Antibody Response In Recipients Research Articles

Persistent and robust antibody responses to ChAdOx1-S Oxford-AstraZeneca (ChAdOx1-S, Covishield) SARS-CoV-2 vaccine observed in Ugandans across varied baseline immune profiles.

Understanding SARS-CoV-2 vaccine-induced antibody responses in varied antigenic and serological prior exposures can guide optimal vaccination strategies for enhanced immunogenicity. We evaluated spike (S)-directed IgG, IgM, and IgA antibody optical densities (ODs) and concentrations to the two-dose ChAdOx1-S Oxford-AstraZeneca (ChAdOx1-S, Covishield) SARS-CoV-2 vaccine in 67 Ugandans, categorised by prior infection and baseline S-IgG histories: uninfected and S-IgG-negative (n = 12); previously infected yet S-IgG-negative (n = 17); and previously infected with S-IgG-positive status (n = 38). Antibody dynamics were compared across eight timepoints from baseline till nine months. S-IgG antibodies remained consistently potent across all groups. Individuals with prior infections maintained robust S-IgG levels, underscoring the endurance of hybrid immunity. In contrast, those without prior exposure experienced an initial surge in S-IgG after the primary dose but no subsequent significant increase post-boost. However, they reached levels parallel to the previously exposed groups. S-IgM levels remained moderate, while S-IgA persisted in individuals with prior antigen exposure. ChAdOx1-S, Covishield vaccine elicited robust and sustained antibody responses in recipients, irrespective of their initial immune profiles. Hybrid immunity showed higher responses, aligning with global observations. Early post-vaccination antibody levels could predict long-term immunity, particularly in individuals without virus exposure. These findings can inform vaccine strategies and pandemic management.

Serological Response to COVID-19 and Its Association With Measles-Rubella (MR)-Containing Vaccines.

Epidemiological studies suggest that coronavirus disease 2019 (COVID-19) has a less severe disease course and a more favorable prognosis among children. Childhood vaccines and heterologous immunity have been suggested as reasons for this. Additionally, the structural similarity between the measles, rubella, and severe acute respiratory syndrome coronavirus2 (SARS-CoV-2) virus particles may affect immune responses. The objective of this study was to compare COVID-19 antibody titers and disease severity between measles-rubella (MR) vaccinated and unvaccinated children. Additionally, we aimed to evaluate and compare the antibody response in recipients of a single dose and two doses of the MR vaccine. The study was prospective and comparative and included 90 COVID-19-positive children aged nine months to 12 years. The study was registered under the clinical trials registry of India (CTRI/2021/01/030363). COVID-19 antibody titers were measured at two weeks, six weeks, and 12 weeks, along with the assessment of MR antibody titers. COVID-19 antibody titers and disease severity were compared between MR-vaccinated and MR-unvaccinated children. The comparison of COVID-19 antibody titers between recipients of a single dose and two doses of MR vaccine was also conducted. The results showed significantly higher median COVID-19 antibody titers at all time points during follow-up in the MR-vaccinated group (P<0.05). However, the two groups had no significant difference in the disease severity. Moreover, there was no difference in the antibody titers of MR one dose and two dose recipients. Exposure to even a single dose of MR-containing vaccine enhances the antibody response against COVID-19. However, randomized trials are necessary to further explore this subject.

Differential dengue antibody responses in recipients of a Zika DNA vaccine are governed by dengue immune history

