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Molecular-level human leukocyte antigen (HLA) mismatch is a powerful biomarker of rejection; however, few studies have explored its use in heart transplant recipients, and none have attempted to use the results of separate algorithms synergistically. Here we tested the hypothesis that a combination of HLAMatchmaker and Predicted Indirectly Recognizable HLA Epitopes (PIRCHE-II) can be used to identify more patients at low risk of rejection.We studied 274 recipient/donor pairs enrolled in the Clinical Trials in Organ Transplantation in Children (CTOTC) performing class I and II HLA genotyping by next-generation sequencing to determine eplet mismatch (epMM) load and PIRCHE-II score. Correlation with clinical outcomes was performed on 131 cases.Of the 131 patients, 100 without pre-formed donor specific antibody (DSA) were used to identify cutoffs for the Class I, HLA-DR, and HLA-DQ epMM load and PIRCHE-II score for risk of developing post-transplant DSA (epMM: Class I/DR/DQ = 9/9/6; PIRCHE-II: 141/116/111) and antibody-mediated rejection (ABMR) (epMM: 9/8/8; PIRCHE-II: 157/80/201). Patients with above cut-off epMM load appear to be less likely to develop DSA and ABMR if their PIRCHE-II score is below cut-off (high epMM/high PIRCHE-II: 12.3%-20.3% DSA and 9%-13.5% ABMR vs high epMM/low PIRCHE-II: 4%-10% DSA and 0%-2% ABMR).For the first time in a pediatric heart transplant cohort, immunologic risk cut-offs for DSA and ABMR have been established. When used together, epMM load and PIRCHE-II score allow us to reclassify a portion of cases with high epMM load as having a lower risk for developing DSA and ABMR.

Background Desmoid-Type Fibromatosis (DTF) is a rare mesenchymal neoplasm with a locally invasive pattern and high risk of local recurrence after surgery. Historically, the standard treatment for DTF was surgical resection. However, considering the difficulty of achieving surgical eradication, the possible unnecessary morbidity and the unpredictability of the natural history, a wait-and-see approach has been proposed for asymptomatic DTF. Methods We analyzed 87 consecutive patients with histologically-proven sporadic primary DTF, first recurrence or residual disease managed at our institution between 2000 and 2018. Patients and tumor-related variables were reviewed and analyzed. Two different treatment strategies were adopted according to different time periods: in the “early period” (2000–2010) patients underwent surgical treatment irrespective of the clinical presentation, whereas in the “late period” (2012–2018) asymptomatic patients used to undergo a wait-and-see strategy. The event-free survival (EFS) was compared trough a pre-post comparison. Results In the early period, surgery was performed in 51 (94.4%) patients and watchful waiting in 3 (5.6%). In the late period, the watchful waiting group accounted for 24 (72.7%) patients and the surgical group for 9 (27.3%). No statistically independent prognostic factors were found. EFS did not show statistically significant differences between early and late period groups. Conclusion Wait-and-see policy has shown to be equivalent to upfront surgery in terms of EFS; therefore, a conservative approach is recommended in asymptomatic patients diagnosed with DTF that can be followed through watchful waiting.

Chronic lung allograft dysfunction (CLAD) is the major complication limiting long-term survival in lung transplant recipients (LTRs), with those developing donor-specific anti-human leukocyte antigen (HLA) antibodies (DSAs) previously found to have increased risk for CLAD. However, as DSA responses vary in timing of development, specificity, breadth, persistence, and complement-binding capacity, we hypothesized that these characteristics would impact CLAD and survival outcomes.We retrospectively analyzed DSA characteristics and outcomes in a single-center cohort of 582 LTRs who had serum samples collected prospectively from 2010 to 2016. Luminex-based single antigen bead assays were performed to assess DSA.DSAs were detected in 247 LTRs (42%), of which 124 (21.3%) were de novo DSAs and 53 (9.1%) were complement-binding (C1q+). CLAD developed in 208 LTRs (35.7%) during the follow-up period, with 67.8% determined as bronchiolitis obliterans syndrome phenotype and 32.2% as restrictive allograft syndrome phenotype. We found a shorter time to CLAD in LTRs with persistent DSAs (p = 0.04) and HLA-DQ-specific DSAs (p = 0.03). LTRs who developed C1q+ DSAs had significantly shorter time to CLAD (p0.001), with 100% of C1q+ DSAs being persistent and no differences between CLAD phenotypes. CLAD-free survival was significantly reduced in LTRs who developed C1q+ DSAs (p = 0.001), HLA-DQ-specific DSAs (p = 0.03), and multiple DSAs (p = 0.02).Together, our findings demonstrate that DSA characteristics of persistence, HLA-DQ specificity, and C1q+ DSAs are associated with shorter time to CLAD. Additionally, C1q+, HLA-DQ-specific, and multiple DSAs are associated with decreased CLAD-free survival. These characteristics may improve DSA risk stratification for deleterious outcomes in LTRs.

