Borderline rejection in ABO-incompatible kidney transplantation.

INTRODUCTION: The clinical results of ABO-incompatible (ABOi) and ABO-compatible (ABOc) kidney transplantation (KT) are similar. Protocol kidney biopsies (PKB) of ABOi transplant recipients show positivity for C4d without evidence of antibody-mediated rejection (ABMR), but little is known about the histologic progression. METHOD: We evaluated histologic parameters in PKB at 12 months and also compared clinical outcome at 1 year. This is a prospective observational study conducted between 2009 and 2013. We performed 146/30 ABOc/ABOi consecutive living-donor KT with PKB as well as additional indication biopsies. In the ABOi group, the desensitization protocol consisted of rituximab, plasma exchange or immunoadsorption, and immunoglobulins. RESULTS: In indication biopsies during the first year, T-cell-mediated rejection Banff ≥immunoadsorption was 8.2% vs 6.7% (P=.561) and ABMR 4.8% vs 13.3% (P=.095). At 1 year, PKB (ABOc/ABOi) showed differences in borderline rejection lesions (6.8% vs 23.3% [P=.012]) and in C4d positivity in the ABOi group (P=.001). Interstitial fibrosis and tubular atrophy (IFTA) lesions (ABOc/ABOi) were 68.4% vs 63.2% (P=.348). Transplant glomerulopathy was 0.7% vs 3.3% (P=.373) at 1 year. CONCLUSIONS: Our PKB ABOi series shows at 1 year more borderline lesions independent of ABO titers, HLA incompatibility, and the presence of antidonor antibody, but do not show more IFTA nor transplant glomerulopathy. No clinical differences were observed between ABOi and ABO transplants.

Exploring the presence of narcolepsy in patients with schizophrenia.

BACKGROUND: There are several case reports of patients with narcolepsy and schizophrenia, but a systematic examination of the association of both disorders has not been done. The aim of this work is to assess the frequency of narcolepsy with cataplexy in a large consecutive series of adult patients with schizophrenia and schizoaffective disorder. METHODS: We screened 366 consecutive patients with schizophrenia or schizoaffective disorder with a sleep questionnaire and the Epworth Sleepines scale (ESS) exploring narcoleptiform symptoms. Those who screened positive were assessed by a sleep specialist, and offered an HLA determination. CSF hypocretin-1 determination was proposed to those who were HLA DQB1*06:02 positive. RESULTS: On the screening questionnaire, 17 patients had an ESS score ≥11 without cataplexy, 15 had cataplexy-like symptoms with an ESS score < 11, and four had an ESS score ≥11 plus cataplexy-like symptoms. Of those, 24 patients were evaluated by a sleep specialist. Five of these 24 were HLA DQB1*06:02 positive, and three of these five subjects underwent lumbar puncture showing normal hypocretin-1 levels. CONCLUSIONS: Our results suggest that narcolepsy with cataplexy is not an unrecognized disease in adult patients with schizophrenia or schizoaffective disorder.

Assessment of synthetic chimeric multiple antigenic peptides for diagnosis of GB virus C infection.

The use of synthetic peptides of both structural and nonstructural proteins of GB virus C (GBV-C) has been studied for the development of new systems to diagnose infection caused by this virus. In an attempt to increase the antigenicity of linear peptide sequences, chimeric multiple antigenic peptides (MAPs) containing epitopes from E2, NS4, and NS5 GBV-C proteins have been synthesized. The synthetic constructs were evaluated by ELISA to establish whether the epitopes in chimeric branched peptides are more efficiently recognized by the specific antibodies compared to the monomeric linear sequences. Moreover, we have investigated the application of a commercial biosensor instrument for the detection of antibodies against the GBV-C in human serum samples. The results of the immunoassays reported in this work highlight the usefulness of synthetic tetrameric branched peptides containing sequences from envelope and nonstructural GBV-C proteins for the diagnosis of GBV-C infection. The potential clinical value of the MAP(4)(E2-NS5a) for the serodiagnosis of GBV-C infection was demonstrated, thus providing the basis for performing prevalence studies of the infection among the hemodialyzed and hepatitis C virus (HCV)-infected population.

HLA and microtubule-associated protein tau H1 haplotype associations in anti-IgLON5 disease.

