjects; by six months, the seroprotection rate was 66.7% in SLE patients and 60% in healthy control subjects. The seroconversion rate was 76.2% in SLE patients and 80% in healthy controls at three weeks; by six months, the seroconversion rate was 52.4% in SLE patients and 53.3% in healthy controls. The response in SLE patients met the criteria of the European Committee for Proprietary Medicinal Products guidelines at three weeks, while the percentage of seroprotection did not at six months. The clinical disease activity and SLEDAI scores did not differ significantly from before to after vaccination in SLE patients, although the level of anticardiolipin IgG increased at three weeks after vaccination, but with no apparent clinical manifestations.

Conclusions

The A/H1N1 influenza vaccine is safe and effective in SLE patients and has no obvious adverse clinical effects. Treatment with a single immunosuppressive agent or combination therapy also leads to effective humoral immunity in these patients.

Introduction

The A/H1N1 and A/H3N2 influenza viruses have caused potent pandemics. A novel swine influenza A (A/H1N1) virus that clinically mimics seasonal influenza was identified in two children in the United States in March and April 2009 [1], [2] and was responsible for an explosion of respiratory tract infections in Mexico [3]. When the transmission seemed to persist and increase in the Northern Hemisphere during the autumn and winter of 2009, the World Health Organization immediately proclaimed a worldwide pandemic, characterized by uncontained community-level transmission of the A/H1N1 virus in multiple areas of the world [4].

Some patients required admission to intensive care units for acute respiratory distress syndrome or septicaemia [5], [6], [7]. The elderly, the obese, and those with accompanying underlying medical conditions such as chronic obstructive pulmonary disease, immunodeficiency, and neurological diseases tended to have more severe disease [7], [8], [9]. Thus, in 2009 the Advisory Committee on Immunization Practices recommended the use of the monovalent A/H1N1 vaccine to prevent mortality and morbidity from A/H1N1 infection and to mitigate the pandemic [10]. Recent studies had confirmed the safety and immunogenicity of this A/H1N1 vaccine in Taiwanese [11], [12], [13].

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease. A defect in B lymphocytes causes abnormalities in apoptosis and persistent production of autoantibodies [14], [15], [16]. Dysregulation of B cells and immunosuppressive therapy in SLE patients might cause impaired humoral immune responses to the A/H1N1 influenza virus, which can occasionally lead to the complications of pulmonary infection and fatal organ dysfunction.

Previous reports recognized the safety and antibody response to influenza vaccination in SLE patients. Morbidity and mortality caused by A/H1N1 infection were diminished significantly after mass vaccination, although several reports claimed that vaccination might exacerbate autoimmunity [17]. Neither increased generation of autoantibodies nor clinical exacerbation of disease activity was observed in influenza-vaccinated SLE patients [18], but no information describing the safety and efficacy of this new A/H1N1 influenza vaccine in SLE patients is available.

In this report, we describe the clinical manifestations, autoimmunity, and humoral immune response including the seroprotection and seroconversion rates in A/H1N1 influenza-vaccinated SLE patients. The specific antibody response to A/H1N1 influenza virus in SLE patients met the European Committee for Proprietary Medicinal Products (CPMP) guidelines. We also demonstrated immunity in A/H1N1-vaccinated SLE patients under immunosuppressive therapy.

Section snippets

Study design

Twenty-one patients with SLE defined according to the American College of Rheumatology criteria were selected during the 2009–2010 winter and, after giving informed consent, were vaccinated against A/H1N1 influenza virus. All patients were at low SLE disease activity index (SLEDAI scores < 8 and/or stable disease activity (defined as disease not demanding any increase in therapy for at least three weeks)) at the time of enrollment and without any contraindications (egg allergy or previous allergy

