ABSTRACT
HLA molecules play a key role in transplant medicine and disease pathogenesis, being a useful tool in predicting disease progression and identifying potential solid organ donors (SOD). The Coronavirus disease 2019 (SARS-CoV-2) pandemic had a huge worldwide impact, which strongly affected the activity of different transplant programs. So far, it has been shown that HLA type may be a crucial differentiator between individuals who have varying occurrence, morbidity, and mortality response to SARS-CoV-2. In this work, we investigated if differences in the frequency of SOD HLA alleles, were impacted during SARS-CoV-2 pandemic. We performed a retrospective file audit of all HLA-typings done in 2 subsets of SOD pre-pandemic period (ppp) (n = 379) and pandemic period (pp) (n = 351), collected in equivalent timeframes. We discuss data for the major HLA-A, HLA-B, HLA-C, and HLA-DRB1 allele groups at serological phenotyping level. Overall, there was a 7% SOD decrease in the pp. Considering both periods, the most common allele groups were HLA-A2, HLA-B35, HLA-Cw7, HLA-DR7 and HLA-DQ2. For the ppp group, the most common alleles were HLA-A2, HLA-B35, HLA-Cw7, HLADR13 and HLA-DQ2, while in the pp group the most common alleles were HLA-A2, HLA-B44, HLA-Cw7, HLA-DR4 and HLA-DQ2. When comparing both populations at the serological phenotyping level an increased in relative frequency was found for 10, 12, 8, 8 and 2, and a decreased was found for 10, 24, 8, 6 and 5 for HLA-A, -B, -C, -DR and -DQ, respectively. The significant variation within the HLA frequencies between the different pre-pandemic and pandemic groups highlights the value of population-specific HLA-typing. Furthermore, the identification of different frequencies among both populations will impact in patients HLA compatibility with SOD thus impacting their transplantability.
ABSTRACT
Case report Background: Giant cell arteritis (GCA) is an immune-mediated vasculitis affecting large arteries. It has been hypothesized that pathogens including viruses may trigger inflammation within the vessel walls. Human leukocyte antigens' (HLA) genetic studies have previously reported HLA-DR4 (HLA-DRB1* 04 and HLA-DRB1* 01) as susceptibility, and HLA-DR2 (HLA-DRB1* 15 and HLA-DRB1* 16) as protective alleles for GCA. Here we report two cases of large vessel (LV) GCA diagnosed in patients previously suffered from mild coronavirus disese 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2). Case presentation: First case, a 69-year- old male, had a mild COVD-19 three months before the appearance of headache, malaise, and a febrile state associated with extremely increased inflammatory parameters (CRP 2847 mg/dl and IL-6 802.3 pg/ml). Computed tomography examination of the aorta (CTA) and the branches, performed in two occasions six months apart, showed an interesting picture of a migratory arteritis. HLA typing showed: HLA-A* 2,-A* 24;-B* 51,-B* 57;-DRB1* 15,-DRB1* 16;-DQB1* 05,-DQB1* 06;Second case, a 64-year- old female, was evaluated for LV-GCA two months after a mild COVID-19, when she presented with elevated CRP (183mg/dl) and systemic symptoms. Thickening of the ascending aorta and the aortic arch was seen on CTA. Typing of HLA revealed: HLA-A* 2,-A* 11;-B* 27,-B* 35;-DRB1* 14,-DRB1* 15;-DQB1* 05,-DQB1* 06;A whole-body 18F-FDG- PET/ CT performed in both cases revealed inflammation of the ascending, aortic arch, thoracic and abdominal aorta. The first patient had appearance of the inflammatory involvement of the iliac and femoral arteries, while the second patient had an additional pulmonary trunk inflammation. Corticosteroid treatment was introduced in both cases. Due to a progressive inflammatory course of LV-GCA in the first case, the IL-6 inhibitor (tocilizumab) was initiated, leading to a clinical and laboratory improvement. In conclusion, LV-GCA may be considered as an autoimmune disease triggered by SARS-CoV- 2, as one of the broad spectrum of manifestation within the post acute COVID-19. None of the previously known HLA susceptibility alleles for GCA were detected in our patients. In contrast, both patients had DRB1*15 allele, and one of them was DRB1*15/DRB1*16 carrier, suggesting a possibility of losing their protective effect in LV-GCA induced by COVID-19.
ABSTRACT
Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the etiology of an outbreak Covid-19. SARS-CoV-2 has a structural part consisting of spike glycoprotein, nucleoprotein N, membrane M and envelopes small membrane pentamer E. Immunoinformatic approach epitope analysis is developed to identify both weak and robust epitopes. Our study aims to identify several epitopes present in the spike glycoprotein, envelope, and membrane protein from the SARCoV-2 surface, with the help of insilico approach that highly potential as vaccine candidates. Analysis of antigeninicity was performed with the Kolaskar and Tongaonkar Antigenicity software. Epitope Mapping was analyzed using Linear Epitope Prediction Bepired. The structure of proteins with epitope regions was visualized by software Pyrex and PyMOL. Conserve analysis was performed using bio edit software. HLA mimicry was analyzed through HLAPred software. Molecular docking between the epitope with HLA I and HLA II was validated by Chimera and PyMOL software. The toxicity test for candidate vaccine peptides was carried out using ToxinPred software. Our study found seven potential epitope candidates as vaccine candidates. The seven epitopes were derived from spike proteins (5 epitopes), envelope proteins (1 epitope), and membrane proteins (1 epitope). All epitope codes are conserved and are not the same as HLA in Humans. The docking test results show a value with low affinity so that a strong bond can provide a high immune response. Toxicity tests show that all epitopes are non-toxic and safe to use as vaccine ingredients. Seven peptides from the spike, envelope, membrane protein that showed potential as vaccine candidates against Covid-19.
