The association of class I HLA alleles and antibody levels after a single dose of measles vaccine

2003 ◽  
Vol 64 (1) ◽  
pp. 103-109 ◽  
Author(s):  
Robert M Jacobson ◽  
Gregory A Poland ◽  
Robert A Vierkant ◽  
V.Shane Pankratz ◽  
Daniel J Schaid ◽  
...  
Keyword(s):  
Single Dose ◽  
Class I ◽  
Measles Vaccine ◽  
Hla Alleles ◽  
Antibody Levels

scholarly journals Associations between Human Leukocyte Antigen Homozygosity and Antibody Levels to Measles Vaccine

2002 ◽  
Vol 185 (11) ◽  
pp. 1545-1549 ◽  
Author(s):  
Jennifer L. St. Sauver ◽  
Inna G. Ovsyannikova ◽  
Robert M. Jacobson ◽  
Steven J. Jacobsen ◽  
Robert A. Vierkant ◽  
...  
Keyword(s):  
Human Leukocyte Antigen ◽  
Human Leukocyte ◽  
Measles Vaccine ◽  
Leukocyte Antigen ◽  
Antibody Levels

HLA Alleles and Prognosis of PLA2R-Related Membranous Nephropathy

2021 ◽  
pp. CJN.18021120
Author(s):  
Wei-Bo Le ◽  
Jingsong Shi ◽  
Fan Yang ◽  
Si-Wen Gong
Keyword(s):  
Membranous Nephropathy ◽  
Prospective Cohort ◽  
Poor Prognosis ◽  
Significant Risk ◽  
Chinese Patients ◽  
Hla Alleles ◽  
Cox Analysis ◽  
Antibody Levels ◽  
Egfr Decline

Background and objectives Associations between HLA alleles and susceptibility to PLA2R-related membranous nephropathy have been well defined previously in Chinese patients. However, the relationships between HLA alleles and kidney outcome remain unclear. Design, setting, participants, & measurements Five HLA genes (DRB1, DQA1, DQB1, DRB3, and DRB5) were genotyped in a prospective cohort of 392 patients with PLA2R-related membranous nephropathy. The associations between HLA alleles and kidney outcomes were studied. Results A total of 79 HLA alleles were identified in this study. Four HLA alleles, DRB1*13:01 (n=12, HR 3.7, 95% CI 1.8 - 7.8, P < 0.001) , DQB1*06:03 (n=12, HR 3.7, 95% CI 1.8 - 7.8, P < 0.001), DRB1*04:05 (n=12, HR 3.8，95% CI 1.5 - 9.5, P = 0.004) and DQB1*03:02 (n=21, HR 3.1，95% CI 1.4 - 6.7, P = 0.005), were associated with a ≥ 40% eGFR decline during follow-up. DRB1*13:01 and DQB1*06:03 were tightly linked with each other. Forty-four of the 392 patients (11%) carried at least one of the four identified risk HLA alleles in this study. Compared with patients who were negative for all risk HLA alleles, those carrying at least one risk HLA allele had a significant risk of a ≥ 40% eGFR decline during follow-up (HR 3.9, 95% CI 2.3 - 6.7, P < 0.001). After adjusting for age, sex, proteinuria, albumin, eGFR, and anti-PLA2R antibody levels, multivariable Cox analysis showed that patients carrying any of the four risk HLA alleles remained associated with a higher risk of a ≥40% decline in eGFR (HR 4.1, 95% CI 2.3 - 7.1, P < 0.001). Conclusions Carrying any of the HLA alleles, DRB1*13:01/DQB1*06:03, DRB1*04:05 and DQB1*03:02, was independently associated with poor prognosis in Chinese patients with PLA2R-related membranous nephropathy.

scholarly journals Evaluation of Durability of a Single Dose of the Bivalent HPV Vaccine: The CVT Trial

2020 ◽  
Vol 112 (10) ◽  
pp. 1038-1046 ◽  
Author(s):  
Aimée R Kreimer ◽  
Joshua N Sampson ◽  
Carolina Porras ◽  
John T Schiller ◽  
Troy Kemp ◽  
...  
Keyword(s):  
Single Dose ◽  
Hpv Vaccine ◽  
Hpv Vaccination ◽  
Vaccine Trial ◽  
Enzyme Linked Immunosorbent Assay ◽  
Virus Like Particle ◽  
Long Term Follow Up ◽  
Antibody Levels