OBJECTIVES: We investigated the associations with HLA and microtubule-associated protein tau (MAPT) H1 haplotype in anti-IgLON5 disease, a recently identified disorder characterized by gait instability, brainstem dysfunction, and a prominent sleep disorder in association with IgLON5 antibodies and pathologic findings of a novel neuronal-specific tauopathy. METHODS: We compared the HLA alleles and MAPT H1/H1 genotype of 35 patients with anti-IgLON5 with healthy controls. The on-line server tool NetMHCIIpan 3.1 was used to predict the IgLON5 peptide binding to HLA Class II molecules. RESULTS: The HLA-DRB1*10:01-DQB1*05:01 haplotype was overrepresented in patients with anti-IgLON5 disease (OR = 54.5; 95% CI: 22.2-133.9, p < 0.0001). In addition, HLA-DQA was genotyped in 27 patients, and 25 (92.6%) of them had DQ molecules composed by DQA1*01 and DQB1*05 chains compared with 148/542 (27.3%) controls (OR = 43.9; 95% CI: 10.4-185.5, p < 0.0001). Patients DRB1*10:01 positive developed more frequently sleep or bulbar symptoms than those carrying other HLA alleles (70.0% vs 26.7%; p = 0.011). Prediction algorithms identified 2 IgLON5 peptides (1 located in the signal sequence) that showed strong binding to HLA-DRB1*10:01 and other HLA-DRB1, but not to HLA-DQA and HLA-DQB molecules. The MAPT H1/H1 homozygous genotype was present in 20/24 (83.3%) anti-IgLON5 Caucasian patients compared with 54/116 (46.5%) healthy controls (p = 0.0007). CONCLUSIONS: The robust association of anti-IgLON5 disease with distinct HLA Class II molecules supports a primary autoimmune origin. The significant association of MAPT H1 haplotype also suggests that an underlying neurodegenerative process could be involved in anti-IgLON5 disease.

Antibodies to citrullinated human fibrinogen synthetic peptides in diagnosing rheumatoid arthritis.

Since aggressive therapy given early in the rheumatoid arthritis (RA) disease course has the greatest therapeutic potential, early diagnostic tests with both high specificity and sensitivity are desirable. Rheumatoid sera were found to contain antibodies against citrullinated peptides, which are considered to be highly specific markers of RA. In the present work several analogues of the alpha- and beta-chains of fibrin peptides containing different degrees of citrullination have been synthesized and analyzed by ELISA using 111 sera from RA patients. In addition, we have also investigated the synergistic effects of different presentation formats of the synthetic constructs. We have designed chimeric and cyclic peptides that bear different peptide sequences within the same molecule. Our results indicate that the synthesis of peptides bearing fibrinogen and filaggrin domains could be a robust method for the design of useful diagnostic strategies in RA.

[Determination of HLA-A, -B and -DRB1 polymorphism in brain dead organ donors representative of the Colombian general population, 2007-2014].

INTRODUCTION: Genes encoding for human leukocyte antigens (HLA) are highly polymorphic and of great importance in organ transplantation procedures, as determining allelic frequencies in defined populations is taken into account among the scientific criteria for organ allocation. OBJECTIVE: The objective of this study was to establish the antigen HLA-A, -B, and -DRB1 haplotype frequencies in organ donors representative of the Colombian population after brain death. MATERIALS AND METHODS: We conducted a descriptive retrospective study involving 2,506 cadaveric organ donors including an allelic and haplotype analysis of HLA-A, -B and -DRB1; we also determined the Hardy-Weinberg equilibrium. RESULTS: We identified 21, 43 and 15 allelic loci for groups A*, B* and DRB1*, respectively. We detected 1,268 HLA-A, -B and -DR, 409 HLA-A-B, 383 HLA-DR-B, and 218 HLA-A-DR haplotypes. The three loci were found to be in Hardy-Weinberg equilibrium between the number of heterozygotes observed and the expected number, with p values of ;0.05. CONCLUSIONS: This study provides information on the allelic distribution of HLA class I and II in organ donors from the six regions in which Colombia is structurally divided to provide transplant services.

Clinical manifestations of the anti-IgLON5 disease.

