The shortage of deceased donors led to an increase of living related renal transplant performed in the presence of donor-specific antibodies (DSAs) or ABO incompatibilities. There are various desensitization protocols that have been proposed. Here, we describe the outcome of these sensitized patients. This is a prospective cohort study recruiting all kidney transplant recipients from August 2016 until June 2018. Deceased donations, ABO incompatible patients, and sensitized patients who were not prescribed on our desensitization protocol were excluded. Recipients were screened for the presence of HLA-antibodies 1 month before transplant. Those with positive DSA will undergo flow cytometry (risk stratification). We are using a protocol that consisted of intravenous rituximab 200 mg (day -14), intravenous antithymocyte globulin 5mg/kg (day 0-4), plasma exchange post transplant for patients with mean fluorescent intensity (MFI) < 3000, and negative flow cytometry. Those patients with MFI ≥ 3000 or positive flow cytometry need extra cycles pretransplant. A total of 40 patients were recruited, and 20 were sensitized patients. Among the sensitized group 4 of 20 had flow cytometry crossmatch positive, while all had preformed HLA-DSA. A total of 8 of 20 had class I HLA-DSA, 11 of 20 had class II HLA-DSA, and 1of 20 was positive for both class I and II HLA-DSA. Mean immunodominant MFI was 2133.4 (standard deviation [SD], 4451.24) and 1383.7 (SD, 2979.02) for class I and class II, respectively. At 1 year, mean serum creatinine was 108.90 (SD, 25.95) and 118.42 (SD, 31.68) in sensitized and unsensitized patients, respectively. One of 20 unsensitized patients had Banff 1B rejection at 3 months, and there was no significant rejection in sensitized patients at 6 months and 1 year. There was no difference in the occurrence of de novo HLA-DSA between the groups. Desensitization protocols may help to overcome incompatibility barriers in living donor renal transplant. The combination of low-dose rituximab, antithymocyte globulin, and judicious use of plasma exchange has worked well for our cohort.
Matched MeSH terms: Graft Rejection/immunology*; Graft Rejection/prevention & control
Mesenchymal stromal cells (MSCs) are widely used in the clinic because they involve fewer ethical issues and safety concerns compared to other stem cells such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). MSCs derived from umbilical cord Wharton's jelly (WJ-MSCs) have excellent proliferative potential and a faster growth rate and can retain their multipotency for more passages in vitro compared to adult MSCs from bone marrow or adipose tissue. WJ-MSCs are used clinically for repairing tissue injuries of the spinal cord, liver and heart with the aim of regenerating tissue. On the other hand, WJ-MSCs are also used clinically to ameliorate immune-mediated diseases based on their ability to modulate immune responses. In the field of tissue engineering, WJ-MSCs capable of differentiating into multiple cell lineages have been used to produce a variety of engineered tissues in vitro that can then be transplanted in vivo. This review discusses the characteristics of WJ-MSCs, the differences between WJ-MSCs and adult MSCs, clinical studies involving WJ-MSCs and future perspectives of WJ-MSC research and clinical applications. To summarize, WJ-MSCs have shown promise in treating a variety of diseases clinically. However, most clinical trials/studies reported thus far are relatively smaller in scale. The collected evidence is insufficient to support the routine use of WJ-MSC therapy in the clinic. Thus, rigorous clinical trials are needed in the future to obtain more information on WJ-MSC therapy safety and efficacy.
