Measles infection linked to impaired ‘immune memory’
Infection with the measles virus appears to reduce immunity to other pathogens, according to a paper published in Science.
CDC/Molly Kurnit, M.P.H.
The hypothesis that the measles virus could cause “immunological amnesia” by impairing immune memory is supported by early research showing children with measles had negative cutaneous tuberculin reactions after having previously tested positive.
“Subsequent studies have shown decreased interferon signaling, skewed cytokine responses, lymphopenia, and suppression of lymphocyte proliferation shortly after infection,” wrote Michael Mina, MD, from Brigham and Women’s Hospital in Boston, and coauthors.
“Given the variation in the degree of immune repertoire modulation we observed, we anticipate that future risk of morbidity and mortality after measles would not be homogeneous but would be skewed toward individuals with the most severe elimination of immunological memory,” they wrote. “These findings underscore the crucial need for continued widespread vaccination.”
In this study, researchers compared the levels of around 400 pathogen-specific antibodies in blood samples from 77 unvaccinated children, taken before and 2 months after natural measles infection, with 5 unvaccinated children who did not contract measles. A total of 34 the children experienced mild measles, and 43 had severe measles.
They found that the samples taken after measles infection showed “substantial” reductions in the number of pathogen epitopes, compared with the samples from children who did not get infected with measles.
This amounted to approximately a 20% mean reduction in overall diversity or size of the antibody repertoire. However, in children who experienced severe measles, there was a median loss of 40% (range, 11%-62%) of antibody repertoire, compared with a median of 33% (range, 12%-73%) range in children who experienced mild infection. Meanwhile, the control subjects retained approximately 90% of their antibody repertoire over a similar or longer time period. Some children lost up to 70% of antibodies for specific pathogens.
The study did find increases in measles virus–specific antigens in children both after measles infection and MMR vaccination. However the authors did not detect any changes in total IgG, IgA, or IgM levels.
Dr. Mina and associates wrote.
They also noted that controls who received the MMR vaccine showed a marked increase in overall antibody repertoire.
In a separate investigation reported in Science Immunology, Velislava N. Petrova, PhD, of the Wellcome Sanger Institute in Cambridge, England, and coauthors investigated genetic changes in 26 unvaccinated children from the Netherlands who previously had measles to determine if B-cell impairment can lead to measles-associated immunosuppression. Their antibody genes were sequenced before any symptoms of measles developed and roughly 40 days after rash. Two control groups also were sequenced accordingly: vaccinated adults and three unvaccinated children from the same community who were not infected with measles.
Naive B cells from individuals in the vaccinated and uninfected control groups showed high correlation of immunoglobulin heavy chain (IgVH-J) gene frequencies across time periods (R2 = 0.96 and 0.92, respectively) but no significant differences in gene expression (P greater than .05). At the same time, although B-cell frequencies in measles patients recovered to levels before infection, they had significant changes in IgVH-J gene frequencies (P = .01) and decreased correlation in gene expression (R2 = 0.78).
In addition, individuals in the control groups had “a stable genetic composition of B memory cells” but no significant changes in the third complementarity-determining region (CDR3) lengths or mutational frequency of IgVH-J genes (P greater than .05). B memory cells in measles patients, however, showed increases in mutational frequency (P = .0008) and a reduction in CDR3 length (P = .017) of IgVH genes, Dr. Petrova and associates reported.
The study by Mina et al. was supported by grants from various U.S., European, and Finnish foundations and national organizations. Some of the coauthors had relationships with biotechnology and pharmaceutical companies, and three reported a patent holding related to technology used in the study. The study by Petrova et al. was funded by grants to the investigators from various Indonesian and German organizations and the Wellcome Trust. The authors reported no conflicts of interest.
SOURCES: Mina M et al. Science. 2019 Nov 1;366:599-606Petrova VN et al. Sci Immunol. 2019 Nov 1. doi: 10.1126/sciimmunol.aay6125.