OBJECTIVE: To report the presentation, main syndromes, human leukocyte antigen (HLA) association, and immunoglobulin G (IgG) subclass in the anti-IgLON5 disease: a disorder with parasomnias, sleep apnea, and IgLON5 antibodies. METHODS: This was a retrospective clinical analysis of 22 patients. The IgG subclass was determined using reported techniques. RESULTS: Patients' median age was 64 years (range 46-83). Symptoms that led to initial consultation included sleep problems (8 patients; 36%), gait abnormalities (8; 36%), bulbar dysfunction (3; 14%), chorea (2; 9%), and cognitive decline (1; 5%). By the time of diagnosis of the disorder, 4 syndromes were identified: (1) a sleep disorder with parasomnia and sleep breathing difficulty in 8 (36%) patients; (2) a bulbar syndrome including dysphagia, sialorrhea, stridor, or acute respiratory insufficiency in 6 (27%); (3) a syndrome resembling progressive supranuclear palsy (PSP-like) in 5 (23%); and (4) cognitive decline with or without chorea in 3 (14%). All patients eventually developed parasomnia, sleep apnea, insomnia, or excessive daytime sleepiness. HLA-DRB1*10:01 and HLA-DQB1*05:01 were positive in 13/15 (87%) patients; the DRB1*10:01 allele was 36 times more prevalent than in the general population. Among 16 patients with paired serum and CSF samples, 14 had IgLON5 antibodies in both, and 2 only in serum (both had a PSP-like syndrome). Twenty of 21 patients had IgG1 and IgG4 antibodies; the latter predominated in 16. CONCLUSIONS: Patients with IgLON5 antibodies develop a characteristic sleep disorder preceded or accompanied by bulbar symptoms, gait abnormalities, oculomotor problems, and, less frequently, cognitive decline. IgG4 subclass antibodies predominate over IgG1; we confirm a strong association with the HLA-DRB1*10:01 allele.

Clinical factors influencing T-cell receptor excision circle (TRECs) counts following allogeneic stem cell transplantation in adults.

To ascertain the clinical factors involved in T-cell reconstitution after allogeneic stem cell transplantation (SCT), we evaluated serial assessments of lymphocyte subsets by flow cytometry and TRECs levels by quantitative PCR in 83 adult patients. Patient age >25 years, unrelated donor, CMV infection and acute graft-versus-host disease (GVHD) adversely affected CD3(+) and CD8(+) T-cell recovery after SCT (p < 0.05). TRECs were low or undetectable during the first months after transplant and progressively increased thereafter. However, median TRECs of patients did never achieve normal values compared to healthy donors (median follow-up 9 months, range 2-42). Presence and severity of chronic GVHD significantly affected TRECs counts: patients with chronic GVHD had lower TRECs than patients without GVHD at 9, 12 and 24 months after SCT (p = 0.002, p = 0.022, p = 0.015). Patients with limited chronic GVHD had higher TRECs compared to patients with extensive GVHD (p = 0.018). No relationship was observed between fungal or bacterial infections and TRECs. Nonetheless, CMV infection was associated with lower TRECs (p = 0.032). Our data support the concept that adult thymus contributes with a slow but continuous production of thymic T cells to immune reconstitution after SCT. Chronic GVHD is the main factor associated to a delay in TRECs counts recovery.

Reduced-intensity conditioning regimen preserves thymic function in the early period after hematopoietic stem cell transplantation.

OBJECTIVE: To compare T-cell reconstitution in two groups of patients submitted to allogeneic stem cell transplantation (SCT): those receiving reduced-intensity conditioning (RIC, n = 24) and those receiving myeloablative conditioning (MA, n = 27). METHODS: Fifty-one consecutive patients undergoing SCT were evaluated. Serial assessments of lymphocyte subsets and T cell receptor excision circles (TRECs) levels were performed using multiparametric flow cytometry and real-time PCR, respectively. RESULTS: During the first 6 months posttransplant, total and naïve CD4(+) T cell counts were higher after RIC-SCT than after MA-SCT (total CD4(+): p = 0.04, p = 0.08, and p = 0.058; naïve CD4(+): p = 0.14, p = 0.05, and p = 0.01 at 1, 3, and 6 months, respectively). In both groups of patients, TRECs levels were low or undetectable in the first 3 months after SCT and progressively increased during the study. However, a higher proportion of patients with detectable levels of TRECs was observed in RIC-SCT at 1 and 3 months and more patients in this group reached normal levels of TRECs at 6 months post-SCT. In the multivariate analysis, including factors such as type of donor (sibling vs unrelated), dose of CD34(+) cells infused with the graft, patient age, and graft-vs-host disease (GVHD), the most important factor influencing TRECs recovery in the early period after SCT was the type of conditioning regimen. CONCLUSIONS: In this study, the pattern of immune reconstitution after RIC-SCT was different from that of MA-SCT and was characterized by higher posttransplant naïve CD4(+) T cell counts and TRECs levels in the early period after transplant.