Introduction: Human leukocyte antigens (HLA) are a group of unique transmembrane glycoproteins that are ex-pressed on the surface of virtually all types of cells within the human body. These molecules are encoded by a set of highly polymorphic gene sequences known also as the major histocompatibility complex (MHC) and play an essential role in the presentation of antigenic peptides to immune cells for recognition and response. In recent years, various HLA alleles have been found to be associated with different autoimmune and inflammatory diseases such as rheumatoid arthritis, systemic lupus erythematosus (SLE) and allergic rhinitis. Identification of these alleles via HLA typing is necessary for initial screening and diagnosis purposes. Besides that, HLA typing is also used to determine compatibility matching between a donor and a recipient for tissue/organ transplantations in order to prevent graft rejection. Therefore, good quality and quantity of genomic DNA is required. In most scenarios, peripheral blood is chosen as the most reliable source of DNA for analysis, however this approach is seen as invasive and may cause pain and anxiety among the patients, particularly young children and weak subjects. Hence, derivation of genomic DNA from buccal cells as an alternative source material is becoming increasingly popular, especially in PCR-based genetic assays. Some of the most commonly described methods to collect buccal cells include using oral swabs, cytological brushes, mouthwashes and treated cards. Each technique yields varying quantities of DNA with diverse purity levels. In this study, we aim to evaluate the amount and purity of genomic DNA extracted from buccal swabs and brushes as well as blood for screening of selected HLA class II alleles. Methods: Cheek cell samples were col-lected using sterile foam tipped buccal swabs (Whatman) and buccal collection brushes (Gentra Puregene) whereas peripheral blood samples were withdrawn following routine venipuncture techniques. All samples were subjected to DNA extraction according to modified commercial kit protocols. Screening of selected HLA-DRB1 alleles was con-ducted via PCR with sequence-specific primers as established by Bunce et al. 1995. Results: There was no significant difference (p > 0.05) in the total DNA yield obtained from blood and buccal swab samples, which were 17.57μg (± 8.66) and 13.28μg (± 4.81), respectively. All samples exhibited similar 260/280 ratios of about ~1.80 (p > 0.05). However, buccal brush samples contributed the least amount of DNA (0.29μg, ± 0.12) compared to other sources (p < 0.05). The pure genomic DNA isolated from both blood and buccal swab samples were successfully typed for low resolution HLA-DRB1 alleles. Conclusion: Buccal swabs provide good quantity and quality of DNA for screening of HLA alleles with high accuracy and thus can be utilized as a non-invasive substitute for venipuncture.
Graft rejection and disease recurrence are well-recognized complications of liver transplantation (LT) for autoimmune hepatitis (AIH) and autoimmune sclerosing cholangitis (AISC). We describe indications and outcome of LT for childhood AIH and AISC.
Major reconstructive surgery may be extensive and prolonged, and it may cause edema and compromise the flap pedicle if closed under tension. Glycerol-preserved skin allograft (GPA) can provide a means for tension-free closure and temporary cover of the wound. Seven years of analysis on GPA used in conjunction with major reconstruction was undertaken to highlight its indications, results, and outcomes. Forty-seven patients were included, aged between 9 and 73 years. Majority of patients had reconstruction following tumor resection and trauma. The main indication for use of GPA was temporary, loose cover of the wound in 44% of cases; flap pedicle protection in 31% of cases; donor site wound cover in 10%; flap monitoring in one case; and management of flap-related complications in 6% of cases. Free flap reconstruction was performed in 72% of cases. In conclusion, GPA is a useful adjunct in reconstructive surgery. It can be used temporarily to allow tension-free wound closure, as well as to protect the flap pedicle until edema subsides and the pedicle becomes stable. This latter approach allows secondary wound closure and good esthetic outcome.
Since 1998, 42 hand transplants in 30 patients have been performed in countries such as France, United States, China, Austria, Malaysia, Italy, Belgium, Poland, Spain, and Germany. Now, with recent improvements in immunosuppression, the clinical applicability may expand and the ethical obstacles may soon be overcome, allowing multiple US institutions to perform hand allotransplantation. The main purpose of this article is to facilitate access to pertinent details in regards to hand transplantation, such as donor/recipient selection criteria, immunosuppressive therapies, and associated complications. It is a comprehensive literature review compiled from published reports from multiple hand transplant programs throughout the world. Due to its inherent complexity, hand transplantation should only be attempted at institutions within the US capable of orchestrating a specialized multidisciplinary team, and each institution's protocol should be extremely detailed and individualized.