De novo anti-HLA antibodies have the highest incidence in the first year after transplantation

The impact of the kinetics of the anti-HLA antibodies after KTx on the occurrence of acute rejection as well as the better time-point to monitor anti-HLA Abs after transplantation is not completely defined. This prospective study followed 150 patients over 12 months after transplantation. Serum IgG anti-HLA Abs were detected by single antigen beads after typing donors and recipients for loci A, B, C, DR, and DQ. Before KTx, 89 patients did not present anti-HLA Abs and 2% developed “de novo” Abs during the 1st year, 39 patients were sensitized without DSAs, and 13% developed DSA after surgery; all of them presented ABMR. Sensitized patients presented higher acute rejection rates (36.4% versus 13.5%, p<0.001), although 60% of the patients did not present ABMR. Patients, in whom DSA-MFI decreased during the first two weeks after surgery, did not develop ABMR. Those who sustained their levels presented a rate of 22% of ABMR. 85% of patients developed ABMR when MFIs increased early after transplantation (which occurred in 30% of the DSA positive patients). In the ABMR group, we observed an iDSA-MFI sharp drop on the fourth day and then an increase between the 7th and 14th POD, which suggests DSA should be monitored at this moment in sensitized patients for better ABMR prediction.

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Screening strategy for de novo donor‐specific HLA antibodies beyond the first year after kidney transplantation: Personalized or “one size fits all”?

Clinical Transplantation ◽

10.1111/ctr.14170 ◽

2020 ◽

Author(s):

Hasret Cun ◽

Gideon Hönger ◽

Marc Kleiser ◽

Patrizia Amico ◽

Caroline Wehmeier ◽

...

Keyword(s):

Kidney Transplantation ◽

De Novo ◽

Screening Strategy ◽

First Year ◽

Hla Antibodies

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The frequency of MEN 2B related symptoms in patients with a de novo M918T mutation in the RET protooncongene during the first year of life

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/s-2005-862846 ◽

2005 ◽

Vol 113 (S 1) ◽

Author(s):

M Brauckhoff ◽

O Gimm ◽

CL Weiss ◽

K Brauckhoff ◽

H Dralle

Keyword(s):

De Novo ◽

First Year ◽

First Year Of Life ◽

M918t Mutation ◽

Men 2B

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Dravet syndrome associated mutations in GABRA1, GABRB2 and GABRG2 define the genetic landscape of defects of GABAA receptors

Brain Communications ◽

10.1093/braincomms/fcab033 ◽

2021 ◽

Author(s):

Ciria C Hernandez ◽

XiaoJuan Tian ◽

Ningning Hu ◽

Wangzhen Shen ◽

Mackenzie A Catron ◽

...

Keyword(s):

Gabaa Receptor ◽

De Novo ◽

Epileptic Encephalopathy ◽

Dravet Syndrome ◽

First Year ◽

Genes Encoding ◽

Genetic Landscape ◽

Clonic Seizures ◽

Trafficking Defects ◽

First Year Of Life

Abstract Dravet syndrome is a rare, catastrophic epileptic encephalopathy that begins in the first year of life, usually with febrile or afebrile hemiclonic or generalized tonic-clonic seizures followed by status epilepticus. De novo variants in genes that mediate synaptic transmission such as SCN1A and PCDH19 are often associated with Dravet syndrome. Recently, GABAA receptor subunit genes (GABRs) encoding α1 (GABRA1), β3 (GABRB3) and γ2 (GABRG2), but not β2 (GABRB2) or β1 (GABRB1), subunits are frequently associated with Dravet syndrome or Dravet syndrome-like phenotype. We performed next generation sequencing on 870 patients with Dravet syndrome and identified nine variants in three different GABRs. Interestingly, the variants were all in genes encoding the most common GABAA receptor, the α1β2γ2 receptor. Mutations in GABRA1 (c.644T>C, p.L215P; c.640C>T, p.R214C; c.859G>A; V287I; c.641G>A, p.R214H) and GABRG2 (c.269C>G, p.T90R; c.1025C>T, p.P342L) presented as de novo cases, while in GABRB2 two variants were de novo (c.992T>C, p.F331S; c.542A>T, p.Y181F) and one was autosomal dominant and inherited from the maternal side (c.990_992del, p.330_331del). We characterized the effects of these GABR variants on GABAA receptor biogenesis and channel function. We found that defects in receptor gating were the common deficiency of GABRA1 and GABRB2 Dravet syndrome variants, while mainly trafficking defects were found with the GABRG2 (c.269C>G, p.T90R) variant. It seems that variants in α1 and β2 subunits are less tolerated than in γ2 subunits, since variant α1 and β2 subunits express well but were functionally deficient. This suggests that all of these GABR variants are all targeting GABR genes that encode the assembled α1β2γ2 receptor, and regardless of which of the three subunits are mutated, variants in genes coding for α1, β2 and γ2 receptor subunits make them candidate causative genes in the pathogenesis of Dravet syndrome.

