Aspectos técnicos y clínicos de la prueba cruzada de histocompatibilidad en el trasplante de órganos solidos / Technical and clinical aspects of the histocompatibility crossmatch assay in solid organ transplantation

La presencia de anticuerpos dirigidos contra los antígenos leucocitarios humanos (Human Leukocyte Antigens, HLA) que se expresan en las células del donante, es uno de los factores de riesgo más importantes asociados con las complicaciones clínicas después del trasplante. La prueba cruzada es una de las pruebas de histocompatibilidad más eficaces para la detección de anticuerpos específicos contra el donante en los receptores de injertos. En los primeros métodos de la prueba cruzada, se utilizaba la citotoxicidad dependiente del complemento, que es útil para detectar dichos anticuerpos responsables del rechazo hiperagudo del injerto, pero carece de la sensibilidad adecuada. Por ello, se desarrollaron métodos de pruebas cruzadas más sensibles, entre ellas, la prueba cruzada por citometría de flujo que hoy se considera el método preferido. En este artículo se revisa la evolución de la prueba cruzada y los factores más importantes que deben tenerse en cuenta al realizarla y al interpretar los resultados de esta prueba fundamental para la supervivencia a largo plazo del injerto.

The presence of antibodies directed against human leukocyte antigens (HLA) expressed on donor cells is a significant risk factor for serious clinical complications after transplantation. The crossmatch assay is one of the most important tests available for the detection of donor-specific antibodies in potential allograft recipients. Early crossmatch methods utilized complement-dependent cytotoxicity, which is useful for detecting the donor-specific anti- HLA antibodies responsible for hyperacute allograft rejection but lacks adequate sensitivity. Consequently, more sensitive crossmatch methods have been developed, ultimately leading to the flow cytometry crossmatch as the currently preferred methodology. Herein, we review the evolution of the crossmatch assay and the most important factors to consider when performing and interpreting the results of this fundamental assay for ensuring the long-term survival of the transplanted organ.

Neutropenia aloimune neonatal em gêmeas idênticas / Neonatal alloimmune neutropenia in identical twins

A neutropenia aloimune neonatal (NAN) é uma patologia causada pelo antagonismo imunológico, como a doença hemolítica do recém-nascido ou a trombocitopenia aloimune neonatal, mas relacionada aos neutrófilos, em vez de glóbulos vermelhos ou plaquetas. Descreveremos um caso clínico de duas gêmeas idênticas nascidas a termo, com Apgar de 8 e 9, sendo que após algumas horas do nascimento apresentaram febre. Um exame de sangue revelou neutropenia grave que resultou em sepse. O diagnóstico da NAN foi realizado clinicamente e por testes de histocompatibilidade. A prova cruzada por citometria de fluxo foi positiva, usando soro da mãe e suspensões celulares (granulócitos e linfócitos) das gêmeas e do pai. Este teste não fornece informações sobre para qual sistema genético os anticorpos foram positivos, se contra os antígenos específicos de neutrófilos humanos (HNA) ou contra os antígenos leucocitários humanos (HLA). Para o esclarecimento, realizamos o teste de aglutinação de granulócitos (GAT) com um painel de doadores fidelizados e com antígenos HNA1-5 conhecidos, utilizando o soro materno como reagente. Foi também realizada a pesquisa de anticorpos anti-HLA e anti-HNA no soro materno. Os genótipos HLA e HNA foram identificados, permitindo conhecer as especificidades dos anticorpos maternos contra os antígenos dos neutrófilos do marido e das filhas. O diagnóstico de NAN não é realizado na maioria dos hospitais de nosso país e do exterior, devido à dificuldade de execução dos testes de histocompatibilidade, no entanto a prova cruzada por citometria de fluxo pode facilmente ser implantada nos laboratórios clínicos, sendo que está descrita detalhadamente nesse caso clínico.

