Investigation on the Correlation Between Traditional Chinese Medicine Constitution and Pathogenic Factors in Patients with Ankylosing Spondylitis / 广州中医药大学学报

Objective To study the correlation between traditional Chinese medicine(TCM)constitution and pathogenic factors in patients with ankylosing spondylitis(AS).Methods One hundred patients of AS and their family members who had medical consultation in the Fifth Hospital of Xi'an(i.e.,Shaanxi Hospital of Integrated Traditional Chinese and Western Medicine)in August 2019 and September 2020 were selected as the study subjects.The guidelines of Classification and Determination of Traditional Chinese Medicine Constitution issued by the China Association of Chinese Medicine were adopted to determine the traditional Chinese medicine(TCM)constitution types of the study subjects.The sociodemographic information,living habits,clinical symptoms,and TCM constitution types of the AS patients and their family members were collected by means of questionnaires and clinical investigations,and then the pathogenic factors of the patients with AS were investigated.The binomial Logistic regression model was used to analyze the correlation between TCM constitution types and pathogenic factors in patients with AS.Results(1)Among the 100 AS patients,the majority of them had the biased constitutions,and the biased constitutions with the occurrence frequency in descending order were yang deficiency constitution,qi deficiency constitution,and damp-heat constitution,which accounted for 33.00%,14.00%,and 18.00%,respectively.(2)The prevalence rates of AS in the first-,second-,and third-degree relatives of AS patients were 56.25%,40.00%and 25.00%,respectively.For the positive rates of human leukocyte antigen B27(HLA-B27)in AS patients and their family members,HLA-B27 in AS patients was all positive,while the positive rates of HLA-B27 in the first-,second-,and third-degree relatives of AS patients were 44.31%,30.67%and 15.63%,respectively.(3)The results of regression analysis showed that the disease duration of AS patients was significantly correlated with qi deficiency constitution,the grading of sacroiliac arthritis was correlated with qi stagnation constitution,and age was correlated with blood stasis constitution(P＜0.05 or P＜0.01).The results indicated that disease duration and age were the important factors affecting the constitution types of AS patients,and disease duration was closely related to qi deficiency while age was closely related to blood stasis.Conclusion AS is a highly hereditary autoimmune disease,and its onset is associated with HLA-B27.Yang deficiency is the basic constitution type of AS,and damp-heat constitution is the main constitution type in the progression of AS(especially in the active stage of the disease).The prolongation of the disease will exacerbate the illness condition of AS and then the manifestations of qi deficiency will be more obvious.

Expert consensus on the resolution level of the methods for HLA genotyping / 中国输血杂志

Human leukocyte antigen (HLA) genotyping has been widely used in establishing the database of the donors for hematopoietic stem cell, HLA matching selection between the donor and recipient, establishing the database of platelet donors with known HLA genotype, diagnosis of HLA association with diseases, genetics study and other scientific research. With the increasing number of HLA alleles and the development of HLA genotyping technology, there are some controversy in the definition of resolution for HLA genotyping, the description of the results for HLA genotyping between donor and recipient and the determination of HLA matching level. In order to improve the normalization of the definition and interpretation of HLA genotyping resolution, this expert consensus is formulated by many experts from the fields of HLA genotyping in the laboratory and clinical transplantation according to the relevant domestic and foreign literature and clinical practice. The definition of the resolution of HLA genotyping, the methods of HLA genotyping, the description of the results between donor and recipient and HLA matching determination are summarized, which will further standardize HLA genotyping technology and ensure the accuracy of the results for HLA genotyping.

