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Abstract: A 56 year-old, multiparous woman suffering from a myeloproliferative syndrome, who had received multiple red blood cell and platelet transfusions, was the recipient of an allograft of peripheral blood stem cells derived from her HLA-A, B, DR, DQ and DP and ABO identical sister, following myeloablative conditioning. The persistence of severe, isolated thrombopenia resistant to platelet transfusions led to the discovery of anti-HLA class I allo-immunisation. As HLA compatible platelet transfusions did not result in satisfactory platelet increments, we then discovered the simultaneous presence of anti-HPA-1a allo-immunisation. Genotyping of the HPA-1 systems of the patient (HPA-1B/B) and her sister (HPA-1A/B) enabled us to elucidate the mechanism underlying the persistent thrombopenia and the inefficacy of transfusion. In fact, only transfusion of HPA-1B/B platelets (HLA compatible or incompatible) proved to be efficacious. To reduce the level of anti-HPA-1a antibodies, we performed plasmapheresis sessions and used an anti-CD20 monoclonal antibody. It was only on achieving total haematopoietic chimerism, through rapid interruption of the immunosuppression, that we obtained spontaneous normalisation of the platelet count. The present case emphasises the necessity, before undertaking any allograft of haematopoietic stem cells – even if the latter come from a strictly HLA identical member of the family – of performing a search for eventual anti-HPA allo-immunisation. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented about unilateral necrotising toxoplasmic retinochoroiditis as the main clinical manifestation of a peptide transporter deficiency.

Background The standard-of-care protocol, based on plasma exchanges, high-dose intravenous immunoglobulin and optimization of maintenance immunosuppression, can slow down the evolution of antibody-mediated rejection (AMR), but with high interindividual variability. Identification of a reliable predictive tool of the response to AMR treatment is a mandatory step for personalization of the follow-up strategy and to guide second-line therapies. Methods Interrogation of the electronic databases of 2 French university hospitals (Lyon and Strasbourg) retrospectively identified 81 renal transplant recipients diagnosed with AMR without chronic lesions (cg score ≤1) at diagnosis and for whom a follow-up biopsy had been performed 3–6 months after initiation of therapy. Results The evolution of humoral lesions on follow-up biopsy (disappearance versus persistence versus progression) correlated with the risk for allograft loss (logrank test, P  = .001). Patients with disappearance of humoral lesions had ∼80% graft survival at 10 years. The hazard ratio for graft loss in multivariate analysis was 3.91 (P  = .04) and 5.15 (P  = .02) for patients with persistence and progression of lesions, respectively. The non-invasive parameters classically used to follow the intensity of humoral alloimmune response (evolution of immunodominant DSA mean fluorescence intensity) and the decline of renal graft function (estimated glomerular filtration rate decrease and persistent proteinuria) showed little clinical value to predict the histological response to AMR therapy. Conclusion We conclude that invasive monitoring of the evolution of humoral lesions by the mean of follow-up biopsy performed 3–6 months after the initiation of therapy is an interesting tool to predict long-term outcome after AMR treatment. [ABSTRACT FROM AUTHOR]

A second HLA-A[sup *]68 null allele, HLA-A[sup *]6818N, was identified in our laboratory after discrepant results were obtained between class I serological and molecular typing in a male patient suffering from narcolepsy. HLA-A[sup *]6818 N displays a sequence identical to that of the HLAA[sup *]6802 allele, except in exon 2 where 20 nucleotides inserted at codon position 48 are a repeat of the 20 preceding nucleotides. This duplication creates a shift of the reading frame, which leads to a premature non-sense codon at position 59 of the null allele. [ABSTRACT FROM AUTHOR]

Donor-specific antibodies ( DSA) increase the risk of allograft rejection and graft failure. They may be present before transplant or develop de novo after transplantation. Here, we studied the evolution of preformed DSA and their impact on graft outcome in kidney transplant recipients. Using the Luminex Single Antigen assay, we analyzed the sera on the day of transplantation of 239 patients who received a kidney transplant. Thirty-seven patients (15.5%) had pre-existing DSA detected the day of transplantation. After 5 years, the pre-existing DSA disappeared in 22 patients whereas they persisted in 12. Variables associated with DSA persistence were age <50 years ( P = 0.009), a history of previous transplantation ( P = 0.039), the presence of class II DSA ( P = 0.009), an MFI of preformed DSA >3500 ( P < 0.001), and the presence of two or more DSA ( P < 0.001). DSA persistence was associated with a higher risk of graft loss and antibody-mediated rejection. Previously undetected preformed DSA are deleterious to graft survival only when they persist after transplantation. [ABSTRACT FROM AUTHOR]

