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1.
Arch. argent. pediatr ; 120(2): e80-e84, abril 2022. ilus
Article in English, Spanish | LILACS, BINACIS | ID: biblio-1363973

ABSTRACT

El síndrome de erupción medicamentosa con eosinofilia y síntomas sistémicos (drug reaction with eosinophilia and systemic symptoms, DRESS), también conocido como síndrome de hipersensibilidad inducida por medicamentos, es una reacción rara potencialmente mortal que causa una erupción grave y que puede provocar insuficiencia multiorgánica. Como con otras erupciones medicamentosas graves, los linfocitos T específicos para un medicamento tienen una función crucial en el síndrome DRESS. El modelo de hapteno/pro-hapteno, el modelo de interacción farmacológica y el modelo alterado de repertorio de péptidos son tres modelos diferentes desarrollados para describir la relación/interacción entre un medicamento o sus metabolitos y el sistema inmunitario. Analizamos nuestra experiencia con el tratamiento con ciclosporina en un caso de síndrome DRESS resistente a esteroides causado por ácido valproico en una niña y sus resultados clínicos, de laboratorio y de antígeno leucocitario humano (HLA).


Drug reaction with eosinophilia and systemic symptoms (DRESS), also known as drug-induced hypersensitivity syndrome, is a potentially life-threatening rare reaction that causes a severe rash and can lead to multiorgan failure. As in other severe drug eruptions, drug-specific T lymphocytes play a crucial role in DRESS. The hapten/pro-hapten model, pharmacological interaction model, and altered peptide repertoire model are three different models developed to describe the relationship/interaction between a medication or its metabolites and the immune system. We discuss our experience with cyclosporine treatment in a steroid-resistant DRESS syndrome caused by valproic acid in a girl, as well as her clinical, laboratory, and human leukocyte antigens (HLA) study results


Subject(s)
Humans , Female , Adolescent , Eosinophilia/complications , Eosinophilia/chemically induced , Drug Hypersensitivity Syndrome/diagnosis , Drug Hypersensitivity Syndrome/etiology , Valproic Acid/adverse effects , Cyclosporine , Haptens/adverse effects , HLA Antigens/adverse effects
2.
Mem. Inst. Invest. Cienc. Salud (Impr.) ; 19(1)abr. 2021. tab, ilus
Article in Spanish | LILACS, BDNPAR | ID: biblio-1337691

ABSTRACT

El embarazo es la única causa natural de inmunización contra el sistema de Antígenos Leucocitarios Humano (HLA). Durante la gestación hay paso de leucocitos fetales a través de la placenta, lo que puede desencadenar en la madre una respuesta inmunológica contra los antígenos HLA fetales de origen paterno, con la consecuente producción de anticuerpos. El objetivo del estudio fue conocer la prevalencia de sensibilización a antígenos HLA inducida por embarazos en mujeres paraguayas y estudiar las características y especificidades de los anticuerpos encontrados. Realizamos un estudio descriptivo, prospectivo, de corte transversal de 319 mujeres paraguayas, que acudieron al Laboratorio Central de Salud Pública entre abril de 2017 y abril de 2018 utilizando la tecnología LUMINEX para la detección de anticuerpos anti- HLA. Se encontraron anticuerpos anti-HLA en 46% de las mujeres multíparas. Se detectaron anticuerpos contra todos los antígenos testados. La gran mayoría de los sueros resultaron ser poliespecíficos. Concluimos que al aumentar el número de gestas no solo aumenta la probabilidad de una mujer de desarrollar anticuerpos anti- HLA, sino que también parece aumentar la cantidad de especificidades desarrolladas y el título de los anticuerpos


Pregnancy is the only natural cause of immunization against the Human Leukocyte Antigen (HLA) system. During pregnancy, fetal leukocytes pass through the placenta, which can trigger an immunological response in the mother against the fetus paternal HLA antigens, with the consequent production of antibodies. The objective of this study was to determine the prevalence of pregnancy-induced HLA antigen sensitization in Paraguayan women and to study the characteristics and specificities of the antibodies found. We conducted a descriptive, prospective, cross-sectional study of 319 Paraguayan women, who attended the Central Laboratory of Public Health between April 2017 and April 2018 using LUMINEX technology to detect anti-HLA antibodies. We found anti-HLA antibodies in 46% of multiparous women. Antibodies against all tested antigens were detected. The vast majority of the sera exhibited multiple specificities. We conclude that increasing the number of gestations not only increases a woman's likelihood of developing anti-HLA antibodies, but it also appears to increase the number of developed specificities and titers of antibodies


Subject(s)
Humans , Female , Pregnancy , Adult , HLA Antigens , Immunity , Antibodies , Pregnancy , Prevalence
4.
Article in English | WPRIM | ID: wpr-922600