Neonatal alloimmune neutropenia (NAN) is a disease caused by immunological antagonism, such as hemolytic disease of the newborn or neonatal alloimmune thrombocytopenia, but related to neutrophils rather than to red blood cells or platelets. We will describe a clinical case of two identical twins born with Apgar 8 and 9 that started with fever few hours after delivery. A blood test revealed severe neutropenia, which was followed by sepsis. The diagnosis of NAN was done clinically and by histocompatibility testing. Flow cytometry crossmatch was positive, using mother serum and cell suspensions (granulocytes and lymphocytes) from the twin girls and from the father. This test did not provide information about the genetic system for which the antibodies are positive, if against human neutrophil antigens (HNA) or human leucocyte antigens (HLA). To clear this, the granulocyte agglutination test (GAT) was performed with a panel of control donors with known HNA1-5 antigens, using the maternal serum as a reagent. We did also a Luminex screening assay for detection of anti-HLA and anti-HNA antibodies in the mother serum. The HLA and HNA genotypes were identified, which allowed to define specificities in mother's antibodies against the neutrophil surface antigens from her husband and from the twins. The diagnosis of NAN diagnose is not done in most hospitals worldwide, mainly by the difficulty in executing the histocompatibility test. However, the crossmatch by flow cytometry could be easily done in clinical laboratories following the method described in this article.

Expression of Histo-blood Group Antigens in Tumor and Adjacent Normal Breast Tissues as Prognostic Markers of Breast Carcinoma / 한국유방암학회지

PURPOSE: Aberrant glycosylation of the histo-blood group antigens (including the angina bullosa haemorrhagica [ABH]) is often observed during malignant transformation in most types of carcinomas. Data concerning their ethnic distributions are diverse which explains why their biological characteristics have to be studied in different populations. Our aim was to analyze the expression of the histo-blood group (specifically the ABH) antigens in breast carcinoma.METHODS: The expression of the histo-blood group (specifically the ABH) antigens was studied in 109 patients with breast carcinoma using immunohistochemistry. Statistical analysis was performed using χ² and Fisher analyses.RESULTS: The loss of expression of histo-blood group (ABH) antigens in breast carcinoma was observed in 81.13% of patients with blood group O, 37.93% with blood group A, and 96.30% with blood group B. One key finding of this study was that the loss of expression of the ABH antigen was also observed in normal tissues adjacent to the tumor. The loss of expression was associated with higher tumor grade (p < 0.05). Expression of H antigen was observed in 50% of cases with loss of expression of B antigen and was associated with human epidermal growth factor receptor 2 (HER2) overexpression (p < 0.05). The loss of H antigen in patients with blood group O was associated with estrogen receptor expression (p < 0.001). Incompatible A antigen in tumor was expressed in 20.75% of patients with blood group O.CONCLUSION: Loss of the ABH antigens correlated with the Scarff-Bloom-Richardson histologic grading. H antigen was associated with HER2 overexpression in breast cancer. However, further studies are needed to determine the role of incompatible A antigen in mammary carcinogenesis.

Tumor venéreo transmissível canino com resistência quimioterápica e metástase esplênica. Relato de caso / Canine transmissible venereal tumor with chemotherapy resistance and splenic metastasis. Case report

RESUMO O Tumor Venéreo Transmissível Canino (TVTC) é uma neoplasia de células redondas que tem a particularidade de se implantar em mucosas que tenham perdido a sua integridade. Nesse local o tumor prolifera e ocasionalmente origina metástase. Em geral, o tumor responde ao tratamento com sulfato de vincristina, porém a resistência quimioterápica associada ao fenótipo tumoral tem sido documentada. Objetivou-se relatar um caso de TVTC genital de fenótipo citológico misto com metástase esplênica e o insucesso da quimioterapia com sulfato de vincristina, em uma fêmea canina, da raça Australian Cattle Dog, de cinco anos de idade. Após diagnóstico citológico e histológico, o tumor primário foi ainda caracterizado em fase de progressão e mostrou baixa expressão de moléculas do complexo principal de histocompatibilidade (MHC) (4,4 ± 2% classe I e 11 ± 4,1% classe II). A cadela foi submetida à ovariohisterectomia e esplenectomia terapêutica e não apresentou recidiva do tumor após 12 meses de acompanhamento clínico.