The main goal of this study was to examine the nutritional condition of Engraulis anchoita larvae during the austral spring-summer seasons of 2010/2011 and 2012/2013 in highly productive waters in the southwestern Atlantic Ocean called El Rincón. RNA/DNA (RDs) index and derived index of Growth performance (Gpf) were used. Significant differences were observed in average RDs indices for 2010/2011 (5.27 ± 3.26) and 2012/2013 (0.81 ± 0.44). A difference in the years was also observed in Growth performance with higher values in 2010/2011 (2.45 ± 1.83) compared to 2012/2013 (−0.03 ± 0.25). Anchovy larvae captured in 2010/2011 were in good condition (Gpf > 1). During 2012/2013, extremely high larval densities were observed although Gpf values were very low indicating poor larval condition. Chlorophyll dynamics differed between sampled periods, with higher maximum values during spring 2012 as compared to 2010. Concerning chlorophyll concentrations showed a sharp decline in the values for the rest of the 2012/2013 season. We propose that the low larval growth and condition observed during 2012/2013 may have resulted from a decrease in chlorophyll concentrations together with very large larval densities which enhanced the competition for food within the larval population. Our results reinforce the idea that satellite ocean color products can be valuable tools for understanding variability in ecosystem dynamics and its effects on reproductive success in fish. Fil: Diaz, Marina Vera. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; Argentina. Instituto Nacional de Investigaciones y Desarrollo Pesquero; Argentina Fil: Marrari, Marina. Ministerio de Defensa. Armada Argentina. Servicio de Hidrografía Naval. Departamento Oceanografía; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Casa, Valeria. Universidad Nacional de San Martín. Instituto de Investigación en Ingeniería Ambiental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Gattás, Florencia María. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Ecología, Genética y Evolución; Argentina Fil: Pajaro, Marcelo. Instituto Nacional de Investigaciones y Desarrollo Pesquero; Argentina Fil: Macchi, Gustavo Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Subsede Instituto Nacional de Investigación y Desarrollo Pesquero; Argentina

Highlights • Implementing a virtual tumor board program should represent a feasible goal for every health-care provider pursuing clinical excellence. • Even in time of COVID-19, the multidisciplinary commitment to oncologic care should remain imperative, as cancer may not forgive delays. • Working daily with advanced computer technologies, radiologists should lead virtual multidisciplinary tumor boards by present key images.

Purpose Allograft rejection is driven by HLA disparity between donor and recipient despite of the use of various immunosuppression protocols. To better define the risk of allograft failure or complications from overt immunosuppression we applied the epitope-based mismatch approach to quantify the degree of HLA disparity in a in a large multi-center pediatric heart transplant (pHTX) cohort that has been followed for 3-5 years. Methods 274 pHTX recipient/donor pairs were retrospectively HLA genotyped by Next-Generation Sequencing and evaluated for HLA allele (alMM) and eplet mismatch (epMM) loads. HLAMatchmaker version 2.2 was used to determine epMM load at HLA-A/B/C, -DRB1/3/4/5, -DQA1/DQB1 and -DPA1/DPB1. Results Overall, the average total alMM was 13(±2). 76% were ≥5 HLA-A/B/C allele mismatches, 67% were ≥3 HLA-DRB and ≥3 HLA-DQ allele mismatch. The average epMM load was 60 (±17), range 16-112 (Table). 94% of cases had >11 HLA-DR or DQ epMM, a threshold previously shown to be associated with development of HLA donor-specific antibody in renal transplantation. While 159 cases (61.6%) had both DR and DQ epMM >11, only DR epMM or only DQ epMM >11 occurred in 31 (12.0%) and 50 (19.4%) cases, respectively (Figure). Therefore, this cohort can be divided into 3 groups for Class II epMM load: 6% (16) of cases with low, 36% (99) with intermediate and 58% (159) with high load. Conclusion Although this pHTx cohort is highly mismatched, for HLA alleles, there is a large range based on epMM, especially for HLA-DR and -DQ indicating that allele level typing is insufficient for determination of the true degree of mismatching. By correlating these data with clinical parameters, we aim to determine risk stratification based on epMM load in pediatric heart transplantation.

