HLA-DQA1*05:115, the first DQA1 allele described with an alanine at position 59 of alpha-1 domain.

HLA-DQA1*05:115 shows an alanine at position 59 not described previously.

Eight new variants of HLA-DQB1*03 identified by next-generation sequencing.

Genomic sequence of HLA-DQB1*03:01:01:60, -DQB1*03:01:01:61, -DQB1*03:01:01:62, -DQB1*03:01:01:63, -DQB1*03:02:01:23, -DQB1*03:02:01:24, -DQB1*03:02:01:25 and -DQB1*03:03:02:14 alleles in Spanish individuals.

Characterisation of five new variants of HLA-DPA1.

Genomic sequence of HLA-DPA1*01:03:01:73, -DPA1*01:03:01:80, DPA1*01:03:01:82, -DPA1*01:155:01:02, -DPA1*02:02:02:16 alleles in Spanish individuals.

Genomic sequence of five new variants of HLA-DQA1 in non-coding regions.

Characterisation of HLA-DQA1*01:02:01:30, HLA-DQA1*01:03:01:14, HLA-DQA1*03:03:01:20, HLA-DQA1*04:01:01:13, HLA-DQA1*05:05:01:40 alleles in Spanish individuals.

Four new intronic variants of HLA-DQB1 detected by next-generation sequencing.

Characterization of HLA-DQB1*02:02:01:18, -DQB1*02:02:01:19, -DQB1*03:02:01:20 and -DQB1*05:03:01:10 alleles in Spanish individuals.

Genomic sequence of the HLA-B*40:01:02:61, -B*48:01:01:14, and -C*01:02:01:69 alleles.

Characterization of HLA-B*40:01:02:61, -B*48:01:01:14, and -C*01:02:01:69 alleles in Spanish individuals.

Improving the Access of Highly Sensitized Patients to Kidney Transplantation From Deceased Donors: The Spanish PATHI Program With Allocation Based on the Virtual Crossmatch.

BACKGROUND: In 2015, the Spanish National Transplant Organization developed a prioritization system (Program for Access to Transplantation for Highly Sensitized Patients [PATHI]) to increase transplant options for patients with calculated panel-reactive antibodies (cPRAs) ≥98%, based on virtual crossmatch. We describe the experience with the implementation of PATHI and assess its efficacy. METHODS: PATHI registry was used to collect characteristics of donors and patients between June 15, 2015, and March 1, 2018. One-year graft and patient survival and acute rejection were also measured. A Cox model was used to identify factors related to patient death and graft loss and logistical regression for those associated with rejection. RESULTS: One thousand eighty-nine patients were included, and 272 (25%) were transplanted. Transplant rate by cPRA was 54.9%, 40.5%, and 12.8% in patients with cPRA98%, cPRA99%, and cPRA100%, respectively. One-year patient survival was 92.5%. Recipient age ≥60, time under dialysis >7 y, and delayed graft function were mortality risk factors. One-year graft survival was 88.7%. The factor related to graft loss was delayed graft function. The rejection rate was 22%. Factors related to rejection were sex, older recipients, and posttransplant donor-specific antibodies. CONCLUSIONS: A prioritization approach increases transplant options for highly sensitized patients with appropriate short-term postransplant outcomes. Along with other programs, PATHI may inspire other countries to adopt strategies to meet transplant needs of these patients.

Three novel variants of HLA-DQB1*06 identified by next-generation sequencing.

Characterization of HLA-DQB1*06:472, -DQB1*06:02:01:34 and -DQB1*06:04:01:06 alleles in Spanish individuals.

Three novel alleles HLA-A*02:1092, -A*29:01:01:11 and -B*44:03:01:58 identified by next-generation sequencing.

Three novel HLA Class I alleles, -A*02:1092, -A*29:01:01:11 and -B*44:03:01:58, characterized in Spanish individuals.

Four novel HLA alleles: HLA-DPA1*01:03:01:68, -DPA1*01:03:01:71, -DQA1*02:01:01:06, and -DQB1*06:03:01:19.

Four novel HLA Class II alleles, HLA-DPA1*01:03:01:68, -DPA1*01:03:01:71, -DQA1*02:01:01:06, and -DQB1*06:03:01:19, characterized in Spanish individuals.

Identification of four novel HLA-DQA1 alleles: HLA-DQA1*01:01:02:04, 01:04:01:05, 03:03:01:19 and 05:01:01:08.

Four novel HLA-DQA1 alleles, -DQA1*01:01:02:04, -DQA1*01:04:01:05, -DQA1*03:03:01:19 and -DQA1*05:01:01:08, characterized in Spanish individuals.

Identification of three novel HLA class I alleles: HLA-B*15:640, -B*18:01:01:71 and -C*05:275.

Three novel HLA Class I alleles, -B*15:640, -B*18:01:01:71 and -C*05:275, characterized in Spanish individuals.

Mathematical modelling of the waning of anti-RBD IgG SARS-CoV-2 antibody titers after a two-dose BNT162b2 mRNA vaccination.