ABSTRACT The canine transmissible venereal tumor is a type of round cell cancer that have the particularity of implanting in mucous tissue, when they lose their integrity, at which point the tumour proliferates and may even develop metastases. The tumor typically responds well to vincristine sulfate chemotherapy, although there are cases of resistance to the drug correlated with the tumoral phenotype. We describe herein a genital mixed TVTC case with metastases at spleen and failure at vincristine sulfate chemotherapeutic treatment in a five years old Australian Cattle Dog female. After the cytological, histological and cytogenetic diagnostic, the primary tumor was still characterized in progression phase and showed low major histocompatibility complex expression MHC (4,4 ± 2% class I e 11 ± 4,1% class II. The dog underwent therapeutic splenectomy and ovariohysterectomy and did not present tumor recurrence within 12 months of clinical follow-up.

Afectación cardiopulmonar por citomegalovirus en individuos inmunocompetentes / Cardiopulmonary involvement due to cytomegalovirus in immunocompetent individuals

Resumen La infección por Citomegalovirus en adultos sanos suele cursar de forma asintomática o como un cuadro de mononucleosis. La afectación cardiopulmonar en individuos inmunocompetentes es infrecuente y se asocia a mal pronóstico. Su diagnóstico exige una elevada sospecha clínica. Se presenta el caso clínico de un paciente joven que debutó con clínica de neumonía atípica y en el estudio posterior se descubrió miocardiopatía dilatada con disminución de la contractilidad miocárdica. La serología para citomegalovirus fue positiva y el paciente recibió terapia antiviral específica con excelente resultado.

Abstract Cytomegalovirus infection in healthy adults is usually asymptomatic or as signs and symptoms of a mononucleosis. Cardiopulmonary involvement in immunocompetent individuals is uncommon and is associated with a poor prognosis. Its diagnosis requires a high clinical suspicion. The case is presented of a young patient in whom the first clinical sign was an atypical pneumonia, and in the subsequent study a dilated cardiomyopathy with a decrease in myocardial contractility was discovered. The serology for cytomegalovirus was positive, and the patient received specific antiviral therapy, with an excellent outcome.

Everyone has a donor: contribution of the Chinese experience to global practice of haploidentical hematopoietic stem cell transplantation / 医学前沿

Human leukocyte antigen (HLA)-matched donors for hematopoietic stem cell transplantation (HSCT) have long been scarce in China. Haploidentical (haplo) donors are available for the vast majority of patients, but toxicity has limited this approach. Three new approaches for haplo-HSCT originated from Italy, China, and USA in 1990 and have been developed to world-renowned system up to now. The Chinese approach have been greatly improved by implementing new individualized conditioning regimens, donor selection based on non-HLA systems, risk-directed strategies for graft-versus-host disease and relapse, and infection management. Haplo-HSCT has exhibited similar efficacy to HLA-matched HSCT and has gradually become the predominant donor source and the first alternative donor choice for allo-HSCT in China. Registry-based analyses and multicenter studies adhering to international standards facilitated the transformation of the unique Chinese experience into an inspiration for the refinement of global practice. This review will focus on how the new era in which "everyone has a donor" will become a reality in China.

Annual Report of Korean Association of External Quality Assessment Service on Histocompatibility Testing (2018) / 임상검사와정도관리

Here, we report the results of the first histocompatibility proficiency testing (PT) performed by the Korean Association of External Quality Assessment Service in 2018. The directly prepared PT specimens of whole blood, sera, and mononuclear cell suspensions were distributed to participants biannually. The number of participants was comparable to that in the previous external PT program, and the response rate was 88%–100%. The accuracy rates for human leukocyte antigen (HLA) A, B, C, DR, and DQ low and high resolution typing were 100%/100%, 100%/98%, 100%/99%, and 99%/98%, respectively; HLA-B27 typing, 99.1%; T cell and B cell crossmatching, 3.1% and 6.0%, respectively; and HLA antibody screening and identification, 100% and 100%, respectively. The results of HLA crossmatching were not reported from four participants due to poor cell viability. Further improvements of the specimen delivery process, grading criteria for crossmatching, and format of participant summary are warranted.