Abstract Dengue virus (DENV 1–4) and Zika virus (ZIKV) are closely related flaviviruses that induce immunological cross-reactivity. The VRC5283 Zika virus wild type DNA vaccine is the first to complete a Phase 2b trial (NCT03110770). The objective of this study was to test if VRC5283 induced potent ZIKV-specific neutralizing antibodies (NAbs) while avoiding priming of cross-reactive antibodies that could potentially enhance dengue disease. Here, we measured NAbs to DENV1–4 and ZIKV in serum samples obtained from individuals living in dengue-endemic (Puerto Rico) and non-endemic areas (Texas) immunized with VRC5283 at weeks 0, 4, and 8. We performed plaque reduction neutralization tests (PRNT 50) with sera collected at weeks 0 and 16 after final vaccination. Sera were tested for ZIKV isolated in Brazil, and DENV1–4 isolated in Sri Lanka. Most individuals from dengue-endemic areas had NAbs &amp;gt;1:20 to DENV1–4 and ZIKV prior to vaccination, with the highest NAb titers to DENV2. VRC5283 boosted immunity across all flaviviruses in the dengue-endemic cohort, with an 8.47-fold increase in ZIKV, 2.76-fold increase in DENV1, 1.67-fold increase in DENV3 and 2.06-fold increase in DENV4 titers, but did not significantly boost DENV2 titers. Sera from non-endemic areas had no NAbs to DENV1–4 or ZIKV prior to vaccination, and a boost in NAbs following vaccination was observed only to ZIKV. Thus, VRC5283 only induces dengue cross-reactive NAbs in individuals with prior dengue immunity. Ongoing testing with binding assays will further evaluate whether vaccination induced beneficial or enhancing antibodies to DENV1–4. This work was supported by the Intramural Research Program of NIAID.

Serum Metabolic Correlates of the Antibody Response in Subjects Receiving the Inactivated COVID-19 Vaccine.

Metabolites are involved in biological process that govern the immune response to infection and vaccination. Knowledge of how metabolites interact with the immune system during immunization with the COVID-19 vaccine is limited. Here, we report that the serum metabolites are correlated with the magnitude of the antibody response in recipients receiving the inactivated COVID-19 vaccine, which provides critical information for studying metabolism regarding the human immune response to vaccination. 106 healthy volunteers without history of SARS-CoV-2 infection or vaccination were prospectively enrolled to receive the primary series of two doses of inactivated whole-virion SARS-CoV-2 vaccine. The serum samples were collected 2-4 weeks after the second dose. The magnitude of the anti-RBD antibody was quantified using surrogate virus neutralization tests. The profile of metabolites in serum was identified using untargeted metabolomics analysis. The level of anti-RBD antibody 14-28 days after the second dose was significantly elevated and its interpersonal variability was diverse in a wide range. Thirty-two samples at extremes of the anti-RBD antibody titer were selected to discover the metabolic correlates. Two hundred and fifteen differential metabolites associated with antibody response independent of body mass index were identified. Pregnenolone and sphingolipid metabolism might be involved in the modulation of the human antibody response to the inactivated COVID-19 vaccine. We discovered key metabolites as well as those with a related functional significance that might modulate the human immune response to vaccination.

Safety and antibody response of recipients who unexpectedly received undiluted prime dose of BNT162b2 COVID-19 vaccine in Taiwan

We reported 25 recipients (14 females and 11 males) aged from 18 to 65 years who unexpectedly received a primary dose of undiluted BNT162b2 vaccine (180 μg). The most common adverse reactions included injection site pain (n = 22), followed by fever (9), fatigue (8), chest tightness (6), and dizziness (6). The most common laboratory abnormalities were anemia (n = 4) and elevated liver transaminase level (4), followed by abnormal leukocyte counts (3) and elevated D-dimer level (3). The adverse reactions and laboratory abnormalities of these recipients were mild and spontaneously recovered within a few weeks. Significant elevations of anti-SARS-CoV-2 spike IgG titers after a booster dose of the BNT162b2 were found. Similar to reports of BNT162b2 clinical trials, the adverse reactions and laboratory abnormalities of these recipients were mild, and they spontaneously recovered within a few weeks. These results provide clinical and immunological effects of undiluted BNT162b2 vaccine inoculation.

Evaluating the Response and Safety of Inactivated COVID-19 Vaccines in Liver Transplant Recipients.

