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Sex-dependent mechanisms in rheumatic diseases
Elizabeth R Volkmann1, Erica L Herzog2, Carol Feghali-Bostwick3
1UCLA, Los Angeles, CA, USA.
Nature Reviews. Rheumatology
|August 4, 2026
Summary
Sex differences in rheumatic diseases are influenced by immune cells, hormones, and the gut microbiome. Understanding these factors can lead to new preventative therapies for better patient health.
Area of Science:
- Rheumatology
- Immunology
- Endocrinology
- Genetics
Background:
- Sex disparities in rheumatic disease prevalence, clinical presentation, and treatment response are well-documented but poorly understood.
- Both immune and non-immune cells play crucial roles in disease development, with sex hormones significantly impacting cellular functions.
- Multiple factors including sex chromosomes, hormonal regulation, immune responses, gut microbiota, and genetic/epigenetic variations contribute to sex-specific differences in rheumatic diseases.
Purpose of the Study:
- To explore the underlying biological mechanisms driving sex differences in rheumatic diseases.
- To identify potential novel therapeutic targets by understanding the interplay of various biological factors.
- To pave the way for developing sex-specific preventative strategies beyond current immunomodulatory treatments.
Main Methods:
- Review and synthesis of accumulating evidence on sex differences in rheumatic diseases.
- Analysis of the influence of sex hormones on immune and non-immune cell functions.
- Investigation of the roles of sex chromosomes, gut microbiome, and genetic/epigenetic variations.
Main Results:
- Sex differences in rheumatic diseases are multifactorial, involving complex interactions between genetic, hormonal, immunological, and microbial factors.
- Current treatments primarily focus on immunomodulation, potentially overlooking sex-specific pathways.
- Elucidating these biological differences offers opportunities for targeted interventions.
Conclusions:
- A comprehensive understanding of the biological basis of sex differences in rheumatic diseases is crucial for advancing patient care.
- Targeting hormonal pathways and the gut microbiome presents a promising avenue for developing preventative therapies.
- Personalized and sex-specific approaches could significantly improve the prevention and management of rheumatic diseases.
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