ABSTRACT

Antibody-mediated rejection (AMR) is a rare and serious complication after lung transplantation, with no characteristic of pathological manifestation, no systematic standard treatment, and the poor efficacy and prognosis. We reported a case of early AMR after lung transplantation and the relevant literature has been reviewed. A male patient presented with symptoms of cold 99 days after transplantation and resolved after symptomatic treatment. He admitted to the hospital 14 days later because of a sudden dyspnea and fever. Anti-bacteria, anti-fungi, anti-virus, and anti-pneumocystis carinii treatment were ineffective, and a dose of 1 000 mg methylprednisolone did not work too. The patient's condition deteriorated rapidly and tracheal intubation was done to maintain breathing. Serum panel reactive antibody and donor specific antibody showed postive in humen leukocyte antigen (HLA) II antibody. Pathological examination after transbronchial transplantation lung biopsy showed acute rejection. Clinical AMR was diagnosed combined the donor-specific antibody with the pathological result. The patient was functionally recovered after combined treatment with thymoglobuline, rituximab, plasmapheresis, and immunoglobulin. No chronic lung allograft dysfunction was found after 3 years follow up. We should alert the occurrence of AMR in lung transplantation recipient who admitted to hospital with a sudden dyspnea and fever while showed no effect after common anti-infection and anti-rejection treatment. Transbronchial transplantation lung biopsy and the presence of serum donor-specific antibody are helpful to the diagnosis. The treatment should be preemptive and a comprehensive approach should be adopted.


Subject(s)
Graft Rejection , Graft Survival , HLA Antigens , Humans , Isoantibodies , Lung Transplantation/adverse effects , Male
5.
Frontiers of Medicine ; (4): 718-727, 2021.
Article in English | WPRIM | ID: wpr-922504

ABSTRACT

Severe aplastic anemia II (SAA-II) progresses from non-severe aplastic anemia (NSAA). The unavailability of efficacious treatment has prompted the need for haploidentical bone marrow transplantation (haplo-BMT) in patients lacking a human leukocyte antigen (HLA)-matched donor. This study aimed to investigate the efficacy of haplo-BMT for patients with SAA-II. Twenty-two patients were included and followed up, and FLU/BU/CY/ATG was used as conditioning regimen. Among these patients, 21 were successfully engrafted, 19 of whom survived after haplo-BMT. Four patients experienced grade II-IV aGvHD, including two with grade III-IV aGvHD. Six patients experienced chronic GvHD, among whom four were mild and two were moderate. Twelve patients experienced infections during BMT. One was diagnosed with post-transplant lymphoproliferative disorder and one with probable EBV disease, and both recovered after rituximab infusion. Haplo-BMT achieved 3-year overall survival and disease-free survival rate of 86.4% ± 0.73% after a median follow-up of 42 months, indicating its effectiveness as a salvage therapy. These promising outcomes may support haplo-BMT as an alternative treatment strategy for patients with SAA-II lacking HLA-matched donors.


Subject(s)
Anemia, Aplastic/therapy , Bone Marrow Transplantation , Graft vs Host Disease , HLA Antigens , Hematopoietic Stem Cell Transplantation , Humans , Transplantation Conditioning
6.
Chinese Medical Journal ; (24): 2874-2881, 2021.
Article in English | WPRIM | ID: wpr-921192

ABSTRACT

BACKGROUND@#The complement system plays an important role in the immune response to transplantation, and the diagnostic significance of peritubular capillary (PTC) C4d deposition (C4d+) in grafts is controversial. The study aimed to fully investigate the risk factors for PTC C4d+ and analyze its significance in biopsy pathology of kidney transplantation.@*METHODS@#This retrospective study included 124 cases of kidney transplant with graft biopsy and donor-specific antibody (DSA) testing from January 2017 to December 2019 in a single center. The effects of recipient pathological indicators, eplet mismatch (MM), and DSAs on PTC C4d+ were examined using univariate and multivariate logistic regression analyses.@*RESULTS@#In total, 35/124 (28%) were PTC C4d+, including 21 with antibody-mediated rejection (AMR), eight with renal tubular injury, three with T cell-mediated rejection, one with glomerular disease, and two others. Univariate analysis revealed that DSAs (P < 0.001), glomerulitis (P < 0.001), peritubular capillaritis (P < 0.001), and human leukocyte antigen (HLA) B eplet MM (P = 0.010) were the influencing factors of PTC C4d+. According to multivariate analysis, DSAs (odds ratio [OR]: 9.608, 95% confidence interval [CI]: 2.742-33.668, P < 0.001), glomerulitis (OR: 3.581, 95%CI: 1.246-10.289, P = 0.018), and HLA B eplet MM (OR: 1.166, 95%CI: 1.005-1.353, P = 0.042) were the independent risk factors for PTC C4d+. In receiver operating characteristic curve analysis, the area under the curve was increased to 0.831 for predicting PTC C4d+ when considering glomerulitis, DSAs, and HLA B eplet MM. The proportions of HLA I DSAs and PTC C4d+ in active antibody-mediated rejection were 12/17 and 15/17, respectively; the proportions of HLA class II DSAs and PTC C4d+ in chronic AMR were 8/12 and 7/12, respectively. Furthermore, the higher the PTC C4d+ score was, the more serious the urinary occult blood and proteinuria of recipients at the time of biopsy.@*CONCLUSIONS@#PTC C4d+ was mainly observed in AMR cases. DSAs, glomerulitis, and HLA B eplet MM are the independent risk factors for PTC C4d+.


