Monitored COVID-19 vaccine humoral response in immunocompromised solid organ transplant recipients.

The SARS-CoV-2 pandemic has resulted in rapid research and vaccine development to help curtail unchecked transmission. However, these studies cannot be applied as easily among every population, such as immunocompromised individuals. In this study, we observed the humoral response of 70 total heart and renal transplant patients to mRNA SARS-CoV-2 vaccinations to help further understand the effectiveness of vaccination in post-transplant patients following second or booster vaccinations. Antibodies were measured by bead technology to detect IgG, as well as IgG/IgM Rapid Cassette tests for confirmation. Immunocompromised patients had a noticeably lower humoral response than non-immunocompromised populations, with an even lower response among Black patients. Our findings also show for the first time various antibody responses to different motifs of the virus, with the lowest being against the S2 motif. A potential link between the duration of immunosuppression and vaccine response was also observed, where patients on immunosuppressants for longer had a stronger response to vaccination compared to recent transplant patients in our study. In addition, younger transplant recipients had a better humoral response to vaccination, and vaccine effectiveness was disproportionate between races. This finding reinforces the continuation of the guidelines for accelerated vaccination schedules for immunocompromised patients.

Clinically irrelevant circulating human leukocyte antigen antibodies in the presence of ventricular assist devices.

INTRODUCTION: Identification of anti-human leukocyte antigen (HLA) antibodies by single-antigen beads (SAB) allows for prediction of donor-specific crossmatches (virtual crossmatches), thus facilitating the allocation of organs from deceased donors. However, the clinical relevance of HLA antibodies identified by SAB has been less than clear. This study demonstrates that sera from cardiac transplant candidates with a ventricular assist device (VAD) or infection may contain clinically irrelevant antibodies that bind to the beads but not to lymphocytes. METHODS: Investigated were 5 cardiac transplant candidates (3 with VAD, all with infections, and 1 retransplant) with positive HLA antibodies detected by SAB, but negative by cytotoxicity. To determine clinical relevance of the antibodies, flow cytometric crossmatches (FCXM) were performed. Untreated beads and elution buffer-treated beads to dissociate the ß-2 microglobulin and the peptide from the heavy chain were used. RESULTS: The virtual crossmatch data were compared with data from actual FCXMs. Of 40 T-cell and B-cell FCXM, SAB-identified HLA antibodies were predictive for only 1 T-cell and 9 B-cell FCXM outcomes. Patients' sera contained a mixture of antibodies directed against cryptic epitopes on the heavy chain and exposed epitopes. The mean fluorescence intensity of antibodies varied from 1,040 to 11,000. CONCLUSIONS: Sera from cardiac transplant candidates with or without VAD may contain natural antibodies that do not bind to intact antigens on the cell surface. Therefore, great care must be exercised before denying a life-saving transplant to these patients simply on the basis of SAB results.

Organ procurement and transplantation network/united network for organ sharing histocompatibility committee collaborative study to evaluate prediction of crossmatch results in highly sensitized patients.

BACKGROUND: The requirement for a prospective crossmatch limits some organ allocation to local areas. The delay necessitated by the crossmatch restricts the distance across which offers can be made without unduly increasing the ischemia time. A collaborative study involving 14 transplant centers was undertaken by the Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) Histocompatibility Committee to evaluate the accuracy with which the detection of unacceptable human leukocyte antigen (HLA) antigens by most advanced solid phase immunoassays can predict crossmatch results. In addition, using actual patients' unacceptable HLA antigens, the number of compatible donors that would have been available from the OPTN deceased kidney donors during 2002 to 2004 were investigated. METHODS: Panel reactive antibodies were performed by conventional or solid phase assays, and crossmatches were performed by cytotoxicity or flow cytometry. Analyses were stratified for T and B cell and by method of identifying unacceptable HLA antigens and crossmatch techniques. RESULTS: Combination of solid phase immunoassays and flow cytometry crossmatches resulted in a higher prediction rates of positive T cell (86.1%-93.5%) and B-cell crossmatches (91%-97.8%). Prediction of negative crossmatches based on different combination of panel reactive antibodies and crossmatch techniques varied from 14.3% to 57.1%. Furthermore, numerous potential compatible donors were identified for each patient, regardless of their ethnicity, in the OPTN database, when predicted incompatible ones were excluded. CONCLUSIONS: The above results showed that with the advent of solid phase immunoassays, HLA antibodies can now be accurately detected resulting in prediction of crossmatch outcome. This should facilitate organ allocation and prevents shipment of organs to distant incompatible recipients.

