V. Rodrigues et al., SEGREGATION ANALYSIS INDICATES A MAJOR GENE IN THE CONTROL OF INTERLEUKINE-5 PRODUCTION IN HUMANS INFECTED WITH SCHISTOSOMA-MANSONI, American journal of human genetics, 59(2), 1996, pp. 453-461
The Interleukine-5 (IL-5) is a hormone of the immune system that is th
e main regulator of eosinopoiesis, eosinophil maturation and activatio
n, and Immunoglobulin A production. Thus, IL-5 contributes in several
ways to human immune defenses against various pathogens, including hel
minths and infectious agents of the digestive and respiratory tracts.
On the other hand, the increase in eosinophil number and the activatio
n of these cells, which both have been related to elevated IL-5 produc
tion, are the cause of severe pathological disorders, as in asthma or
hypereosinophilic syndromes. Although the immunological pathways leadi
ng to IL-5 synthesis have been identified, the reasons for the large v
ariability observed in IL-5 production among subjects exposed to compa
rable antigenic stimulation are unknown. To investigate the role of ge
netic factors in this variability, we conducted a segregation analysis
in a Brazilian population infected by the helminth parasite Schistoso
ma mansoni. The analysis was performed on IL-5 levels produced by bloo
d mononuclear cells of these subjects after in vitro restimulation wit
h either parasite extracts (IL-5/schistosomula sonicates [SS] phenotyp
e) or a T-lymphocyte mitogen (IL-5/phytohemagglutinin [PHA]). The resu
lts provide clear evidence for the segregation of a codominant major g
ene controlling IL-5/SS and IL-5/PHA production and accounting for 70%
and 73% of the phenotypic variance, respectively; the frequency of th
e allele predisposing to low IL-5 production was similar to.22 for bot
h phenotypes. No significant relationship was found between these gene
s and the gene controlling infection intensities by S. mansoni detecte
d in a previous study. Linkage studies are ongoing to locate those gen
es that would help to characterize the genetic factors involved in pat
hological conditions such as severe helminth infections and allergic d
iseases.