Subject(s)
Allografts , Biopsy , Complement C4b , Graft Rejection , HLA Antigens , HLA-B Antigens , Humans , Kidney Transplantation/adverse effects , Peptide Fragments , Retrospective Studies , Risk Factors
7.
Article in English | WPRIM | ID: wpr-880674

ABSTRACT

The human leukocyte antigen (HLA) molecules encoded within the human major histocompatibility complex are a group of highly conserved cell surface proteins, which are related to antigen recognition. HLA genes display a high degree of genetic polymorphism, which is the basis of individual differences in immunity. Specific HLA genotypes have been highly associated with typical adverse drug reactions. HLA-A*31:01 and HLA-B*15:02 are associated with carbamazepine-induced severe cutaneous adverse reactions, HLA-B*57:01 is related to abacavir-induced drug-induced hypersensitivity syndrome and flucloxacillin/pazopanib-induced drug-induced liver injury, while HLA-B*35:01 is a potential biomarker for predicting polygonum multiflorum-induced liver injury. It is not clear how small drug molecules to interact with HLA molecules and T cell receptors (TCR). There are four mechanistic hypotheses, including the hapten/prohapten theory, the pharmacological interaction concept, the altered peptide repertoire model, and the altered TCR repertoire model.


Subject(s)
Drug-Related Side Effects and Adverse Reactions/genetics , Genotype , HLA Antigens/genetics , Humans , Polymorphism, Genetic
8.
Rev. Nutr. (Online) ; 34: e200034, 2021. tab
Article in English | LILACS | ID: biblio-1250806

ABSTRACT

ABSTRACT Objective To determine the frequency of Human leukocyte antigen alleles and to verify the association of the presence of these alleles with symptoms and other diseases related to celiac disease in patients with autoimmune thyroid diseases. Methods A questionnaire on the symptoms and diseases associated with celiac disease was applied. Genomic deoxyribonucleic acid was extracted by collecting cells from the oral mucosa. The alleles (DQA1*0501; DQB1*0201; DRB1*04) were identified by means of the polymerase chain reaction. Results A total of 110 patients with autoimmune thyroid diseases participated in this study. It was observed that 66.4% of the individuals carried at least one of the alleles assessed and that 58.2% of the individuals were positive for at least one of the DQ2 alleles (DQA1*0501; DQB1*0201) and out of these 18.2% were positive for both DQ2 alleles (DQA1*0501; DQB1*0201). With regard to DQ8 (DRB1*04), 21.8% of the studied population was positive for this allele and 3.6% was positive for both DQ2 (DQA1*0501; DQB1*0201) and DQ8 (DRB1*04). A significant association was found between the presence of the DRB1*04 allele and gastrointestinal symptoms (p=0.02). A significant association of the DRB1*04 allele with type 1 diabetes mellitus (p=0.02) was observed. Conclusion The genetic profiles most commonly associated with celiac disease, such as DQ2 (DQA1*0501; DQB1*0201) and DQ8 (DRB1*04) were around 20.0% prevalent in the studied population. These are risk haplotypes for celiac disease especially when symptoms and diseases related to celiac disease are present. Therefore, it is important to screen patients to investigate a potential diagnosis for celiac disease.


RESUMO Objetivo Determinar a frequência dos alelos do Human leukocyte antigen e verificar a associação da presença desses alelos com sintomas e outras doenças relacionados à doença celíaca em portadores de doenças autoimunes da tireoide. Métodos Aplicou-se um questionário relacionado aos sintomas e doenças associados à doença celíaca. O ácido desoxirribonucleico genômico foi extraído por meio da coleta das células da mucosa bucal. Os alelos (DQA1*0501; DQB1*0201; DRB1*04) foram identificados por meio da reação em cadeia da polimerase. Resultados Participaram deste estudo 110 portadores de doenças autoimunes da tireoide. Observou-se que 66,4% dos indivíduos carregavam pelo menos um dos alelos estudados e que 58,2% dos indivíduos eram positivos para pelo menos um dos alelos DQ2 (DQA1*0501; DQB1*0201) e destes 18,2% foram positivos para ambos alelos do DQ2(DQA1*0501; DQB1*0201). Com relação ao DQ8 (DRB1*04), 21,8% da população estudada eram positivos para esse alelo e 3,6% eram positivos tanto para o DQ2 (DQA1*0501; DQB1*0201) quanto para o DQ8 (DRB1*04). Foi encontrada associação significativa da presença do alelo DRB1*04 com os sintomas gastrointestinais (p=0,02). Houve associação significativa do alelo DRB1*04 com diabetes mellitus tipo 1 (p=0,02). Conclusão O perfil genético mais fortemente associado à doença celíaca, tais como DQ2 (DQA1*0501; DQB1*0201) e DQ8 (DRB1*04) estavam presentes em torno de 20,0% da população estudada, estes são haplótipos de risco para doença celíaca e principalmente na presença de sintomas e doenças relacionadas à doença celíaca. Sendo assim, é importante realizar o rastreamento para investigar um possível diagnóstico para doença celíaca.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Thyroiditis, Autoimmune , Celiac Disease , HLA Antigens , Alleles
9.
Article in Chinese | WPRIM | ID: wpr-828660