New cost-effective human leukocyte antigen testing algorithm for screening of human leukocyte antigen-matched related donor in thalassemia major patient pretransplant workup: A single-center study from resource-constrained settings

Introduction: India has a huge disease burden of thalassemia major with an estimated 40 million carriers and over a million thalassemia major patients. Very few patients are optimally treated, and the standard of care “hematopoietic stem cell transplant” (HSCT) is out of reach for most patients and their families. The cost of HSCT is significant, and a substantial proportion of it goes to human leukocyte antigen (HLA) testing of family members (HLA screening) in hope of getting a matched related donor (MRD) for HSCT. The aim of this study was to establish that a new proposed testing algorithm of HLA typing would be more cost-effective as compared to the conventional HLA screening within MRD families for possible HSCT. Material and Methods: Buccal swab samples of 177 thalassemia patients and their prospective family donors (232) were collected. Using a new HLA testing algorithm, samples were tested for HLA typing in a sequential manner (first HLA-B, then HLA-A, and finally HLA-DR) using the sequence-specific oligonucleotide probe method on the Luminex platform. Results: The new sequential HLA-A, HLA-B, and HLA-DRB1 testing algorithm showed a 49.1% reduction in cost compared to the conventional HLA testing algorithm. Furthermore, 40 patients (22.59%) were found to have HLA-MRD within the family among other samples that were tested. Conclusion: The new HLA testing algorithm proposed in the present study for identifying MRD for HSCT resulted in a substantial reduction in the cost of HSCT workup.

The relationship between uric acid levels and graft function in renal transplant patients who discontinued steroid therapy / Relación entre niveles de ácido úrico y función del injerto en pacientes de trasplante renal que interrumpieron la terapia con esteroides

ABSTRACT Introduction: High uric acid levels are commonly encountered in kidney transplant recipients, and can be associated with allograft dysfunction. Our study aims to examine the relationship between UA levels and graft function in patients discontinuing steroids. Methods: In this single-center-retrospective study, 56 patients discontinued steroid therapy from among 678 RT patients transplanted from living donors between 1999-2020 were included. The mean age of the study group was 45.8±8.8 years. Causes of steroid discontinuation, creatinine levels concurrent with uric acid levels before and after steroid discontinuation (mean 3.9 ± 2.1 years), acute rejection numbers, demographics, durations of dialysis and transplantation, medications, laboratory data, human leukocyte antigen (HLA) mismatch numbers, blood-pressure (BP), body mass index, delayed acute rejection (DAR) numbers (3 months post-transplantation) were all recorded. Results: Creatinine and uric acid levels were seen to have increased after steroid discontinuation, there was a significant relationship between them (p<0.001). Statistically significant correlation was found between increased creatinine levels after steroid discontinuation and graft survival with higher HLA mismatch; 39 (69.6%) patients with mismatch ≥2, and 17 patients with mismatch <2 (30.4%) (p=0.049) . No significant relationship was found between DAR numbers before and after steroid discontinuation, and creatinine levels after steroid discontinuation. Conclusion: Per model obtained as a result of multivariate linear analysis, hyperuricemia and HLA mismatch numbers (p= 0.048 and p= 0.044, respectively) are independent predictive factors for graft dysfunction in patients discontinuing steroids. Accordingly, negative effects of modeling should be kept in mind for long-term graft survival in patients who plan to continue with steroid-sparing regimens.

RESUMEN Introducción: Con frecuencia se registran niveles elevados de ácido úrico en receptores de trasplantes renales que pueden estar asociados a disfunción de aloinjerto. El presente estudio tiene por objeto examinar la relación entre los niveles de AU y la función del injerto en pacientes que interrumpieron la terapia con esteroides. Métodos: En este estudio retrospectivo en un solo centro participaron 56 pacientes con interrupción de la terapia con esteroides de un total de 678 pacientes con TR receptores de trasplante de donantes vivos en el período 1999-2020. La edad promedio de la población de estudio fue de 45,8 ± 8,8 años. En el estudio se registraron causas de la interrupción de la terapia con esteroides, niveles de creatinina concurrentes con niveles de ácido úrico antes y después de la interrupción de la terapia con esteroides (promedio de 3,9 ± 2,1 años), números de rechazo agudo, datos demográficos, duraciones del período de diálisis y trasplante, medicación (uso de inmunosupresores, antihipertensivos), datos de laboratorio, números de desajuste del antígeno leucocitario humano (HLA), presión arterial (PA), índice de masa corporal, números de rechazo agudo retardado (DAR) (3 meses después del trasplante). Resultados: Se observó que los niveles de creatinina y ácido úrico aumentaron tras interrumpir la administración de esteroides, con una relación significativa entre ambos (p<0,001). Se identificó una correlación estadísticamente significativa entre el aumento en los niveles de creatinina tras la interrupción de la terapia de esteroides y la supervivencia del injerto con un mayor desajuste de HLA: 39 pacientes (el 69,6%) con desajuste ≥2 y 17 (el 30,4%) pacientes con desajuste <2 (p=0,049). No se encontró una relación significativa entre el número de DAR antes y después de la interrupción del tratamiento con esteroides, así como en los niveles de creatinina tras la interrupción de la terapia con esteroides. Conclusión: De acuerdo con el modelo obtenido como resultado del análisis lineal multivariable, la hiperuricemia y los números de desajuste de HLA (p=0,048 y p=0,044, respectivamente) constituyen factores predictivos independientes para la disfunción del injerto en pacientes que interrumpen la terapia con esteroides. En consecuencia, se deben tener en cuenta los efectos negativos del modelado para la supervivencia del injerto a largo plazo en pacientes que planean proseguir con regímenes con reducción de la administración esteroides.

