Kidney transplantation is the preferred therapeutic option for end-stage renal disease; however, the alloimmune response is still the leading cause of renal allograft failure. To better identify immunologic disparities in order to evaluate HLA compatibility between the donor and the recipient, the concept of eplet load has arisen. Regular kidney function monitoring is essential for the accurate and timely diagnosis of allograft rejection and the appropriate treatment. Donor-derived cell-free DNA (dd-cfDNA) has been proposed as a potential biomarker of acute rejection and graft failure in kidney transplantation. The proportion of plasma dd-cfDNA was determined in forty-two kidney patients at 1 month after transplantation. A total of eleven (26.2%) patients had a dd-cfDNA proportion of ≥1.0%. The only pretransplant variable related to dd-cfDNA > 1.0% was the HLA class II eplet mismatch load, mainly the HLA-DQB1 eplet mismatch load. Furthermore, dd-cfDNA was able to discriminate the patients with antibody-mediated rejection (AbMR) (AUC 87.3%), acute rejection (AUC 78.2%), and troubled graft (AUC 81.4%). Increased dd-cfDNA levels were associated with kidney allograft deterioration, particularly rejection, as well as a greater HLA class II eplet mismatch load. Consequently, combining dd-cfDNA determination and HLA eplet mismatch load calculation should improve the assessment of the risk of short- and long-term allograft damage.

Background: Determining the infiltration of carcinomas is essential for the proper follow-up and treatment of cancer patients. However, it continues to be a diagnostic challenge for pathologists in multiple types of tumors. In previous studies (carried out in surgical specimens), the protein COL11A1 has been postulated as an infiltration marker mainly expressed in the extracellular matrix (ECM). We hypothesized that a differential expression of COL11A1 may exist in the peritumoral stroma of tumors that have acquired infiltrating properties and that it may be detected in the small biopsies usually available in normal clinical practice. Material and methods: In our study, we performed immunohistochemical staining in more than 350 invasive and noninvasive small samples obtained via core needle biopsy (CNB), colonoscopy, or transurethral resection of bladder tumor (TURBT) of breast, colorectal, bladder, and ovarian cancer. Results: Our results revealed that COL11A1 immunostaining had a sensitivity to classify the samples into infiltrative vs. noninfiltrative tumors of 94% (breast), 97% (colorectal), >90% (bladder), and 74% (ovarian); and a specificity of 97% (breast), 100% (colorectal), and >90% (bladder). In ovarian cancer, the negative predictive value (0.59) did not present improvement over the usual histopathological markers. In all samples tested, the cumulative sensitivity was 86% and the specificity 96% (p < 0.0001). Conclusions: COL11A1-positive immunostaining in small biopsies of breast, colon, bladder and ovarian cancer is an accurate predictive marker of tumor infiltration that can be easily implemented in daily clinical practice.

Background/Objectives: Some lung transplant (LungTx) recipients do not achieve the expected lung function within the first year, a condition known as baseline lung allograft dysfunction (BLAD). Our objective was to analyze the risk factors associated with BLAD, focusing on the variables associated with a higher risk of developing a more intense alloimmune response. Methods: We carried out a prospective study including 88 LungTx recipients. BLAD was defined as failure to reach 80% of the predicted value for forced expiratory volume in one second (FEV1) and/or forced vital capacity (FVC) on two tests conducted at least three weeks apart. Tacrolimus time in therapeutic range (TTR) and mycophenolic acid area under the curve (MPA AUC_0–12h) were measured at the third month. Donor–recipient compatibility was assessed using HLA eplet mismatch analysis, performed via HLA Matchmaker 3.1. Results: BLAD patients showed greater eplet mismatch burden (67, IQR 20 vs. 55, IQR 22, p = 0.018) and had been exposed to a lower TTR (26.6%, IQR 14.0% vs. 39.6%, IQR 24.3%, p = 0.039) and less frequently to an adequate third-month MPA AUC_0–12 > 30 mg × h/L (57.1% vs. 89.2%, p = 0.020). DR/DQ eplet mismatches (β = −0.348, p = 0.002) and third-month MPA AUC_0–12 (β = 0.285, p = 0.009) were independently associated with six-month predicted FEV1%. Conclusions: Among other variables, BLAD and initial lung graft function are associated with greater eplet discordance and lower immunosuppressive drug exposure, suggesting a potential role of underlying alloimmune responses in their pathogenesis.