ABSTRACT

Allogeneic stem cell transplantation (allo-SCT) is currently the only curative option for patients with X-linked agammaglobulinemia (XLA). In this study, patient 1 aged 4 years who underwent allogeneic peripheral blood stem cell transplantation (allo-PBSCT) from HLA-mismatched unrelated donor; patient 2 aged 24 years (childhood onset) with primary cutaneous acral CD8 T cell lymphoma who underwent allo-PBSCT from haploidentical relative donor. Both were treated by reduced toxicity myeloablative conditioning with post-transplantation cyclophosphamide (PTCy), anti-thymocyte globulin (ATG), methotrexate (MTX) and cyclosporine (CsA) for graft-versus-host-disease (GVHD) prophylaxis. In patient 1, neutrophil and platelet engraftment were observed on day 11 post-transplantation; the donor chimerism dropped on day 90 post-transplantation, and recovered on day 150 with donor lymphocyte infusion (DLI). In patient 2, neutrophil and platelet engraftment were observed on days 20 and 87 post-transplantation respectively, with complete donor chimerism on day 30 post-transplantation. The serum levels of IgG, IgM and IgA and the percentage of CD19 B cells in peripheral blood of patients 1 and 2 returned to normal within 2 months and more than 1 year after transplantation respectively. There was no evidence of acute GVHD for the two patients. Patient 1 developed a limited type of skin chronic GVHD after DLI, which disappeared after anti-GVHD treatment. This is the first report of successful treatment for two XLA patients using PTCy with allo-PBSCT from HLA-mismatched unrelated donor or haploidentical donor, combining with improved conditioning, which expands the pool of eligible donors for patients with XLA.


Subject(s)
Agammaglobulinemia , Therapeutics , Genetic Diseases, X-Linked , Therapeutics , Graft vs Host Disease , HLA Antigens , Hematopoietic Stem Cell Transplantation , Humans , Peripheral Blood Stem Cell Transplantation , Treatment Outcome , Unrelated Donors , Young Adult
10.
Gac. méd. Méx ; 155(3): 243-248, may.-jun. 2019. tab
Article in English, Spanish | LILACS | ID: biblio-1286499

ABSTRACT

Resumen Introducción: La enfermedad renal crónica representa parte del gasto en salud en general; una potencial etiología es la relacionada con variaciones, ausencia o presencia de algunos alelos del human leucocyte antigen (HLA). Método: Se realizó el análisis de 1965 reportes de HLA sin etiología determinada y de 1361 donadores renales. Se llevó a cabo tecnología Luminex con base en fluorimetría de flujo celular para los locus A, B, DRB1 y DQA. Se realizó análisis con tablas de contingencia para determinar razón de momios (RM) e intervalos de confianza (IC). Se efectuó análisis cuantitativo. Resultados: De 101 alelos encontrados, 13 presentaron asociación, siete con riesgo para enfermedad renal crónica, de los cuales el más significativo fue HLA-DR17, con RM = 3.91 (IC 95 % = 2.96-5.17), y el de mayor significación de protección fue HLA-DR9, con RM = 0.043 (IC 95 % = 0.005-0.3224). Conclusiones: Es necesario entender que las enfermedades renales pueden estar ligadas a procesos inmunológicos, en los que se tiene que conocer la asociación de la ausencia o presencia de algún alelo.


Abstract Introduction: Chronic kidney disease accounts for part of overall health expenditure; a potential etiology is related to variations, absence or presence of some human leukocyte antigen (HLA) alleles. Method: An analysis of HLA reports of 1965 kidney recipients with no determined etiology, and 1361 kidney donors was performed. It was carried out with Luminex based in cell flow fluorometry for the A, B, DRB1 and DQA loci. An analysis was performed with contingency tables in order to determine the odds ratio (OR) and confidence intervals (CI). Quantitative analysis was also carried out. Results: Of the 101 alleles found, 13 showed association, 7 with risk for chronic kidney disease, with the most significant being HLA-DR17 with an OR of 3.91 (95 % CI = 2.96-5.17) and the one with the highest significance for protection being HLA-DR9, with an OR of 0.043 (95 % CI = 0.005-0.3224). Conclusions: It is necessary to understand that kidney diseases can be associated with yet unknown immune processes, where the association of the absence or presence of any allele should be known.