Abstract Background The authors investigated the durability of vaccine efficacy (VE) against human papillomavirus (HPV)16 or 18 infections and antibody response among nonrandomly assigned women who received a single dose of the bivalent HPV vaccine compared with women who received multiple doses and unvaccinated women. Methods HPV infections were compared between HPV16 or 18-vaccinated women aged 18 to 25 years who received one (N = 112), two (N = 62), or three (N = 1365) doses, and age- and geography-matched unvaccinated women (N = 1783) in the long-term follow-up of the Costa Rica HPV Vaccine Trial. Cervical HPV infections were measured at two study visits, approximately 9 and 11 years after initial HPV vaccination, using National Cancer Institute next-generation sequencing TypeSeq1 assay. VE and 95% confidence intervals (CIs) were estimated. HPV16 or 18 antibody levels were measured in all one- and two-dose women, and a subset of three-dose women, using a virus-like particle-based enzyme-linked immunosorbent assay (n = 448). Results Median follow-up for the HPV-vaccinated group was 11.3 years (interquartile range = 10.9–11.7 years) and did not vary by dose group. VE against prevalent HPV16 or 18 infection was 80.2% (95% CI = 70.7% to 87.0%) among three-dose, 83.8% (95% CI = 19.5% to 99.2%) among two-dose, and 82.1% (95% CI = 40.2% to 97.0%) among single-dose women. HPV16 or 18 antibody levels did not qualitatively decline between years four and 11 regardless of the number of doses given, although one-dose titers continue to be statistically significantly lower compared with two- and three-dose titers. Conclusion More than a decade after HPV vaccination, single-dose VE against HPV16 or 18 infection remained high and HPV16 or 18 antibodies remained stable. A single dose of bivalent HPV vaccine may induce sufficiently durable protection that obviates the need for more doses.

scholarly journals Gamma interferon levels among Bangladeshi children after measles vaccination

2015 ◽  
Vol 40 (3) ◽  
pp. 118-121
Author(s):  
S Sultana ◽  
S Tabassum ◽  
A Nessa ◽  
M Jahan
Keyword(s):  
Immune Response ◽  
Single Dose ◽  
Measles Virus ◽  
Mononuclear Cells ◽  
Gamma Interferon ◽  
Age Group ◽  
Measles Vaccine ◽  
Live Virus ◽  
Significant Difference ◽  
Measles Vaccination

Gamma interferon (IFN-?) plays an important role in the immune response to live measles virus vaccination. To study the immune response to measles vaccination, IFN-? level was estimated in 30 children. Of these, 24 children vaccinated with a single dose of measles vaccine at nine months of age and 06 children vaccinated with a second dose during the Measles Catch-up Immunization campaign. Measles vaccine strain was cultured in Vero cell line and the Tissue Culture Infective Dose (TCID)50 was used as standard live virus. Peripheral blood Mononuclear cells (PBMCs) was separated by Ficoll- Hypaque density gradient centrifugation and stimulated with measles virus antigens and mitogens (lectin), cultured in CO2 and IFN-? level was measured from culture supernatant by ELISA. On stimulation with measles antigen and lectin respectively, IFN-? level was highest (105 pg/ml and 226.54 pg/ml) in the 109-120 months age group while it was lowest (12.97±8.16 pg/ml and 13.16±8.0 pg/ml) in the 61-72 months age group. No significant difference was observed in IFN-? level after stimulation with either measles antigen or lectin among well-nourished (p<0.8) and mal-nourished (p<0.7) children suggesting that nutritional status did not have any effect on IFN-? level. However, IFN-? level was higher in children who received two dose of measles vaccine than those who received a single dose (p<0.001).Bangladesh Med Res Counc Bull 2014; 40 (3): 118-121

Anti-Leukemia Activity of Alloreactive NK Cells in Haploidentical HSCT in Pediatric Patients: Re-Defining the Role of Activating and Inhibitory KIR

