Response to Flu Vaccine Varies in Lupus
Race and the presence of hematologic abnormalities were among the factors influencing response to influenza vaccine among patients with systemic lupus erythematosus, a prospective study found.
African-American patients were three times more likely to mount a successful response to vaccination than were patients of European ancestry (95% CI 1.07 to 9.94, P=0.03), according to Judith A. James, MD, PhD, of the University of Oklahoma in Oklahoma City, and colleagues.
However, a high response to the vaccine was seen in only one-third of patients with hematologic manifestations of lupus -- and in none of the patients with hemolytic anemia (P=0.01), the researchers reported in the August issue of Arthritis & Rheumatism.
As treatment for systemic lupus erythematosus has improved in recent years, lowering mortality rates from complications such as renal disease, infections have become a more common cause of morbidity and mortality.
Accordingly, immunization against influenza has become standard of care for lupus patients.
However, previous studies have yielded limited and conflicting data on individual responses to the vaccine and on the effects of immunization on lupus disease activity.
To more fully explore the issues involved, James and colleagues enrolled 72 patients and an equal number of healthy controls, collecting blood samples before vaccination and at two, six, and 12 weeks after the immunization.
Response to the vaccine was classified as low or high according to scores calculated from total antibody concentrations, relative affinity of serum antibodies, and levels of hemagglutination inhibition.
Among the cohort of patients, more than 90% were women and 44% were African-American.
Mean age was 43, and median age at lupus diagnosis was 31.
The median number of American College of Rheumatology (ACR) lupus criteria was 5.8.
Overall, the humoral immune response following immunization was lower among lupus patients compared with controls, although high responders to the vaccine achieved antibody responses that were closer to the responses seen in controls.
The stronger response to the vaccine among African-American patients could not be explained by differences in age, as the average ages of low and high responders were similar.
"This discrepancy in vaccine responsiveness may be due to the impact of HLA haplotypes in the different racial groups, although this requires further investigation," the researchers wrote.
Patients with low responses had more American College of Rheumatology (ACR) lupus criteria than high responders (6 versus 5, P=0.05), with almost two-thirds of low responders having six or more criteria.
Aside from hemolytic anemia, low responders also had higher prevalences of thrombocytopenia, lymphopenia, and leukopenia, although the differences were not statistically significant.
More of the high responders had a discoid rash, while no differences were seen between the low and high response groups in renal disease or arthritic complications.
The use of prednisone was associated with low response, with 67% of low responders having taken the steroid in doses of 10 mg or higher per day compared with 47% of those who had higher responses to the vaccine (P=0.04).
The use of other medications such as methotrexate and azathioprine did not appear to influence immunization response, the researchers observed.
Certain patterns of autoantibodies also differed between low and high responders.
For instance, low responders more often had an increase in antinuclear antibody (14% versus 8%), while 22% of high responders had decreases in titers of this antibody.
Low responders also were more likely to have a disease flare.
Within six weeks of vaccination, 14 patients had experienced a flare, 71.4% of whom were low responders (P=0.01).
When the researchers looked for characteristics among these patients who flared, they found no correlation for baseline disease activity, number of ACR lupus criteria, or age at diagnosis.
Certain ACR criteria were more common among patients who flared, including renal involvement, central nervous system manifestations, and hematologic abnormalities, but the numbers were inadequate for statistical analysis.
One factor that did correlate with flare was baseline serum interferon (IFN)-α activity.
The mean IFN-α activity among patients who flared was 19.3 standard deviations above the mean in healthy controls, compared with 2.7 among those without flare (P=0.04).
"The relationships between IFN activity, vaccination responses, and subsequent disease flares need to be confirmed in a larger cohort, and the biologic significance of these processes should be examined," wrote James and colleagues.
Further studies of biomarkers that might help predict vaccine responses and flares could help identify patients who could benefit from more intensive lupus treatment before they are given vaccines, they concluded.
The study was supported by the National Institutes of Health and by the Kirkland Foundation.