A Prospective Phase I/II Study of Docetaxel, Cisplatin and Continuous Capecitabine in Advanced Oesophago-Gastric Cancer (NWCOG-3).

AIMS: This open-label prospective phase I/II dose-escalation study determined the maximum tolerated dose (MTD) and then evaluated response, safety and feasibility of a novel combination of docetaxel, cisplatinum and capecitabine (DCC) in chemotherapy-naive patients with advanced oesophago-gastric carcinoma. MATERIALS AND METHODS: Patients with adenocarcinoma or squamous cell carcinoma of the oesophagus or stomach, of good performance status, deemed too advanced for curative treatment, were given systematically increasing doses of 3 weekly DCC to ascertain the MTD. Phase II administered up to six cycles of DCC at the MTD, assessing response and toxicity. RESULTS: Between November 2007 and November 2012, 15 patients were recruited into phase I and 41 into phase II. The MDT was a 21 day cycle of docetaxel 60 mg/m2 IV day 1, cisplatinum 60 mg/m2 IV day 1 and oral capecitabine 1000 mg/m2 daily in two divided doses for days 1-21. The most common phase II grade 3-4 toxicities were neutropenia 88% (10% febrile neutropenia), fatigue 15%, sensory neuropathy 10% and non-neutropenic infection 10%. The overall response rate was 51%, median progression-free survival was 7.4 months (confidence interval 6.7-9.4) and median overall survival was 10.9 months (confidence interval 7.7-13.7). CONCLUSION: DCC was tolerable and feasible with promising efficacy, and may be suitable for future investigation in both first-line metastatic and neoadjuvant settings.

Three new HLA class I alleles with synonymous mutations: HLA-A*03:01:62, -C*07:02:82 and -C*12:03:42.

Three new HLA class I alleles with synonymous mutations were identified.

Retinopatía por radiación secundaria a tratamiento de carcinoma de seno maxilar: un caso dramático / Radiation retinopathy secondary to treatment of maxillary sinus carcinoma: a dramatic case

Caso clínico: Un varón de 53 años consulta por pérdida de visión en ojo derecho tras irradiación de carcinoma de seno maxilar derecho. La exploración funduscópica muestra hemorragias, exudados, edema macular e isquemia retiniana periférica, compatibles con una retinopatía por radiación. La evolución es tórpida a pesar de tratamiento con láser e inyecciones intravítreas de bevacizumab, finalizando en evisceración del ojo afecto. Discusión: La retinopatía por radiación debe tenerse en cuenta ante cualquier pérdida de visión tras irradiación de cabeza y cuello. El seguimiento oftalmológico a largo plazo de estos pacientes es fundamental para conseguir un diagnóstico precoz (AU)

Clinical case: A 53-year old male presented with visual impairment in right eye after irradiation of right maxillary sinus carcinoma. Funduscopy shows radiation retinopathy: haemorrhages, exudates, macular oedema, and peripheral retinal ischaemia. A poor outcome was achieved despite laser treatment and intravitreal injections of bevacizumab, resulting in evisceration of the affected eye. Discussion: Radiation retinopathy must be considered in any loss of vision after head and neck irradiation. Ophthalmological long-term follow-up of these patients is essential for an early diagnosis (AU)

Radiation retinopathy secondary to treatment of maxillary sinus carcinoma: a dramatic case. / Retinopatía por radiación secundaria a tratamiento de carcinoma de seno maxilar: un caso dramático.

CLINICAL CASE: A 53-year old male presented with visual impairment in right eye after irradiation of right maxillary sinus carcinoma. Funduscopy shows radiation retinopathy: haemorrhages, exudates, macular oedema, and peripheral retinal ischaemia. A poor outcome was achieved despite laser treatment and intravitreal injections of bevacizumab, resulting in evisceration of the affected eye. DISCUSSION: Radiation retinopathy must be considered in any loss of vision after head and neck irradiation. Ophthalmological long-term follow-up of these patients is essential for an early diagnosis.