PurposeTo evaluate the response and safety of an inactivated vaccine (Sinovac Life Sciences Co., Ltd., Beijing, China) for coronavirus disease 2019 (COVID-19) in liver transplant (LTx) recipients from China.Patients and MethodsThirty-five recipients post LTx from the First Affiliated Hospital of Zhejiang University School of Medicine who received inactivated vaccine from June to October 2021 were screened. Information regarding vaccine side effects and clinical data were collected.ResultsThirty-five LTx recipients were enrolled, with a mean age of 46 years, and most patients were male (30, 85.71%). All the participants had a negative history of COVID-19 infection. Predictors for negative response in the recipients were interleukin-2 receptor (IL-2R) induction during LTx, shorter time post LTx and application of a derivative from mycophenolate acid (MPA). No serious adverse events were observed during the progress of vaccination or after the vaccination.ConclusionLTx recipients have a substantially partial immunological response to the inactivated vaccine for COVID-19. IL-2R induction during LTx, a shorter time post LTx and the application of a derivative from MPA seem to be predictors for a negative serological immunoglobulin G (IgG) antibody response in recipients. The findings require booster vaccination in these LTx recipients.

Convalescent plasma for pediatric patients with SARS-CoV-2-associated acute respiratory distress syndrome.

There are no proven safe and effective therapies for children who develop life-threatening complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Convalescent plasma (CP) has demonstrated potential benefit in adults with SARS-CoV-2, but has theoretical risks.We present the first report of CP in children with life-threatening coronavirus disease 2019 (COVID-19), providing data on four pediatric patients with acute respiratory distress syndrome. We measured donor antibody levels and recipient antibody response prior to and following CP infusion. Infusion of CP was not associated with antibody-dependent enhancement (ADE) and did not suppress endogenous antibody response. We found CP was safe and possibly efficacious. Randomized pediatric trials are needed.

RhCMV serostatus and vaccine adjuvant impact immunogenicity of RhCMV/SIV vaccines

Rhesus cytomegalovirus (RhCMV) strain 68-1-vectored simian immunodeficiency virus (RhCMV/SIV) vaccines are associated with complete clearance of pathogenic SIV challenge virus, non-canonical major histocompatibility complex restriction, and absent antibody responses in recipients previously infected with wild-type RhCMV. This report presents the first investigation of RhCMV/SIV vaccines in RhCMV-seronegative macaques lacking anti-vector immunity. Fifty percent of rhesus macaques (RM) vaccinated with a combined RhCMV-Gag, -Env, and -Retanef (RTN) vaccine controlled pathogenic SIV challenge despite high peak viremia. However, kinetics of viral load control by vaccinated RM were considerably delayed compared to previous reports. Impact of a TLR5 agonist (flagellin; FliC) on vaccine efficacy and immunogenicity was also examined. An altered vaccine regimen containing an SIV Gag-FliC fusion antigen instead of Gag was significantly less immunogenic and resulted in reduced protection. Notably, RhCMV-Gag and RhCMV-Env vaccines elicited anti-Gag and anti-Env antibodies in RhCMV-seronegative RM, an unexpected contrast to vaccination of RhCMV-seropositive RM. These findings confirm that RhCMV-vectored SIV vaccines significantly protect against SIV pathogenesis. However, pre-existing vector immunity and a pro-inflammatory vaccine adjuvant may influence RhCMV/SIV vaccine immunogenicity and efficacy. Future investigation of the impact of pre-existing anti-vector immune responses on protective immunity conferred by this vaccine platform is warranted.