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3002-3002 ◽  
Author(s):  
Daniela Pende ◽  
Stefania Marcenaro ◽  
Michela Falco ◽  
Stefania Martini ◽  
Maria Ester Bernardo ◽  
...  
Keyword(s):  
T Cell ◽  
Nk Cells ◽  
Nk Cell ◽  
Cell Subset ◽  
Hla Class I ◽  
Class I ◽  
Leukemia Cells ◽  
Hla Alleles ◽  
Time Points ◽  
Selection Of

Abstract T-cell depleted hematopoietic stem cell transplantation from haploidentical donors (haplo-HSCT) has been reported to benefit from the graft-versus-leukemia effect mediated by natural killer (NK) cells when donor displays NK alloreactivity versus the recipient. NK alloreactivity is mediated by NK receptors, namely Killer Ig-like receptors (KIR) which are specific for allotypic determinants that are shared by different HLA-class I alleles (referred to as KIR ligands). It is known that KIR2DL1 recognizes HLA-C alleles characterized by Lys at position 80 (C2 group), KIR2DL2/3 recognize HLA-C alleles characterized by Asn at position 80 (C1 group), KIR3DL1 recognizes HLA-B alleles sharing the Bw4 supertypic specificity (Bw4 group) and KIR3DL2 recognizes HLA-A3 and –A11 alleles. KIR2D/3DL are inhibitory receptors that, upon engagement with the cognate ligand, inhibit lysis. Activating KIRs, highly homologous in the extracellular domain to the inhibitory counterparts, are KIR2DS1, KIR2DS2 and KIR3DS1, but only KIR2DS1 has been shown to specifically recognize C2 group of alleles expressed on B-EBV cells. We analyzed 21 children with leukemia receiving haplo-HSCT from a relative after a myeloablative conditioning regimen; in all pairs, the expression of a given KIR ligand (HLA class I allele) of the donor was missing in the patient (i.e. KIR ligand-mismatched haplo-HSCT). T-cell depletion was performed through positive selection of CD34+ cells; no pharmacological immune suppression was employed after HSCT. KIR genotype of all donors was evaluated to detect the presence of the various inhibitory and activating KIR genes. Phenotypic analyses were performed on NK cells derived from the donor and the patient at different time points after HSCT. Thanks to the availability of new mAbs able to discriminate between the inhibitory and the activating forms of a certain KIR, we could identify the alloreactive NK cell subset at the population level. These alloreactive NK cells express the KIR specific for the KIR ligand-mismatch (permissive inhibitory KIR) and the activating KIR (if present), while they do not express all inhibitory KIR specific for the patient HLA alleles and NKG2A. Thus, in most instances, we could precisely identify the size of the alloreactive NK cell subset in the donor and in the reconstituted repertoire of the recipient. Functional assays were performed to assess alloreactivity, using appropriate B-EBV cell lines and, if available, patient’s leukemia blasts. In some cases, also NK cell clones were extensively studied, for phenotype and receptor involvement in killing activity. We found that, in most transplanted patients, variable proportions of donor-derived alloreactive NK cells displaying anti-leukemia activity were generated and maintained even at late time-points after transplantation. Donor-derived KIR2DL1+ NK cells isolated from the recipient displayed the expected capability of selectively killing C1/C1 target cells, including patient leukemia blasts. Differently, KIR2DL2/3+ NK cells displayed poor alloreactivity against leukemia cells carrying HLA alleles belonging to the C2 specificity. Unexpectedly, this was due to recognition of C2 by KIR2DL2/3, as revealed by receptor blocking experiments and by binding assays of soluble KIR to HLA-C transfectants. Remarkably, however, C2/C2 leukemia blasts were killed by KIR2DL2/3+ (or by NKG2A+) NK cells that co-expressed KIR2DS1. This could be explained by the ability of KIR2DS1 to directly recognize C2 on leukemia cells. A role for the KIR2DS2 activating receptor in leukemia cell lysis could not be established. Taken together, these findings provide new information on NK alloreactivity in haplo-HSCT that may greatly impact on the selection of the optimal donor.

