Characterisation of the novel HLA-B*07:02:01:110 allele by next-generation sequencing.

HLA-B*07:02:01:110 differs from the HLA-B*07:02:01:01 allele by two nucleotide substitutions in the 3'UTR.

Discovery of the novel HLA-C*07:1052 allele, a variant of HLA-C*07:02:01:01, in a Greek individual.

Characterization of the novel HLA-C*07:1052 allele in a Greek individual using next-generation sequencing.

Genomic sequence of the HLA-A*24:587 allele identified in a Greek individual.

Characterization of the novel HLA-A*24:587 allele in a Greek individual using next-generation sequencing.

HLA-B*51:380, a novel HLA-B allele with one exonic mutation identified in a Greek individual.

Characterization of the novel HLA-B*51:380 allele in a Greek individual using next-generation sequencing.

Identification of the novel HLA-A*01:426 allele in a Greek bone marrow donor.

Characterization of the novel HLA-A*01:426 allele in a 21-year-old Greek male bone marrow donor.

Identification of the novel HLA-A*02:09:01:04 allele in a Greek individual.

Characterization of the novel HLA-A*02:09:01:04 allele in a 36-year-old Greek female.

Demographic, Clinical and Immunogenetic Profiles of a Greek Cohort of COVID-19 Patients.

The present cross-sectional study consists of a comprehensive analysis of epidemiological, laboratory, and clinical characteristics of COVID-19 patients in relation to their immunogenetic profiles. We studied 125 COVID-19 patients comprising different stages of disease severity; non-hospitalized (mild n = 69) and hospitalized (n = 56). Analysis of disease characteristics revealed no major differences between males and females of each group of patients while hospitalized patients were older and presented with comorbidities. A positive allele association was observed for HLA-DRB1*01 in total COVID-19 patients versus healthy controls. Subgrouping of COVID-19 patients in mild and hospitalized further identified a statistically significant increase in HLA-DRB1*01 in mild COVID-19 patients versus controls. The frequency of A*11, A*23, and DRB1*09 alleles was higher, while the frequency of C*12 was lower, in hospitalized patients versus healthy controls albeit with uncorrected statistical significance. The identification of specific allele associations may provide useful future markers for disease susceptibility in order to allow successful clinical management of COVID-19 patients.

Repetitively Administered Low-Dose Donor Lymphocyte Infusion for Prevention of Relapse after Allogeneic Stem Cell Transplantation in Patients with High-Risk Acute Leukemia.

BACKGROUND: Patients with high-risk acute leukemia have a high risk of relapse after allogeneic stem cell transplantation (allo-SCT). In an effort to reduce the relapse rate, various therapeutic methods have been implemented into clinical practice. Among them, prophylactic donor lymphocyte infusion (pro-DLI) has shown significant efficacy. However, the widespread application of pro-DLI has been restricted mostly due to concerns regarding the development of graft versus host disease (GVHD). In the present study, we tested the safety and efficacy of a novel method of prophylactic-DLI based by repetitive administration of low lymphocyte doses. METHODS: DLI was administered to patients with high-risk acute leukemia at a dose of 2 × 106/kg CD3-positive cells. DLI at the same dose was repeated every two months for at least 36 months post-allo-SCT, or until relapse or any clinical or laboratory feature suggested GVHD, whichever occurred first. Forty-four patients with a median age of 53 years (range 20-67) who underwent allo-SCT between 2011 and 2020 were included in our study. Thirty-three patients with high-risk acute myeloid leukemia (AML) and 11 with high-risk acute lymphoblastic leukemia (ALL) after allo-SCT from a matched sibling (MSD, no = 38 pts) or a matched-unrelated donor (MUD, no = 6 pts) received pro-DLI. Twenty-three patients were in CR1, all with unfavorable genetic features; 12 patients were in CR2 or beyond; and 9 patients had refractory disease at the time of transplant. Ten out of 23 patients in CR1 had detectable minimal residual disease (MRD) at the time of allo-SCT. Disease risk index (DRI) was high and intermediate in 21 and 23 patients, respectively. Conditioning was myeloablative (MAC) in 36 and reduced intensity (RIC) in 8 patients, while GVHD prophylaxis consisted of cyclosporine-A in combination with low-dose alemtuzumab in 39 patients or with low-dose MTX in 5 patients, respectively. RESULTS: Thirty-five patients completed the scheduled treatment and received a median of 8 DLI doses (range 1-35). Fifteen out of 35 patients received all planned doses, while DLI was discontinued in 20 patients. Reasons for discontinuation included GVHD development in nine, donor unavailability in seven, disease relapse in three, and secondary malignancy in one patient, respectively. Nine patients were still on treatment with DLI, and they received a median of four (range 2-12) doses. Fourteen percent of patients developed transient grade-II acute GVHD while 12% developed chronic GVHD post-DLI administration. Acute GVHD was managed successfully with short course steroids, and four out of five patients with cGVHD were disease-free and off immunosuppression. With a median follow-up of 44 months (range 8-120), relapse-free (RFS) and overall survival (OS) were 74%, (95% CI, 54-87%) and 78%, (95% CI, 58-89%) respectively, while the cumulative incidence of non-relapse mortality (NRM) was 13% (95% CI, 4-28%). The cumulative incidence of relapse in patients with intermediate and high DRI is 7% and 15%, respectively. CONCLUSION: Prolonged-up to three years-low-dose pro-DLI administered every two months is safe and effective in reducing relapse rate in patients with high-risk acute leukemia. The low-dose repetitive administration DLI strategy reduced the risk of DLI-mediated GVHD, while the prolonged repeated administration helped in preventing relapse, possibly by inducing a sustained and prolonged immunological pressure on residual leukemic cells. This novel strategy deserves testing in larger cohort of patients with high-risk acute leukemia.

Shared epitope and polymorphism of MICA and NKG2D encoding genes in Greek and Polish patients with rheumatoid arthritis.

The present study aimed to analyse and compare the distribution of MICA (rs1051792) and NKG2D/KLRK1 (rs1154831, rs1049174, rs2255336) polymorphisms in 61 Greek and 100 Polish patients with rheumatoid arthritis in relation to the presence of the HLA-DRB1 shared epitope and clinical parameters. Genotyping of selected polymorphism was performed using real-time PCR. HLA-DRB1 shared epitope alleles segregated differently in Greek and Polish patients but in both populations were detected in over 60% of cases. The rs1051792-A variant was more common among SE-positive Polish patients (p = 0.003) while the rs1049174-G allele was more frequently observed in Greeks than in Poles (p < 0.001). Moreover, among Greek patients, the rs1051792-GG homozygotes more frequently presented with anti-CCP antibodies and rheumatoid factor (RF), while carriers of the rs1049174-G variant and rs1154831-CC homozygotes were characterized by lower disease activity scores (p < 0.05 in all cases). These results imply that, in addition to the HLA-DRB1 SE alleles, MICA and NKG2D polymorphisms may also play a role in rheumatoid arthritis.