Background: After exposure to SARS-CoV-2 and/or vaccination there is an increase in serum antibody titers followed by a non-linear waning. Our aim was to find out if this waning of antibody titers would fit to a mathematical model. Methods: We analyzed anti-RBD (receptor binding domain) IgG antibody titers and the breakthrough infections over a ten-month period following the second dose of the mRNA BNT162b2 (Pfizer-BioNtech.) vaccine, in a cohort of 54 health-care workers (HCWs) who were either never infected with SARS-CoV-2 (naïve, nHCW group, n=27) or previously infected with the virus (experienced, eHCW group, n=27). Two mathematical models, exponential and power law, were used to quantify antibody waning kinetics, and we compared the relative quality of the goodness of fit to the data between both models was compared using the Akaik Information Criterion. Results: We found that the waning slopes were significantly more pronounced for the naïve when compared to the experienced HCWs in exponential (p-value: 1.801E-9) and power law (p-value: 9.399E-13) models. The waning of anti-RBD IgG antibody levels fitted significantly to both exponential (average-R2: 0.957 for nHCW and 0.954 for eHCW) and power law (average-R2: 0.991 for nHCW and 0.988 for eHCW) models, with a better fit to the power law model. In the nHCW group, titers would descend below an arbitrary 1000-units threshold at a median of 210.6 days (IQ range: 74.2). For the eHCW group, the same risk threshold would be reached at 440.0 days (IQ range: 135.2) post-vaccination. Conclusion: Two parsimonious models can explain the anti-RBD IgG antibody titer waning after vaccination. Regardless of the model used, eHCWs have lower waning slopes and longer persistence of antibody titers than nHCWs. Consequently, personalized vaccination booster schedules should be implemented according to the individual persistence of antibody levels.

HLA-DQA1*05:01:11, a novel HLA-DQA1 allele with an ochre stop codon.

The DQA1*05:01:11 allele shows the TAA (UAA) stop codon instead of the common DQA1 TGA (UGA) stop codon.

Identification of three novel HLA class II alleles: HLA-DQA1*02:28, -DQA1*05:01:08:02 and -DQB1*03:02:01:13.

Three novel HLA Class II alleles, -DQA1*02:28, -DQA1*05:01:08:02 and -DQB1*03:02:01:13, characterized in Spanish individuals.

Four new HLA-DPA1 intronic variants detected by next-generation sequencing.

Four novel HLA-DPA1 alleles, -DPA1*01:03:01:59, -DPA1*01:03:01:60, -DPA1*02:01:01:30, and -DPA1*02:01:01:31, characterized in Spanish individuals.

New HLA-DQB1 intronic variants detected by next-generation sequencing.

Four novel HLA-DQB1 alleles, -DQB1*02:02:01:08, -DQB1*02:01:01:11, -DQB1*03:01:01:30 and -DQB1*03:01:01:36, characterized in Spanish individuals.

RNA and protein expression analysis of HLA-DQB1*03:01:01:21Q allele: A null allele renamed as HLA-DQB1*03:01:01:21N.

The characterization of the expression profile of HLA questionable alleles (Q) is clinically relevant in allogeneic hematopoietic stem cell transplantation (HSTC) because an aberrant expression of these alleles could lead to transplantation-related complications. HLA-DQB1*03:01:01:21Q shows a substitution at the donor splice site of intron 3 that potentially could affect the expression of this allele. In order to determine their expression profile at RNA and protein level, we analyzed the presence of the HLA-DQ7 molecule by complement-dependent cytotoxicity test (CDC) and flow cytometry, and their RNA processing by cDNA analyses and sequencing by Sanger methods. Our results reveal that HLA-DQ7 is not detectable by serological methods, this is confirmed by cDNA methods demonstrating the absence of specific HLA-DQB1*03:01:01:21Q mRNA, probably due to an intron 3 retention that creates a premature TGA stop codon, leading to mRNA degradation via nonsense-mediated decay (NMD). These findings demonstrate that the HLA-DQB1*03:01:01:21Q allele is nonexpressed, thus it has been renamed as DQB1*03:01:01:21N.

Influence of past infection with SARS-CoV-2 on the response to the BNT162b2 mRNA vaccine in health care workers: Kinetics and durability of the humoral immune response.

BACKGROUND: SARS-CoV-2 vaccines are an invaluable resource against COVID-19. Current vaccine shortage makes it necessary to prioritize distribution to the most appropriate segments of the population. METHODS: This is a prospective cohort study of 63 health care workers (HCWs) from a General Hospital. We compared antibody responses to two doses of BNT162b2 mRNA COVID-19 vaccine between HCWs with previous SARS-CoV-2 infection (experienced HCWs) and HCWs without previous infection (naïve HCWs). FINDINGS: Seven days after the first vaccine dose, HCWs with previous infection experienced a 126-fold increase in antibody levels (p<0·001). However, in the HCW naïve group, response was much lower and only five showed positive antibody levels (>50 AU). After the second dose, no significant increase in antibody levels was found in experienced HCWs, whereas in naïve HCWs, levels increased by 16-fold (p<0·001). Approximately two months post-vaccination, antibody levels were much lower in naïve HCWs compared to experienced HCWs (p<0·001). INTERPRETATION: The study shows that at least ten months post-COVID-19 infection, the immune system is still capable of producing a rapid and powerful secondary antibody response following one single vaccine dose. Additionally, we found no further improvement in antibody response to the second dose in COVID-19 experienced HCWs. Nonetheless, two months later, antibody levels were still higher for experienced HCWs. These data suggest that immune memory persists in recovered individuals; therefore, the second dose of the COVID-19 vaccine in this group could be postponed until immunization of the remaining population is complete.

Description of four new HLA alleles: HLA-B*40:02:01:26, HLA-DQB1*03:01:29, HLA-DQB1*04:02:01:12, and HLA-DPB1*1195:01.

Four novel HLA alleles, HLA-B*40:02:01:26, HLA-DQB1*03:01:01:29, HLA-DQB1*04:02:01:12 and HLA-DPB1*1195:01, detected in Spanish individuals.