The extra X chromosome and autoimmune susceptibility in Klinefelter syndrome.
Elisa Gatta, Andrea Delbarba, Virginia Maltese et al.
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In 30 seconds
This systematic review and meta-analysis assessed autoimmune susceptibility in people with Klinefelter syndrome (47,XXY), using studies of autoimmune disease and serological markers. Eight studies were included in the qualitative synthesis and six studies (8 datasets) in the quantitative analysis, covering 2289 individuals with Klinefelter syndrome and 51 250 114 controls. Klinefelter syndrome was associated with higher odds of autoimmune outcomes than control status (OR 23.25, 95% CI 9.96-54.31). The association was stronger for clinically manifest disease than for isolated autoantibody positivity, although between-study heterogeneity was moderate to substantial.
Key findings
- Overall autoimmune susceptibility was higher in Klinefelter syndrome than in controls (OR 23.25, 95% CI 9.96-54.31; I2 = 66.4%).
- The association was stronger for clinically manifest autoimmune disease (OR 48.46, 95% CI 17.68-132.87) than for isolated autoantibody positivity (OR 9.99, 95% CI 1.18-84.77).
- Reported conditions included systemic lupus erythematosus, Sjögren syndrome, systemic sclerosis, autoimmune thyroid disease, and type 1 diabetes mellitus.
Why it matters
The findings link sex chromosome complement with autoimmune susceptibility and suggest that the association extends beyond serological markers to clinically overt disease. Awareness of this pattern may help clinicians consider autoimmune comorbidity when assessing people with Klinefelter syndrome, while recognising that the pooled estimates vary across studies.
What to keep in mind
The quantitative synthesis included six studies and showed moderate-to-substantial heterogeneity (I2 = 66.4%), limiting certainty about the consistency of the pooled association.