Pretransplant CD28 Biomarker (Levels of Expression and Quantification of Molecules per Cell) in Peripheral CD4+ T Cells Predicts Acute Rejection Episodes in Liver and Kidney Recipients.

BACKGROUND: Acute rejection (AR) remains a significant cause of graft loss. Better approaches to predict AR are being investigated. Surface CD28 protein is essential for T-cell proliferation and survival as well as cytokine production. PATIENTS AND METHODS: Pretransplant CD4+CD28+ peripheral T cells were examined in 30 liver recipients (LRs) and 31 kidney recipients (KRs) by flow cytometry. RESULTS: Pretransplant CD4+CD28+ T cells in LRs were significantly lower in rejectors than nonrejectors (P = .002). Furthermore, the total number of CD28 molecules per cell in LRs (P = .02) as well as KRs (P = .047) was significantly lower in rejectors than nonrejectors. The healthy group did not display differences when compared with patients with end-stage liver disease or renal failure; however, stratification analysis displayed higher levels of CD4+CD28+ when compared with rejected LRs (P = .04) but not KRs. CD28 levels <41.94% were able to discriminate LRs at high risk of AR (P = .003). Similarly, a total number of CD28 molecules ≤8359 (P = .031) in LRs and ≤7669 (P = .046) in KRs correlated with high risk of AR. CONCLUSION: The preliminary results presented herein exhibit a fast and noninvasive method that assists clinicians to prevent AR by monitoring CD4+CD28+ peripheral T cells.

Report From the First and Second Spanish Killer Immunoglobulin-Like Receptor Genotyping Workshops: External Quality Control for Natural Killer Alloreactive Donor Selection in Haploidentical Stem Cell Transplantation.

An important factor affecting the success in the setting of related haploidentical hematopoietic stem cell transplantation (HSCT) is the graft-versus-leukemia effect mediated by natural killer (NK) cells when the donor displays NK alloreactivity versus the recipient. NK cell function is regulated by killer immunoglobulin-like receptors (KIR) and it has been described that donor KIR genotype influences transplantation outcome. This has led to a requirement of laboratories to have a quality assurance program for validation and control of their KIR genotyping methods. The goal of the 1st and 2nd Spanish KIR Genotyping Workshops was to provide an external proficiency testing program in KIR genotyping for Spanish immunology and transplant laboratories. These workshops were conducted during the years 2014-2016 and consisted of 17 participating laboratories typing a set of 20 samples. The presence/absence of 16 mandatory KIR loci (2DL1, 2DL2, 2DL3, 2DL4, 2DL5, 2DS1, 2DS2, 2DS3, 2DS4, 2DS5, 2DP1, 3DL1, 3DL2, 3DL3, 3DS1, and 3DP1) was evaluated per sample. Methods for KIR genotyping included polymerase chain reaction with the use of sequence-specific primers and sequence-specific oligoprobes. Consensus typing was reached in all samples, and the performance of laboratories in external proficiency testing was satisfactory in all cases. The polymorphism detected in the small sample studied in both workshops is indicative of an ample variety of KIR gene profiles in the Spanish population.

Extension of the Kubelka-Munk theory to an arbitrary substrate: a Monte Carlo approach.

In this work we review and-to some extent-upgrade one of the main theories of light flux through homogeneous isotropic media, namely, the Kubelka-Munk (K-M) theory, and in particular the later expansion made by Kubelka to obtain the reflectance of a specimen when a substrate lies underneath. We have completed this solution by calculating the transverse energy density in the specimen and the transmission of the whole. We show that this last result-compatible with Kubelka's upgrade for layered media-also allows for the calculation of the specimen/substrate absorption split. In order to validate these expressions, the results were reproduced by means of a Monte Carlo simulation working on a layered medium under the same assumptions as the K-M theory. Interestingly, the numerical procedure introduces new capabilities in the model regarding the history of any absorbed or outgoing elemental light beam, such as the recording of its time-of-flight through a given system.

X-linked thrombocytopenia in a female with a complex familial pattern of X-chromosome inactivation.

The Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disorder characterized by thrombocytopenia, eczema and various degrees of immune deficiency caused by mutations in the WAS gene, which encodes the WASP protein, the expression of which is restricted to haematopoietic cells. Mild allelic variants are associated with X-linked thrombocytopenia (XLT). Female carriers tend in general to be asymptomatic as a consequence of a positive selection of cells with an active normal X chromosome, which results in a non-random inactivation of the mutated gene in affected cell lineages. We report on six female members of the same family carrying the mutated WAS allele p.V332A, which is known to be associated with XLT. One of them had presented severe thrombocytopenia from birth. Western blotting showed the WASP protein in peripheral blood cells to be normal in size and expression, and scanning electron microscopy revealed a normal distribution of microvilli on T cells. X-chromosome inactivation-pattern analysis showed total inactivation of the non-mutated paternal X chromosome in the patient's peripheral blood cells. All the other female family members were healthy and presented varying X-chromosome inactivation patterns, ranging from random X chromosome inactivation to total X-chromosome inactivation of the mutated chromosome. Our results in these female carriers of p.V332A show that manifestation of the disease requires a total inactivation of the non-mutated X chromosome and allow us to confirm that clinical manifestations in female carriers are highly dependent not only on the mutation characteristics but also on the X-chromosome inactivation pattern of affected line.

Epiretinal membrane surgery: anatomic and functional outcomes.

OBJECTIVE: To study the influence of anatomic preoperative characteristics (based on the parameter, foveal central thickness, measured by optical coherence tomography) and functional characteristics (based on the parameter, best corrected visual acuity, [BCVA]) on functional recovery after epiretinal membrane (ERM) surgery. METHODS: A total of 88 eyes (of 86 patients), on whom a vitrectomy due to ERM was performed during a 3 years period were reviewed in this longitudinal, prospective study. An analysis was made of, ERM aetiology, BCVA, presence or absence of metamorphopsia, lens status, and central foveal thickness. Data relating to surgery and local complications, changes in BCVA, and changes in foveal central thickness were collected during the follow-up period. RESULTS: An improvement was in observed in BCVA in 82%, as well as a decrease in foveal thickness in 79% of the eyes which underwent surgery, both of these being statistically significant (P<.01). However, most of the patients showed different grades of oedema and/or macular thickening in the postoperative period. A significant correlation was found between preoperative and postoperative BCVA (P=.001), and also between preoperative and postoperative central foveal thickness (P=.004), but not between BCVA and foveal thickness. CONCLUSIONS: There is functional recovery in terms of BCVA in more than 80% of the patients after ERM surgery. Most of the eyes showed persistent macular thickening, but this did not seem to have influenced the final BCVA. The best determinant of postoperative functional recovery (postoperative visual acuity) is, in our experience, the preoperative BCVA, and not the macular thickness.

Cirugía de las membranas epirretinianas: resultados anatómicos y funcionales / Epiretinal membrane surgery: anatomic and functional outcomes

Objetivo: Estudiar la implicación de las características preoperatorias anatómicas (según el parámetro del grosor foveal central, determinado mediante tomografía de coherencia óptica) y funcionales (según el parámetro de la mejor agudeza visual corregida, [MAVC]) en la recuperación funcional tras la cirugía de las membranas epirretinianas maculares (MEM). Métodos: En este estudio prospectivo, longitudinal se incluyeron 88 ojos (de 86 pacientes), intervenidos mediante vitrectomía debido a MEM, en un período de 3 años. Se analizaron: etiología de la MEM, MAVC, existencia o no de metamorfopsia, estado del cristalino, y grosor foveal central. Asimismo se recogieron los datos relativos a la cirugía y las complicaciones derivadas de la misma, así como los cambios observados en la MAVC y en el grosor foveal a lo largo del período de seguimiento. Resultados: Se produjo mejoría de la MAVC en el 82% de los casos, así como una disminución del grosor foveal en el 79% de los casos intervenidos, ambos estadísticamente significativos (p<0,01). Sin embargo, la mayor parte de los pacientes exhibieron grados variables de edema y/o engrosamiento macular en el postoperatorio. Se halló correlación significativa entre la MAVC preoperatoria y postoperatoria (p=0,001), así como entre el grosor foveal central preoperatorio y postoperatorio (p=0,004), pero no entre la MAVC y el grosor foveal. Conclusiones: Se produce una recuperación funcional en términos de MAVC en más del 80% de los pacientes tras cirugía de MEM. La mayor parte de los ojos muestran persistencia del engrosamiento macular, si bien este no parece tener influencia en la agudeza visual final. El mejor determinante de recuperación funcional postoperatoria (agudeza visual postoperatoria) parece ser, en nuestra experiencia, la agudeza visual preoperatoria y no el grosor macular(AU)