Clinical Predictors of Donor Antibody Titer and Correlation with Recipient Antibody Response in a COVID-19 Convalescent Plasma Clinical Trial

ABSTRACT Background Convalescent plasma therapy for COVID-19 relies on the transfer of anti-viral antibody from donors to recipients via plasma transfusion. The relationship between clinical characteristics and antibody response to COVID-19 is not well defined. We investigated predictors of convalescent antibody production and quantified recipient antibody response in a convalescent plasma therapy clinical trial. Methods Multivariable analysis of clinical and serological parameters in 103 confirmed COVID-19 convalescent plasma donors 28 days or more following symptom resolution was performed. Mixed effects regression models with piecewise linear trends were used to characterize serial antibody responses in 10 convalescent plasma recipients with severe COVID-19. Findings Mean symptom duration of plasma donors was 11.9±5.9 days and 7.8% (8/103) had been hospitalized. Antibody titers ranged from 0 to 1:3,892 (anti-receptor binding domain (RBD)) and 0 to 1:3,289 (anti-spike). Multivariable analysis demonstrated that higher anti-RBD and anti-spike titer were associated with increased age, hospitalization for COVID-19, fever, and absence of myalgia (all p Interpretation Advanced age, fever, absence of myalgia, fatigue, blood type and hospitalization were associated with higher convalescent antibody titer to COVID-19. Despite variability in donor titer, 80% of convalescent plasma recipients showed significant increase in antibody levels post-transfusion. A more complete understanding of the dose-response effect of plasma transfusion among COVID-19 patients is needed to determine the clinical efficacy of this therapy. Trial Registration NCT04340050 Funding Department of Surgery University of Chicago, National Institute of Allergy and Infectious Diseases (NIAID) Collaborative Influenza Vaccine Innovation Centers (CIVIC) contract 75N93019C00051

Missing self triggers NK cell-mediated chronic vascular rejection of solid organ transplants

Current doctrine is that microvascular inflammation (MVI) triggered by a transplant -recipient antibody response against alloantigens (antibody-mediated rejection) is the main cause of graft failure. Here, we show that histological lesions are not mediated by antibodies in approximately half the participants in a cohort of 129 renal recipients with MVI on graft biopsy. Genetic analysis of these patients shows a higher prevalence of mismatches between donor HLA I and recipient inhibitory killer cell immunoglobulin-like receptors (KIRs). Human in vitro models and transplantation of β2-microglobulin-deficient hearts into wild-type mice demonstrates that the inability of graft endothelial cells to provide HLA I-mediated inhibitory signals to recipient circulating NK cells triggers their activation, which in turn promotes endothelial damage. Missing self-induced NK cell activation is mTORC1-dependent and the mTOR inhibitor rapamycin can prevent the development of this type of chronic vascular rejection.

Superior immunogenicity of HCV envelope glycoproteins when adjuvanted with cyclic-di-AMP, a STING activator or archaeosomes.

Three decades after the discovery, hepatitis C virus (HCV) is still the leading cause of liver transplantation and poses a major threat to global health. In spite of recent advances in the development of direct acting antivirals, there is still a need for a prophylactic vaccine to limit the virus spread and protect at-risk populations, especially in developing countries, where the cost of the new treatments may severely limit access. The use of recombinant HCV glycoproteins E1E2 (rE1E2) in combination with the MF59, an oil-in-water emulsion-based adjuvant, has previously been shown to reduce the rate of chronicity in chimpanzees and to induce production of cross-neutralizing antibodies and cellular immune responses in human volunteers. To further improve neutralizing antibody responses in recipients along with robust T cell responses, we have explored the immunogenicity of different adjuvants when formulated with the HCV rE1E2 vaccine in mice. Our data show that cyclic di-adenosine monophosphate (c-di-AMP) and archaeosomes elicit strong neutralizing antibodies similar to those elicited using aluminum hydroxide/monophosphoryl lipid A (Alum/monophos. /MPLA) and MF59. However, both c-di-AMP and archaeosomes induced a more robust cellular immune response, which was confirmed by the detection of vaccine-specific poly-functional CD4+ T cells. We conclude that these adjuvants may substantially boost the immunogenicity of our E1E2 vaccine. In addition, our data also indicates that use of a partial or exclusive intranasal immunization regimen may also be feasible using c-di-AMP as adjuvant.

