DT-04. Antibodies to human leukocyte antigens (HLA) in patients with multiple myeloma

Summary

According to published data, up to 50% of newly diagnosed multiple myeloma (MM) patients can present with renal insufficiency, 20% with severe renal impairment and 10% requiring dialysis. Patients with MM account for about 2% of the dialysis population, but have a 2.77-times higher risk of death compared to other dialysis patients (Wirk B., 2011). Due to the low overall survival of patients with MM undergoing dialysis, kidney transplantation may be an alternative option for renal replacement therapy for carefully selected patients (Heybeli C. et al., 2022). The presence of pre-existing anti-HLA antibodies at a high titer in the patient is associated with the difficulty of selecting a compatible donor and the risk of humoral rejection of the transplant. The aim of our study was to determinine the frequency of anti-HLA antibodies in patients with multiple myeloma.

Materials and methods

The study included 38 patients with MM who were treated at the Russian Research Institute of Hematology and Transfusiology since 2016 to 2023. The median age of the examined patients was 55 years (range 41-75 years). The male/female ratio is 17 to 21. The period from diagnosis to the date of anti-HLA antibody determination ranged from 3 to 36 months. Main part of the patients (92%, 35 cases) received bortezomib-based therapy. Detection of anti-HLA antibodies in blood serum samples was carried out using the LIFECODES LifeScreen Deluxe kits (Immucor Transplant Diagnostics, USA) and Luminex 200 multiparameter analyzer (Luminex Corporation, USA). The result was evaluated as positive at mean fluorescence intensity (MFI) more than 500 units.

Results and discussion

Allosensitizing events in the anamnesis were established only in females. Transfusions of blood components were carried out for 33.3% of females (7 patients). Of note, 90.5% of females (19 patients) had a history of pregnancy: 1-2 pregnancies in 10 cases, 3 or more pregnancies in 9 cases. All females who underwent transfusion of blood components had previous pregnancies (2 to 5). Myeloma nephropathy was detected in 13.2% of patients (5 cases, 4 males and 1 female). Antibodies to HLA antigens were detected in 7.9% of cases (3 patients). Antibodies to HLA class I antigens were found in 2 out of 38 examined patients. E.g., patient M. is a female, 64 years old, pregnancy – 1, transfusion of blood components – 0, with maximum MFI value of 3044. Patient K. is also a female, 63 years old, pregnancy – 2, transfusion of blood components – 0, with maximum MFI value of 526. Antibodies to HLA class II antigens were found in one patient (female, 44 years old, 4 pregnancies, no blood transfusions, maximum MFI value of 791). The frequency of antibodies to class I and II HLA-antigens in the examined patients did not significantly differ (5.3% vs. 2.6%, p=0.6). According to medical history, the presence of anti-HLA antibodies in the examined females was most likely a consequence of pregnancy. The established degree of sensitization was intermediate (MFI in the range of 500-3000) according to the approach of Borovkova N.V. et al. Patients with anti-HLA antibodies had not renal insufficiency at the time of examination.

Conclusion

The frequency of anti-HLA antibodies in patients with multiple myeloma was 7.9%. Significant differences in the frequency of antibodies to class I and class II HLA antigens have not been established.

Keywords

Allosensitizing event, anti-HLA antibodies, multiple myeloma.