Objective: To study the influence of anatomic preoperative characteristics (based on the parameter, foveal central thickness, measured by optical coherence tomography) and functional characteristics (based on the parameter, best corrected visual acuity, [BCVA]) on functional recovery after epiretinal membrane (ERM) surgery. Methods: A total of 88 eyes (of 86 patients), on whom a vitrectomy due to ERM was performed during a 3 years period were reviewed in this longitudinal, prospective study. An analysis was made of, ERM aetiology, BCVA, presence or absence of metamorphopsia, lens status, and central foveal thickness. Data relating to surgery and local complications, changes in BCVA, and changes in foveal central thickness were collected during the follow-up period. Results: An improvement was in observed in BCVA in 82%, as well as a decrease in foveal thickness in 79% of the eyes which underwent surgery, both of these being statistically significant (P<0.01). However, most of the patients showed different grades of oedema and/or macular thickening in the postoperative period. A significant correlation was found between preoperative and postoperative BCVA (P=0.001), and also between preoperative and postoperative central foveal thickness (P=0.004), but not between BCVA and foveal thickness. Conclusions: There is functional recovery in terms of BCVA in more than 80% of the patients after ERM surgery. Most of the eyes showed persistent macular thickening, but this did not seem to have influenced the final BCVA. The best determinant of postoperative functional recovery (postoperative visual acuity) is, in our experience, the preoperative BCVA, and not the macular thickness(AU)

Complement component C6 deficiency in a Spanish family: implications for clinical and molecular diagnosis.

Complement component C6 deficiency is a genetic disease presenting as increased susceptibility to invasive Neisseria meningitidis infections. This disorder has rarely been diagnosed in the Spanish population. In this work we report the immunochemical and molecular characterization of complement C6 deficiency in a Spanish patient showing no detectable functional activity of either the classical or alternative complement pathways and reporting a history of several episodes of meningococcal meningitis. The levels of individual complement components C3, C4, C5, C7, C8 and C9 were within the normal range. However, C6 level was low in the patient's serum as measured by radial immunodiffusion. Exon-specific polymerase chain reaction and sequencing of the C6 gene revealed a previously described homozygous single base deletion in exon 6 (c.821delA), leading to a shift in the reading frame that caused the generation of a downstream stop codon, which, in turn, provoked the truncation of the C6 protein (p.Gln274fs). To our knowledge, this is the first report on the c.821delA mutation in the Spanish population, which has previously only been identified in individuals of African ancestry. Characterization of this mutation was thought interesting in order to elucidate its source and help understand the molecular basis of this uncommon deficiency in our population. Moreover, this report highlights the importance of complement screening in cases of repeated meningococcal infections in order to establish its involvement and to consider adequate clinical recommendations such as prophylactic antibiotics or meningococcal vaccines and, subsequently, for genetic counselling.

Post-transplant increase in soluble human leukocyte antigen-G associated with non-severe cardiac allograft vasculopathy.

