scholarly journals Treatment of Anti-HLA Donor-Specific Antibodies Results in Increased Infectious Complications and Impairs Survival after Liver Transplantation

2020 ◽  
Vol 9 (12) ◽  
pp. 3986
Author(s):  
Sinem Ünlü ◽  
Nils Lachmann ◽  
Maximilian Jara ◽  
Paul Viktor Ritschl ◽  
Leke Wiering ◽  
...  

Donor-specific anti-human leukocyte antigen antibodies (DSA) are controversially discussed in the context of liver transplantation (LT). We investigated the relationship between the presence of DSA and the outcome after LT. All the LTs performed at our center between 1 January 2008 and 31 December 2015 were examined. Recipients < 18 years, living donor-, combined, high-urgency-, and re-transplantations were excluded. Out of 510 LTs, 113 DSA-positive cases were propensity score-matched with DSA-negative cases based on the components of the Balance of Risk score. One-, three-, and five-year survival after LT were 74.3% in DSA-positive vs. 84.8% (p = 0.053) in DSA-negative recipients, 71.8% vs. 71.5% (p = 0.821), and 69.3% vs. 64.9% (p = 0.818), respectively. Rejection therapy was more often applied to DSA-positive recipients (n = 77 (68.1%) vs. 37 (32.7%) in the control group, p < 0.001). At one year after LT, 9.7% of DSA-positive patients died due to sepsis compared to 1.8% in the DSA-negative group (p = 0.046). The remaining causes of death were comparable in both groups (cardiovascular 6.2% vs. 8.0%; p = 0.692; hepatic 3.5% vs. 2.7%, p = 0.788; malignancy 3.5% vs. 2.7%, p = 0.788). DSA seem to have an indirect effect on the outcome of adult LTs, impacting decision-making in post-transplant immunosuppression and rejection therapies and ultimately increasing mortality due to infectious complications.

Author(s):  
Kohei Unagami ◽  
Hideki Ishida ◽  
Miyuki Furusawa ◽  
Kumiko Kitajima ◽  
Toshihito Hirai ◽  
...  

Abstract Background Tacrolimus (TAC) is a key immunosuppressant drug for kidney transplantation (KTx). However, the optimal serum trough level of TAC for good long-term outcomes remains unclear. This study aimed to investigate the relationship between the maintenance TAC trough level and the appearance of de novo donor-specific anti-human leukocyte antigen (HLA) antibodies (dnDSAs). Methods A total of 584 KTx recipients were enrolled in this study, of whom 164 developed dnDSAs during the follow-up period and 420 did not. Results We found no significant relationship between TAC trough level during the follow-up period and dnDSA incidence. Patients who developed dnDSAs had a significantly greater number of HLA-A/B/DR mismatches (3.4 ± 1.3 versus 2.8 ± 1.5; P &lt; 0.001), were more likely to have preformed DSAs (48.2% versus 27.1%; P &lt; 0.001) and showed poor allograft outcome. Conclusions There was no clear relationship between TAC trough level and dnDSA incidence for KTx recipients whose TAC trough levels were kept within the narrow range of 4–6 ng/mL during the immunosuppression maintenance period.


Author(s):  
Olimpia Sipak ◽  
Aleksandra Rył ◽  
Anna Grzywacz ◽  
Maria Laszczyńska ◽  
Małgorzata Zimny ◽  
...  

Human leukocyte antigen G (HLA-G) is observed in immune system cells and other organs. It is a class Ib molecule, which plays a pivotal role in the implantation and maintenance of pregnancy. The aim of this study was to assess the relationship between serum sHLA-G levels and the HLA-G allele in parental pairs with complicated obstetric histories. The clinical material consisted of 210 women and 190 men with the experience of a complicated or an unsuccessful pregnancy. The control group included parents―89 women and 86 men―lacking complicated obstetric histories. We applied genetic analysis methods: isolation of genomic DNA, sequencing, and determination of serum sHLA-G levels. There were no statistically significant differences in the frequencies of the HLA-G −725 C>G polymorphism between particular experimental groups compared with the control group (p > 0.05). The median sHLA-G levels in the women with the HLA-G10101 allele (15.4 U/mL) were significantly higher than in the women with other alleles (p < 0.05). The HLA-G 10101 allele seems to protect against antiphospholipid syndrome, which may be associated with increased serum sHLA-G levels in its carriers. The relationship between serum sHLA-G levels and the HLA-G polymorphisms in the Polish population requires further investigation.


Author(s):  
Sri Lestari KS ◽  
Eryati Darwin ◽  
Tjut Nurul Alam Jacoeb ◽  
Djong Hon Tjong

Psoriasis vulgaris is chronic skin disease that is linked to genetics and immune system. The most important predisposing genetic factor is human leukocyte antigen (HLA). This study was performed to determine the relationship between HLA-Cw6 allele and psoriasis vulgaris and the changes of nucleotide base squences, using observation method with a cross sectional comparative study. Samples were selected using consecutive sampling of 30 patients with psoriasis vulgaris attending the Dermatology and STD polyclinic at DR. M. Djamil Hospital. 30 healthy volunteers were selected as controls. The subjects’ medical history was recorded followed by a dermatological examination, collection of samples, DNA isolation, then primers were designed for HLA-Cw6 allele, genes were sequencing and finally analyzed using PCR-SSP. The results were 20% of patients with psoriasis vulgaris carried HLA-Cw6 allele, while it was absent in the control group. This difference is statistically significant at the 5% level (p = 0.024). We found the changes of nucleotide base formations of HLA-Cw6. In conclusion, based on these observations, presence of the HLA-Cw6 allele is an important genetic risk factor for developing psoriasis vulgaris.


