Increased Levels of sCD30 Have No Impact on the Incidence of Early ABMR and Long-Term Outcome in Intermediate-Risk Renal Transplant Patients With Preformed DSA

Background: It is still incompletely understood why some patients with preformed donor-specific anti-HLA antibodies (DSA) have reduced kidney allograft survival secondary to antibody-mediated rejection (ABMR), whereas many DSA-positive patients have favorable long-term outcomes. Elevated levels of soluble CD30 (sCD30) have emerged as a promising biomarker indicating deleterious T-cell help in conjunction with DSA in immunologically high-risk patients. We hypothesized that this would also be true in intermediate-risk patients.Methods: We retrospectively analyzed pre-transplant sera from 287 CDC-crossmatch negative patients treated with basiliximab induction and tacrolimus-based maintenance therapy for the presence of DSA and sCD30. The incidence of ABMR according to the Banff 2019 classification and death-censored allograft survival were determined.Results: During a median follow-up of 7.4 years, allograft survival was significantly lower in DSA-positive as compared to DSA-negative patients (p < 0.001). In DSA-positive patients, most pronounced in those with strong DSA (MFI > 5,000), increased levels of sCD30 were associated with accelerated graft loss compared to patients with low sCD30 (3-year allograft survival 75 vs. 95%). Long-term survival, however, was comparable in DSA-positive patients irrespective of sCD30 status. Likewise, the incidence of early ABMR and lesion score characteristics were comparable between sCD30-positive and sCD30-negative patients with DSA. Finally, increased sCD30 levels were not predictive for early persistence of DSA.Conclusion: Preformed DSA are associated with an increased risk for ABMR and long-term graft loss independent of sCD30 levels in intermediate-risk kidney transplant patients.

New Biomarkers of Hymenoptera Venom Allergy in a Group of Inflammation Factors

Hymenoptera venom allergy significantly affects the quality of life. Due to the divergences in the results of the available test and clinical symptoms of patients, the current widely applied diagnostic methods are often insufficient to classify patients for venom immunotherapy (VIT). Therefore it is still needed to search for new, more precise, and accurate diagnostic methods. Hence, this research aimed to discover new biomarkers of Hymenoptera venom allergy in a group of inflammation factors using set of multi-marker Bioplex panel. The adoption of a novel methodology based on Luminex/xMAP enabled simultaneous determination of serum levels of 37 different inflammatory proteins in one experiment. The study involved 21 patients allergic to wasp and/or honey bee venom and 42 healthy participants. According to univariate and multivariate statistics, soluble CD30/tumor necrosis factor receptor superfamily, member 8 (sCD30/TNFRSF8), and the soluble tumor necrosis factor receptor 1 (sTNF-R1) may be considered as effective prognostic factors, their circulating levels were significantly decreased in the allergy group (p-value < 0.05; the Area Under the Curve (AUC) ~0.7; Variable Importance in Projection (VIP) scores >1.2). The obtained results shed new light on the allergic inflammatory response and may contribute to modification and improvement of the diagnostic and monitoring methods. Further, large-scale studies are still needed to explain mechanisms of action of studied compounds and to definitively prove their usefulness in clinical practice.

Soluble CD30 Levels in the Sera of Patients With Psoriasis in Myanmar

Background: Although psoriasis is a Th1-dominant disease, certain investigations have also revealed the involvement of Th2 cells in the disease. Soluble CD30 (sCD30) is predominantly associated with various Th2 diseases. Therefore, the role of sCD30 in psoriasis requires further evaluation. Objectives: To evaluate the association between sCD30 and psoriasis. Methods: In this cross-sectional analytical study, the association between serum sCD30 levels and psoriasis was evaluated using enzyme-linked immunosorbent assay in sera obtained from patients with psoriasis. Results: The results indicated elevated sCD30 levels in 79 patients with psoriasis, and the levels were significantly higher in those with a prolonged duration of disease (duration > 10 years). Furthermore, there was a significant positive correlation between the duration of disease (years) and sCD30 (pg/mL) levels. These findings suggest that sCD30 is a useful marker for chronicity of psoriasis. Conclusion: Elevated sCD30 levels in psoriasis are associated with disease duration, and they may reflect the chronicity of psoriasis. Further research is required to determine the role of sCD30 in psoriasis.