Subject(s)
Humans , Tissue Donors , Renal Insufficiency, Chronic/genetics , Transplant Recipients , HLA Antigens/genetics , Retrospective Studies , Risk Factors , Cohort Studies , Kidney Transplantation/methods , Alleles , Renal Insufficiency, Chronic/surgery , Protective Factors , Fluorometry
11.
Rev. Assoc. Med. Bras. (1992) ; 65(6): 830-833, June 2019. graf
Article in English | LILACS | ID: biblio-1012983

ABSTRACT

SUMMARY OBJECTIVE Even though stress has been long known as a provocative factor for Graves' disease, its relationship with Hashimoto's thyroiditis is more controversial. Studies on this topic are scanty. This paper aims to report a case of stress-induced Hashitoxicosis. RESULTS Here we report a case of Hashitoxicosis induced by a psychological stressful event in a 28-year-old woman with Hashimoto's thyroiditis. She had remained stably euthyroid for 12 years. She was first observed in April 2016, while euthyroid. She came back after 11 months because of fatigue and palpitations, in the absence of neck pain. Thyroid function tests revealed moderate thyrotoxicosis (undetectable TSH; FT4 36.94 pmol/L, normal values 9.0-24.46; FT3 13.50 pmol/L, normal values 3.07-6.14) with negative TSH-receptor antibodies. In the previous three months, she had experienced a psychological stressful event. Inflammatory markers were negative, and the white cell count was normal. Thyroid ultrasound revealed a modest increase in vascularization. Transient subclinical hypothyroidism ensued after seven weeks and spontaneously recovered. On the last visit, the patient was still on euthyroidism. (TSH 1.01 mU/L; FT4 9.22 pmol/L; FT3 3.98 pmol/L). We also performed HLA serotyping and genotyping. CONCLUSION This case demonstrates that, similarly to Graves' disease, Hashitoxicosis can also be triggered by stressful life events.


RESUMO OBJETIVO Mesmo que o estresse seja conhecido há muito tempo como um fator provocativo para a doença de Graves, sua relação com a tireoidite de Hashimoto é mais controversa. Estudos sobre esse tema são escassos. O objetivo deste artigo é relatar um caso de Hashitoxicose induzida por estresse. RESULTADOS Aqui nós relatamos um caso de Hashitoxicose induzido por um evento psicológico estressante em uma mulher de 28 anos com tireoidite de Hashimoto. Ela permaneceu estável eutireoidiana por 12 anos. Ela veio a nossa observação pela primeira vez em abril de 2016, enquanto eutireoidiana. Voltou após 11 meses por causa de fadiga e palpitações, na ausência de dor no pescoço. Testes de função tireoidiana revelaram uma tireotoxicose moderada (TSH indetectável; T4F 36,94 pmol/L, valores normais 9,0-24,46; FT3 13,50 pmol/L, valores normais 3,07-6,14) com anticorpos negativos para o receptor de TSH. Nos últimos três meses ela experimentou um evento psicológico estressante. Os marcadores inflamatórios foram negativos e a contagem de leucócitos foi normal. A ultrassonografia da tireoide revelou um aumento modesto da vascularização. Hipotireoidismo subclínico transitório ocorreu após sete semanas e se recuperou espontaneamente. Na última visita, a paciente ainda estava em eutireoidismo. (TSH 1,01 mU/L; FT4 9,22 pmol/L; FT3 3,98 pmol/L). Também realizamos a sorotipagem e a genotipização do HLA. CONCLUSÃO Este caso demonstra que, similarmente à doença de Graves, também a Hashitoxicose pode ser desencadeada por eventos estressantes da vida.


Subject(s)
Humans , Female , Adolescent , Stress, Psychological/complications , Hashimoto Disease/psychology , HLA Antigens/genetics , Stress, Psychological/genetics , Thyroxine/blood , Thyrotropin/blood , Hashimoto Disease/genetics , Serogroup , Genotype
12.
An. bras. dermatol ; 94(3): 287-292, May-June 2019. tab
Article in English | SES-SP, LILACS, SES-SP, SESSP-ILSLPROD, SES-SP, SESSP-ILSLACERVO, SES-SP | ID: biblio-1011110

ABSTRACT

Abstract: Background: Renal transplant recipients are submitted to immunosuppression to avoid graft rejection, which makes them susceptible to various conditions. Furthermore, these individuals present malignant tumors more frequently than the general population, including nonmelanoma skin cancer. The individual genetic basis that acts in the pathogenesis of cutaneous cancer may present a protection or susceptibility factor for disease development. One of these factors is the HLA complex. Objective: To investigate HLA alleles association to the occurrence of nonmelanoma skin cancer in renal transplant recipients from São Paulo State. Methods: A total of 213 patients (93 renal transplant recipients with nonmelanoma skin cancer and 120 renal transplant recipients without nonmelanoma skin cancer) were evaluated by retrospective and cross-sectional study. Epidemiological, clinical and HLA typing data were found in databases. HLA class I (A, B) and class II (DR) alleles were compared to establish their association with nonmelanoma skin cancer. Results: Comparing renal transplant recipients with and without nonmelanoma skin cancer, the HLA-B*13 allele was associated with higher risk of developing nonmelanoma skin cancer while B*45 and B*50 alleles were associated with protection. Study limitations: The HLA A, B and DR alleles identification for the kidney transplantation routine is done by low and medium resolution techniques that do not allow discrimination of specific alleles. Conclusion: The involvement of HLA alleles in nonmelanoma skin cancer in renal transplant recipients was confirmed in this study. Renal transplant recipients with HLA-B*13 showed higher risk for developing a skin cancer (OR= 7.29) and should be monitored for a long period of time after transplantation.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Skin Neoplasms/genetics , Kidney Transplantation/adverse effects , HLA Antigens/genetics , Skin Neoplasms/etiology , Skin Neoplasms/epidemiology , Brazil/epidemiology , HLA-A Antigens/genetics , HLA-B Antigens/genetics , HLA-DR Antigens/genetics , Case-Control Studies , Cross-Sectional Studies , Retrospective Studies , Genetic Predisposition to Disease/genetics , Alleles , Transplant Recipients
13.
Arq. neuropsiquiatr ; 77(4): 239-247, Apr. 2019. tab, graf
Article in English | LILACS | ID: biblio-1001352