Expert consensus on perioperative nursing standards for pediatric kidney transplantation / 器官移植

Pediatric kidney transplant recipients differ from adult counterparts in primary disease, physiology, psychology, organ function and immune status and their perioperative treatment and nursing management are different from those of adult kidney transplantation. To standardize holistic perioperative nursing regimens for pediatric kidney transplantation, Surgery Nursing Committee of Shanghai Nursing Association organized national medical and nursing experts in the fields of transplantation to jointly draft "expert consensus on perioperative nursing standards for pediatric kidney transplantation " (abbreviated as "consensus"). After three rounds of online expert inquiry, all revised opinions were jointly discussed combined with literature evidence, and the expert consensus was finally reached. The highlights of perioperative treatment and nursing care for pediatric kidney transplantation were summarized and stated, including preoperative evaluation, preoperative and postoperative nursing care, which were of scientific and practical value.

Association between HLA-B*27:04 and genetic susceptibility to ankylosing spondylitis in Hunan Province / 中南大学学报(医学版)

Objective:Human leukocyte antigen(HLA)B27 is a susceptibility allele of ankylosing spondylitis(AS),and HLA-B27 antigen typing is an important indicator for clinical diagnosis of AS,but current typing methods such as sequence specific primer polymerase chain reaction(PCR-SSP)still possess limitation.Therefore,this study aims to analyze the correlation between B27 subtypes and susceptibility to AS in Hunan Province by applying high-resolution polymerase chain reaction-sequence-based typing(PCR-SBT). Methods:Peripheral blood of 116 patients with suspected AS(suspected AS group)and 121 healthy volunteers(control group)admitted to the Second Xiangya Hospital from January 2020 to December 2020 were collected for HLA-B genotyping by PCR-SBT.Among the patients in the suspected AS group,23 patients were finally diagnosed with AS(confirmed AS group),and the remaining 93 undiagnosed patients served as the non-confirmed AS group.PCR-SBT and PCR-SSP were used to detect HLA-B27 typing in 116 patients with suspected AS,and the results of the 2 methods were compared. Results:The HLA-B27 allele frequency in the suspected AS group was significantly higher than that in the control group[11.63%vs 2.48%;P<0.001,odds ratio(OR)=5.18,95%confidence interval(CI)2.097 to 12.795].B*27:04,B*27:05,B*27:06,and B*27:07 were detected in the suspected AS group and the control group.The frequency of the B*27:04 allele in the suspected AS group was significantly higher than that in the control group(9.48%vs 1.24%;P<0.001,OR=8.346,95%CI 2.463 to 28.282).The positive rate of B27 in the suspected AS group and the confirmed AS group(B27+/+ and B27+/-)was significantly higher than that in the control group(χ2=16.579,P<0.001;χ2=94.582,P<0.001,respectively).Among the confirmed AS group,21 were HLA-B27 carriers,and the B27 positive rate in the confirmed AS group was 91.3%.PCR-SBT could achieve high resolution typing of the HLA-B gene locus,with higher sensitivity,specificity,positive predictive value,negative predictive value,and accuracy than PCR-SSP. Conclusion:PCR-SBT typing analysis shows a strong correlation between HLA-B * 27:04 and AS in Hunan province.The PCR-SBT method can be used as the preferred option for the auxiliary diagnosis of clinical AS.

