Gender balance in patients with systemic lupus erythematosus

Factors are reviewed that contribute to the contemporary view of a disproportionate prevalence and incidence of SLE in females. Recent studies on the epidemiology of SLE report that global incidences and prevalences of SLE for Caucasian and Black populations are of the order of 5.5 and 13.1 per year...

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Main Authors: Margery-Muir, A., Bundell, C., Nelson, D., Groth, David, Wetherall, J.
Format: Journal Article
Published: 2016
Online Access:http://hdl.handle.net/20.500.11937/50719
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author Margery-Muir, A.
Bundell, C.
Nelson, D.
Groth, David
Wetherall, J.
author_facet Margery-Muir, A.
Bundell, C.
Nelson, D.
Groth, David
Wetherall, J.
author_sort Margery-Muir, A.
building Curtin Institutional Repository
collection Online Access
description Factors are reviewed that contribute to the contemporary view of a disproportionate prevalence and incidence of SLE in females. Recent studies on the epidemiology of SLE report that global incidences and prevalences of SLE for Caucasian and Black populations are of the order of 5.5 and 13.1 per year and 81 and 212 per 100,000 persons respectively. Both parameters displayed age dependent variation over a 90-year lifespan. The female to male (F:M) incidence of SLE varied with age, being approximately 1 during the first decade of life, followed by a sharp increase to 9 during the 4th decade, thence declining in subsequent decades before an increase during the 7th or 8th decade. A cognate review of SLE diagnosis in neonates revealed a F:M ratio of ˜. 1.2, consistent with the epidemiology review and the sporadic nature of SLE. Notional estimates of disease duration showed a steady increase from a base level for both males and females. The linear trend line for males was always lower than the trend line for females, supporting clinical experience that SLE is a more severe disease in males. Over a 14-year interval ending in 2012, the notional duration of SLE increased from 10-15. years to 20-25. years, probably reflecting advances in diagnosis and clinical practice.A metastudy of SLE concordance in twins revealed a 75% discordance in monozygotic twins compared to a 95% discordance in dizygotic twins confirming the importance of environmental factors in susceptibility to SLE. The elevated discordance in dizygotic SLE twins (and between siblings) suggests a role for the intrinsic genomic sexual dimorphism due to divergence of Y chromosome regulatory loci from their X chromosome homologues due to lack of recombination of mammalian sex chromosomes over evolutionary time.Estimates were made of the incidences of SLE in males and females based on population data for nine autosomal deficiency loci of major effect, plus expected male prevalence associated with Klinefelter's syndrome and female prevalence associated with Triple X syndrome. These genetic abnormalities accounted for ˜. 4% of female and ˜. 23% of male Caucasoid prevalence and for SLE resulting in a F:M ratio of ˜. 0.17. It may be deduced therefore that the impressive preponderance of SLE in females arises from a combination of environmental triggers and susceptibility loci of relatively small effect acting between the interval from the mini-puberty of childhood to the peak of reproductive adulthood. It is in this cohort of females, and especially in the Black population, that combinations of loci of minor effect acting together with environmental factors initiate defective apoptosis resulting in consequential autoimmune disease especially SLE. We postulate that because apoptosis is itself a very complex process, and defective apoptosis is an important contributor to SLE, there will be many combinations of susceptibility loci and environmental stimuli that can result in SLE (and other autoimmune disease(s)), of varying severity.
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spelling curtin-20.500.11937-507192017-09-13T15:41:03Z Gender balance in patients with systemic lupus erythematosus Margery-Muir, A. Bundell, C. Nelson, D. Groth, David Wetherall, J. Factors are reviewed that contribute to the contemporary view of a disproportionate prevalence and incidence of SLE in females. Recent studies on the epidemiology of SLE report that global incidences and prevalences of SLE for Caucasian and Black populations are of the order of 5.5 and 13.1 per year and 81 and 212 per 100,000 persons respectively. Both parameters displayed age dependent variation over a 90-year lifespan. The female to male (F:M) incidence of SLE varied with age, being approximately 1 during the first decade of life, followed by a sharp increase to 9 during the 4th decade, thence declining in subsequent decades before an increase during the 7th or 8th decade. A cognate review of SLE diagnosis in neonates revealed a F:M ratio of ˜. 1.2, consistent with the epidemiology review and the sporadic nature of SLE. Notional estimates of disease duration showed a steady increase from a base level for both males and females. The linear trend line for males was always lower than the trend line for females, supporting clinical experience that SLE is a more severe disease in males. Over a 14-year interval ending in 2012, the notional duration of SLE increased from 10-15. years to 20-25. years, probably reflecting advances in diagnosis and clinical practice.A metastudy of SLE concordance in twins revealed a 75% discordance in monozygotic twins compared to a 95% discordance in dizygotic twins confirming the importance of environmental factors in susceptibility to SLE. The elevated discordance in dizygotic SLE twins (and between siblings) suggests a role for the intrinsic genomic sexual dimorphism due to divergence of Y chromosome regulatory loci from their X chromosome homologues due to lack of recombination of mammalian sex chromosomes over evolutionary time.Estimates were made of the incidences of SLE in males and females based on population data for nine autosomal deficiency loci of major effect, plus expected male prevalence associated with Klinefelter's syndrome and female prevalence associated with Triple X syndrome. These genetic abnormalities accounted for ˜. 4% of female and ˜. 23% of male Caucasoid prevalence and for SLE resulting in a F:M ratio of ˜. 0.17. It may be deduced therefore that the impressive preponderance of SLE in females arises from a combination of environmental triggers and susceptibility loci of relatively small effect acting between the interval from the mini-puberty of childhood to the peak of reproductive adulthood. It is in this cohort of females, and especially in the Black population, that combinations of loci of minor effect acting together with environmental factors initiate defective apoptosis resulting in consequential autoimmune disease especially SLE. We postulate that because apoptosis is itself a very complex process, and defective apoptosis is an important contributor to SLE, there will be many combinations of susceptibility loci and environmental stimuli that can result in SLE (and other autoimmune disease(s)), of varying severity. 2016 Journal Article http://hdl.handle.net/20.500.11937/50719 10.1016/j.autrev.2017.01.007 restricted
spellingShingle Margery-Muir, A.
Bundell, C.
Nelson, D.
Groth, David
Wetherall, J.
Gender balance in patients with systemic lupus erythematosus
title Gender balance in patients with systemic lupus erythematosus
title_full Gender balance in patients with systemic lupus erythematosus
title_fullStr Gender balance in patients with systemic lupus erythematosus
title_full_unstemmed Gender balance in patients with systemic lupus erythematosus
title_short Gender balance in patients with systemic lupus erythematosus
title_sort gender balance in patients with systemic lupus erythematosus
url http://hdl.handle.net/20.500.11937/50719