HLA matching at the epitope level offers new opportunities to identify suitable donors for transplant patients. The International HLA Epitope Registry (www.Epregistry.com.br) describes for the various HLA loci, repertoires of eplets including those that correspond to epitopes experimentally verified with specific antibodies. There are also many eplets which have remained as theoretical entities because no informative antibodies have been found. Which of them have immunogenic potential or conversely, might be considered as non-epitopes that cannot elicit specific antibody responses? This question is important for the application of epitope-based HLA matching in clinical transplantation. Correct predictions of B-cell epitopes on antigenic proteins are essential to the effective design of microbial vaccines and the development of specific antibodies used in immunotherapy and immunodiagnostics but prediction programs based on structural and physiochemical properties of amino acid residues are generally ineffective. Recent prediction programs based on three-dimensional structures of antigen-antibody complexes are more promising. One such program is called ElliPro developed by Ponomarenko. This report describes studies demonstrating that ElliPro can predict alloantibody responses to HLA-ABC eplets. Antibody-verified eplets have amino acid residues with much higher ElliPro scores than eplets for which no specific antibodies have been found. The latter group includes residues with very low ElliPro scores; they appear to represent eplets that might be classified as non-epitopes. In conclusion, ElliPro offers a new approach to characterize epitope repertoires that are clinically relevant in HLA matching.

The concept that HLA antibodies recognize epitopes is leading to new approaches of HLA matching at the epitope level. HLA-DQ plays an important role and many studies have identified structurally defined DQ epitopes specifically recognized by antibodies; they have been recorded in the International HLA Epitope Registry http://www.epregistry.com.br but the list is still incomplete. Pregnancy offers an attractive model to study antibody responses to HLA epitopes. The current analysis was done on 42 DQ-reactive post-pregnancy sera tested in binding assays with a panel of DQ heterodimers. The reactivity of 29 sera corresponded fully to the presence of antibody-verified DQA and DQB epitopes recorded in the Registry. Analysis of the remaining 13 sera led to the identification of additional antibody-defined DQB and DQA epitopes. We have designed the first version of an eplet map for DQ alleles which includes antibody-defined DQA and DQB epitopes and shows sequence positions with polymorphic residues which can be used in HLA epitology studies to identify new antibody-defined DQ epitopes.

This case report describes DQ6-reactive serum antibody reactivity in a patient who types as DQ6. DNA typing showed DQB1*06:09 on the antibody producer and serum reactivity with DQB1*06:01, *06:02 and *06:03 but not with *06:04 and *06:09. HLAMatchmaker serum analysis showed antibody reactivity with a new antibody verified 85VA eplet on DQB but additional reactivity with DQB1*02:01 could not be readily interpreted. After applying the nonself-self algorithm of HLA immunogenicity we have identified a new DQB epitope structurally described as 140A(2) + 130R + 135D and shared by DQB1*02:01 and DQB1*05:01 and DQB1*06:02 of the immunizer. (C) 2016 Elsevier B.V. All rights reserved.