Adult-onset atypical (type 1) diabetes: additional insights and differences with type 1A diabetes in a European Mediterranean population.

OBJECTIVE: In 1997, the American Diabetes Association proposed two subcategories for type 1 diabetes: type 1A or immunomediated diabetes and type 1B or idiopathic diabetes characterized by negative beta-cell autoimmunity markers, lack of association with HLA, and fluctuating insulinopenia. The aim of this study was to examine clinical characteristics, beta-cell function, HLA typing, and mutations in maturity-onset diabetes of the young (MODY) genes in patients with atypical type 1 diabetes (type 1 diabetes diagnosed at onset, without pancreatic autoantibodies and fluctuating insulinopenia). RESEARCH DESIGN AND METHODS: Eight patients with atypical type 1 diabetes (all men, 30.7 +/- 7.6 years) and 16 newly diagnosed age- and sex-matched patients with type 1A diabetes were studied retrospectively. Islet cell, GAD, tyrosine phosphatase and insulin antibodies, and basal and stimulated plasma C-peptide were measured at onset and after 1 year. HLA-DRB1-DQA1-DQB1 typing and screening for mutations in the HNF-1alpha and HNF-4alpha genes were performed from genomic DNA. RESULTS: Atypical patients displayed significantly higher BMI and better beta-cell function at onset and after 12 months. Three patients carried protective or neutral type 1 diabetes haplotypes, five patients displayed heterozygosity for susceptible and protective haplotypes, and seven patients showed Asp(beta57). We found a nondescribed variant Pro436Ser in exon 10 of the HNF-4alpha gene in one atypical patient without susceptible haplotypes. CONCLUSIONS: In our population, there are atypical forms of young adult-onset ketosis-prone diabetes initially diagnosed as type 1 diabetes, differing from type 1 diabetes in the absence of beta-cell autoimmunity, persistent beta-cell function capacity, fluctuating insulin requirements and ketosis-prone episodes, as well as clinical features of type 2 diabetes. Only one subgroup could be strictly classified as having type 1B diabetes. Additional information is still needed to improve our understanding of the mechanisms that finally lead to the disease.

Antiphospholipase A2 Receptor Antibody Levels Predict the Risk of Posttransplantation Recurrence of Membranous Nephropathy.

BACKGROUND: Secretory phospholipase A2 receptor (PLA2R) is the target antigen of the auto-antibodies produced in most (∼ 70%) patients with primary membranous nephropathy (pMN). The applicability of anti-PLA2R1 antibody monitoring for the prediction of MN recurrence in kidney transplant recipients still is a matter of debate. METHODS: We sought to characterize the presence and concentration of anti-PLA2R antibodies by enzyme-linked immunosorbent assay (ELISA) in a cohort of 21 patients with pMN before and after transplantation to evaluate whether anti-PLA2R concentrations could predict pMN recurrence. RESULTS: The presence of pMN recurrence was significantly correlated with the existence of a positive ELISA assay at graft biopsy or with high level of anti-PLA2R1 activity before transplantation (P = 0.03). In the receiver operating characteristic analysis, anti-PLA2R levels (cut-off of 45 U/mL) during the pretransplantation period accurately predicted pMN recurrence, with a sensitivity of 85.3%, specificity of 85.1%, negative predictive value of 92%, and an area under the curve of 90.8%. This finding supports the hypothesis that anti-PLA2R cause pMN recurrence in humans and indicates the need to prove in an experimental model. Furthermore, 6 of 7 patients with recurrence were carriers of HLA DQA1* 05:01/05 and DQB1* 02:01, confirming these DQ alleles as those associated with higher anti-PLA2R levels. CONCLUSIONS: This study is the first to demonstrate pretransplantation circulating anti-PLA2R antibodies in a cohort of renal transplant recipients who prospectively developed recurrent disease. Currently, anti-PLA2R levels measured by ELISA may be a rational tool to establish the risk of MN recurrence in renal allograft recipients.