Autologous hybrid cell fusion vaccine in a spontaneous intermediate model of breast carcinoma

Breast cancer is among the most common malignancies affecting women and reproductively intact female dogs, resulting in death from metastatic disease if not treated effectively. To better manage the disease progression, canine mammary tumor (CMT) cells derived from malignant canine mammary cancers were fused to autologous dendritic cells (DCs) to produce living hybrid-cell fusion vaccines for canine patients diagnosed with spontaneous mammary carcinoma. The high-speed sorting of rare autologous canine patient DCs from the peripheral blood provides the autologous component of fusion vaccines, and fusion to major histocompatibility complex-unmatched CMT cells were produced at high rates. The vaccinations were delivered to each patient following a surgical resection 3 times at 3-week intervals in combination with immuno-stimulatory oligonucleotides and Gemcitabine adjunct therapy. The immunized patient animals survived 3.3-times longer (median survival 611 days) than the control patients (median survival 184 days) and also appeared to exhibit an enhanced quality of life. A comparison of vaccinated patients diagnosed with inflammatory mammary carcinoma resulted in a very short median survival (42 days), suggesting no effect of vaccination. The data showed that the development of autologous living DC-based vaccine strategies in patient animals designed to improve the management of canine mammary carcinoma can be successful and may allow an identification of the antigens that can be translatable to promote effective immunity in canine and human patients.

Doctors Discussing “the Root of Koreans”: Medical Genetics and the Korean Origin, 1975–1987 / 의사학

Anthropological genetics emerged as a new discipline to investigate the origin of human species in the second half of the twentieth century. Using the genetic database of blood groups and other protein polymorphisms, anthropological geneticists started redrawing the ancient migratory history of human populations. A peculiarity of the Korean experience is that clinical physicians were the first experts using genetic data to theorize the historical origin of the respective population. This paper examines how South Korean physicians produced the genetic knowledge and discourse of the Korean origin in the 1970s and 1980s. It argues that transnational scientific exchange led clinical researchers to engage in global anthropological studies. The paper focuses on two scientific cooperative cases in medical genetics at the time: the West German-South Korean pharmacogenetic research on the Korean population and the Asia-Oceania Histocompatibility Workshop. At the outset, physicians introduced medical genetics into their laboratory for clinical applications. Involved in cooperative projects on investigating anthropological implications of their clinical work, medical researchers came to use their genetic data for studying the Korean origin. In the process, physicians simply followed a nationalist narrative of the Korean origin rather than criticizing it. This was partially due to their lack of serious interest in anthropological work. Their explanations about the Korean origin would be considered “scientific” while hiding their embracing of the nationalist narrative.

UV induced surface modification on improving the cytocompatibility of metallocene polyethylene

ABSTRACT Demand for medical implants is rising day by day as the world becomes the place for more diseased and older people. Accordingly, in this research, metallocene polyethylene (mPE), a commonly used polymer was treated with UV rays for improving its biocompatibility. Scanning electron microscopy (SEM) images confirmed the formation of crests and troughs, which depicts the improvement of surface roughness of mPE substrates caused by UV etching. Accordingly, the contact angle measurements revealed that the wettability of mPE-2.5 J/cm2 (68.09º) and mPE-5 J/cm2 (57.93º) samples were found to be increased compared to untreated mPE (86.84º) indicating better hydrophilicity. Further, the UV treated surface exhibited enhanced blood compatibility as determined in APTT (untreated mPE- 55.3 ± 2.5 s, mPE-2.5 J/cm2 - 76.7 ± 4.1 s and mPE-5 J/cm2 - 112.3 ± 2 s) and PT (untreated mPE - 24.7 ± 1.5 s, mPE- 2.5 J/cm2 - 34.3 ± 1.1 s and mPE-5 J/cm2 - 43 ± 2 s) assay. Moreover, the treated mPE-2.5 J/cm2 (4.88%) and mPE-5 J/cm2 (1.79%) showed decreased hemolytic percentage compared to untreated mPE (15.40%) indicating better safety to red blood cells. Interestingly, the changes in physicochemical properties of mPE are directly proportional to the dosage of the UV rays. UV modified mPE surfaces were found to be more compatible as identified through MTT assay, photomicrograph and SEM images of the seeded 3T3 cell population. Hence UV-modified surface of mPE may be successfully exploited for medical implants.