2020 ◽  
Vol 9 (3) ◽  
pp. 708 ◽  
Author(s):  
Isabel Legaz ◽  
Francisco Boix ◽  
Manuela López ◽  
Rafael Alfaro ◽  
José A. Galián ◽  
...  

The significance of human leukocyte antigen (HLA) matching and preformed donor-specific antibodies (DSAs) in liver transplantation remains unclear. The aim of this study was to analyze the presence of DSAs in a large cohort of 810 liver recipients undergoing liver transplant to determine the influence on acute (AR) or chronic liver rejection (CR), graft loss and allograft survival. DSAs were identified using complement dependent cytotoxicity crossmatch (CDC-CM) and multiplexed solid-phase-based flow cytometry assay (Luminex). CDC-CM showed that a 3.2% of liver transplants were positive (+CDC-CM) with an AR frequency of 19.2% which was not different from that observed in negative patients (−CDC-CM, 22.3%). Only two patients transplanted with +CDC-CM (7.6%) developed CR and suffered re-transplant. +CDC-CM patients showed a significantly lower survival rate compared to −CDC-CM patients (23.1% vs. 59.1%, p = 0.0003), developing allograft failure within the first three months (p < 0.00001). In conclusion, we have demonstrated a relationship between the presence of preformed DSAs and the low graft liver survival, indicating the important role and the potential interest of performing this analysis before liver transplantation. Our results could help to detect patients with an increased risk of graft loss, a better choice of liver receptors as well as the establishment of individualized immunosuppressive regimens.


2012 ◽  
Vol 20 (3) ◽  
pp. 279-285 ◽  
Author(s):  
Junichi Shindoh ◽  
Yasuhiko Sugawara ◽  
Sumihito Tamura ◽  
Junichi Kaneko ◽  
Noriyo Yamashiki ◽  
...  

2010 ◽  
Vol 10 (4) ◽  
pp. 282-286 ◽  
Author(s):  
Erkan Yılmaz ◽  
Arman Çekmen ◽  
Emre Akkuş ◽  
Bülent Önal ◽  
Ali Uğur Özalp ◽  
...  

Etiologies of Renal Cell Carcinoma (RCC) are not clear despite of the fact that many risk factors have been suggested. Especially in high stages RCC can affect the immune system in various ways. Human Leukocyte Antigens (HLA) may play a complementary role in the activation between the tumor and immunity. Our aim was to determine the existence of the relationship between HLA system and RCC. By using the standard microlymphocytotoxic method of Terasaki in our study, the HLA A, B, DR and DQ antigen types of 20 patients with RCC Stage Ti and T2 were compared with the control group consisting of healthy 30 people. In our RCC patient group, HLA-A23(9) and DQ7(3) antigens were significantly higher than the control group statistically (p=0.005, p=0.0028; respectively). HLA-A10, DQi, DR10 and B44 antigens were significantly higher in the control group than the patient group (p=0.011; for all). The findings made us suggest that the people, carrying the antigens which were detected in the patient group, were at high risk for RCC and the people, carrying the protective antigens that were detected in the control group were at less risk for RCC. There may be a dramatic regression for the patients who underwent immunotherapy and HLA expression, which is known to play role in tumor biology, may direct the effects of immunotherapeutic agents. Immunologic description and destruction is avoided in case of change or disappearance of HLA expression by cancer cells. Further investigations which will be performed in our population in the future will be more illuminating to confirm those results. We have concluded that, HLA profiles may be evaluated for detection the people at risk of RCC, the prognosis of the patients and their treatments.


2019 ◽  
Vol 2 (4) ◽  
pp. 193-200
Author(s):  
Bénédicte Larivière-Durgueil ◽  
Rémi Boudet ◽  
Marie Essig ◽  
Stéphane Bouvier ◽  
Ali Abdeh ◽  
...  

Objective: To assess the recurrence of PD catheter migration after the introduction of a walnut ballast. Materials and Methods: Retrospective study from 1999 to 2014 of PD patients followed in Limousin. Were compared two groups: ballast group (patients who benefited from the establishment of stainless steel ballast at the intraperitoneal catheter extremity) with 26 patients and control group with 204 patients. The primary endpoint was the occurrence of an episode catheter’s migration after ballast’s establishment. Secondary objectives were (i) to determine the causal factors leading to the catheter weighting, (ii) to ensure the safety of the procedure on the following criteria: infectious complications, mechanicals complications, epurations criteria, and catheter’s survival. Results: More than one year after the implementation of the ballast, no recurrent migration was observed in 86.6% of cases. It wasn’t found an increased risk of infections (OR = 0.5, 95% CI [0.22, 1.13]) or mechanical complications (OR = 1.77- 95% CI [0.77, 4.05]) between the two groups. The adequation criteria were similar: KT / V total : 2.37 in the control group and 2.28 in the ballast group (p = 0.63). The survival of the ballast catheter was comparable among the two groups (p = 0.983). Three causal factors that led to the ballast were identified: automated peritoneal dialysis (APD) (OR = 0.38, 95% CI [0.16, 0.9]), the failure from the first use of the catheter (OR = 19.48, CI 95 % [7.67, 49.48]) and the incarceration of the omentum (OR = 15.84, 95% CI [5.81, 43.21]). Conclusion: The ballast used in these study appears to prevent recurrence of migration, without any impact in terms of infectious or mechanical complications, or on the dialysis criteria or on catheter’s survival. However this catheter does currently not have an EC authorization


2020 ◽  
Vol 5 (12) ◽  
pp. 2202-2211
Author(s):  
Arnaud Del Bello ◽  
Olivier Thaunat ◽  
Moglie Le Quintrec ◽  
Oriol Bestard ◽  
Antoine Durrbach ◽  
...  

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