ABSTRACT

ABSTRACT Objective: To study the genetic susceptibility to neuromyelitis optica (NMO) as well as the relationship between HLA genotypes and susceptibility to the disease in the southern Brazilian population. Methods: We analyzed patients with NMO, who met criteria for Wingerchuk's diagnosis of NMO, with detected serum anti-AQP4-IgG antibody. The HLA genotyping was performed by high-resolution techniques (Sanger sequencing) in patients and controls. The HLA genotypes were statistically compared with a paired control population. Results: The HLA genotyping revealed the diversity of the southern Brazilian population whose HLA profile resembled European and Asian populations. Some alleles had statistical correlations with a positive association (increased susceptibility) with NMO, particularly the HLA-DRB1*04:05 and *16:02. Conclusions: In our study, the HLA genotype was different to that previously reported for other Brazilian populations. Although our study had a small cohort, HLA genotypes were associated with increased susceptibility to NMO for HLA-DRB1*04:05 and *16:02. The alleles of HLA class I HLA-A*02:08 and *30:09, HLA-B*08:04 and *35:04 showed an association before the Bonferroni correction.


RESUMO Objetivo: Estudar a suscetibilidade genética a neuromielite óptica (NMO) assim como sua relação com o genótipo HLA na população do sul do Brasil. Métodos: Nós analisamos pacientes com NMO que preenchiam os critérios diagnósticos de Wingerchuk para NMO, com presença do anticorpo anti-AQP4-IgG no soro. O genótipo HLA foi realizado usando técnicas de alta resolução (sequenciamento de Sanger) em pacientes e controles. Genótipos HLA foram estatisticamente comparados com uma população controle pareada. Resultados: Genotipagem HLA revelou a diversidade da população sul brasileira cujo perfil HLA lembra as populações europeia e asiática. Alguns alelos tiveram correlação estatística com associação positiva (suscetibilidade aumentada) com NMO, particularmente o HLA-DRB1*04:05 e *16:02. Conclusões: Em nosso estudo, o genótipo HLA foi diferente do previamente relatado em outras populações brasileiras. Embora o número de pacientes tenha sido pequeno, HLA específicos foram associados com suscetibilidade aumentada a NMO para HLA-DRB1*04:05, *16:02. Os alelos HLA classe I HLA*02:08 e *30:09, HLA-B*08:04 e *35:04 tiveram associação antes da correção de Bonferroni.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Young Adult , Genes, MHC Class I/genetics , Neuromyelitis Optica/genetics , Genes, MHC Class II/genetics , Genetic Predisposition to Disease/genetics , Alleles , HLA Antigens/genetics , Reference Values , Brazil , Case-Control Studies , Polymerase Chain Reaction , Gene Frequency , Genotype
14.
Article in English | WPRIM | ID: wpr-766015

ABSTRACT

BACKGROUND: Human leukocyte antigen class I (HLA-I) molecules play important roles in regulating immune responses. Loss or reduction of HLA-I expression has been shown to be associated with prognosis in several cancers. Regulatory T-cells (Tregs) also play critical functions in immune response regulation. Evaluation of HLA-I expression status by the EMR8-5 antibody and its clinical impact in breast cancer have not been well studied, and its relationship with Tregs remains unclear. METHODS: We evaluated HLA-I expression and Treg infiltration by immunohistochemistry in 465 surgically resected breast cancer samples. We examined the correlation between HLA-I expression and Treg infiltration and clinicopathologic characteristics and survival analyses were performed. RESULTS: Total loss of HLA-I expression was found in 84 breast cancer samples (18.1%). Univariate survival analysis revealed that loss of HLA-I expression was significantly associated with worse disease-specific survival (DSS) (p = .029). HLA-I was not an independent prognostic factor in the entire patient group, but it was an adverse independent prognostic factor for DSS in patients with advanced disease (stage II–IV) (p = .031). Treg numbers were significantly higher in the intratumoral stroma of HLA-I–positive tumors than in HLA-I–negative tumors (median 6.3 cells/high power field vs 2.1 cells/high power field, p < .001). However, Tregs were not an independent prognostic factor in our cohort. CONCLUSIONS: Our findings suggest that the loss of HLA-I expression is associated with poor prognosis in breast cancer patients, highlighting the role of HLA-I alterations in immune evasion mechanisms of breast cancer. HLA-I could be a promising marker that enables the application of more effective and precise immunotherapies for patients with advanced breast cancer.