Activación de la célula T, alteraciones en el lupus eritematoso sistémico, una revisión narrativa / T-cell activation, alterations in systemic lupus erythematosus: A narrative review

Resumen La activación de los linfocitos T se inicia a través de la presentación de antígenos endógenos o exógenos por células presentadoras de antígenos a través del complejo mayor de histocompatibilidad, el cual se une a un receptor especializado presente en los linfocitos T. Este reconocimiento desencadena una cascada de señalización intracelular que conlleva a un aumento en la expresión de integrinas, modificaciones del citoesqueleto y producción de factores de transcripción involucrados en la liberación de citocinas y mediadores inflamatorios. Uno de los inductores más importantes en la activación celular es el complejo enzimático con acción tirosina cinasa. Las cinasas que pertenecen a la familia SRC (SFK), FYN y LCK están involucradas en un gran número de procesos importantes en la activación, modulación de la respuesta linfocitaria y el desarrollo de enfermedades autoinmunes. La regulación de la señalización de las cinasas, así como de proteínas adaptadoras involucradas en la activación del linfocito T, son fundamentales para mantener el umbral de activación y modulación de la respuesta del linfocito. La fosforilación de sitios de regulación positiva de estas proteínas es importante para permitir una configuración activa de la proteína y de esta forma su máxima capacidad como cinasa. La fosforilación de los sitios de regulación negativa conlleva a una configuración cerrada de la proteína de tal forma que reduce su función de cinasa e inhibe su función. Las alteraciones en la señalización por modificación de algunas proteínas citoplasmáticas se asocian en algunos casos al desarrollo de enfermedades autoinmunes, como el lupus eritematoso sistémico. En condiciones fisiológicas, el complejo receptor de linfocitos T se reagrupa con complejos proteicos que interactúan armónicamente para generar una sen al interna. Los eventos de señalización alterados son en parte los responsables de una expresión anómala de citocinas, entre ellas la interleucina-6 (IL-6), IL-10, IL-2, IFN y CD40 ligando; estas modificaciones alteran la capacidad de los linfocitos T para sobre estimular a los linfocitos B, traduciéndose en un aumento en la producción de autoanticuerpos y en el desencadenamiento de la enfermedad autoinmune.

Abstract The activation of T cells is initiated by the presentation of exogenous or endogenous antigens, by antigen presenting cells through the major histocompatibility complex, which binds to a special receptor on T cells. This acknowledgement triggers a cascade of intracellular signalling that leads to an increase in integrin expression, cytoskeletal modifications, and transcription factors production involved in the liberation of cytokines and inflammatory mediators. One of the most important inducers in cell activation is the enzymatic complex with tyrosine kinase action. The kinases which belong to the SRC (SFK) LCK and FYN family have been involved in a large number of important processes in the activation and modulation of the T cells response, as well as in the development of autoimmune diseases. Regulating the kinases signalling, as well as the adapter proteins involved in T cell activation, is essential for maintaining an activation threshold, as well as the modulation of cell response. The phosphorylation of the positive regulation sites of these proteins is important to allow an active configuration of the protein and thereby its maximum capacity as kinase. The phosphorylation of negative regulation sites leads to a closed configuration of the protein that reduces its kinase function, and thereby inhibits its own function. The alteration in signalling by the modification of certain cytoplasmic proteins in some cases is associated with the development of autoimmune diseases, such as systemic lupus erythematosus. Under physiological conditions the T cell receptor complex regroups with protein complexes that interact harmonically to generate an internal signal. The altered signalling events are partly responsible for an anomalous expression of cytokines, including the interleukin-6 (IL-6), IL-10, IL-2, IFN, and CD40 linking, these modifications affects the cells ability to over-stimulate T and B cells, resulting in an increased production of autoantibodies and the triggering of the autoimmune disease.

Skewed Dendritic Cell Differentiation of MyD88-Deficient Donor Bone Marrow Cells, Instead of Massive Expansion as Myeloid-Derived Suppressor Cells, Aggravates GVHD