Antibodies Are Required for Complete Vaccine-Induced Protection against Herpes Simplex Virus 2.

Herpes simplex virus 2 (HSV-2) 0ΔNLS is a live HSV-2 ICP0 - mutant vaccine strain that is profoundly attenuated in vivo due to its interferon-hypersensitivity. Recipients of the HSV-2 0ΔNLS vaccine are resistant to high-dose HSV-2 challenge as evidenced by profound reductions in challenge virus spread, shedding, disease and mortality. In the current study, we investigated the requirements for HSV-2 0ΔNLS vaccine-induced protection. Studies using (UV)-inactivated HSV-2 0ΔNLS revealed that self-limited replication of the attenuated virus was required for effective protection from vaginal or ocular HSV-2 challenge. Diminished antibody responses in recipients of the UV-killed HSV-2 vaccine suggested that antibodies might be playing a critical role in early protection. This hypothesis was investigated in B-cell-deficient μMT mice. Vaccination with live HSV-2 0ΔNLS induced equivalent CD8+ T cell responses in wild-type and μMT mice. Vaccinated μMT mice shed ~40-fold more infectious HSV-2 at 24 hours post-challenge relative to vaccinated wild-type (B-cell+) mice, and most vaccinated μMT mice eventually succumbed to a slowly progressing HSV-2 challenge. Importantly, passive transfer of HSV-2 antiserum restored full protection to HSV-2 0ΔNLS-vaccinated μMT mice. The results demonstrate that B cells are required for complete vaccine-induced protection against HSV-2, and indicate that virus-specific antibodies are the dominant mediators of early vaccine-induced protection against HSV-2.

Reactogenicity and immunogenicity of measles-rubella combined vaccine in school-entry-aged subjects with naturally acquired measles immunity.

The reintroduction of measles-rubella combined (MR) vaccination to Japan raised concerns about adverse events as well as immunogenicity related to booster immunization in subjects with naturally acquired immunity to measles or rubella. The time course of reactogenicity and antibody responses in recipients with pre-existing immunity to measles through natural infection was observed. Eighteen children aged 80-104 months received MR booster vaccination; 16 of them had had previous rubella vaccination. There were virtually no clinical reactions related to booster vaccination, and a highly significant antibody response to rubella antigen, whereas the antibody rise to measles was statistically significant but poor. Vaccination of individuals already immune is not harmful. Booster immunization to rubella for Japanese children is vitally important.

MICA Molecules in Disease and Transplantation, a Double-Edged Sword?

Major histocompatibility complex class I chain-related member A (MICA) encodes a stress-induced cellsurface glycoprotein that is expressed in keratinocytes, fibroblasts and gastrointestinal epithelium, among others. MICA is not associated with β2-microglobulin and does not appear to present peptides. MICA displays a high degree of allele polymorphism within the non-classical HLA gene loci. The functional significance of these polymorphisms is unknown, although certain changes in protein amino acid sequence cause an abnormal expression or affinity with NKG2D, its ligand on the surface of NK, γδ-T and CD8+ lymphocytes, affecting NK-cell activation and T-cell response modulation. Indeed, many tumoral cells express MICA on their surface, and circulating soluble MICA also triggers NKG2D downregulation and impairs lymphocyte cytotoxicity in tumoral escape. This demonstrates the therapeutic potential of anti-MICA antibodies to overcome immune suppression and trigger tumor destruction. MICA also affects organ transplants outcome, as MICA antigens elicit a very powerful antibody response in recipients of organ allografts. NKG2D ligand induction might also participate in the amplification loop that leads to tissue damage during acute graft vs. host disease. MICA is also an important candidate gene for a number of clinically significant diseases, including diabetes, rheumatoid arthritis, and other autoimmune diseases. This updated version of our previous review highlights the advantages and limitations of MICA gene studies in several pathologies and transplantation, and critically discusses the most recent and updated findings in this rapidly evolving field. Keywords: MICA, transplant, tumours, polymorphism, natural killer (NK), NKG2D, NKG2DL, HLA, MHC, allele frequencies, homeostasis