Purpose Incidence of and risk factors for chronic lung allograft dysfunction (CLAD) in lung transplantation for cystic fibrosis (CF) are not established. Methicillin resistant staphylococcus aureus (MRSA) is associated with CF morbidity but its association with CLAD is unclear. We aimed to describe CLAD incidence and assess if pre-transplant MRSA colonization is associated with CLAD. Methods Retrospective cohort analysis of patients receiving a lung transplant for CF from 6/2005-3/2018 at the University of Pittsburgh Medical Center. Patients with Burkholderia species were excluded. Colonization was defined as at least one positive culture in the year before transplant. CLAD was defined by ISHLT criteria. We used competing risks methods to estimate CLAD incidence and assess associations between MRSA and CLAD. Results Of 101 patients 34% were colonized with MRSA (n=34), 87% with Pseudomonas (n=88), and 31% with Aspergillus (n=31). Median post-transplant survival was 10.8 years and did not differ by MRSA colonization (p=0.50). CLAD incidence was 25% (95% CI 16-35%) at 5 years and 37% (95% CI 27-52%) at 10 years. BOS accounted for 74% (n=20/27) of cases, RAS 22% (n=6/27), and there was 1 mixed phenotype. CLAD incidence at 5 years was 45% (95% CI 25-62%) for MRSA colonized vs 18% (95% CI 9-29%) for non-colonized patients (Figure 1). Adjusting for established CLAD risk factors and co-colonization with Pseudomonas and Aspergillus, MRSA was associated with increased incidence of CLAD (SDH 2.53, 95% CI 1.16-5.51). Among 6-month survivors, MRSA colonization was associated with increased incidence of CLAD (SDH 2.66, 95% CI 1.03-6.88) adjusting for episodes of acute cellular rejection and recurrence of pre-transplant organisms. Conclusion Incidence of CLAD in our cohort of CF recipients is low and varies by pre-transplant microbiota. MRSA colonization may be a risk factor for CLAD, perhaps reflecting differences in microbiome composition and associated host-microbiome interactions.

Purpose Long-term survival in lung transplant recipients (LTR) is limited in large part due to chronic lung allograft dysfunction (CLAD). Donor-specific antibodies (DSA) have been previously associated with more rapid high-grade rejection and mortality. Characteristics of these DSA may predict which antibodies are more harmful than others. The purpose of this investigation was to determine if C1q+ DSA is associated with increased CLAD in LTRs versus no DSA and C1q- DSA. Methods This was a single-center, retrospective cohort study of adult LTRs. Clinical data was extracted from the electronic medical record and laboratory systems. Patients were tested by Luminex Single Antigen Bead (SAB) IgG and C1q. IgG-SAB MFI > 1000 and C1q-SAB MFI > 500 were considered positive. DSA that were positive at more than one time point were classified as persistent, while those that were not were considered transient. Patients were grouped as no DSA, C1q- DSA, or C1q+ DSA. The primary outcome was CLAD. Secondary outcomes included CLAD subtypes of bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS). Outcomes were assessed using Kaplan-Meier methods and multivariable Cox regression with a time-dependent covariate. Results 582 LTRs were analyzed. 335 (57.6%) had no DSA, 194 (33.3%) were DSA+ C1q-, and 53 (9.1%) were DSA+ C1q+. Of 247 LTRs who developed any DSA, Class II DSA (206 LTRs, 84%) were more common than Class I DSA (106, 43%), including those with both classes. 177 LTRs (72%) had persistent DSA, including all 53 with C1q+ DSA . There was no difference in time to CLAD for any DSA vs no DSA (p=0.26). Patients with persistent DSA had shorter time to CLAD vs no DSA and transient DSA (p=0.04) and trended towards significance on multivariable assessment (HR: 1.70 95%CI: 1.00-2.92, p=0.05). DSA+ Cq1+ had shorter time to CLAD vs no DSA and DSA+ C1q- (p Conclusion Persistent DSA were associated with shorter time to CLAD. C1q+ DSA were associated with increased hazard of CLAD, BOS, and RAS. Larger cohorts are needed to evaluate other clinical outcomes.