Prevalence and Significance of Pre-Formed Anti-HLA Antibodies in Hematopoietic Stem Cell Transplant Recipients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1174-1174
Author(s):  
Darshan Gautam Gandhi ◽  
Jennifer Holter ◽  
Mohamad Khawandanah ◽  
Robert B. Epstein ◽  
Julie Stoner ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Graft Failure ◽  
Hla Antigens ◽  
Class Ii ◽  
Class I ◽  
Hla Antibodies ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
Antibody Levels

Abstract Abstract 1174 Poster Board I-196 Introduction: The presence of sensitization to HLA antigens has been an important consideration in solid organ transplantation. It is considered a standard process to check for donor-specific allogeneic (allo) antibodies (DSA) and monitor formation of such antibodies post-transplant which could predict early and late graft failure. Most of the current data regarding the importance of anti-HLA (human leukocyte antigen) antibodies is available from renal transplant where presence of HLA antibodies is clearly associated with an increased risk of early graft loss up to the magnitude of 21%. It is routine to perform desensitization to alleviate these antibodies in an effort to enhance their chances of engraftment. The role of and approach to prior sensitization in the hematopoietic stem cell transplantation (HSC) setting is far less clear. This is of unique importance as a wider range of donor cell sources and transplant applications are utilized to treat hematologic diseases. Many of our patients have had multiple transfusions in the past, been pregnant or have had prior HLA mismatched allograft, all of which predispose to development of anti-HLA antibodies. Here we analyze the prevalence of Class I and Class II antibodies as a primary goal and also see if they correlate with graft survival. Methods: 52 patients were followed between July 2008 and July 2009 with hematologic malignancies including leukemia's, lymphoma's, multiple myeloma and others. 37/52 underwent transplantation of which 14 were unrelated donor (URD), 5 cord blood (CB) and 8 sibling (sib) transplants. Donors with corresponding HLA were excluded. Post-transplantation with day 100 antibody testing was performed in eligible patients. Antibody determination was done by testing the patients' sera with a panel of fluorescent beads coated with single HLA antigens using a solid-phase Luminex™ platform. Cut-point of 1500 [mean fluorescence intensity (MFI) ≥ 1500 defined as positive] was used for performing statistical analyses. The prevalence of positive antibody levels was compared among the transplant groups using a Fisher's exact test. Level of expression of antibodies was evaluated with MFI <500 considered negative, 500-1500 weak, 1500-3000 intermediate and >3000 strong. High resolution HLA typing was performed. Results: Class I antibodies were positive in 24 out of 52 total (46%) with 95% CI: 32% to 61%.14/37 (38%) who underwent transplantation (95% CI: 22% to 55%), 12/27 (44%) undergoing allo transplant, CB (20%), sib (38%), and URD (57%) were positive. The prevalence did not differ significantly among the transplant groups (p=0.3). Class II antibodies were positive in 8 out of 52 total (15%) with 95% CI: 7% to 28%. 5/37 (14%) who underwent transplantation (95% CI: 5% to 29%), 4/27 (15%) undergoing allo transplant, Sib (0%), CB (20%) and URD (21%) were positive. The prevalence did not differ significantly among the transplant groups (p=0.6). In females, 18/28 (64%) were positive for Class I or Class II antibodies of which 5/6 (83%) underwent URD transplants. Persistent antibody levels were detected in 3 of 4 patients tested at day 100 post transplant. Conclusions: Based on this limited pilot study we conclude that there is a high prevalence of anti-HLA antibodies present in recipients at the time of HSC transplantation. However detection of such antibodies did not jeopardize engraftment from various donor sources when HLA donor specific reactions are excluded. Bray et al showed higher incidence of graft failure associated with DSA. Takanashi et al showed that in CB transplants, antibodies were not significant unless the corresponding HLA was present in the CB unit. Based on these studies, we excluded donors with corresponding HLA. All but one patient, in whom donor specific anti-HLA antibodies were identified, achieved sustained marrow engraftment. The long term implications of antibody evolution and specificity to sustained marrow engraftment, graft vs. host and graft vs. tumor effects remain to be clarified. A larger prospective study will need to be conducted to definitely evaluate these relationships including our own which is currently under way. Disclosures: No relevant conflicts of interest to declare.