CD30, a marker to detect the high-risk kidney transplant recipients.

BACKGROUND: Sensitization of potential renal transplant recipients may impact the selection of donors and the outcome of transplant. Another element of the potential kidney transplant recipient immune system that provides useful information regarding the transplant outcome is the immunologic CD30 molecule. METHODS AND RESULTS: This study shows a significant correlation between the pre-transplant high level of soluble CD30 and increased incidence of post-transplant infection. Only 7/34 (20.6%) of the patients who had a low level of sCD30 (< 90 U/mL) developed infection as compared with the 25/58 (43.1%) of the patients who had a high level (> 90 U/mL) of sCD30 (p < 0.04). Higher level of sCD30 pre-transplant was also correlated with the increased level of serum creatinine (p < 0.05) and pre-transplant malignancy (p < 0.04). A significant higher level of sCD30 was also noted among females (74%), as compared with males (50%) with p < 0.03. In addition, significant effect of 3-6 human leukocyte antigen (HLA) mismatches on rejection was seen. CONCLUSIONS: These results show that higher pre-transplant immunologic reactivity measured by sCD30 level was associated with post-transplant outcome. The high level of sCD30 among females may indicate an active immunologic status, perhaps because of previous pregnancies.

Pre-transplant level of soluble CD30 is associated with infection after heart transplantation.

BACKGROUND: One immunologic element of the immune system is the CD30 molecule which belongs to the TNF-R superfamily. CD30 can serve as a T-cell signal transducing molecule and is expressed by a subset of activated T lymphocytes, CD45RO(+) memory T cells. Augmentation of soluble CD30 during kidney transplant (Tx) rejection has been reported. Our study was to determine if the level of sCD30 prior to heart transplant (HTx) could categorize the patients (pts) into high or low immunologic risk for post-Tx outcome. METHODS: Pre-Tx sera from 100 consecutive HTx recipients were studied. sCD30 was detected by ELISA using the commercially available CD30 monoclonal antibody. Level of sCD30 was correlated with two-yr Tx outcome. RESULTS: Significant correlation was seen between the high level of sCD30 and lower incidence of infection. Four of the 35 pts with pre-Tx high level of sCD30 level (>90 U/mL) developed infection post-Tx. However, 31/65 pts who had a low level of sCD30 (<90 U/mL) developed infection post-transplantation (p < 0.0003). No remarkable differences were noted with the other clinical parameters, including mean hospitalization, 3A biopsy rejection or death. CONCLUSIONS: We report for the first time that the high level of sCD30 prior to the HTx may be associated with a higher immunologic ability of the pts and therefore, may have a protective effect in the development of infection post-Tx.

Analysis of human leukocyte antigens in patients with internal derangement of the temporomandibular joint.

PURPOSE: Spondyloarthropathy includes the subcategory of reactive arthritis (ReA). Spondyloarthropathies are commonly associated with certain human leukocyte antigen (HLA) alleles. Because we identified bacteria associated with ReA within the temporomandibular joint (TMJ), we now evaluate the frequency of HLA alleles in patients with TMJ pathology. PATIENTS AND METHODS: HLA typing of 129 patients (121 females and 8 males) performed by standard microcytotoxicity technique. Thirty patients had only class I (HLA-A and -B loci) evaluated. Ninety-nine patients had both class I and class II (HLA-DR loci) evaluated. Identification of alleles at the C locus was not performed. The antigenic frequency in the study group was compared to US white control subjects using a 2-tailed Fisher's exact test with a Bonferroni multiple comparison adjustment. RESULTS: The following class I HLA alleles, -A1 (32%), -A2 (50%), -A3 (33%), -B7 (23%), -B14 (14%), -B35 (20%), and -B44 (36%), including the B7 cross-reactive group (CREG) (49%) and class II alleles -DR1 (25%) and -DR4 (34%), were found to have an increased frequency in our patient group. CONCLUSIONS: Our study shows an increased frequency of several alleles that have been previously associated with arthropathy, and the alleles of the B7 CREG, in patients with TMJ pathology. Patients with these alleles may have an increased risk for the development of internal derangement of the TMJ as a consequence of the bacterial/infectious agents and host interactions with the subsequent cytokine/inflammatory response being influenced by their HLA phenotype.