Purpose To appraise the role of stereotactic body radiation therapy (SBRT) in patients with lung metastasis from primary soft tissue sarcoma. Methods Twenty-eight patients (51 lesions) were analysed. All patients were in good performance status (1–2 eastern cooperative oncology group (ECOG)), unsuitable for surgical resection, with controlled primary tumour and the number of lung metastases was ⩽4. In a risk adaptive scheme, the dose prescription was: 30 Gy/1 fr, 60 Gy/3 fr, 60 Gy/8 fr and 48 Gy/4 fr. Treatments were performed with Volumetric Modulated Arc Therapy. Clinical outcome was evaluated by thoracic and abdominal computed tomography (CT) scan before SBRT and than every 3 months. Toxicity was evaluated with Common Terminology Criteria for Adverse Events (CTCAE) scale version 4.0. Results Leiomyosarcoma (36%) and synovial sarcoma (25%) were the most common histologies. Five patients (18%) initially presented with pulmonary metastasis, whereas 23 (82%) developed them at a median time of 51 months (range 11–311 months) from the initial diagnosis. The median follow-up time from initial diagnosis was 65 months (5–139 months) and from SBRT was 21 months (2–80 months). No severe toxicity (grades III–IV) was recorded and no patients required hospitalisation. The actuarial 5-years local control rate (from SBRT treatment) was 96%. Overall survival at 2 and 5 years was 96.2% and 60.5%, respectively. At last follow-up 15 patients (54%) were alive. All other died because of distant progression. Conclusions SBRT provides excellent local control of pulmonary metastasis from soft tissue sarcoma (STS) and may improve survival in selected patients. SBRT should be considered for all patients with pulmonary metastasis (PM) and evaluated in a multidisciplinary team.

Donor-specific alloantibodies (DSA) to HLA-DP may cause antibody-mediated rejection (AMR), especially in re-transplants. We describe the immunization history of a patient who received 3 kidney transplants; the 3rd kidney was completely matched except at DPA1 and DPB1. Prior to the 3rd transplant, single antigen bead analysis (SAB) showed DSA reactivity against DPA1 shared by the 1st and 3rd donors, but B and T flow crossmatch (FXM) results were negative. Within 11 days the 3rd transplant underwent acute C4d+ AMR which coincided with the presence of complement (C1q)-binding IgG1 DSA against donor DPA1 and DPB1. Using HLAMatchmaker and SAB, we provide evidence that eplet (epitope) spreading on DPA1 and eplet sharing on differing DPB1 alleles of the 1st and 3rd transplants was associated with AMR. Since weak DSA to DPA1/DPB1 may induce acute AMR with negative FXM, donor DPA1/DPB1 high resolution typing should be considered in sensitized patients with DP-directed DSA.

This study addresses the reactivity patterns of human cytotoxic HLA class I epitope-specific monoclonal antibodies in Ig-binding and complement component C1q-binding Luminex assays in comparison with complement-dependent lymphocytotoxicity data reported at the 13th International HLA Workshop. Some monoclonal antibodies reacted similarly with epitope-carrying alleles in all three assays but others showed different reactivity patterns. These reactivity differences were analyzed with HLAMatchmaker and we incorporated the concept that eplets are essential parts of structural epitopes which can contact the six Complementarity Determining Regions (CDRs) of antibody. The data show that technique-dependent reactivity patterns are associated with distinct differences between polymorphic amino acid configurations on eplet-defined structural epitopes. The findings have been viewed in context of antigen-antibody complex formation that results in the release of free energy necessary to stabilize binding and to induce conformational changes in the antibody molecule to expose the C1q binding site, the first step of complement activation. Moreover the amount of free energy should be sufficient to induce a conformational change of C1q thereby initiating the first stages of the classical complement cascade leading to lymphocytotoxicity. The complement-fixing properties of HLA antibodies require not only specific recognition of eplets but also depend on interactions of other CDRs with critical amino acid configurations within the structural epitope. Eplet-carrying alleles that lack such configurations may only bind with antibody. This concept is important to our understanding whether or not complement-fixing donor-specific HLA antibodies can initiate antibody-mediated rejection.

This article highlights the data currently available on the activity of targeted medical treatment in a subgroup of rare entities within soft tissue sarcomas, including inflammatory myofibroblastic tumor, alveolar soft part sarcoma, solitary fibrous tumor, malignant perivascular epithelioid cell tumor (PEComa), and clear cell sarcoma.

