EDITORIAL - Unraveling the etiology of systemic autoimmune diseases: peering into the preclinical phase of disease

[Guest guest]

Journal of Rheumatology

Editorial

Sep 2009

Unraveling the Etiology of Systemic Autoimmune Diseases: Peering into

the Preclinical Phase of Disease

Systemic lupus erythematosus (SLE), along with systemic sclerosis and

Sjögren’s disease, is marked by a striking female predominance, with

women representing at least 90% of patients1. Incidence rates for SLE

among African-American women peak in the reproductive years (i.e.,

ages 20–40)2,3, but in other populations, the highest age-specific

incidence rates occur after age 40 years4–6. What accounts for this

female predominance in these specific diseases? Scientific focus on X-

or Y- chromosome genes and on the role of estrogen and testosterone in

immune response in animals7 has evolved and expanded during the past

20 years to include DNA methylation and epigenetic alteration of gene

expression8. One potential sex-mediated mechanism involves CD40L

overexpression, which can occur only in women since CD40L is encoded

on the X chromosome9. This type of genetic and molecular research

offers promising avenues for understanding the etiology of systemic

autoimmune diseases and the development of new therapies. Additional

insights into disease risk and pathogenesis can also be gained from an

epidemiologic perspective, focusing on the experiences of individuals

and populations.

In this issue, Ulff-Møller, et al examine the influence of pregnancy

and pregnancy outcomes on the risk of SLE10. This cohort study

encompasses the entire population of Denmark (about 4.4 million), with

a 30-year followup period (1974–2004). The classification of SLE for

the purpose of this study was based on a national database of

hospitalization records, with the first record of SLE in the database

taken as the age at SLE diagnosis. Reproductive history, defined as a

pregnancy resulting in a live birth, was obtained from the national

hospital registry. Other types of birth outcomes were also obtained

from the hospitalization and other national databases.

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Read the rest of the editorial here:

http://www.jrheum.org/content/36/9/1853.full

Not an MD