The authors describe an A*68 allele present at the molecular level but not expressed at the cell surface. This non expression results from the deletion of one nucleotide in exon 1, which causes a shift of the reading frame leading to an early non-sense codon in the same exon[sup Note]. [ABSTRACT FROM AUTHOR]

Background: Non-adherence with immunosuppressant medication (MNA) fosters development of de novo donor-specific antibodies (dnDSA), rejection, and graft failure (GF) in kidney transplant recipients (KTRs). However, there is no simple tool to assess MNA, prospectively. The goal was to monitor MNA and analyze its predictive value for dnDSA generation, acute rejection and GF. Methods: We enrolled 301 KTRs in a multicentric French study. MNA was assessed prospectively at 3, 6, 12, and 24 months (M) post-KT, using the Morisky scale. We investigated the association between MNA and occurrence of dnDSA at year 2 post transplantation, using logistic regression models and the association between MNA and rejection or graft failure, using Cox multivariable models. Results: The initial percentage of MNA patients was 17.7%, increasing to 34.6% at 24 months. Nineteen patients (8.4%) developed dnDSA 2 to 3 years after KT. After adjustment for recipient age, HLA sensitization, HLA mismatches, and maintenance treatment, MNA was associated neither with dnDSA occurrence, nor acute rejection. Only cyclosporine use and calcineurin inhibitor (CNI) withdrawal were strongly associated with dnDSA and rejection. With a median follow-up of 8.9 years, GF occurred in 87 patients (29.0%). After adjustment for recipient and donor age, CNI trough level, dnDSA, and rejection, MNA was not associated with GF. The only parameters associated with GF were dnDSA occurrence, and acute rejection. Conclusions: Prospective serial monitoring of MNA using the Morisky scale does not predict dnDSA occurrence, rejection or GF in KTRs. In contrast, cyclosporine and CNI withdrawal induce dnDSA and rejection, which lead to GF. [ABSTRACT FROM AUTHOR]

Huit laboratoires pilotes de l’EFS ont déployé en 2016 une technique de séquençage HLA nouvelle génération HOLOTYPE (OMIXON). Depuis, des typages ont été menés sur les locus A et B (13704), C, DRB1, DRB3, DQB1 (13516), DPB1 et DQA1 (4735). Deuxx cent dix-sept nouveaux polymorphismes ont été identifiés, représentant en moyenne 2.3 nouveaux allèles/1000 typages/locus. Ces mutations ont été différenciées selon qu’elles s’accompagnent d’une modification de la résolution 6 digits seulement ( n = 65, séquence protéique inchangée), d’une modification de la résolution 4 digits, mais pas de la haute résolution ( n = 117) ou d’une modification de la haute résolution ou de la création d’un allèle nul ( n = 35, modification de l’expression des domaines présentant les peptides antigéniques). Les fréquences observées pour chacun de ces types de mutations/1000 typages/locus sont : A * : 0.6, 0.1, 0.1 ; B * : 0.6, 1.1, 0.4 ; C * : 1, 2.4, 0.4 ; DRB1 * : 1.2, 1.6, 0.3 et DRB3 * 0.0, 0.1, 0.0 ; DQB1 * : 0.6, 1, 0.1 ; DPB1 * : 0.6, 1.7, 0 ; DQA1 * : 1.7, 1.7, 0.6. Ces données confirment le faible polymorphisme des gènes de la classe II en dehors de l’exon 2. Néanmoins, le plus grand nombre des mutants modifiant la séquence protéique concernent les domaines non impliqués dans la présentation de l’antigène, particulièrement pour les locus C, DRB1, DPB1 et DQA1 car non explorés systématiquement avant le NGS. Deux nouveaux allèles nuls HLA-B * et C * (indétectables par les autres méthodes de typage : codon stop dans l’exon 1) ont été identifiés qui auraient pu constituer un mismatch pour une allogreffe non apparentée. Le NGS permet donc de détecter des mutants ayant un impact clinique réel (allèles nuls) ou qui reste à estimer (allèles exprimés) [ABSTRACT FROM AUTHOR]

The HLA-A*02:305N new allele lacks a nucleotide in exon 4 compared to HLA-A*02:01:01 allele. [ABSTRACT FROM AUTHOR]

The new allele HLA-B*15:220 is associated with a conserved haplotype. [ABSTRACT FROM AUTHOR]

Two new HLA-C alleles were identified in a volunteer bone marrow donor by sequence-based typing. [ABSTRACT FROM AUTHOR]