GB virus C (GBV-C) / hepatitis G virus (HGV): towards the design of synthetic peptides-based biosensors for immunodiagnosis of GBV-C/HGV infection.

In the present study, new putative epitopes located in structural (E2) and non-structural (NS3) proteins of GBV-C/HGV were identified by computer-aided prediction of antigenicity and synthesized in solid-phase, following an Fmoc/tBut strategy, for their use in immunoassays. The corresponding synthetic peptides were used as antigens in ELISA assays and in real-time biospecific interaction measurements. This last approach allowed direct detection of GBV-C/HGV-specific antibodies in human sera. Good correlations were obtained between the biospecific interaction analysis and the ELISA. To verify the performance of these new assays in comparison to the existing recombinant E2 protein commercial test, antibodies to synthetic peptides were searched for in different panels of serum samples. The main conclusion of this work is the usefulness of E2 peptides in the detection of antibodies. Moreover, the NS3 peptide could be exploited to improve the sensitivity of the currently available test. Our results offer a new approach to develop new diagnostic peptide based biosensors for serodiagnosis of GBV-C/HGV infection.

Liposome entrapment and immunogenic studies of a synthetic lipophilic multiple antigenic peptide bearing VP1 and VP3 domains of the hepatitis A virus: a robust method for vaccine design.

Multiple antigen peptides (MAP) have been demonstrated to be efficient immunological reagents for the induction of immune responses to a variety of infectious agents. Several peptide domains of the hepatitis A virus (HAV) capsid proteins, mainly VP1 and VP3, are the immunodominant targets for a protective antibody response. In the present study we analyse the immunogenic properties of a tetrameric heterogeneous palmitoyl-derivatised MAP containing two defined HAV peptide sequences, VP1(11-25) and VP3(102-121), in rabbits immunised with either Freund's adjuvant or multilamellar liposomes. The immune response was evaluated with a specific enzyme immunoassay using MAP[VP1+VP3], VP1 and VP3 as targets. The avidity of the immune response was measured by a non-competitive enzyme-linked immunosorbent assay and by the surface plasmon resonance technology. Antisera raised against the lipo-MAP peptide entrapped in liposomes demonstrated high avidity of binding with affinity rate constants approximately one order of magnitude greater than those obtained with the Freund's protocol.

[Clinical, metabolic, immunologic and genotypic characteristics in non-pediatric patients with type 1A diabetes mellitus. Onset and short-term prognosis]. / Características clínicas, metabólicas, inmunológicas y genotípicas de un grupo de adolescentes y adultos con diabetes mellitus tipo 1A. Inicio y pronóstico a corto plazo.

BACKGROUND AND OBJECTIVE: Around 50% of new cases of type 1 diabetes mellitus (DM1) are seen in subjects aged above 15 years. It is of particular interest the characterization of such a population. THE AIMS OF OUR STUDY WERE: a) to characterize a group of non-pediatric subjects with DM1 at the onset of the disease; b) to evaluate the prognosis of the disease under conventional intensive insulin therapy, and c) to investigate the presence of mutations in the HNF-1* gene in those subjects who did not display pancreatic autoimmune markers. SUBJECTS AND METHOD: All subjects with an age >= 15 and 35 years recently diagnosed DM1 (1998-2001) were included in the study. Pancreatic cell function was assessed by glucagon test (at onset and at 12 months). The presence of pancreatic autoantibodies, GAD, IA2 and IAA was evaluated. HLA class II genes and the 10 exons of HNF-1* gene were analyzed from genomic DNA. RESULTS: We studied 86 subjects (32 women, 23.9 [5.3] year-old). Eighty percent of subjects were positive for any of the studied autoantibodies. Alone or in combination, GAD was positive in 68.6% of subjects, IA2 in 45.3% and IAA in 27.9% of them. Most frequent haplotype was DRB1*0301-DQA1*0501-DQB*0201. There were no differences with regard to clinical, metabolic or genetic characteristics among those subjects with or without presence of pancreatic autoantibodies (at onset and at 12 months). We did not find mutations in the HNF-1* gene in any of the subjects included in our study. After 12 months of follow-up, cell function remained unaltered in comparison with that observed at the onset of the disease. CONCLUSIONS: Clinical, immunological and HLA characteristics of a non-pediatric DM1 population are in agreement with expected results. The absence of pancreatic autoimmune markers neither rules out the existence of type 1A diabetes mellitus nor is associated with mutations in the MODY-3 gene. A therapeutic programme using conventional intensified insulin treatment prevents the impairment of insulin secretory capacity for a short-term follow-up.

