Influenza vaccination responses in human systemic lupus erythematosus: impact of clinical and demographic features

Abstract

Objective: Vaccination against common pathogens, such as influenza, is recommended for patients with systemic lupus erythematosus (SLE) to decrease infections and improve health. However, most reports describing the vaccination response are limited to evaluations of SLE patients with quiescent disease. This study focuses on understanding the clinical, serologic, therapeutic, and demographic factors that influence the response to influenza vaccination in SLE patients with a broad range of disease activity.

Methods: Blood specimens and information on disease activity were collected from 72 patients with SLE, at baseline and at 2, 6, and 12 weeks after influenza vaccination. Influenza-specific antibody responses were assessed by determining the total serum antibody concentration (B(max)), relative affinity (K(a)), and level of hemagglutination inhibition in the plasma. Using a cumulative score, the patients were evenly divided into groups of high or low vaccine responders. Autoantibody levels were evaluated at each time point using immunofluorescence tests and standard enzyme-linked immunosorbent assays.

Results: Compared to high responders, low responders to the vaccine were more likely to have hematologic criteria (P = 0.009), to have more American College of Rheumatology classification criteria for SLE (P = 0.05), and to be receiving concurrent prednisone treatment (P = 0.04). Interestingly, European American patients were more likely to be low responders than were African American patients (P = 0.03). Following vaccination, low responders were more likely to experience disease flares (P = 0.01) and to have increased titers of antinuclear antibodies (P = 0.04). Serum interferon-α activity at baseline was significantly higher in patients in whom a flare occurred after vaccination compared to a matched group of patients who did not experience a disease flare (P = 0.04).

Conclusion: Ancestral background, prednisone treatment, hematologic criteria, and evidence of increased likelihood of disease flares were associated with low antibody responses to influenza vaccination in SLE patients.

Copyright © 2011 by the American College of Rheumatology.

Figures

Figure 1. SLE patients with poor antibody responses have reduced humoral immunity compared to healthy controls following influenza vaccination

Plasma from SLE patients (case) and normal healthy controls (control) were tested for humoral immune responses to the influenza vaccine. Cases were divided into high and low responders based upon cumulative rank as outlined in the methods section of the manuscript. Shown are the log10 transformed ratios of post-vaccination to pre-vaccination measurements for (A) antibody concentration (Bmax), (B) antibody affinity (Ka), and (C) hemagglutination inhibition (HAI). Panel D shows the overall vaccine response, expressed as the difference of the percentile ranks (postvacc minus prevacc). Shown are box and whisker plots where the middle line is the median, the box represents the middle 50% of the data, and the whiskers extend to the minimum and maximum values. P-values are derived from nonparametric Mann-Whitney tests using a Bonferroni multiple comparison correction.

Figure 2. Patients with low influenza vaccination responses have more hematologic SLE classification criteria and more steroid use

Subjects were divided into high (gray bar) and low (white bar) responders to influenza vaccination. Shown are the number of individuals that (A) met the indicated ACR SLE classification criteria, **p = 0.009 by exact permutation Chi-square test, (B) exhibited specific aspects of hematological disorders, *p = 0.01 by exact permutation Chi-square test, (C) taking specific medications, *p = 0.037 by Fisher’s exact test and (D) exhibiting specific autoantibodies prior to vaccination.

Figure 3. Patients with low responses to influenza vaccination have increases in autoantibody levels and new specificities after vaccination

Autoantibody titers were measured in sera from the initial (pre-vaccination) and post-vaccination time-points. Shown is the number of (A) low responders or (B) high responders with a two-fold increase (solid gray bar), a two-fold decrease (hatched bar), or new onset (solid black bar) of the specified autoantibody, *p = 0.045 by conditional logistic regression.

Figure 4. SLE disease flares are more frequent in low responders at 6 weeks, but not 12 weeks, after influenza vaccination

High and low antibody responders to influenza vaccination were evaluated for the presence of flares using the SELENA-SLEDAI method (24, 25) for all individuals at six and twelve weeks post vaccination. Shown is the total number of individuals experiencing no flare (white bars), mild/moderate flare (dotted bars), or severe flares (gray bar) (A), the vaccine responsiveness (high or low) of individuals with a flare at 6 weeks post vaccination (B), and the vaccine responsiveness (high or low) of individuals with a flare at 12 weeks post vaccination (C).

Figure 5. Patients that flare at six weeks post vaccination had higher baseline IFN alpha serum activity

Patients were divided into individuals that had a flare (flare) and age and race matched SLE patients that did not have a flare during the course of the study (no flare). Shown is the serum IFN alpha activity at baseline and two weeks in the patients that had a flare at 6 weeks (panel A, p value determined by unpaired t test) and those with a flare at 12 weeks (panel B, no significance by unpaired t test). Each symbol represents one individual and the mean and standard error of the mean are shown.