C1q-Binding HLA Antibodies Do Not Predict Platelet Transfusion Failure in TRAP Study Participant

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1562-1562
Author(s):  
Rachael P. Jackman ◽  
Douglas Bolgiano ◽  
Mila Lebedeva ◽  
Sherrill J. Slichter ◽  
Philip J. Norris
Keyword(s):  
Conflicts Of Interest ◽  
Fluorescent Antibody ◽  
Study Participant ◽  
Class I ◽  
Detection Methods ◽  
Antibody Detection ◽  
Hla Antibodies ◽  
Luminex Assay ◽  
Single Antigen ◽  
Antibody Levels

Abstract Introduction: In the Trial to Reduce Alloimmunization to Platelets (TRAP) study, 101 of the 530 subjects became clinically refractory (CR) to platelet transfusions in the absence of detectable antibodies against HLA as measured by the lymphocytotoxicity assay (LCA). Using more sensitive bead-based detection methods we have previously demonstrated that while many of these LCA- patients do have anti-HLA antibodies, that these low to moderate level antibodies do not predict refractoriness. In addition to being less sensitive then bead based methods, the LCA screen only detects complement-binding antibodies. As these antibodies could be important for platelet rejection, we assessed if previously undetected complement-binding antibodies could account for some of the refractoriness seen in LCA- patients. Methods: 169 LCA- (69 CR, 100 non-CR) and 20 LCA+ (10 CR, 10 non-CR) subjects were selected from the TRAP study. Anti-class I HLA IgG and C1q binding antibodies were measured in serum or plasma using two different multi-analyte, semi-quantitative, bead-based fluorescent antibody detection assays: the LabScreen mixed Luminex assay, and the LabScreen single antigen class I assay with or without added EDTA (One Lambda). Groups were compared using an unpaired t-test, a=0.05, and correlation between variables was also assessed. Results: New measurements of anti-class I HLA IgG antibodies reliably reproduced earlier data with a strong correlation between the old and new measurements (R2=0.9736, p<0.0001). While some of the LCA- subjects did have detectable C1q-binding anti-class I HLA antibodies, and some LCA+ subjects did not, levels of these antibodies were significantly higher among LCA+ subjects (p<0.0001). Levels of C1q-binding anti-class I HLA antibodies were not significantly different between CR and non-CR among either the LCA- or LCA+ subjects. Conclusions: While complement-binding anti-class I HLA antibody levels were higher in the LCA+ subjects, higher levels of these antibodies were not seen in CR LCA+ patients as compared with non-CR LCA+ patients. Complement-binding anti-class I HLA antibodies do not account for refractoriness seen among the LCA- TRAP subjects. This work confirms that low to mid level anti-class I antibodies do not drive refractoriness to platelets, and suggests that antibody-independent mechanisms cause refractoriness in patients lacking higher levels of anti-HLA antibodies. Disclosures No relevant conflicts of interest to declare.

Positive Effect of Single-Dose Measles Vaccination in Reducing the Incidence of Pneumonia in Children with Measles

2020 ◽  
Author(s):  
Zafer Bağcı ◽  
Yunis Yusuf Daki
Keyword(s):  
Single Dose ◽  
Length Of Hospital Stay ◽  
Vaccination Rate ◽  
Hospitalization Rate ◽  
High Morbidity ◽  
Measles Vaccine ◽  
Hospitalization Rates ◽  
Training And Research ◽  
Measles Vaccination ◽  
Positive Effect

Abstract Aim Measles is a worldwide common, highly infectious and vaccine-preventable contagious disease with high morbidity and mortality rates. We investigated the effects of administering single-dose measles vaccination in children with measles on the incidence of pneumonia and hospitalization. Materials and methods We retrospectively analysed the hospital records of children aged 0–18 years who were diagnosed with measles within a year before the study in a training and research hospital in Mogadishu, Somalia. We compared the measles vaccine ratios, hospitalization rates, hospitalization duration and pneumonia development rates. Results We found that 34 (15.6%) patients had received measles vaccination, while 184 (84.4%) did not receive the vaccination. All the vaccinated patients received only a single dose of the vaccine. The proportion of those who had received pneumonia vaccine (14/34, 41.2%) was significantly lower than that of those who had never received a dose of measles containing vaccine (179/184, 97.3%) (p = 0.001). Moreover, patients who were immunized [n = 3 (3.1%)] had a significantly lower hospitalization rate than those who were not immunized [n = 94 (96.9%)] (p = 0.001). Conclusion The risk of pneumonia in children with measles vaccination, rate of hospitalization and length of hospital stay was significantly lower in children who had received even a single dose of the vaccine when compared with that in those who had not vaccinated. The results of this study reiterate the need for more effective global measles vaccination.

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