Studies of cell-mediated immune responses to influenza vaccination in systemic lupus erythematosus.
OBJECTIVE
Both antibody and cell-mediated responses are involved in the defense against influenza. In patients with systemic lupus erythematosus (SLE), a decreased antibody response to subunit influenza vaccine has been demonstrated, but cell-mediated responses have not yet been assessed. This study was therefore undertaken to assess cell-mediated responses to influenza vaccination in patients with SLE.


METHODS
Fifty-four patients with SLE and 54 healthy control subjects received subunit influenza vaccine. Peripheral blood mononuclear cells and sera were obtained before and 1 month after vaccination. Cell-mediated responses to A/H1N1 and A/H3N2 vaccines were evaluated using an interferon-gamma (IFNgamma) enzyme-linked immunospot assay and flow cytometry. Antibody responses were measured using a hemagglutination inhibition test.


RESULTS
Prior to vaccination, patients with SLE had fewer IFNgamma spot-forming cells against A/H1N1 compared with control subjects and a lower frequency of IFNgamma-positive CD8+ T cells. After vaccination, the number of IFNgamma spot-forming cells increased in both patients and control subjects, although the number remained lower in patients. In addition, the frequencies of CD4+ T cells producing tumor necrosis factor and interleukin-2 were lower in patients after vaccination compared with healthy control subjects. As expected for a subunit vaccine, vaccination did not induce a CD8+ T cell response. For A/H3N2-specific responses, results were comparable. Diminished cell-mediated responses to influenza vaccination were associated with the use of prednisone and/or azathioprine. The increase in A/H1N1-specific and A/H3N2-specific antibody titers after vaccination was lower in patients compared with control subjects.


CONCLUSIONS
In addition to a decreased antibody response, cell-mediated responses to influenza vaccination are diminished in patients with SLE, which may reflect the effects of the concomitant use of immunosuppressive drugs. This may render these patients more susceptible to (complicated) influenza infections.
Holvast
Albert
A
Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. B.Holvast@int.umcg.nl
van Assen
Sander
S
de Haan
Aalzen
A
Huckriede
Anke
A
Benne
Cornelis A
CA
Westra
Johanna
J
Palache
Abraham
A
Wilschut
Jan
J
Kallenberg
Cees G M
CG
Bijl
Marc
M
D000328:Adult; D005260:Female; D006304:Health Status; D006801:Humans; D007111:Immunity, Cellular; D016867:Immunocompromised Host / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects*; D007251:Influenza, Human / Q000517:prevention & control*; D007371:Interferon-gamma / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy / Q000276:immunology* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000276:immunology*
D007166:Immunosuppressive Agents; D007252:Influenza Vaccines; D007371:Interferon-gamma