ABSTRACT
Background: The polymorphic Human Leukocyte Antigens (HLA) play an important role in determining the best matched donor in a haematopoietic stem cell transplant (HSCT). Hence, accurate HLA typing results are crucial to determine the successfulness of a transplant. Most of the patients of hematologic diseases will receive blood transfusion regularly. There is a potential discrepancy result or ambiguous results when a patient already received non-leukoreduced blood component prior to blood sampling for HLA typing. Aims: To determine differences between the HLA typing result from the DNA extracted from blood sample and buccal swab sample. Methods: Blood sample and buccal swab sample were collected from a total of 66 patients with different hematologic diseases and plan to go for haematopoietic stem cell transplant. These patients received at least one pack of red blood cell or platelet between 1 and 14 days prior to blood sample taken. DNA was extracted from all 66 blood samples and 66 buccal swab samples. All samples were typed for six loci (HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQB1 and HLA-DPB1) with Next Generation Sequencing (NGS). NGS was performed in all those samples using the NGSgo-MX6-1 kit. After the library preparation by using NGSgo-LibrX ligation reagents and the NGSgoIndX adapter, it was sequenced in iSeq 100. The results were then analysed with NGSengine software. The results for blood sample and buccal swab sample were then compared. Results: Out of 66 patients, 25 patients received either red blood cell or platelet component prior to blood sample taken for HLA typing. One patient received red blood cell and plasma and the others received red blood cell and platelets before the sample was taken. There are no differences between the HLA typing result from the DNA extracted from blood sample or buccal swab sample for all the 66 patients. The sequencing noise level for both DNA extracted from blood and buccal swab was well separated from the alleles as we can see from the base variation plot. Summary/Conclusions: This preliminary study only focus on the adult patients with hematologic diseases (ALL, AML, CML, MDS, multiple myeloma, DLBCL, hemophagocytic lymphohistiocytosis, NKT Cell lymphoma and severe aplastic anaemia) for the past 1 year. From the findings of this study, blood samples from the patient who underwent blood transfusion can be used for HLA typing instead of using buccal swab samples. This will lower the risk of Covid-19 infection among the healthcare worker who performs the buccal swab sampling from the patient with unknown status of Covid-19 infectivity. However, an extensive study with the appropriate number of samples needed to confirm this finding in the near future.
ABSTRACT
BACKGROUND AND AIMS: A Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), presents with severe pneumonia and fatal systemic complications. Currently, SARS-CoV- 2 vaccines are effective in reducing the risk of onset and severity of the disease. However, autoimmune diseases, including anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), have been reported as rare complications of the COVID-19 vaccine. Although the mechanism of ANCA vasculitis remains unknown, the genetic background, environmental factors and infections are involved in the development of the disease. Genome-wide association studies have identified several AAV-related haplotypes, including the human leukocyte antigen (HLA)-DRB1∗09: 01 allele. Here, we report a case of AAV with a risk HLA allele after SARS-CoV-2 vaccination (Pfizer-BioNTech) and a literature review. METHOD: Case report: A 71-year-old woman visited a clinic complaining of fever (37.0-37.5°C) and malaise, 1 week after receiving second dose of COVID-19 vaccine (Pfizer-BioNTech). Two months after her first dose, her serum creatinine (Cr) level had increased from 0.86 mg/dL to 1.2 mg/dL with high titer of MPO-ANCA (280 IU/mL, normal value <3.5 IU/mL). Urinary microscopy revealed a red blood cell count of 30-49/high power field and a urinary protein-creatinine ratio of 1.06 g/gCr. We diagnosed MPO-AAV with manifestations of renal involvement, general symptoms and the presence of ANCA, as a cause of renal progressive glomerulonephritis. A course of corticosteroids and intravenous cyclophosphamide was initiated. After treatment, her general symptoms and urinary abnormalities disappeared, and renal insufficiency was improved as well. Three months later, the MPO-ANCA titer decreased to 27.4 IU/mL. We examined a human leukocyte antigen (HLA) haplotype and her allele was HLA-DRB1∗09:01, which is a known risk allele of MPO-ANCAassociated vasculitis. RESULTS: Review: Until November 30, 2021, we searched PubMed, including the case report study and seven cases have been reported as De novo AAV after SARS-CoV-2 vaccination. The mean age of patients was 72.5 years (three women and four men). The onset of symptomatic symptoms, such as fever, headache and malaise, ranged from the day after the first dose to 2 weeks after the second dose;consequently, renal dysfunction was detected. In six patients (except for our case), histological findings showed pauci-immune crescentic glomerulonephritis. Most patients received initial induction immunosuppressive therapy, including corticosteroids and cyclophosphamide, followed by maintenance therapy. The renal involvement of six patients improved, but one patient with severe renal dysfunction developed end-stage renal disease. Information on HLA allele was not available in any case. CONCLUSION: This is the first case report of De novo AAV after SARS-CoV-2 vaccination in a patient with AAV susceptible HLA-DRB1∗09:01 allele. (Table Presented).