Risk Factors for Type 1 Diabetes Recurrence in Immunosuppressed Recipients of Simultaneous Pancreas-Kidney Transplants.

Patients with type 1 diabetes (T1D) who are recipients of pancreas transplants are believed to rarely develop T1D recurrence in the allograft if effectively immunosuppressed. We evaluated a cohort of 223 recipients of simultaneous pancreas-kidney allografts for T1D recurrence and its risk factors. With long-term follow-up, recurrence was observed in approximately 7% of patients. Comparing the therapeutic regimens employed in this cohort over time, lack of induction therapy was associated with recurrence, but this occurs even with the current regimen, which includes induction; there was no influence of maintenance regimens. Longitudinal testing for T1D-associated autoantibodies identified autoantibody positivity, number of autoantibodies, and autoantibody conversion after transplantation as critical risk factors. Autoantibodies to the zinc transporter 8 had the strongest and closest temporal association with recurrence, which was not explained by genetically encoded amino acid sequence donor-recipient mismatches for this autoantigen. Genetic risk factors included the presence of the T1D-predisposing HLA-DR3/DR4 genotype in the recipient and donor-recipient sharing of HLA-DR alleles, especially HLA-DR3. Thus, T1D recurrence is not uncommon and is developing in patients treated with current immunosuppression. The risk factors identified in this study can be assessed in the transplant clinic to identify recurrent T1D and may lead to therapeutic advances.

Comparative analysis of methods for collection and measurement of cytokines and immunoglobulins in cervical and vaginal secretions of HIV and HPV infected women.

The goal of these studies was to distinguish which of two techniques [cervicovaginal lavage (CVL) and cervical wick (SS)] is the optimal collection method for the measurement of the local immunological response in human papillomavirus (HPV) and HIV infected women. The following parameters were measured in 24 paired samples from 15 women (9 HIV+, 6 HIV-): total protein, immunoglobulin levels, HPV-specific antibodies, and Th1-Th2 cytokines. In addition, relative mRNA levels from CVL cell pellets were compared to protein levels from CVL supernatants. The total protein (2-fold) and IgG concentration (10-fold) are higher in the SS samples, were reproducible (%CV<3) and these levels correlated (P<0.0001) with their paired CVL sample. Type-specific HPV-L1 IgG and IgA antibodies were detected in CVL and SS (r>0.28, P<0.008) with excellent reproducibility (CV<3.0%). However, SS (%CV>18) failed to yield reproducible results for the cytokine assays as compared to the CVL (%CV<5.0). Furthermore, no correlations were found between relative mRNA levels from CVL cell pellet and cytokine protein levels in CVL supernatants. The CVL sample's superior reproducibility in the cytokine assays makes this the better collection method. In addition, cytokine protein level's failure to correlate with mRNA suggests tight regulation of cytokine genes or production from a different cell population.