Cardiac allograft vasculopathy (CAV) is the single most important long-term limitation to heart transplantation. This study aimed to assess the value of monitoring soluble human leukocyte antigen-G (sHLA-G) during the first year post-transplantation to predict the severity of CAV, in 21 out of 77 heart recipients assessed by intravascular ultrasound (IVUS). Serum sHLA-G concentration increased after transplant in recipients free of severe CAV, but decreased in recipients suffering from severe CAV, significant differences between these two groups were found 6 to 12 months post-transplantation. The optimal value of the change in post-transplant sHLA-G for identifying severe CAV was ≥0.062%, which maximized sensitivity (80%) and specificity (100%). Importantly, increases in post-transplant sHLA-G were inversely associated with severe CAV, but directly associated with human cytomegalovirus reactivation. In addition, recipients presenting non-severe CAV or an increased sHLA-G post-transplantation, showed higher numbers of CD8(+)CD28(-) T cells and a down-modulation of CD28 on CD4(+) lymphocytes, which typically identifies CD8(+) regulatory T cells and anergic/tolerogenic T helper cells, respectively. In conclusion, quantification of sHLA-G might offer a complementary non-invasive method for identifying recipients at risk of more severe CAV and who might benefit from earlier preventive therapies, although these results need to be confirmed in larger series.

C1q-fixing human leukocyte antigen assay in immunized renal patients: correlation between Luminex SAB-C1q and SAB-IgG.

BACKGROUND: There is no consensus about the impact of thresholds of complement-fixing antibody assays. Recently, a C1q-SAB assay has been developed to identify complement-fixing HLA antibodies with high sensitivity and specificity. Our aim was to determine the correlation between IgG single antigens beads (SAB) and C1q-SAB assay results among patients on the renal waiting list. PATIENTS AND METHODS: Serum samples from immunized renal waiting list patients as well as negative and positive controls were valided by Luminex (LMX). These sera, which were positive for 166 antibody specificities, were tested for HLA class I in parallel by LMX-IgG and LMX-C1q. RESULTS: Comparison of antibody detection revealed no correlation based on median fluorescent intensity (MFI), levels between the IgG SAB and the C1qSAB assay (P > .05). IgG-positive sera with MFIs as low as 700 were able to fix C1q, whereas other sera with MFIs as high 14,500 did not. Furthermore, there appeared to be disparities in the profiles of class I antigens able to fix C1q-SAB. In our series, only 34% class I IgG SAB antibodies were also C1qSAB+. In several patients, we detected C1qSAB+ against IgGSAB- that was surely due to IgM antibodies. So, the C1qSAB assay detected IgM antibodies that fix complement. CONCLUSION: These data suggested that the C1q-SAB assay could be an important method to evaluate pretransplant virtual crossmatch and to define nonpermitted specificities (C1q-fixing) in kidney transplantation.

Evolution of soluble forms of CD86, CD95 and CD95L molecules in liver transplant recipients.

Co-stimulatory factors such as CD86 and apoptotic molecules such as CD95 and CD95L required to start and to turn off the allogenic immune response may also be present as soluble proteins. To determine the role of the soluble forms of CD86 (sCD86), CD95 (sCD95) and CD95L (sCD95L) in the outcome of liver transplants, we analyzed the circulating levels of these molecules in patients subjected to liver transplantation in the pre-operative period and during the first month post-transplantation. Serum samples were obtained from sixty-nine first orthotopic liver transplants (OLT). The patients were classified into acute rejection (AR=24) and not acute rejection (NAR=45), or considering the presence of chronic active hepatitis B or C (VP=30) or other primary liver diseases (VN=39). The levels of sCD86, sCD95 and sCD95L were analyzed by solid phase sandwich enzyme-linked immunoabsorbent assays. Our results first showed that the pre-transplantation serum levels of sCD86 in the AR group were significantly higher than in the NAR group (1007±82U/mL vs. 739±46U/mL, p=0.006), and in the post-transplantation period these levels decreased sharply. Second, the levels of sCD95L and sCD95 in the pre-transplantation period did not point to statistically significant differences between the AR and NAR groups. Considering primary liver disease, the pre-transplantation levels of sCD86 and sCD95L in the VP group were significantly higher than those of the VN group (VP, 977±69U/mL vs. VN, 722±51U/mL, p<0.002, and VP, 482±78pg/mL vs. VN, 221±31pg/mL, p=0.002, respectively). Multivariate analysis revealed that only the pre-transplantation levels of sCD86 were independently associated with the development of episodes of acute rejection (p=0.005, OR=2.1, IC 95%=1.27-3.47). In conclusion, the present work shows that primary liver disease could influence the pre-transplantation levels of sCD86 and sCD95L. High pre-transplantation serum levels of sCD86 could favor the development of episodes of acute rejection.