Graft-versus-host disease (GVHD), a life-threatening complication after bone marrow transplantation (BMT), is induced by activation of alloreactive donor T cells. Our previous study demonstrated that transplantation of myeloid differentiation factor 88 (MyD88)-deficient knockout (KO) bone marrow (BM) resulted in aggravation of GVHD. Here, to understand the cellular mechanism, we performed longitudinal in vivo imaging and flow cytometric analyses followed by transcriptome and functional examination of donor MyD88-KO BM progenies in GVHD hosts, using a major histocompatibility complex-matched but minor histocompatibility antigen-mismatched C57BL/6→BALB.B model. In GVHD hosts with MyD88-KO BMT, donor BM-derived CD11b+Gr-1+ cells were found to undergo cell death, a fate significantly different from the explosive expansion shown by the wild type (WT) counterparts, and also from the moderate expansion of the WT or MyD88-KO BM-derived cells in non-GVHD hosts. It was also revealed that MyD88-KO CD11b+Gr-1+ cells preferred differentiation into CD11c+ dendritic cells (DCs) to expansion as myeloid-derived suppressor cells in GVHD hosts or in high inflammatory in vitro conditions. These CD11c+ DCs comprised the majority of MyD88-KO CD11b+Gr-1+ apoptotic cells in GVHD hosts. Their ability to cross-present alloantigens of host origin contributed to the enhancement of T cell alloreactivity, causing GVHD aggravation and eventually death through the killing function of activated T cells. These results provide insights into the roles of MyD88 in myelopoiesis of donor BM and the protective effects in GVHD hosts, helpful information for development of a strategy to control GVHD.

Results of Questionnaire Survey of Current Immune Monitoring Practice of Transplant Clinicians and Clinical Pathologists in Korea: Basis for Establishment of Harmonized Immune Monitoring Guidelines / 대한이식학회지

Detection of significant alloimmune response, which affects graft function and survival by effective immune monitoring, is critical for treatment decision making. However, there is no consensus regarding immune monitoring (IM) for kidney transplantation (flow KT) in Korea. The IM protocol may be affected by the level of immunological risk, the methods of desensitization and the availabilities of resources such as laboratory support and cost of tests. Questionnaire surveys designed to identify the current practices regarding immune monitoring of KT among transplant clinicians and clinical pathologists in Korea and eventually provide a basis for the establishment of harmonized immune monitoring guidelines in KT were administered as part of a Korean Society for Transplantation Sponsored Research Project. The survey results revealed significant variations in IM protocols and interpretation of tests affecting treatment decisions between institutes. Moreover, the results revealed a need to expand the histocompatibility tests into high resolution HLA typing in multiple loci and non-HLA antibody tests that facilitate the epitope analysis and eventually virtual crossmatching. The results of the questionnaire survey from clinical pathologists are addressing the urgent need for the standardization of interpretation and harmonization of results reporting in single antigen bead based HLA antibody identification. Finally, communication between clinicians and clinical pathologists to meet the clinical expectations regarding various immune monitoring tests is needed.

Morfometria do osso esterno e sua correlação com o volume pulmonar / Sternum bone morphology and its correlation with lung volume

Este estudo teve por objetivo desenvolver um modelo matemático que a partir da extensão do osso esterno fornecesse o tamanho do pulmão compatível para o receptor. Foram coletadas as medidas antropométricas do tórax de 250 indivíduos, através de exame de tomografia computadorizada. Os resultados apontam que a medida do osso esterno (distância da incisura jugular até processo xifóide) apresenta correlação positiva com todas as outras medidas do tórax (medida ântero-posterior e látero-medial entre II e III costela, e ápice à base de ambos os pulmões). Entretanto, o volume pulmonar e sua relação com o osso esterno apresentam discrepâncias quando analisados sob a correlação de Pearson, pois a relação entre a medida da incisura jugular ao processo xifóide e a medida do ápice à base do pulmão direito e esquerdo, apresenta correlação positiva média (0,31-0,6). Já a medida da incisura jugular ao processo xifóide com a medida ântero-posterior e látero-medial do tórax, apresenta correlação significativa baixa (0-0,3). Então, a análise estatística da correlação de Pearson demonstrou ser inviável o desenvolvimento da fórmula, pois esta não seria confiável já que funcionaria para cerca de apenas 39% dos pacientes. Assim, o melhor método para determinar o doador para o transplante, continua sendo a análise de fatores de risco, a capacidade vital forçada do doador e receptor com estatura maior do que a do doador.