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De novo donor-specific HLA antibodies reduce graft survival rates and increase the risk of kidney transplant rejection: A single-center retrospective study

Transplant Immunology ◽

10.1016/j.trim.2021.101430 ◽

2021 ◽

pp. 101430

Author(s):

Wei Liu ◽

Jie Zhao ◽

Zhong-Yu Kang ◽

Yan-Li Xiao ◽

Li Yang ◽

...

Keyword(s):

Retrospective Study ◽

Kidney Transplant ◽

Graft Survival ◽

De Novo ◽

Transplant Rejection ◽

Survival Rates ◽

Single Center ◽

Hla Antibodies

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Standard induction with basiliximab versus no induction in low immunological risk kidney transplant recipients: study protocol for a randomized controlled trial

Trials ◽

10.1186/s13063-021-05253-1 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Aziza Ajlan ◽

Hassan Aleid ◽

Tariq Zulfiquar Ali ◽

Hala Joharji ◽

Khalid Almeshari ◽

...

Keyword(s):

Kidney Transplant ◽

De Novo ◽

Controlled Trial ◽

Controlled Clinical Trial ◽

First Year ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Double Blind ◽

Donor Specific Antibodies

Abstract Background Induction therapy with IL-2 receptor antagonist (IL2-RA) is recommended as a first-line agent in low immunological risk kidney transplant recipients. However, the role of IL2-RA in the setting of tacrolimus-based immunosuppression has not been fully investigated. Aims To compare different induction therapeutic strategies with 2 doses of basiliximab vs. no induction in low immunologic risk kidney transplant recipients as per KFSHRC protocol. Methods Prospective, randomized, double blind, non-inferiority, controlled clinical trial Expected outcomes 1. Primary outcomes: Biopsy-proven acute rejection within first year following transplant 2. Secondary outcomes: a. Patient and graft survival at 1 year b. eGFR at 6 months and at 12 months c. Emergence of de novo donor-specific antibodies (DSAs) Trial registration The study has been prospectively registered at clinicaltrials.gov (NTC: 04404127). Registered on 27 May 2020.

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Importance and What to Watch Out for De Novo Donor Specific Anti-HLA Antibodies after Kidney Transplantation

Journal of Korean Medical Science ◽

10.3346/jkms.2018.33.e228 ◽

2018 ◽

Vol 33 (34) ◽

Author(s):

Chul Woo Yang

Keyword(s):

Kidney Transplantation ◽

De Novo ◽

Hla Antibodies

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Acute nonlymphocytic leukemia following etoposide and cisplatin combination chemotherapy for advanced non-small-cell carcinoma of the lung

Blood ◽

10.1182/blood.v70.5.1412.bloodjournal7051412 ◽

1987 ◽

Vol 70 (5) ◽

pp. 1412-1417 ◽

Cited By ~ 2

Author(s):

MJ Ratain ◽

LS Kaminer ◽

JD Bitran ◽

RA Larson ◽

MM Le Beau ◽

...

Keyword(s):

Combination Chemotherapy ◽

Advanced Nsclc ◽

De Novo ◽

Cumulative Risk ◽

Late Complications ◽

Small Cell ◽

First Year ◽

Acute Nonlymphocytic Leukemia ◽

Acute Monoblastic Leukemia ◽

High Doses

Combination chemotherapy is frequently used in the therapy of advanced non-small-cell lung cancer (NSCLC), but late complications are rarely recognized because of the short survival of most patients. Of 119 patients with advanced NSCLC treated with cisplatin and other drugs, four patients developed acute nonlymphocytic leukemia (ANLL). All four patients received etoposide and cisplatin with or without vindesine. Leukemia was diagnosed at 13, 19, 28, and 35 months after start of treatment. Three patients had morphologic and/or cytogenetic features of acute leukemia with significant monoblastic involvement; the fourth patient had trilineage dysplasia and cytogenetic abnormalities more commonly associated with therapy-related leukemia. Detailed analysis of the subgroup who survived longer than 1 year (24 patients) suggests that high cumulative doses of etoposide are leukemogenic; the median etoposide dose was 6,795 mg/m2 (first year only) in the four leukemic patients compared with 3,025 mg/m2 in the 20 nonleukemic patients (P less than .01). The rate of ANLL was 0.30 per person-year after the first year (95% confidence limits 0.11 to 0.90), with a cumulative risk of 15% +/- 11% at 2 years, and 44% +/- 24% at 2.5 years. We conclude that high doses of etoposide are potentially leukemogenic, and can induce a syndrome with features of acute monoblastic leukemia de novo that is distinct from other secondary leukemias.

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