[Intravitreal triamcinolone acetonide use in diffuse persistent diabetic macular edema]. / Uso de triamcinolona intravítrea en el tratamiento del edema macular diabético difuso persistente.

PURPOSE: To determine the efficacy of intravitreal triamcinolone injections (iv TA) for diffuse persistent diabetic macular oedema (DMO) based on the functional parameter of modification in best corrected visual acuity (BCVA) and the anatomic parameter of quantitative changes in central macular thickness, as determined by optical coherence tomography (OCT). The secondary outcome is to analyse the safety of the procedure. METHODS: In this retrospective study, 16 patients (22 eyes) were included over a period of six months. Type and time of evolution of diabetes mellitus, previous treatments, BCVA, lens status, intraocular pressure (IOP) and central macular thickness, were analysed. During the follow-up period were collected: number of injections, changes in BCVA, IOP, central macular thickness, and complications observed. RESULTS: Improvement in BCVA was recorded in 30.77%, 47.37% and 52.63%, at one, three and six months, respectively (P<.05 at 3 months). The IOP increased in 57.69% at one month, and 75 and 47.05%, at 3 and 6 months, respectively (P<.05 at 3 months). Progression of cataracts was found in 22.72%. No cases of endophthalmitis were observed. CONCLUSIONS: Intravitreal TA is a good therapeutic option for patients with persistent DMO, increasing BCVA and decreasing central macular thickness in the short term, with a percentage of clinical resolution of more than 70%. However, due to the transient effect, and potential adverse effects, it should be administered to selected refractory cases with caution.

Uso de triamcinolona intravítrea en el tratamiento del edema macular diabético difuso persistente / Intravitreal triamcinolone acetonide use in diffuse persistent diabetic macular edema

Propósito: Explorar la eficacia de las inyecciones de triamcinolona intravítrea (TA iv) en el edema macular diabético (EMD) difuso persistente, según el parámetro funcional de la modificación en la mejor agudeza visual corregida (MAVC) y el parámetro anatómico del cambio cuantitativo en el espesor foveal central, determinado por tomografía de coherencia óptica (OCT). El objetivo secundario es analizar la seguridad del procedimiento. Métodos: En este estudio retrospectivo se incluyeron 16 pacientes (22 ojos), en un periodo de seis meses. Se analizó tipo y tiempo de evolución de la diabetes mellitus, tratamientos previos, MAVC, estado del cristalino, presión intraocular (PIO) y espesor macular central. A lo largo del seguimiento se recogieron datos relativos al número de inyecciones, así como a cambios en MAVC, PIO, grosor foveal, y complicaciones observadas. Resultados: Se produjo mejoría en la MAVC en el 30,77, 47,37 y 52,63%, al mes, 3 y 6 meses, respectivamente (p<0,05 a los 3 meses). Se observó incremento de la PIO en el 57,69% al mes, y en el 75% y 47,05%, a los 3 y 6 meses (p<0,05 a los 3meses). Se cuantificó una disminución en el grosor foveal al mes, 3 y 6 meses (p<0,05). Se observó progresión de catarata en 22,72%. No se apreció ningún caso de endoftalmitis. Conclusiones: La TA iv es una buena opción terapeútica para los pacientes con EMD persistente, mejorando la MAVC y reduciendo el grosor macular a corto plazo, con porcentajes de resolución clínica de más del 70%. Sin embargo, su efecto transitorio y sus potenciales efectos adversos hacen que deba administrarse en casos refractarios con precaución(AU)

