Pro-Inflammatory and Dysfunctional Immunologic Changes and Risk for Infection in the Older Kidney Transplant Recipient. (4th October 2017)

• Record Type: Journal Article
• Authors: Liang, Emily; Beaird, Omer; Rossetti, Maura; Sidwell, Tiffany; Groysberg, Victoria; Karlamangla, Arun; Cole, Steve; Reed, Elaine; Schaenman, Joanna
• Is Part Of: Open forum infectious diseases. Volume 4(2017)Supplement 1
• Page Start: S226
• Page End: S226
• Publication Date: 2017-10-04
• Subjects: Communicable diseases -- Periodicals; Medical microbiology -- Periodicals; Infection -- Periodicals; 616.9
• DOI: 10.1093/ofid/ofx163.469
• Languages: English
• ISSNs: 2328-8957

Abstract

Abstract: Background: Compared with younger patients on similar immunosuppression regimens, older solid organ transplant recipients experience increased rates of infection and death, but decreased rates of rejection; however, rejection episodes are often difficult to reverse. The mechanism behind this vulnerability has yet to be defined. Methods: Peripheral blood mononuclear cells were isolated from 23 older ( 3 age 60) and 37 matched younger (ages 30–59) kidney transplant recipients 3 months after transplantation. Immunophenotyping was performed by multiparameter flow cytometry. RNA extraction was performed on banked PBMCs. Isolated RNA was converted to fluorescent cRNA and hybridized to Illumina Human HT-12 v4 BeadArrays. Gene expression values were quantile-normalized and log2-transformed for mixed effect linear model analyses to identify differential expression as a function of age, adjusted for induction type, donor type, and sex. Statistical analysis was performed using Jmp Pro 11 or R software. Results: Older kidney transplant recipients had a statistically significant increase in frequency of classical, pro-inflammatory monocytes (29.5% vs. 14.7%, P = 0.019) and a decrease in frequency of non-classical anti-inflammatory monocytes (69.1% vs. 81.3%, P = 0.019). The frequency of senescent CD8+CD57+CD28- T cells was increased in older patients ( P = 0.036), as well as in those with episodes of infection or CMV reactivation ( P = 0.035). Genes differentially expressed in older patients revealed an over-representation of inflammatory genes and an underrepresentation of genes associated with the antiviral immune response. Tables : Top 10 genes upregulated or downregulated in older compared with younger patients. Conclusion: Older kidney transplant recipients displayed increased frequency of senescent T cells, which was associated with increased rates of infection. In addition, we observed pro-inflammatory changes marked by increase in pro-inflammatory monocyte subtypes. Increased levels of inflammation were also reflected by changes in gene expression. These findings may explain the increase in adverse clinical outcomes in older patients, and suggest future avenues for patient risk stratification and individualization of immune suppression after solid organ transplantation. Disclosures: All authors: No reported disclosures.