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Immunology 2018
J u l y 0 5 - 0 7 , 2 0 1 8
V i e n n a , A u s t r i a
Page 59
Journal of Clinical Immunology and Allergy
ISSN 2471-304X
1 5
t h
I n t e r n a t i o n a l C o n f e r e n c e o n
Immunology
S
ex-related disparities in the immune response manifesting female
disadvantage in autoimmune diseases whereas improved outcomes over
males following injuries and infections are well known. Whereas the role of sex
hormones in modulating the immune response is well accepted, the potential
contribution of X chromosome (ChrX)-related sex differences in the context of
common genetic polymorphisms has not been well investigated. The fact that
females carry two parental ChrXs whereas males carry only one suggests sex
differences in the load of common polymorphic alleles. Furthermore, random
ChrX inactivation, which is unique to females, results in cellular mosaicism
for the expression of X-linked polymorphic alleles, possibly causing additional
sex-related differences in cellular variability. Thus, we tested whether ChrX
mosaicism manifests skewed white blood cell responses following injuries
in humans. Serial blood samples were analysed for ChrX inactivation-ratios
(XCI-R) testing methylation at the polymorphic HUMARA locus in neutrophils
and lymphocytes from female trauma patients (n=99). About a third of the
patients presented trauma-induced change in XCI-R of 30% or greater over
initial during the hospital course. XCI-R changes correlated with the severity
of trauma, ventilator support and pneumonia. XCI-R kinetics of neutrophils
and lymphocytes indicated that more marked changes occurred during the
earlier phases of injury or at the onset of post-injury complications like sepsis
or pneumonia. During the recovery phase, XCI-R tended to return to initial
values similar to that found at admission. The findings indicate that during the
innate immune response, female patients may manifest acute and reversible
immune cell selection through subtle phenotypic differences driven by
respective polymorphic parental ChrXs. X-linked cellular mosaicism in females
with variable responsiveness to dynamically changing pathophysiological
conditions, together with an apparent lack of this mechanism in males, implies
differences in immuno-modulatory mechanisms, which may contribute to sex-
based outcome differences in the critically ill.
Biography
Zoltan Spolarics has received his MD from the Semmelweis
Medical University in 1980 and PhD degree from the Hungarian
Academy of Sciences in 1989. He had postdoctoral trainings
at Semmelweis Biochemistry Institute and later in the USA at
the Medical College of Virginia, Richmond VA then Louisiana
State University Medical Center, New Orleans LA. Since 1993,
he is a principal investigator at Rutgers-New Jersey Medical
School, Newark NJ, USAwhere he leads NIH-sponsored studies
investigating various aspects of the innate immune response.
He published over 80 peer-reviewed papers in reputed journals,
has been serving on NIH scientific review panels and journal
editorial boards, Shock and Critical Care Medicine.
spolaric@njms.rutgers.eduTrauma-induced X-linked white blood cell selection
contributes to a sex-biased innate immune response in humans
Zoltan Spolarics, Yong Qin, Pena Geber
Department of Surgery, Rutgers-New Jersey Medical School, Newark, NJ, USA
Zoltan Spolarics et al., Insights Allergy Asthma Bronchitis 2018, Volume: 4
DOI: 10.21767/2471-304X-C1-002