HLA alleles associated with asparaginase hypersensitivity in Chinese children

Asparaginase is an important drug to treat childhood haematological malignancies. Data on the association between human leukocyte antigens (HLA) and asparaginase hypersensitivity among Chinese are lacking. We conducted a retrospective study to identify HLA alleles associated with asparaginase hypersensitivity among Chinese children with acute lymphoblastic leukaemia (ALL), mixed phenotype leukaemia and non-Hodgkin lymphoma (NHL), who received asparaginases with HLA typing performed between 2009 and 2019. 107 Chinese patients were analysed. 66.3% (71/107) developed hypersensitivity to at least one of the asparaginases. HLA-B*46:01 (OR 3.8, 95% CI 1.4–10.1, p < 0.01) and DRB1*09:01 (OR 4.3, 95% CI 1.6–11.4, p < 0.01) were significantly associated with l-asparaginase hypersensitivities, which remained significant after adjustment for age, gender and B cell ALL [HLA-B*46:01 (adjusted OR 3.5, 95% 1.3–10.5, p = 0.02) and DRB1*09:01 (OR 4.4, 95% CI 1.6–13.3, p < 0.01)].

ANTíGENOS HLA ESTÃO ASSOCIADOS A RISCO DE DIABETES MELLITUS PÓS-TRANSPLANTE?

Introdução: Diabetes mellitus pós-transplante (DMPT) tem impacto na morbidade e na mortalidade em receptores de transplante renal, uma vez que aumenta o risco de complicações cardiovasculares e de perda do enxerto renal. Os fatores de risco para DMPT podem ser divididos em modificáveis e não modificáveis. Ainda há controversas sobre a influência do sistema de antígenos leucocitários humanos (Human Leukocyte Antigens ou HLA) no risco de DMPT. Objetivo: Verificar prevalência para DMPT e sua relação com fatores genéticos. Métodos: Foram avaliados 450 pacientes submetidos ao transplante renal e realizada a investigação quanto à associação entre antígenos HLA-A, -B e -DR e DMPT. As frequências dos antígenos HLA-A, -B e -DR foram comparadas entre receptores com e sem diagnóstico de DMPT, ao longo de três anos após o transplante. Resultados: Na população de estudo, 60% eram do sexo masculino, 47,2% eram negros e 57,8% receberam rim de doador falecido. DMPT foi diagnosticado em 61 pacientes (13,5%), 315 (70%) permaneceram com níveis glicêmicos normais e 74 (16,5%) desenvolveram glicemia de jejum alterada. Associações positivas de DMPT foram observadas em relação aos antígenos HLA-A23 (18% vs 8,7%, P=0,024) e HLA-A29 (13,1% vs 5,1%, P=0,017) e associação negativa com o antígeno HLA-A68 (4,9% vs 14,1%, P=0,046). Conclusão: Encontramos relação estatística entre DMPT e HLA- A23, HLA-A29 e HLA-A68, porém, estudos com maior número de indivíduos são necessários para comprovar definitivamente a associação entre antígenos HLA e o risco de DMPT.

Optimal Immunosuppression Strategy in the Sensitized Kidney Transplant Recipient

Patients with previous sensitization events against anti-human leukocyte antigens (HLA) often have circulating anti-HLA antibodies. Following organ transplantation, sensitized patients have higher rates of antibody-mediated rejection (AMR) compared to those who are non-sensitized. More stringent donor matching is required for these patients, which results in a reduced donor pool and increased time on the waitlist. Current approaches for sensitized patients focus on reducing preformed antibodies that preclude transplantation; however, this type of desensitization does not modulate the primed immune response in sensitized patients. Thus, an optimized maintenance immunosuppressive regimen is necessary for highly sensitized patients, which may be distinct from non-sensitized patients. In this review, we will discuss the currently available therapeutic options for induction, maintenance, and adjuvant immunosuppression for sensitized patients.