Demographics

Twenty-one SLE patients and 15 normal controls were enrolled into this study. All SLEDAI scores of the SLE patients were <8 before vaccination. One SLE patient (4.8%) and six (40%) of the normal controls had received the seasonal trivalent influenza vaccination in winter 2009 before this H1N1 vaccination (p = 0.013). Eighteen (85.7%) of the SLE patients and eight controls (53.3%) had never before received an influenza vaccination (p = 0.058). The demographic features of the SLE patients and normal

Discussion

Published studies of trivalent influenza vaccination (A/H1N1, A/H3N2, and type B influenza) in SLE patients investigated whether disease activity and autoantibodies change after vaccination, especially in patients with pre-existing nephritis or neurological manifestations [25], [26], [27], [28], [29], [30], [31]. Recent reports proved the safety of trivalent influenza vaccination in patients with quiescent SLE, but the vaccine may have lower efficacy [32] and patients may have reduced humoral

Acknowledgements

The authors thank Dr. Feng-Yee Chang, Dr. Hui-Kang Sytwu, and Dr. Tzong-Shi Chiueh for their assistance in virus vaccinations; Mr. Shan-Yuan Kuo and Mr. Chen-Hung Chen for their clinical supervision; and Mrs. Li-Hsiu Wu, Ms. Tan-Me Liu, and Mr. Chih-Chieh Wang for their technical support.

References (52)

  • T.M. Govaert et al.

    Immune response to influenza vaccination of elderly people: a randomized double-blind placebo-controlled trial

    Vaccine

    (1994)
  • I. De Bruijn et al.

    Annually repeated influenza vaccination improves humoral responses to several influenza virus strains in healthy elderly

    Vaccine

    (1997)
  • W.A. Keitel et al.

    Efficacy of repeated annual immunization with inactivated influenza virus vaccines over a five-year period

    Vaccine

    (1997)
  • Centers for Disease Control and Prevention (CDC)

    Swine influenza A (A/H1N1) infection in two children—Southern California, March–April 2009

    MMWR Morb Mortal Wkly Rep

    (2009)
  • R.J. Garten et al.

    Antigenic and genetic characteristics of swine-origin 2009 A(A/H1N1) influenza viruses circulating in humans

    Science

    (2009)
  • Centers for Disease Control and Prevention (CDC)

    Outbreak of swine-origin influenza A (A/H1N1) virus infection—Mexico, March–April 2009

    MMWR Morb Mortal Wkly Rep

    (2009)
  • World Health Organization

    New influenza A (A/H1N1) virus: global epidemiological situation, June 2009

    Wkly Epidemiol Rec

    (2009)
  • A. Kumar et al.

    Critically ill patients with 2009 influenza A(A/H1N1) infection in Canada

    JAMA

    (2009)
  • ANZIC Influenza Investigators et al.

    Critical care services and 2009 A/H1N1 influenza in Australia and New Zealand

    N Engl J Med

    (2009)
  • S. Jain et al.

    Hospitalized patients with 2009 A/H1N1 influenza in the United States, April–June 2009

    N Engl J Med

    (2009)
  • F.S. Dawood et al.

    Emergence of a novel swine-origin influenza A (A/H1N1) virus in humans

    N Engl J Med

    (2009)
  • Centers for Disease Control and Prevention (CDC)

    Intensive-care patients with severe novel influenza A(A/H1N1) virus infection—Michigan, June 2009

    MMWR Morb Mortal Wkly Rep

    (2009)
  • Centers for Disease Control and Prevention (CDC)

    Use of influenza A (A/H1N1) 2009 monovalent vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2009

    MMWR Recomm Rep

    (2009)
  • S. Yurasov et al.

    Defective B cell tolerance checkpoints in systemic lupus erythematosus

    J Exp Med

    (2005)
  • A.E. Pugh-Bernard et al.

    B cell receptor signaling in human systemic lupus erythematosus

    Curr Opin Rheumatol

    (2006)
  • U. Mercado et al.

    Influenza vaccination of patients with systemic lupus erythematosus

    Rev Invest Clin

    (2004)
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