The zooplankton community of Marguerite Bay was studied during austral fall of 2001 and 2002 using net and concurrent environmental data. Interannual differences were observed in zooplankton species composition, developmental stages, and abundances, which were linked to unusually high chlorophyll concentrations in the Bellingshausen Sea and Marguerite Bay during spring–summer 2000/2001. Copepod abundance was significantly higher in 2001 than in 2002 (46.3 and 28.3 ind m −3 in 2001 and 2002, respectively). During 2001, the copepod community was dominated by two species. Calanoides acutus , a herbivore, and Metridia gerlachei , an omnivore, accounted for 46% and 45% of the community, respectively. During 2002, however, several species were relatively abundant, including M. gerlachei , Ctenocalanus spp., C. acutus , Oithona spp., and Paraeuchaeta spp. Euphausiids also showed a rapid population response to high chlorophyll levels in 2001. Even though average total euphausiid (juvenile/adult) abundances were similar during both years (0.20 and 0.15 ind m −3 for 2001 and 2002, respectively), species composition showed marked interannual differences due to varying life history strategies among species. Thysanoessa macrura , which has a relatively rapid development from larval to juvenile stages between spring and fall of the same year, was the most abundant euphausiid in 2001. In contrast, Euphausia crystallorophias and Euphausia superba juvenile/adult populations increased in 2002, owing to a slower development in which larval stages overwinter and recruit to juveniles during the following spring/summer. Other zooplankton groups those were abundant in Marguerite Bay, but showed little variability between years, included ostracods, pteropods, chaetognaths, medusae, amphipods, and mysids. Summer phytoplankton concentrations strongly influenced copepods and euphausiids; however, there were no clear associations between zooplankton distributions and fall environmental conditions (i.e., pigment concentrations and surface salinity) or bottom depth. It is notable that ostracods and pteropods had the highest abundances of non-copepod zooplankton.

The vertical distribution patterns of the dominant zooplankton in the vicinity of Marguerite Bay on the west side of the Antarctic Peninsula were studied during austral fall of 2001 and 2002, using net and concurrent environmental data. Vertical distributions of zooplankton usually were similar to those reported for other Antarctic regions. Maximum abundances of the copepods Ctenocalanus spp. and Calanus propinquus , the euphausiids Euphausia superba , Euphausia crystallorophias , and Thysanoessa macrura , and appendicularians primarily occurred in shallow Antarctic Surface Water ( Oncaea spp., mysids, and ostracods had the deepest distributions (>250 m), in warmer modified Circumpolar Deep Water. Other dominant copepods ( Calanoides acutus , Metridia gerlachei , Oithona spp., Paraeuchaeta spp., and Rhincalanus gigas ), pteropods, and chaetognaths had depths of maximum abundance within the pycnocline or in deeper warmer waters. Overlapping depth distributions suggest that E. superba would have the highest prey encounter rates with M. gerlachei , Ctenocalanus spp., C. propinquus , and Oithona spp. during fall, although most of the copepod community was deeper than the euphausiid community. Even though the three euphausiid species occupied similar depth ranges on average, at any given location E. superba , E. crystallorophias , and T. macrura depths of maximum abundance often did not overlap, suggesting vertical habitat partitioning behavior. The vertical patterns of copepods, euphausiids, amphipods, and mysids did not have a consistent association with the distributions of pigments, temperature, salinity, or density. Instead, the observed vertical distributions are mainly attributed to different behaviors, including seasonal vertical migration to deeper water for overwintering (i.e., C. acutus , R. gigas , ostracods, chaetognaths, pteropods) and vertical habitat partitioning to reduce competition (i.e., euphausiids). Migration into deep water and aggregation behavior (i.e., euphausiids) also reduce the risk of predation.

