Poor predictability of QuantiFERON-TB assay in recipients and donors for tuberculosis development after kidney transplantation in an intermediate-TB-burden country.

BACKGROUND: Tuberculosis (TB) is a common opportunistic infection after kidney transplantation (KT). The QuantiFERON-TB-Gold In-Tube test (QFT) is widely used for assessing latent TB; however, it is currently unclear whether the pre-KT QFT of the recipient and donor can predict post-KT TB. METHODS: We retrospectively reviewed patients who received KT between January 2009 and December 2015 at Seoul National University Hospital. The QFT was performed in 458 KT recipients and 239 paired living donors, and 138 KT recipients underwent both the QFT and tuberculin skin test (TST). After excluding 12 patients diagnosed as having clinically latent TB, we evaluated whether the QFT of the recipient and donor was predictive for new-onset active TB after KT. RESULTS: The QFT was positive in 101 (22.1%) recipients and associated with clinically latent TB before KT (P < 0.05). However, agreement between the TST and QFT was poor (κ = 0.327). Post-KT TB occurred in 1 of 95 recipients with a positive QFT, and 2 cases of TB occurred among 351 patients with a negative or indeterminate QFT. The incidence of TB was 242 cases/100,000 person-years among 446 KT recipients with a median follow-up of 30.2 months. The QFT of recipients could not predict post-KT TB in Poisson regression analysis (relative risk [RR], 1.847; 95% confidence interval [CI], 0.168-20.373; P = 0.616). Of 234 living donor-recipient pairs, the QFT of the recipient (RR, 5.012; 95% CI, 0.301-83.430; P = 0.261) and QFT of the donor (RR, 1.758; 95% CI, 0.106-29.274; P = 0.694) could not predict post-KT TB. CONCLUSION: The QFT of recipients or living donors pre-KT cannot predict the short-term development of post-KT TB in an intermediate TB-burden country.

Granulocyte colony-stimulating factor treatment ameliorates lupus nephritis through the expansion of regulatory T cells.

BACKGROUND: Granulocyte colony-stimulating factor (G-CSF) can induce regulatory T cells (Tregs) as well as myeloid-derived suppressor cells (MDSCs). Despite the immune modulatory effects of G-CSF, results of G-CSF treatment in systemic lupus erythematosus are still controversial. We therefore investigated whether G-CSF can ameliorate lupus nephritis and studied the underlying mechanisms. METHODS: NZB/W F1 female mice were treated with G-CSF or phosphate-buffered saline for 5 consecutive days every week from 24 weeks of age, and were analyzed at 36 weeks of age. RESULTS: G-CSF treatment decreased proteinuria and serum anti-dsDNA, increased serum complement component 3 (C3), and attenuated renal tissue injury including deposition of IgG and C3. G-CSF treatment also decreased serum levels of BUN and creatinine, and ultimately decreased mortality of NZB/W F1 mice. G-CSF treatment induced expansion of CD4+CD25+Foxp3+ Tregs, with decreased renal infiltration of T cells, B cells, inflammatory granulocytes and monocytes in both kidneys and spleen. G-CSF treatment also decreased expression levels of MCP-1, IL-6, IL-2, and IL-10 in renal tissues as well as serum levels of MCP-1, IL-6, TNF-α, IL-10, and IL-17. When Tregs were depleted by PC61 treatment, G-CSF-mediated protective effects on lupus nephritis were abrogated. CONCLUSIONS: G-CSF treatment ameliorated lupus nephritis through the preferential expansion of CD4+CD25+Foxp3+ Tregs. Therefore, G-CSF has a therapeutic potential for lupus nephritis.

Desensitization Using Bortezomib and High-dose Immunoglobulin Increases Rate of Deceased Donor Kidney Transplantation.

Combination therapy of intravenous immunoglobulin (IVIG) and rituximab showed a good transplant rate in highly sensitized wait-listed patients for deceased donor kidney transplantation (DDKT), but carried the risk of antibody-mediated rejection. The authors investigated the impact of a new combination therapy of bortezomib, IVIG, and rituximab on transplantation rate.This study was a prospective, open-labeled clinical trial. The desensitization regimen consisted of 2 doses of IVIG (2  g/kg), a single dose of rituximab (375  mg/m), and 4 doses of bortezomib (1.3  mg/m). The transplant rate was analyzed. Anti-Human leukocyte antigen (HLA) DRB antibodies were determined by a Luminex solid-phase bead assay at baseline and after 2, 3, and 6 months in the desensitized patients.There were 19 highly sensitized patients who received desensitization and 17 patients in the control group. Baseline values of class I and II panel reactive antibody (%, peak mean fluorescence intensity) were 83  ±â€Š 16.0 (14952  ±  5820) and 63  ±  36.0 (10321  ±  7421), respectively. Deceased donor kidney transplantation was successfully performed in 8 patients (42.1%) in the desensitization group versus 4 (23.5%) in the control group. Multivariate time-varying covariate Cox regression analysis showed that desensitization increased the probability of DDKT (hazard ratio, 46.895; 95% confidence interval, 3.468-634.132; P = 0.004). Desensitization decreased mean fluorescence intensity values of class I panel reactive antibody by 15.5% (20.8%) at 2 months. In addition, a liberal mismatch strategy in post hoc analysis increased the benefit of desensitization in donor-specific antibody reduction. Desensitization was well tolerated, and acute rejection occurred only in the control group.In conclusion, a desensitization protocol using bortezomib, high-dose IVIG, and rituximab increased the DDKT rate in highly sensitized, wait-listed patients.