Renal transplantation in systemic lupus erythematosus: outcome and prognostic factors in 50 cases from a single centre.

BACKGROUND: End-stage renal disease (ESRD) is an important cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). OBJECTIVES: To analyze the outcome and prognostic factors of renal transplantation in patients with ESRD due to SLE from January 1986 to December 2013 in a single center. RESULTS: Fifty renal transplantations were performed in 40 SLE patients (32 female (80%), mean age at transplantation 36±10.4 years). The most frequent lupus nephropathy was type IV (72.2%). Graft failure occurred in a total of 15 (30%) transplantations and the causes of graft failure were chronic allograft nephropathy (n=12), acute rejection (n=2), and chronic humoral rejection (1). The death-censored graft survival rates were 93.9% at 1 year, 81.5% at 5 years, and 67.6% at the end of study. The presence of deceased donor allograft (P=0.007) and positive anti-HCV antibodies (P=0.001) negatively influence the survival of the renal transplant. The patient survival rate was 91.4% at the end of the study. Recurrence of lupus nephritis in renal allograft was observed in one patient. CONCLUSION: Renal transplantation is a good alternative for renal replacement therapy in patients with SLE. In our cohort, the presence of anti-HCV antibodies and the type of donor source were related to the development of graft failure.

DQB1 locus alone explains most of the risk and protection in narcolepsy with cataplexy in Europe.

STUDY OBJECTIVE: Prior research has identified five common genetic variants associated with narcolepsy with cataplexy in Caucasian patients. To replicate and/or extend these findings, we have tested HLA-DQB1, the previously identified 5 variants, and 10 other potential variants in a large European sample of narcolepsy with cataplexy subjects. DESIGN: Retrospective case-control study. SETTING: A recent study showed that over 76% of significant genome-wide association variants lie within DNase I hypersensitive sites (DHSs). From our previous GWAS, we identified 30 single nucleotide polymorphisms (SNPs) with P < 10(-4) mapping to DHSs. Ten SNPs tagging these sites, HLADQB1, and all previously reported SNPs significantly associated with narcolepsy were tested for replication. PATIENTS AND PARTICIPANTS: For GWAS, 1,261 narcolepsy patients and 1,422 HLA-DQB1*06:02-matched controls were included. For HLA study, 1,218 patients and 3,541 controls were included. MEASUREMENTS AND RESULTS: None of the top variants within DHSs were replicated. Out of the five previously reported SNPs, only rs2858884 within the HLA region (P < 2x10(-9)) and rs1154155 within the TRA locus (P < 2x10(-8)) replicated. DQB1 typing confirmed that DQB1*06:02 confers an extraordinary risk (odds ratio 251). Four protective alleles (DQB1*06:03, odds ratio 0.17, DQB1*05:01, odds ratio 0.56, DQB1*06:09 odds ratio 0.21, DQB1*02 odds ratio 0.76) were also identified. CONCLUSION: An overwhelming portion of genetic risk for narcolepsy with cataplexy is found at DQB1 locus. Since DQB1*06:02 positive subjects are at 251-fold increase in risk for narcolepsy, and all recent cases of narcolepsy after H1N1 vaccination are positive for this allele, DQB1 genotyping may be relevant to public health policy.