The effects of hypoxia on silencing HLA⁃G expression and biological behaviors of JEG⁃3 cells and EPAS1 / 安徽医科大学学报

Objective@#To investigate the effect of silencing human leukocyte⁃associated antigen⁃G ( HLA⁃G) expression in the chorionic trophoblast cell line JEG⁃3 cells under hypoxic conditions on the biological function of JEG⁃3 cells and through the hypoxia response pathway of endothelial PAS1 region protein 1 (EPAS1)is involved in the molecular mechanism of preeclampsia under high altitude hypoxia. @*Methods@#The expression of HLA⁃G in JEG⁃3 cells was inhibited by transfection of small interfering RNA (siRNA) . The JEG⁃3 cells after transfection were divided into four groups : normoxic control group , hypoxic control group , normoxic inhibition group , and hypoxic inhibition group. CCK⁃8 test and Transwell test were used to detect the proliferation and invasion ability of the cells in four groups ; The effects of four groups of apoptosis and cell cycle were detected by flow cytometry; HLA⁃G and EPAS1 mRNA and protein expression levels were detected by real⁃time fluorescence quantitative PCR ( qPCR) and Western blot.@*Results @#① Compared with the normoxic control group , hypoxic control group , normoxic inhibition group , and hypoxic inhibition group could reduce the proliferation activity and invasion ability of JEG⁃3 cells , and significantly increase the apoptosis rate. The hypoxic control group and hypoxic inhibition group also produced anobvious necrotic cell population ; Under the condition of hypoxia , after reducing the expression of HLA⁃G , the cell necrosis rate was further aggravated ; Whether under normoxia or hypoxia , inhibition of HLA⁃G expression caused the cells to be blocked in the G1 phase. ② Compared with the normoxic control group , hypoxia control group , normoxic inhibition group , and hypoxia inhibition group decreased the expression of HLA⁃G protein , and hypoxia and inhibition of HLA⁃G had a synergistic effect; Hypoxia⁃inducible factors⁃2α ( HIF⁃2α ) , vascular endothelial growth factor(VEGF) and endothelin⁃1(ET⁃1) protein expression could be added , inhibition of HLA⁃G decreased the expression of inducible nitric oxide synthase( NOS2) . @*Conclusion@#In the hypoxic environment , silencing HLA⁃G may affect the biological behavior of trophoblast through the EPAS1 hypoxic response pathway and participate in the occurrence and development of preeclampsia.

Genetic susceptibility to drug-induced liver injury / 中华肝脏病杂志

Drug-induced liver injury (DILI) risk prediction, diagnosis establishment, clinical management, and all other aspects are facing great challenges. Although the current understanding of its pathogenesis is still incomplete, research over the past 20 years has shown that genetic susceptibility may play an important role in the occurrence and development of DILI. In recent years, pharmacogenomics studies have further revealed the association between human leukocyte antigen (HLA) genes, some non-HLA genes, and hepatotoxicity from certain drugs. However, due to the lack of well-designed, prospective, large-sample cohort validation and low positive predictive values, there may still be some way to go before the current results can be truly translated into clinical practice for precise prediction and prevention of DILI risk.

Research progress on kidney transplantation rejection associated with non-HLA antibody / 器官移植

Human leukocyte antigen (HLA) is a product encoded by HLA gene complex, which is located on the short arm of chromosome 6 and is the main target of alloimmunity. However, positive HLA antibody is not responsible for all kinds of rejections in kidney transplantation. Non-HLA antibody is the product of donor gene expression in allogeneic kidney transplantation. Intraoperative ischemia-reperfusion injury, the interaction between alloimmunity and autoimmunity and the mediation of extracellular vesicles may trigger immune system response and promote the production of non-HLA antibody. Multiple studies have demonstrated that non-HLA antibody is an important factor of inducing rejection and affecting the outcomes of kidney transplantation. Consequently, the types and formation mechanism of non-HLA antibody in kidney transplantation were reviewed, and research progress on kidney transplantation rejection associated with non-HLA antibody was summarized, aiming to provide reference for in-depth study of kidney transplantation rejection associated with non-HLA antibody.