Levels of Soluble CD30 and CD26 and Their Clinical Significance in Patients with Primary Immune Thrombocytopenia

Background. sCD30 and sCD26 are correlated with autoimmune diseases. However, little research has been done on the relationship between them and primary immune thrombocytopenia (ITP). Methods. This study enrolled 47 patients diagnosed with ITP in the Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences (Tianjin, China), from January 2015 to August 2015. The peripheral blood of all subjects was collected. The mRNA expression of CD30 was quantified by RT-PCR, and concentrations of sCD30 and sCD26 were measured by ELISA. Patient characteristics, CD30 mRNA levels, and sCD30 and sCD26 concentrations were analyzed. Results. The concentration of sCD30 was higher in active ITP patients (median, 35.82 ng/mL) than in remission ITP patients (median, 23.12 ng/mL; P=0.021) and healthy controls (median, 25.11 ng/mL; P=0.002). Plasma sCD26 levels decreased in remission ITP patients compared with that in healthy controls (median, 599.4 ng/mL vs. 964.23 ng/mL; P=0.004). Ratios of sCD26/sCD30 in active ITP patients decreased compared with those in controls (P=0.005). Increased sCD30 was positively correlated with hemorrhage (r=0.493, P=0.017) in ITP patients while little relationship was identified between sCD26 and ITP. Conclusion. Since sCD30 levels and sCD26/sCD30 ratios may contribute to the activity of the disease, they may be used to assess ITP disease activity.

Comparative Analysis of Cytokines of Tumor Cell Lines, Malignant and Benign Effusions Around Breast Implants

Background More than 700 women have developed an anaplastic large T cell lymphoma (ALCL) surrounding textured surface breast implants, termed breast implant–associated ALCL (BIA-ALCL). Most patients with BIA-ALCL present with an accumulation of fluid (delayed seroma) around the implant. However, benign seromas without malignant cells complicating scar contracture, implant rupture, trauma, infection, and other causes are more common. For proper patient management and to avoid unnecessary surgery, a simple diagnostic test to identify malignant seromas is desirable. Objectives The aim of this study was to develop an ancillary test for the diagnosis of malignant seromas and to gain insight into the nature of the malignant cells and their microenvironment. Methods We employed an immunologic assay on only 50 µL of aspirated seroma fluid. The assay measures 13 cytokines simultaneously by flow cytometry. To establish a baseline for clinical studies we measured cytokines secreted by BIA-ALCL and cutaneous ALCL lines. Results Our study of cell line culture supernatants, and 8 malignant compared with 9 benign seromas indicates that interleukin 9 (IL-9), IL-10, IL-13, IL-22, and/or interferon γ concentrations &gt;1000 pg/mL distinguish malignant seromas from benign seromas. IL-6, known to be a driver of malignant cells, is also elevated in benign seromas and does not distinguish them from malignant seromas. Conclusions The cytokine assay introduced in this study can be used together with levels of soluble CD30 to identify malignant seromas. Validation of these findings in a larger prospective patient cohort is warranted. The unique pattern of cytokine expression in malignant effusions surrounding breast implants gives further insight into the pathogenesis and cells of origin of BIA-ALCL. Level of Evidence: 5

Immunological Alterations due to Hemodialysis Might Interfere with Early Complications in Renal Transplantation

Background. Chronic or intercurrent alterations of the immune system in patients with end-stage renal disease (CKD) and intermittent hemodialysis (CKD5D, HD) have been attributed to an acute rejection of renal allograft. Methods. Leukocyte subsets in flow cytometry, complement activation, and concentrations of TGFβ, sCD30 (ELISA), and interleukins (CBA) of fifteen patients eligible for renal transplantation were analyzed before, during, and after a regular HD. Results. Before HD, the median proportion of CD8+ effector cells, CD8+ CCR5+ effector cells, and HLA-DR+ regulatory T cells as well as the median concentration of soluble CD30 increased and naive CD8+ T cells decreased. During HD, there was a significant decrease in CD4- CD8- T cells (p<0.001) and an increase in CD25+ T cells (p=0.026), sCD30 (p<0.001), HLA-DR+ regulatory T cells (p=0.005), and regulatory T cells (p=0.003). TGFβ and sCD30 increased significantly over time. The activity of the classical complement pathway started to slightly increase after the first hour of HD and lasted until fifteen minutes after finishing dialysis. The decrease in the functional activity of the alternative pathway was only transient and was followed by a significant increase within 15 minutes after finishing the treatment. Conclusion. HD might interact with the allograft outcome by influencing T cell subsets and activation of the complement system in a biphasic course.