Unit:
Faculty of MedicineLibrary of the School of Health Sciences
Author:
Argyriou Evangelia
Dissertation committee:
Κουτσιλιέρης Μιχαήλ, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Τζιούφας Αθανάσιος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Βουλγαρέλης Μιχαήλ, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Μαυραγάνη Κλειώ, Αναπληρώτρια Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Σιμοπούλου Μαρία, Αναπληρώτρια Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Αγγελογιάννη Παναγούλα, Αναπληρώτρια Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Κοτσιφάκη Ελένη, Αναπληρώτρια Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Original Title:
Η συμβολή του γονιδίου LILRA3 στην παθογένεια του συνδρόμου Sjogren
Translated title:
LILRA3 gene contribution in Sjogren's syndrome pathogenesis
Summary:
Primary Sjögren’s Syndrome (pSS) is a systematic autoimmune disease,
characterized by increased risk for B non-Hodgkin lymphoma (B-NHL) development.
While the deleted variation of the Leukocyte immunoglobulin-like receptor A3
(LILRA3) gene has been identified as a risk factor for both lymphomagenesis and
pSS development in Caucasian populations, the functional LILRA3 variant was
found to increase susceptibility for Rheumatoid Arthritis (RA), Systemic Lupus
Erythematosous (SLE) and pSS in Chinese population. Moreover functional LILRA3
gene has been linked to increased LILRA3 protein serum levels, as previously
reported.
LILRA3 is a soluble immunoreceptor which binds to MHC-I molecules, is secreted
by monocytes and B-cells and induces NK and CD8⁺ T cells production, triggering
inflammatory responses. The aim of our case-control study was to estimate the
prevalence of LILRA3 gene variants, quantitate LILRA3 protein serum levels and
explore potential clinical and serological associations in pSS population.
402 patients meeting the classification criteria for pSS (ACR/EULAR classification
criteria, 2016) and 381 healthy Controls (ΗC) of similar age and sex distribution all
of Greek origin were included. pSS patients were further stratified according to the
presence and the type of lymphoma in 301 SS-nL (SS-non Lymphoma group) and in
101 SS-L (Lymphoma) group. On the basis of the age of SS onset, SS patients were
further stratified into younger (≤40 years) [SS-nL ≤40 (n = 52), SS-L ≤40 (n = 23)]
and older (>40 years) age of disease onset [SS-nL >40 years (n = 249), SS-L >40
years (n = 78)]. LILRA3 gene polymorphisms were detected using polymerase chain
reaction (PCR). We identified three genetic variations: homozygous-non deleted or
functional or wild type type (+/+), heterozygous (+/-) and homozygous deleted (-/-).
LILRA3 protein serum levels were measured by Enzyme-Linked Immunosorbent
Assay (ELISA). All statistical analyses were performed using SPSS and Graphpad
Prism 5 and the level of statistical significance was defined to 5%.
There was no difference in the frequency of LILRA3 genetic variants between the
whole pSS population and HC. When pSS patients were stratified according to the
age of disease onset, only the SS-L group with disease onset ≤ 40 years displayed
105
statistically significant higher rates of the wild type variant of the LILRA3 gene
compared to HC (100% vs 82.9%, p=0.03). In line with this observation, LILRA3
protein serum levels were also found to be significantly elevated in SS-L group ≤40
years, compared to SS-nL and HC ≤40 years (1.77 ± 1.45 ng/mL vs 0.89 ± 0.61
ng/mL vs. 0.46 ± 0.43 ng/mL, p-values 0.049 and 0.001, respectively). Moreover,
LILRA3 serum levels were also significantly increased in SS-L group ≤40 years
compared to those with disease onset later in life (1.77 ± 1.45 ng/mL vs 0.66 ± 0.89
ng/mL p=0.007).
While no differences in LILRA3 gene variants were detected between pSS and HC
groups, increased rates of the functional wild type LILRA3 gene together with
heightened LILRA3 serum protein levels were found in SS-L patients with age of SS
onset ≤40 years. Given the previously reported role of the LILRA3 functional variant
in promoting inflammation and the aggressive clinical phenotypes observed in
younger SS individuals, the present findings further support a potential contributory
role of the LILRA3 variant in lymphoproliferaion related to young onset pSS, through
fueling of chronic inflammatory responses.
Main subject category:
Health Sciences
Keywords:
LILRA3, Sjogren's syndrome
Number of references:
318