Subject(s)
Breast Neoplasms , Breast , Cohort Studies , HLA Antigens , Humans , Immune Evasion , Immunohistochemistry , Immunotherapy , Leukocytes , Lymphocytes, Tumor-Infiltrating , Major Histocompatibility Complex , Prognosis , T-Lymphocytes, Regulatory
15.
Article in English | WPRIM | ID: wpr-719716

ABSTRACT

PURPOSE: In the presence of interferon, proteasome subunits are replaced by their inducible counterparts to form an immunoproteasome (IP) plays a key role in generation of antigenic peptides presented by MHC class I molecules, leading to elicitation of a T cell‒mediated immune response. Although the roles of IP in other cancers, and inflammatory diseases have been extensively studied, its significance in breast cancer is unclear. MATERIALS AND METHODS: We investigated the expression of LMP7, an IP subunit, and its relationship with immune system components in two breast cancer cohorts. RESULTS: In 668 consecutive breast cancer cohort, 40% of tumors showed high level of LMP7 expression, and tumors with high expression of LMP7 had more tumor-infiltrating lymphocytes (TILs) in each subtype of breast cancer. In another cohort of 681 triple-negative breast cancer patients cohort, the expression of LMP7 in tumor cells was significantly correlated with the amount of TILs and the expression of interferon-associated molecules (MxA [p < 0.001] and PKR [p < 0.001]), endoplasmic reticulum stress-associated molecules (PERK [p=0.012], p-eIF2a [p=0.001], and XBP1 [p < 0.001]), and damage-associated molecular patterns (HMGN1 [p < 0.001] and HMGB1 [p < 0.001]). Patients with higher LMP7 expression had better disease-free survival outcomes than those with no or low expression in the positive lymph node metastasis group (p=0.041). CONCLUSION: Close association between the TIL levels and LMP7 expression in breast cancer indicates that better antigen presentation through greater LMP7 expression might be associated with more TILs.


Subject(s)
Antigen Presentation , Breast Neoplasms , Breast , Cohort Studies , Disease-Free Survival , Endoplasmic Reticulum , HLA Antigens , HMGB1 Protein , Humans , Immune System , Interferons , Lymph Nodes , Lymphocytes, Tumor-Infiltrating , Neoplasm Metastasis , Peptides , Proteasome Endopeptidase Complex , Triple Negative Breast Neoplasms
16.
Article in Chinese | WPRIM | ID: wpr-773742

ABSTRACT

The best time of tumor intervention is before the formation of tumor. However,due to the limited number of tumor cells,it is difficult to quantify tumor cells and immunity by the current methods available( such as CTC,ct DNA). This affects the tumor prevention in this period,and the in-depth detection,intervention and evaluation of traditional Chinese medicine( TCM)( tumor) prevention. Due to the limitations of the current detection,the evaluation system turns to detect tumor neoantigen-specific CTL( naCTL) that are directly relating to tumor cells and proliferate to high order of magnitudes after activation,and immune repertoire( TCR/BCR/HLA) effective diversity,introduces immune checkpoints,uses information of " disease" in Western medicine and " syndrome" in TCM( prevention),and sets up a multi-dimensional statistical immunity model using a variety of data analysis and related algorithms. This model can amplify the ultra-early information of tumor,indirectly evaluate the quantity and status of tumor cells,and provide quantitative measurement and new evaluation methods for the normalization of immunity and TCM( tumor) prevention. This model is not only one of important evaluation methods for resisting tumor immunity and treating TCM( tumor) prevention,but also will reveal the scientific connotation of TCM syndrome from the perspective of immunology.


Subject(s)
Drugs, Chinese Herbal , HLA Antigens , Humans , Medicine, Chinese Traditional , Neoplasms , Allergy and Immunology , Receptors, Antigen, B-Cell , Receptors, Antigen, T-Cell
17.
Article in Chinese | WPRIM | ID: wpr-776740

ABSTRACT

OBJECTIVE@#To assess the value of next-generation sequencing (NGS)-based single nucleotide polymorphism (SNP) haplotyping for preimplantation genetic diagnosis (PGD) for beta-thalassemia coupled with human leukocyte antigen (HLA) matching.@*METHODS@#Three couples were recruited. Couple 1 both carried a β (IVS-2-654) variation and had previously given birth to a son with β thalassemia major. Couple 2 respectively carried (cd41-42) and β (IVS-2-654) but had no history of pregnancy. Couple 3 respectively carried β (CD17) and β (IVS-2-654), and had a daughter carrying β (CD17).@*RESULTS@#For couple 1, NGS-SNP typing identified two embryos not only unaffected with thalassemia but also with matched HLA. One blastocyst was transferred and resulted in successful pregnancy. A healthy baby was born at 39th week of gestation. Its umbilical blood was used to treat the sick brother through hemopoietic stem cell transplantation. For couple 2, seven blastocysts were obtained. Second transplantation has resulted in successful pregnancy. Prenatal diagnosis was consistent with PGD. For couple 3, two blastocysts not only unaffected with thalassemia but also with no pathogenic copy number variations were obtained. Transfer of one blastocyte resulted in successful pregnancy, and prenatal diagnosis was consistent with PGD.@*CONCLUSION@#NGS-based SNP typing is an useful tool for selecting embryos unaffected with beta-thalassemia and matched HLA through PGD.