Expression of HLA-G in the peripheral blood and cancerous tissues of patients with papillary thyroid cancer / 中华内分泌外科杂志

Objective:To examine the expression of human leukocyte antigen G (HLA-G) in the peripheral blood and cancerous tissues of patients with papillary thyroid carcinoma (PTC) .Methods:The expression of soluble HLA-G (sHLA-G) in the peripheral blood of 50 individuals with PTC (PTC group) , 25 patients with benign thyroid tumors (BTT group) from Department of Thyroid and Breast Surgery, Beilun branch of the First Affiliated Hospital of Zhejiang University and 20 healthy controls (healthy control group) from physical examination center was assessed by ELISA. Immunohistochemical examination of HLA-G levels was also performed on tissue specimens from patients in the PTC and BTT groups, and their correlation with clinicopathological features of thyroid cancer was analyzed. SPSS 19.0 was used for statistical analysis. The measurement data of normal distribution were tested by two independent samples t test. Chi square test was used to compare the rates between the two groups. Results:The sHLA-G expression in peripheral blood was 21.33 (±5.54) , 22.73 (±4.99) , and 18.29 (±4.43) ng/mL in the preoperative PTC, BTT, and healthy control groups, respectively. Compared to the healthy group, sHLA-G levels were considerably higher in the PTC and BTT groups, with statistically significant differences (totally P < 0.05) . There was no significant difference in statistically sHLA-G levels between the BTT and PTC groups ( P > 0.05) . The positive HLA-G expression rate in PTC tissues was 78% (39/50) . There was no evidence of HLA-G expression in common tissues adjacent to PTC. HLA-G was not expressed in benign tumors. HLA-G was linked with the PTC tumor diameter, and the rate of positive expression was considerably greater with tumor diameters >1 cm than with those ≤1 cm ( P<0.05) . The rate of HLA-G positive expression was not significantly correlated with sex, age, multiple foci, extra-glandular invasion, metastasis of lymph nodes, or the TNM stage in PTC individuals ( P > 0.05) . Conclusions:HLA-G is significantly expressed at high levels in PTC tissues, is correlated with the tumor diameter, and may probably have a significant role in this disease. Peripheral blood sHLA-G may be associated with thyroid tumorigenesis, and its value in PTC requires further verification.

Application of traditional teaching combined with PBL in the teaching of transfusion medicine——taking Clinical Blood Transfusion Testing Technique as an example / 中国输血杂志

【Objective】 To explore the application effect of traditional teaching combined with problem based learning (PBL) in the teaching of transfusion medicine taking the chapter of Human Leukocyte Antigen System and Testing in Clinical Blood Transfusion Testing Technique as an example. 【Methods】 Firstly, practical problems in chapter Human Leukocyte Antigen System and Testing were analyzed. Then, in response to the key and difficult points in the teaching of this chapter, examples were given to illustrate the practical application of traditional teaching combined with PBL in the teaching of Clinical Blood Transfusion Testing Technique from the aspects of teaching objectives, teaching processes, course implementation and implementation effects. The teaching effectiveness was evaluated through a questionnaire. 【Results】 Traditional teaching combined with PBL helped students grasp important knowledge and techniques, break down thinking barriers, grasp internal connections and characteristics, simplify the learning process, stimulate interest in learning and enhance team collaboration. Meanwhile, students' exploration and innovation abilities could be further cultivated through extracurricular expansion by teachers, thus achieving ideal teaching effect. The questionnaire showed that over 90% of the students consider that combining traditional teaching with PBL was beneficial for improving teaching effect. 【Conclusion】 In the teaching of transfusion medicine, adopting traditional teaching combined with PBL according to the textbook content can improve the teaching effect, which is beneficial for the cultivation of comprehensive talents.