Background Although HLA-C matching is not considered in kidney transplantation, several reports have shown that anti-HLA-C antibodies are associated with rejection and graft failure. DNA-based typing methods can now accurately determine HLA-C compatibility and sensitive assays such as Luminex with single alleles can identify HLA-C antibodies. HLA-C displays considerable amino acid polymorphism that can be translated into a structurally defined epitope repertoire. Methods We have analyzed post-allograft nephrectomy sera from 45 HLA-C mismatched cases submitted by 15 laboratories worldwide participating in the 15th International Histocompatibility Workshop. All of them had HLA class I antibodies detected by a Luminex-based solid phase method using single-allele beads. This study addressed the determination of antibodies against donor HLA-C mismatches. Analysis of antibody reactivity patterns was performed using HLAMatchmaker, a structurally based matching program that considers 56 HLA-C eplets to define antibody-reactive epitopes. Many eplets shared by groups of HLA-C antigens, whereas others are also shared with HLA-A and/or HLA-B antigens. Results Twenty-seven patients (60%) had donor-specific HLA-C antibodies, significantly less than the donor-specific antibodies induced by HLA-A and HLA-B mismatches. HLA-C antibody responses correlated with the eplet loads of the HLA-C mismatches. There were 352 instances whereby a donor HLA-C eplet was mismatched and for 84 (24%) of them there was antibody reactivity with a particular eplet (69 instances) or an eplet pair (15 instances). The latter generally consisted of mismatched eplets paired with self-eplets shared between the immunizing HLA-C alleles and HLA alleles of the patient. Several HLA-C eplets exhibited a relatively high immunogenicity as evidenced by their frequencies of specific antibodies. Conclusion These findings demonstrate the importance of HLA-C mismatching in humoral sensitization and that HLA-C epitopes can induce specific antibodies. They illustrate the usefulness of HLAMatchmaker in understanding donor-specific antibody reactivity patterns and the determination of HLA mismatch acceptability when transplantation is considered.

article i nfo Article history: Serum analysis of patients considered for retransplantation has a potential limitation that the rejected allograft may absorb HLA antibodies. We have determined how the highly sensitive micro bead-based Luminex antibody-binding assay with single antigens can detect donor-specific HLA antibodies (DSA) in patients before and after surgical removal of a rejected allograft. This analysis was done for 65 allograft nephrectomy (allonx) cases contributed by 16 laboratories worldwide. In the HLA-A,B and -DRB1 mismatch categories the incidence of DSA reactivity pre-allonx and post-allonx was 64% vs 87% (p=0.0033) and 57% vs 86% (p=0.001), respectively. The frequencies of individual reactive antigens were also lower before allonx: for HLA-A,B antigens: 49% vs 75% (p

SeaWiFS chlorophyll a distributions between 1997 and 2004 were investigated in relation to sea-ice dynamics for waters west of the Antarctic Peninsula (55–75°S, 50–80°W) in order to better understand the reproductive patterns and recruitment success of the Antarctic krill, Euphausia superba . Climatology patterns showed that the Bellingshausen Sea and Marguerite Bay region usually had higher chlorophyll a concentrations, which persisted throughout austral spring and summer, compared with more northern regions along the Antarctic Peninsula and the western Scotia Sea. These predictable and long-lasting phytoplankton accumulations could provide krill with the food levels required for successful reproduction and larval survival. Unusually high krill reproduction in 2000/2001 was coincident with above-average chlorophyll a concentrations throughout most of the study area and resulted in the largest juvenile recruitment (in 2001/2002) since 1981. High larval densities (up to 132 ind m −3 ) at the shelf break along the Antarctic Peninsula may have resulted, in part, from krill spawning in the Bellingshausen Sea. In general, ice-edge blooms were only a significant feature in the southern sectors of our study area, particularly in the Bellingshausen Sea and, thus, may not support krill reproduction in the northern Peninsula region as previously believed. Instead, phytoplankton blooms during spring in the northern region appeared to be governed by shelf-break processes, such as upwelling of iron-rich deep water. Interannual differences in sea ice also probably contributed to the variability in larval krill abundances observed in Marguerite Bay. Sea ice melted early in 2000/2001, allowing elevated phytoplankton blooms to develop. In contrast, sea ice persisted throughout spring and summer 2001/2002 limiting phytoplankton accumulation, particularly in southern Marguerite Bay. Thus, the early and extended availability of elevated chlorophyll a concentrations during spring and summer 2000/2001, particularly in the vicinity of Marguerite Bay and to the south in the Bellingshausen Sea, as well as reduced sea ice in coastal areas, likely supported the unusually high densities of larval krill observed during fall in waters west of the Antarctic Peninsula.