To the Editor: Solid organ transplant recipients (SOTRs) require lifelong, high-dose immunosuppressive therapy, resulting in an increased risk of immune-related comorbidities. While a prior study reported an increase in specific immune-mediated inflammatory diseases (IMIDs) among pediatric SOTRs, evidence characterizing these risks in the general SOTR population remains limited.1 Our study aimed to investigate the incidence of selected IMIDs in SOTRs utilizing the Korea Healthcare Bigdata Platform.
This nationwide cohort study was performed using integrated data from multiple Korean government agencies from January 1, 2012, to December 31, 2021. The SOTR cohort (n = 14,577) was propensity score-matched to a control cohort at a 1:1 ratio based on demographics and comorbidities (Table I, Supplementary Fig 1, available via Mendeley at https://data.mendeley.com/datasets/tp59mymyc7/1). Patients who underwent more than 1 transplantation were excluded. The main outcome was the risk of IMIDs in the SOTR cohort compared with control cohort. Multivariable Cox proportional hazards models were used to estimate adjusted hazard ratios for 15 predefined IMID outcomes. In sensitivity analyses, Poisson regression was used to estimate incidence rate ratios for each IMID between cohorts.2 More details provided in Supplementary Methods and Tables, available via Mendeley at https://data.mendeley.com/datasets/tp59mymyc7/1.
Table I.
Demographic characteristics of the solid organ transplant recipient cohort and the control cohort before and after propensity score-matching
| Characteristics | Prematching, patients, no. (%) |
Postmatching, patients, no. (%) |
||||
|---|---|---|---|---|---|---|
| SOTR (N = 18,065) |
Control (N = 796,276) |
SMD | SOTR (N = 14,577) |
Control (N = 14,577) |
SMD | |
| Age (y), mean (SD) | 58.30 (11.18) | 56.32 (16.40) | 0.141 | 60.68 (9.90) | 61.44 (11.03) | 0.054 |
| Sex, n (%) | 0.370 | 0.099 | ||||
| Male | 11,897 (65.86) | 382,361 (48.02) | 9455 (64.86) | 10,157 (69.68) | ||
| Female | 6168 (34.14) | 413,915 (51.98) | 5122 (35.14) | 4420 (30.32) | ||
| Insurance type, n (%) | 0.354 | 0.051 | ||||
| Standard | 15,505 (85.83) | 763,381 (95.87) | 12,906 (88.54) | 12,695 (87.09) | ||
| Medicaid | 2560 (14.17) | 32,895 (4.13) | 1671 (11.46) | 1882 (12.91) | ||
| Area of residence, n (%) | 0.009 | 0.005 | ||||
| Urban area | 7998 (44.27) | 348,674 (43.79) | 6389 (43.83) | 6424 (44.07) | ||
| Rural area | 10,067 (55.73) | 447,602 (56.21) | 8188 (56.17) | 8153 (55.93) | ||
| Underlying disease, n (%) | ||||||
| Congestive heart failure | 2711 (15.01) | 29,478 (3.70) | 0.396 | 1862 (12.77) | 2275 (15.61) | 0.099 |
| Liver disease | 5373 (29.74) | 9388 (1.18) | 0.861 | 4647 (31.88) | 5457 (37.44) | 0.167 |
| Chronic kidney disease | 11,746 (65.02) | 15,254 (1.92) | 1.799 | 8421 (57.77) | 7611 (52.21) | 0.158 |
SMD, Standardized mean difference; SOTR, solid organ transplant recipient.
The SOTR cohort comprised 7887 kidney, 5458 liver, 648 heart, and 584 other organ transplant recipients. No increased risk of most IMIDs was observed among SOTRs (Fig 1, Supplementary Fig 2, Table III, available via Mendeley at https://data.mendeley.com/datasets/tp59mymyc7/1). However, SOTRs exhibited a lower risk of alopecia areata (AA) than controls (AA; adjusted hazard ratio, 0.55; 99% CI, 0.32-0.97). In the sensitivity analysis using Poisson regression (Supplementary Fig 3, available via Mendeley at https://data.mendeley.com/datasets/tp59mymyc7/1), risks were lower for both AA (incidence rate ratio, 0.57; 95% CI, 0.43-0.77) and psoriasis vulgaris (psoriasis vulgaris; incidence rate ratio, 0.59; 95% CI, 0.42-0.82). Subgroup analyses stratified by demographics, organ type, donor type, and ABO incompatibility revealed no significant association with the risk of IMIDs (Supplementary Figs 4 to 7, available via Mendeley at https://data.mendeley.com/datasets/tp59mymyc7/1). Although statistical power for most IMIDs was <0.8, it exceeded 0.8 for AA in the Poisson regression model (Supplementary Figs 8 and 9, available via Mendeley at https://data.mendeley.com/datasets/tp59mymyc7/1).
Fig 1.
Risks of incident immune-mediated inflammatory diseases in the solid organ transplant recipient cohort compared with the control cohort. The confidence interval was set at 99.67% but is presented as 99% for simplicity.
Over a mean 4.2-year follow-up, most IMID risks in SOTRs were not increased compared to controls. Our results are consistent with the United States study reporting a decreased incidence of AA.3 Incorporating the sensitivity analyses, our findings suggest that SOTRs may have a reduced risk of AA and psoriasis vulgaris. Given that T cells play a critical role in both the pathogenesis of IMIDs and transplant immunology, high-dose immunosuppressive therapy in SOTRs may contribute to the observed lower risk of these IMIDs.4 However, because the risk of bullous pemphigoid did not decrease despite the frequent use of mycophenolate mofetil in SOTRs, these findings cannot be explained solely by pharmacological factors. Moreover, variations in healthcare utilization among SOTRs may influence the diagnosis of IMIDs. Taken together with the increasing life expectancy of SOTRs, future studies are warranted to focus on the development of IMIDs.5 Limitations include a homogeneous ethnicity, lack of information regarding immunosuppressive regimens, potential detection bias under claim-based study design, and a limited observation duration. Lastly, the limited number of events and subsequent lower statistical power preclude definitive conclusions. Nevertheless, our population-based study offers comprehensive clinical insights into the risk of IMIDs among SOTRs.
Conflicts of interest
None disclosed.
Footnotes
Drs Jeon, Kim, Heo and Author Son contributed equally as first authors.
Funding sources: This work was supported by the Yonsei Fellowship, funded by Lee Youn Jae (JIS). This research was also supported by a grant from the Korea Health Technology Research and Development Project through the Korea Health Industry Development Institute (KHIDI), the Ministry of Health & Welfare, Republic of Korea (grant number: HI23C1506; SL).
IRB approval status: This research was supported by data from the Korea Healthcare Bigdata of the Ministry of Health and Welfare. The research number of this study is 2023-00034. The requirement for informed consent was waived owing to the use of de-identified data.
Contributor Information
Jae Il Shin, Email: SHINJI@yuhs.ac.
Solam Lee, Email: solam@yonsei.ac.kr.
Eung Ho Choi, Email: choieh@yonsei.ac.kr.
References
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