Study on the extensibility of platelet donor gene database in Shaanxi / 中国输血杂志

【Objective】 To analyze the commonality and characteristics between voluntary blood donors and hematopoietic stem cell donors in this region, and explore the potential for integration and development between China Marrow Donors Program (CMDP) and voluntary blood donors, especially platelet donor databases, so as to improve recruitment success rate and inventory rate. 【Methods】 The database modeling and comparison methods were used to screen and stratify the matching and integration degree between the voluntary blood donors in recent 10 years and the marrow donors in the Shaanxi Branch of CMDP. The frequencies of HLA-A,-B alleles, HPA alleles and haplotypes were calculated with Arlequin 3. 5. 2. 2 software, and the matching probability of different platelet donor reserve pools was conducted according to the phenotypic frequencies. 【Results】 Among the voluntary donors with known HLA genotypes in this region, according to their blood donation behavior,the active blood donors excavated were divided into the first, second, third and fourth echelons of platelet donor reserve pools, with 696, 2 752, 9 092 and 12 028 donors, respectively. The first echelon had the highest proportion of 10-50 times of platelet donations and 10-20 times of whole blood donations, with 13.65% and 26.01%, respectively. The second echelon had 10-20 times of whole blood donations and 10-50 times of platelet donations, accounted for 15.04% and 1.38%, respectively, which were significantly different from other echelons' blood donation characteristics (P<0.05). With a database size of the existing platelet donor bank adding the first and second echelons (n=4 955), there was a 69.02% probability of matching at least one donor with matching HLA-A-B phenotype. When considering the matching ABO and HPA phenotypes, the probability of finding at least one donor with fully matching HLA, HPA and ABO isotype (type B as an example) was 48. 73%. 【Conclusion】 The three groups of whole blood donation, apheresis platelet donation and marrow donation in Xi'an area have a large cross-distribution. Compared with expanding the storage capacity from scratch, the active blood donors in CMDP database are the largest back-up force of platelet donors. While expanding the effective storage capacity, it can minimize the cost of building platelet donor bank and the demand for resources.

Analysis of Gene Recombination between HLA-B and -DRB1, HLA-DQB1 and -DPB1 Loci / 中国实验血液学杂志

OBJECTIVE@#To investigate the recombinations within the human leukocyte antigen (HLA) region in two families.@*METHODS@#Genomic DNA was extracted from the peripheral blood specimens of the different family members. HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1 loci were genotyped using polymerase chain reaction-sequence specific oligonucleotide probing technique (PCR-SSO) and next-generation sequencing technique. HLA haplotype was determined by genetic analysis of the pedigree.@*RESULTS@#The haplotypes of HLA-A*11:01~C*03:04~B*13:01~DRB1*12:02~DQB1*03:01~DPB1*05:01:01G and HLA-A*03:01~C*04:01~B*35:03~DRB1*12:01~DQB1*03:01~DPB1*04:01:01G in the family 1 were recombined between HLA-B and HLA-DRB1 loci, which formed the haplotype of HLA-A*11:01~C*03:04~B*13:01~DRB1* 12:01~DQB1*03:01~DPB1*04:01:01G. The haplotypes of HLA-A *02:06~C*03:03~B*35:01~DRB1*08:02~DQB1*04:02~ DPB1*13:01:01G and HLA-A *11:01~C*07:02~B*38:02~DRB1*15:02~DQB1*05:01~DPB1*05:01:01G in the family 2 were recombined between HLA-DQB1 and HLA-DPB1 loci, which formed the haplotype of HLA-A*02:06~C*03:03~B*35:01~ DRB1*08:02~DQB1*04:02~DPB1*05:01:01G.@*CONCLUSION@#The gene recombination events between HLA-B and -DRB1, HLA-DQB1 and -DPB1 loci were found respectively in two Chinese Han families.

Association between exonic polymorphisms of human leukocyte antigen-G gene and non-segmental vitiligo in the Korean population