Determinación del polimorfismo de HLA-A, -B y -DRB1 en donantes de órganos con muerte encefálica representativos de la población general colombiana, 2007-2014 / Determination of HLA-A, -B and -DRB1 polymorphism in brain dead organ donors representative of the Colombian general population, 2007-2014

Resumen Introducción. Los genes que codifican para el sistema de antígenos leucocitarios humanos (Human Leukocyte Antigen, HLA) son muy polimorfos y de gran importancia en procedimientos de trasplante de órganos, ya que la determinación de las frecuencias alélicas en poblaciones específicas se tiene en cuenta entre los criterios científicos para la asignación de órganos. Objetivo. Establecer las frecuencias antigénicas y haplotípicas de HLA-A, -B y -DRB1 en donantes de órganos con muerte encefálica, representativos de la población colombiana. Materiales y métodos. En este estudio descriptivo retrospectivo de 2.506 donantes cadavéricos de órganos, se hizo un análisis alélico y de haplotipos de HLA-A, -B y -DRB1, y se determinó el equilibrio de Hardy-Weinberg. Resultados. Se encontraron 21, 43 y 15 grupos alélicos para los loci A*, B* y DRB1*, respectivamente. Se detectaron 1.268 haplotipos HLA-A, -B y -DR, 409 haplotipos HLA A-B, 383 haplotipos HLA-B-DR y 218 haplotipos HLA-A-DR. Los tres loci se encontraban en equilibrio de Hardy-Weinberg entre el número de heterocigóticos observados y el esperado, con valores de p<0,05. Conclusiones. En este estudio se proporciona información sobre la distribución de los alelos HLA de clase I y II en la población de donantes de órganos provenientes de las seis regionales en las que está dividido el país para la prestación de servicios de trasplante.

Abstract Introduction: Genes encoding for human leukocyte antigens (HLA) are highly polymorphic and of great importance in organ transplantation procedures, as determining allelic frequencies in defined populations is taken into account among the scientific criteria for organ allocation. Objective: The objective of this study was to establish the antigen HLA-A, -B, and -DRB1 haplotype frequencies in organ donors representative of the Colombian population after brain death. Materials and methods: We conducted a descriptive retrospective study involving 2,506 cadaveric organ donors including an allelic and haplotype analysis of HLA-A, -B and -DRB1; we also determined the Hardy-Weinberg equilibrium. Results: We identified 21, 43 and 15 allelic loci for groups A*, B* and DRB1*, respectively. We detected 1,268 HLA-A, -B and -DR, 409 HLA-A-B, 383 HLA-DR-B, and 218 HLA-A-DR haplotypes. The three loci were found to be in Hardy-Weinberg equilibrium between the number of heterozygotes observed and the expected number, with p values of <0.05. Conclusions: This study provides information on the allelic distribution of HLA class I and II in organ donors from the six regions in which Colombia is structurally divided to provide transplant services.

Antibodies against ß-fibrin synthetic peptides: a study of their association with the immunogenetic background and disease course of rheumatoid arthritis patients.

Preliminary studies have shown the potential application for the diagnosis of Rheumatoid Arthritis (RA) patients with a severe disease course of an epitopic domain of ß-fibrin. The aim of the present work was the analysis of the presence of antibodies against several ß-fibrin synthetic peptides in relation to the immunogenetic background and disease course in a clinically well-defined RA patient cohort. Our results indicated that positive patients against anti-ß-fibrin synthetic peptides have a higher percentage of HLA-DRB1 shared epitope (SE) than negative patients. We also observed that the presence of SE alleles was significantly associated with a higher level of anti-[Cit(376)]ßfib(365-383) antibodies. When analyzing the effect of different SE alleles, we found a significant positive association between carriers of QRRAA allele and [Cit(376)]ßfib(365-383) (Odds ratio 3.77; CI95%: 1.41-10.08). These results suggest that the anti-ß-fibrin status is associated with the immunogenetic background of RA patients.

Effect of synthetic peptides belonging to E2 envelope protein of GB virus C on human immunodeficiency virus type 1 infection.

The use of synthetic peptides as HIV-1 inhibitors has been subject to research over recent years. Although the initial therapeutic attempts focused on HIV-coded enzymes, structural HIV proteins and, more specifically, the mechanisms that the virus uses to infect and replicate are now also considered therapeutic targets. The interest for viral fusion and entry inhibitors is growing significantly, given that they are applicable in combined therapies or when resistance to other antiretroviral drugs is seen and that they act before the virus enters the cell. The 124 synthetic sequences of the GBV-C E2 envelope protein have been obtained by SPPS. The interaction of certain GBV-C peptide sequences with the HIV-1 fusion peptide has been proven through the use of biophysical techniques. We also show how GBV-C E2 domains notably decrease cellular membrane fusion and interfere with the HIV-1 infectivity in a dose-dependent manner, highlighting their potential utility in future anti-HIV-1 therapies.