HLA Sensitization and Allograft Bone Graft Incorporation

Achieving union between host bone and massive structural allografts can be difficult. Donor and recipient human leukocyte antigen (HLA) mismatches and recipient antibody response to donor HLA antigens might affect union. In a prospective multiinstitutional study, we enrolled a consecutive series of patients receiving cortex-replacing, massive structural bone allografts to determine the rate of donor-specific HLA antibody sensitization and to investigate the potential effect of such HLA alloantibody sensitization on allograft incorporation. HLA typing of patients and donors was determined by molecular typing methods. Donor-specific HLA sensitization occurred in 57% of the patients but had no demonstrable effect on graft incorporation or union. The type of host-allograft junction did have a major effect on graft incorporation. Cortical-to-cortical allograft-to-host junctions healed more slowly (mean, 542 days) than corticocancellous to corticocancellous allograft-to-host junctions (mean, 243 days). Although HLA sensitization does not appear to delay structural allograft bone incorporation, further followup is required to determine if there is an association between HLA sensitization and long-term graft survival. Based on these preliminary data, measures to further minimize or modulate HLA sensitization or response are not indicated at present for the purposes of improving structural bone allograft union. Level II, prognostic study.

Cytomegalovirus-specific CD4 T-cell and glycoprotein B specific antibody response in recipients of allogenic stem cell transplantation

Background The human cytomegalovirus (HCMV) causes severe complications in immunosuppressed patients, resulting in increased morbidity and mortality. The immunological components important for the control of HCMV are still not completely understood. Objective and study design To evaluate the importance of cellular and humoral immunity in stem cell transplant (SCT) recipients, we analysed levels of HCMV specific IFN-γ producing CD4 + cells and glycoprotein B (gB) specific antibodies in HCMV positive SCT patients with and without reactivation episodes after SCT. Results and conclusion Patients without HCMV reactivation episodes showed a slow but steady increase in both parameters after SCT, indicating that initial high levels of gB specific antibodies or HCMV specific CD4 + IFN-γ+ cells are not necessary to prevent reactivation of HCMV. In contrast, patients with reactivation episodes showed a steep, significant increase in HCMV specific CD4 + IFN-γ+ counts just prior to HCMV reactivation, followed by a decline after the reactivation period. Patients who underwent only a single reactivation generated significant higher amounts of CD4 + IFN-γ+ cells, than did patients with further reactivation episodes. The course of gB specific antibodies for reactivating patients was different, with significantly higher average values in the patients with HCMV reactivation. This indicates that patients with a HCMV reactivation exhibit a stronger humoral dominated immune response.

In Vivo Recognition by the Host Adaptive Immune System of Microencapsulated Xenogeneic Cells

Microencapsulation is under consideration as a means of enabling pancreatic islet transplantation. To understand better the ongoing destructive host response, we examined whether the adaptive immune system of the recipient recognized polymer-encapsulated xenogeneic cells implanted intraperitoneally. Balb/c mice were implanted with xenogeneic Chinese hamster ovary cells, inside and outside poly(hydroxyethyl methacrylate-methyl methacrylate) microcapsules, and responses were compared with xenografted Chinese hamster skin (positive control). Capsules were localized within an agarose rod. Splenocyte proliferation upon rechallenge in vitro, antibody titer in serum, and Th1/2 polarization (assessed by interleukin-4 and interferon-gamma in supernatants of antigen-challenged splenocytes and immunoglobulin [Ig]G1 and IgG2a antibody isotypes in serum) were measured. Encapsulation did not prevent a strong recipient antibody response. Splenocyte proliferation in vitro did not differ after priming by implanted cells, inside or outside capsules. Thus, the capsule membrane did not prevent indirect recognition of shed antigens. However, after 10 days of implantation, proliferation was lower than that induced by skin grafts, although this difference disappeared by 2 months. This transient T-cell suppression was unexpected because encapsulated cell viability was already compromised by 10 days. The influence of Th1/2 bias did not explain the observed suppression. Cells inside capsules elicited a consistent Th2 response, whereas cells outside capsules elicited a mixed response, and skin xenografts showed an initial Th2 response that became mixed by 2 months. Encapsulation does not prevent host immune responses, but the inflammatory response to the implanted biomaterials or xenogeneic cells may be responsible both for encapsulated cell death and transient T-cell suppression.

Demographic Factors That Influence the Neutralizing Antibody Response in Recipients of Recombinant HIV‐1 gp120 Vaccines

We compared neutralizing antibody responses in human immunodeficiency virus (HIV) type 1 gp120 vaccine recipients by age, sex, and race. Four phase 1 or 2 trials involving 505 vaccinated subjects were analyzed. Age and sex had no detectable effect on neutralizing antibody responses. However, race influenced the response to one vaccine, MN gp120, in alum. Four inoculations with this vaccine generated higher serum titers of neutralizing antibodies in African Americans than in whites. Despite potent neutralization of T cell line-adapted HIV-1, serum from these African Americans failed to neutralize primary HIV-1 isolates. Neutralizing antibody responses did not differ between races when SF2 gp120 in MF-59 was administered either alone or with recombinant canarypox vCP205; they also did not differ when vCP1452 was administered either alone or with AIDSVAX B/B in alum. These data indicate that race may affect the neutralizing antibody response to some gp120 immunogens. To fully evaluate immunogenicity, clinical trials of candidate vaccines should enroll diverse populations of subjects.

Incidence and role of antibody in graft injury: How can it best be monitored?

Alloantibodies, either preexisting or de novo developed, are associated with hyperacute, acute, and chronic rejection. Human leukocyte antigens (HLAs) are one of the major causal contributors of recipient antibody response. The average percent posttransplant antibodies specific for HLAs is 14.2% in 113 lung, 19.3% in 278 liver, 20.9% in 3,979 kidney, and 22.8% in 393 heart transplant recipients with a functioning graft. Within 1-year of follow-up, 21 of 244 (8.6%) antibody-positive patients experienced graft rejection, which is significantly higher than that found in an HLA antibody-negative patient group (43/1421∗100% = 3%, P = .00003). Other polymorphic antigens such as MHC class I—related chain and endothelial cell-specific antigens are also capable of inducing antibody responses related to allograft rejection. The mechanism of antibody-mediated allograft rejection remains controversial; however, endothelial cells are considered the primary target of antibody-mediated rejection. Most pathological changes can be interpreted as a result of vascular damage and ensuing pathological compensation including tissue repair. Because alloantibody is closely correlated to rejection, we advise that posttransplant antibody be monitored. The most commonly used antibody detection techniques and their advantages and disadvantages are discussed in detail.

Mismatch-specific anti-HLA antibody production following aorta transplants.

In this study, we have investigated the nature and magnitude of the immunological response after implantation of human aortic segments. Five recipients of aortic segment replacement were studied for anti-HLA antibody production (specificity and Ig class), CD3, CD4, and CD8 T cell subpopulation dynamics, and aortic wall thickness. Mismatch-specific IgG antibodies to HLA class I and HLA class II antigens were first detected 1-3 months after implantation and persisted in high concentrations for at least 1 year. Computer tomography scanning showed a progressive thickness of the aortic wall. Also the absolute number of CD3, CD4, and CD8 positive lymphocytes increased progressively after implantation. In conclusion, as was observed earlier for heart valve allografts, human implanted aortic segments induce a strong anti-HLA antibody response in recipients. We speculate that these antibodies have the potential to harm the implant, for example, by having an impact on luminal narrowing.