Background: Vitiligo is a pigmentary skin disorder characterised by a chronic and progressive loss of melanocytes. Although several theories have been suggested to the pathogenesis of vitiligo, an autoimmune process leading to melanocyte destruction appears most likely. Human leukocyte antigen-G is a non-classic, major histocompatibility complex Class I molecule that plays an important role in the suppression of the immune response. Several recent studies have provided evidences that polymorphisms in the human leukocyte antigen-G gene might be related with autoimmune diseases. Objectives: The aim of this study was to decide whether exonic single nucleotide polymorphisms in human leukocyte antigen-G contribute to the risk of developing non-segmental vitiligo in the Korean population. Methods: To evaluate the associations between exonic single nucleotide polymorphisms (rs1630223 [Ala5Ala] and rs12722477 [Leu134Ile]) of human leukocyte antigen-G and vitiligo, 244 patients with vitiligo and 398 healthy controls were recruited. Genotyping was performed using Fluidigm 192.24 Dynamic Array with EP1 (Fluidigm Corp., CA). The SNP type assay (Fluidigm Corp., CA), which employs allele-specifically designed fluorescences (FAM or VIC) primers and a common reverse primer was applied and the data were analysed using the EP1 single nucleotide polymorphisms genotyping analysis software to obtain genotype calls. Results: Two exonic single nucleotide polymorphisms (rs1630223 and rs12722477) exhibited significant associations with susceptibility and remained a statistically significant association following Bonferroni correction. These two single nucleotide polymorphisms were located within a block of linkage disequilibrium. Haplotypes G-C and A-A comprising rs1630223 and rs12722477 demonstrated a significant association with non-segmental vitiligo. Limitations: The protein expression level of patients with vitiligo and controls was not studied and a replication study of the genetic association in an independent group was not managed. Conclusion: Our results suggest that exonic human leukocyte antigen-G polymorphisms (rs1630223 and rs12722477) are associated with the development of non-segmental vitiligo.

Human leukocyte antigen Class II alleles associated with acral lentiginous melanoma in Mexican Mestizo patients: A case-control study

Background: Melanoma is an aggressive cutaneous cancer. Acral lentiginous melanoma is a melanoma subtype arising on palms, soles, and nail-units. The incidence, prevalence and prognosis differ among populations. The link between expression of major histocompatibility complex Class II alleles and melanoma progression is known. However, available studies report variable results regarding the association of melanoma with specific HLA Class II loci. Aims: The aim of the study was to determine HLA Class II allele frequencies in acral lentiginous melanoma patients and healthy Mexican Mestizo individuals. Methods: Eighteen patients with acral lentiginous melanoma and 99 healthy controls were recruited. HLA Class II typing was performed based on the sequence-specific oligonucleotide method. Results: Three alleles were associated with increased susceptibility to develop acral lentiginous melanoma, namely: HLA-DRB1*13:01; pC = 0.02, odds ratio = 6.1, IC95% = 1.4–25.5, HLA-DQA1*01:03; pC = 0.001, odds ratio = 9.3, IC95% = 2.7–31.3 and HLA-DQB1*02:02; pC = 0.01, odds ratio = 3.7, IC95% = 1.4–10.3. Limitations: The small sample size was a major limitation, although it included all acral lentiginous melanoma patients seen at the dermatology department of Dr. Manuel Gea González General Hospital during the study period. Conclusion: HLA-DRB1*13:01, HLA-DQB1*02:02 and HLA-DQA*01:03 alleles are associated with increased susceptibility to develop acral lentiginous melanoma in Mexican Mestizo patients.

Correlation of caries occurrence in primary teeth using human leukocyte antigen typing and maternal and physiochemical factors

Background: Dental caries being the leading health issue worldwide has no specific cure due to its multifactorial etiology and genetic susceptibility. Hence, this paper attempted to correlate the clinical and hereditary factors between mother and child, to predict the caries occurrence in child in future, and thereby implement early preventive measures. Aim: The aim of the study was to look for an association between maternal and child's human leukocyte antigen (HLA)-DR4 levels and relate it with other physiochemical factors to assess caries susceptibility in children. Methodology: Saliva samples were collected from children who were in the age group of 0–6 years and their mothers by spitting method and swab method. The clinical indicators such as Decayed, Missing, and Filled Teeth, decayed, extraction needed, and filled teeth, salivary flow rate, and pH were recorded by clinical evaluation. The Streptococcus mutans count was measured by culture plate followed by colony count method, and the HLA-DR4 factor was assessed using ELISA. Results: The results revealed a statistically significant correlation between the physiochemical factors of the mother and the child. The genetic factor in which the HLA-DR4 caries indicator was checked also has a strong association between the mother and the offspring. