Albert Einstein Medical Center Philadelphia, PA, United States
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Anna-Kay Palmer1 and Irene Tan2, 1Albert Einstein Medical Center, Philadelphia, PA, 2Einstein Medical Center Philadelphia, Bala Cynwyd, PA
Background/Purpose: Immune-related genes located on the X chromosome are known to be important in the regulation of sex hormones and immune tolerance. It has been postulated that a dose relationship exists between the X chromosome and certain female predominant autoimmune diseases most notable for an increase of SLE in patients with triple X syndrome compared to females with XX karyotype. We investigate the proportion of individuals with Klinefelter syndrome (KS) karyotype 47, XXY and triple X syndrome karyotype 47, XXX who developed Sjogren's syndrome (SjS) compared with the general population.
Methods: This is a retrospective, multicenter, observational study using the TrinetX global research database. Using ICD-10 codes, we identified patients with the karyotype 47, XXY (KS) and 47, XXX (Triple X syndrome) from 6/1/2000 to 6/1/2023 who developed Sjogren's syndrome at any time. This was compared with the prevalence of SjS in the general population within the same time frame.
Results: A total of 120,908,054 patients were queried on 6/1/2023 on the Global Collaborative Network. A total of 221,821 patients with Sjogren's syndrome (188,581 or 85% females; 33,279 or 15% males) were found in general population.A total of 1,637 patients have KS identified by 47, XXY karyotype and 2,467 patients have triple X syndrome identified by karyotype 47,XXX. A total of 10 patients with KS were found to have SjS and 13 patients with triple X syndrome have SjS. Prevalence of SjS in general population is 0.18% (0.16% in females; 0.027% in males). There is a 22.6-fold increase in SjS in KS when compared with male patients in the general populations; and a 3-fold increase in SjS in patients with Triple X syndrome compared to females in the general population.
Conclusion: In this real-world, real-time study, extra X chromosome in Klinefelter syndrome and triple X syndrome have a non-proportional, synergistic dose effect on the risk of developing Sjogren's syndrome when compared with males and females in the general population, respectively.
Table 1. Proportion of Sjogren’s syndrome patients in general population, Klinefelter syndrome karyotype 47, XXY and in triple X syndrome karyotype 47, XXX.