This study aimed at developing a mathematical model that can provide the compatible lung size for the recipient from the length of the sternum bone. Anthropometric chest measurements of 250 individuals were collected through a CT scan. The results indicate that the measurement of the sternum bone (distance from the jugular notch to the xiphoid process) shows a positive correlation with all other thorax measurements (antero-posterior and medial-posterior measurement between ribs II and III, and apex-to-base on both lungs). However, lung volume and its correlation to the sternal bone present discrepancies when analyzed under Pearson's correlation, since the relation between the jugular notch measurement and the apex measurement at the base of the right and left lungs shows a positive correlation mean (0.31-0.6). The measurement of the jugular notch in the xiphoid process with the anterior-posterior and medial-medial measurements, presents a low significant correlation (0-0.3). Therefore, the statistical analysis of the Pearson's correlation showed that the formula could not be applied since it would not be reliable since it would work for only 39% of the patients. Thus, the best method to determine the donor for transplantation remains the analysis of risk factors, the forced vital capacity of the donor, and the recipient being taller than the donor.

Histoplasmosis aguda diseminada en un niño inmunocompetente / Acute disseminated histoplasmosis in an immunocompetent child

La histoplasmosis es una patología endémica en Colombia. La verdadera incidencia en nuestro país es desconocida. En niños inmunocompetentes generalmente es un proceso autolimitado. Algunos casos pueden resultar un dilema diagnóstico por su amplio espectro de manifestaciones clínicas y diagnósticos diferenciales o por las dificultades de su confirmación sobre todo en zonas endémicas. Describimos el caso de un niño inmunocompetente con histoplasmosis diseminada aguda e importante compromiso respiratorio resaltando los dilemas que podrían presentarse en su diagnóstico y manejo.

Histoplasmosis is an endemic pathology in Colombia but its real incidence in the country is unknown. In non-immunocompromised children, the mycosis is mainly a self-limited process. In endemic zones certain cases may represent a diagnostic dilemma due to the broad spectrum of clinical manifestations that complicate differential diagnosis and hinder the proper diagnosis. We describe the case of an immunocompetent child diagnosed with acute disseminated histoplasmosis who exhibited extensive respiratory involvement highlighting the dilemmas faced when attempting to establish the diagnosis and defining management.

Human leukocyte antigen allele linkage disequilibrium and haplotype structure in volunteer bone marrow donors of Paraná State

Abstract Background Bone marrow transplantation has been used in the treatment of various diseases, especially hematologic diseases. The success of this treatment, among other factors, requires human leukocyte antigens (HLA) compatibility between patient and donor. Knowing the human leukocyte antigens allele group and haplotype frequencies as well as the linkage disequilibrium between alleles of different human leukocyte antigens loci can shorten the search time for a compatible bone marrow donor. Objective To assemble and analyze data on human leukocyte antigens frequencies available in the Laboratory of Immunogenetics and Histocompatibility (LIGH) database of the Universidade Federal do Paraná adding an estimation of the Hardy-Weinberg equilibrium and linkage disequilibrium. Methods The sample was composed of seven populations grouped by self-declared ancestry or inferred from the surname as follows: Laboratory of Immunogenetics and Histocompatibility database (all groups), descendants of Italians, Poles, and Asians, Afro-Brazilians, Mulattos (mixed ancestry) and Amerindians. Human leukocyte antigens genotyping was carried out using the polymerase chain reaction-sequence specific primers (PCR-SSP) and -sequence specific oligonucleotide (PCR-SSO) technologies. Results There were high frequencies of the HLA-A*02, HLA-B*35 and HLA-DRB1*13 allelic groups in all groups. The same was observed for the HLA-A*01-B*08-DRB1*03 haplotype except for Asian descendants. It was observed that the human leukocyte antigens Laboratory of Immunogenetics and Histocompatibility database and the Asian group are not in Hardy-Weinberg equilibrium. The Italian, Polish, Asian, Mulatto and Amerindian descendants showed haplotypes in complete linkage disequilibrium. Our results were compared with data on the human leukocyte antigens in the Paraná population available from the Brazilian Voluntary Bone Marrow Donor Registry (REDOME) and data published on the population of Curitiba and the northern region of Paraná. Conclusions Haplotypes frequent in the Asian group were not the most frequently observed in the Laboratory of Immunogenetics and Histocompatibility database and the National Bone Marrow Donor Registry for the state of Paraná. Linkage disequilibrium information may prove useful in the search for bone marrow donors for patients awaiting a suitable donor.