Subject(s)
DNA Copy Number Variations , Female , Fertilization in Vitro , HLA Antigens , Genetics , Haplotypes , High-Throughput Nucleotide Sequencing , Humans , Male , Polymorphism, Single Nucleotide , Pregnancy , Preimplantation Diagnosis , beta-Thalassemia , Diagnosis , Genetics
18.
Article in Chinese | WPRIM | ID: wpr-774325

ABSTRACT

OBJECTIVE@#To estimate the size of HLA -Ⅰ class typed platelet apheresis donor bank.@*METHODS@#A total of 16062 blood samples from Chinese Han voluntary unrelated marrow donors in Jiangsu were included in this study. Luminex-SSO was used to detect the HLA -Ⅰ class(A,B locus) antigens. The probability of finding at least one HLA matched unrelated donor was calculated based on the HLA -I class phenotype frequency.@*RESULTS@#The population genetic data of HLA -Ⅰ class in Jiangsu were obtained, the optinal bans size in HLA typed apheresis plateler donor registry databane hrad been estimated by evaluating the population genetic data of HLA-1 class same donor.@*CONCLUSION@#The establishment of HLA-1 class typed apheresis platelet donor bank with a total size of 1500 persons is acceptable, which can satisty the patients with phenotype freguency>0.002 to find at least 1 phenotype same donor in 95% probavility.


Subject(s)
Bone Marrow , Bone Marrow Transplantation , HLA Antigens , Histocompatibility Testing , Humans , Plateletpheresis , Registries , Tissue Donors
19.
Frontiers of Medicine ; (4): 45-56, 2019.
Article in English | WPRIM | ID: wpr-771319

ABSTRACT

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.


Subject(s)
China , Donor Selection , Graft vs Host Disease , Allergy and Immunology , HLA Antigens , Allergy and Immunology , Hematologic Neoplasms , Allergy and Immunology , General Surgery , Hematopoietic Stem Cell Transplantation , Histocompatibility , Histocompatibility Testing , Humans , Randomized Controlled Trials as Topic , Transplantation Conditioning
20.
Einstein (Säo Paulo) ; 17(1): eAO4477, 2019. tab, graf
Article in English | LILACS | ID: biblio-984373

ABSTRACT

ABSTRACT Objective To described the allele and haplotype frequencies of human leukocyte antigen genes at the -A, -B loci and human platelet antigen genes for human platelet antigen systems 1 to 9, 11 and 15 in blood. Methods We included 867 healthy unrelated volunteer donors who donated platelets between January 2011 and December 2014. Microarray genotyping was performed using a BeadChip microarray. Medium resolution typing of the human leukocyte antigen at loci A and B was carried out using sequence-specific oligonucleotide probe hybridization. We used multivariate analysis and our human leukocyte antigen population was compared to data from the United States national bone marrow donor program. Human platelet antigen results were compared to a literature review and data from around the world. Results Our human leukocyte antigen haplotype results were more similar to those of hispanics, followed by caucasians. Likewise, our human platelet antigen sample is more similar to those of Argentina, Rio Grande do Sul and Italy. Conclusion This was the first article that discusses human platelet antigen and human leukocyte antigen data together. Rare genotypes or antibody associations can make patient management difficult. A blood bank with genotyped donors allows for optimal transfusion and can contribute to better results. Our information can serve as basis for a database of platelet antigen polymorphisms.


RESUMO Objetivo Descrever as frequências alélicas e haplotípicas de genes dos antígenos leucocitários humanos nos loci -A,- B e dos antígenos plaquetários humanos para os sistemas HPA-1 a 9, 11 e 15. Métodos Foram incluídos 867 doadores voluntários, saudáveis, não relacionados, que doaram plaquetas por aférese entre janeiro de 2011 e dezembro de 2014. A genotipagem foi realizada usando microarray BeadChip. A tipificação de resolução intermediária dos antígenos leucocitários humanos loci A e B foi realizada por meio de hibridização com sonda para oligonucleotídeos por sequência específica. Utilizamos análises multivariadas e o antígeno leucocitário humano de nossa população foi comparado com a do programa nacional de doadores de medula óssea norte-americano. Já os resultados dos antígenos plaquetários humanos foram comparados à revisão da literatura e a dados de populações de outros países. Resultados Os resultados do haplótipo de antígenos leucocitários humanos são mais parecidos com os dos hispânicos, seguidos dos caucasianos. Igualmente, a amostra de antígenos plaquetários humanos foi mais semelhante às da Argentina, do Rio Grande do Sul e da Itália. Conclusão Este foi o primeiro artigo a discutir antígenos plaquetários e leucocitários humanos simultaneamente. Genótipos raros ou associações de anticorpos podem dificultar o manejo clínico do paciente. Um banco de sangue com doadores genotipados permite um melhor resultado e transfusão possíveis. Estas informações podem servir de base para um banco de dados sobre polimorfismos de antígenos plaquetários.


Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Aged , Polymorphism, Genetic/genetics , Haplotypes/genetics , Antigens, Human Platelet/genetics , Alleles , Genotyping Techniques/methods , HLA Antigens/genetics , Tissue Donors , Platelet Transfusion , Gene Frequency/genetics , Genotype
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