Rheumatoid arthritis onset in postmenopausal women: Does the ACPA seropositive subset result from genetic effects, estrogen deficiency, skewed profile of CD4+ T-cells, and their interactions?

Rony Sapir-Koren, Gregory Livshits*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

13 Scopus citations

Abstract

Rheumatoid arthritis (RA) incidence displays a differentiated age-dependent female-to-male ratio in which women outnumber men. Evidence that the peak incidence of RA in women coincides with menopause age, suggests a potential estrogenic role to disease etiology. Estrogens exert physiologically both stimulatory and inhibitory effects on the immune system. Epidemiologic and animal model studies with estrogen deprivation or supplementation suggested estrogens as to play, mainly, a protective role in RA immunopathology. In this review, we propose that some yet unidentified disturbances associated with estrogen circulating levels, differentiated by the menopausal status, play a major role in women's RA susceptibility. We focus on the interaction between estrogen deprivation and genetic risk alleles for anti-citrullinated protein antibodies (ACPA) seropositive RA, as a major driving force for increased immune reactivity and RA susceptibility, in postmenopausal women. This opens up new fields for research concerning the association among different irregular estrogenic conditions, the cytokine milieu, and age/menopausal status bias in RA.

Original languageEnglish
Pages (from-to)145-163
Number of pages19
JournalMolecular and Cellular Endocrinology
Volume431
DOIs
StatePublished - 15 Aug 2016

Funding

FundersFunder number
Israel Science Foundation1018/13

    Keywords

    • ACPA
    • Cytokines
    • Estrogens
    • Gene-environment interactions
    • HLA-DRB1 SE
    • Smoking

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