Purpose: To determine the efficacy of intravitreal triamcinolone injections (iv TA) for diffuse persistent diabetic macular oedema (DMO) based on the functional parameter of modification in best corrected visual acuity (BCVA) and the anatomic parameter of quantitative changes in central macular thickness, as determined by optical coherence tomography (OCT). The secondary outcome is to analyse the safety of the procedure. Methods: In this retrospective study, 16 patients (22 eyes) were included over a period of six months. Type and time of evolution of diabetes mellitus, previous treatments, BCVA, lens status, intraocular pressure (IOP) and central macular thickness, were analysed. During the follow-up period were collected: number of injections, changes in BCVA, IOP, central macular thickness, and complications observed. Results: Improvement in BCVA was recorded in 30.77%, 47.37% and 52.63%, at one, three and six months, respectively (P<.05 at 3 months). The IOP increased in 57.69% at one month, and 75 and 47.05%, at 3 and 6 months, respectively (P<.05 at 3 months). Progression of cataracts was found in 22.72%. No cases of endophthalmitis were observed. Conclusions: Intravitreal TA is a good therapeutic option for patients with persistent DMO, increasing BCVA and decreasing central macular thickness in the short term, with a percentage of clinical resolution of more than 70%. However, due to the transient effect, and potential adverse effects, it should be administered to selected refractory cases with caution(AU)

CD28 and KIR2D receptors as sensors of the immune status in heart and liver transplantation.

Viral infections and cellular acute rejection (AR) condition immunosuppressive therapy and compromise the evolution of allografts. Immune monitoring can be useful for ascertaining rejection and for differentiating allo-reaction from activation induced by infections. This work analyzes the usefulness of monitoring the expression of CD28 and KIR2D receptors in peripheral blood T lymphocytes by flow cytometry, to ascertain the immune response in heart and liver transplant recipients. In both types of transplant, the up-regulation of CD28 in CD4(+) lymphocytes in the periods of greatest AR frequency indicates an effective allo-response, whereas the post-transplantation emergence of circulating CD8(+)CD28(-) and CD8(+)CD28(-)KIR2D(+) T cells correlates with better early clinical results. Cytomegalovirus (CMV) infection, but not hepatitis C virus (HCV) or other infections, abrogated both CD28 up-regulation and CD8(+)CD28(-)KIR2D(+) T-cell expansion. Our results show that monitoring the expression of CD28 and KIR2D receptors on T lymphocytes might be considered as sensors of the immune status of heart and liver recipients.

Divergences in KIR2D+ natural killer and KIR2D+CD8+ T-cell reconstitution following liver transplantation.

Natural killer (NK) and CD8(+) T cells may be active elements in the allograft response, but little is known about their role in liver transplantation. Some of these cells express killer immunoglobulin-like receptors (KIRs), which after binding specific ligands may transmit inhibitory/activating signals. In this study, circulating NK and CD8(+) T cells expressing CD158a/h (KIR2DL1/S1) or CD158b/j (KIR2DL2/3/S(2)) receptors were analyzed in 142 liver recipients by flow cytometry. They were underrepresented in patients before transplantation, but following transplantation, whereas the KIR2D(+) NK subsets experienced a late recuperation (day 365) mainly in C2-homozygous patients developing early acute rejection, recovery of the 2 CD8(+)KIR2D(+) T cells started earlier, showing significant differences on day 365 between patients without acute rejection and those suffering from it (p = 0.004 and p < 0.0001, respectively). These differences were also evident when the human leukocute antigen-C genotypes of the recipient were considered. In conclusion, whereas the late recovery of KIR2D(+) NK cells in C2/C2 patients appears to be linked to acute rejection, the increase in early CD8(+)KIR2D(+) T cells in overall liver recipients correlates with a most successful early graft outcome. Therefore, monitoring of KIR2D(+) cells appears to be a useful tool for liver transplant follow-up.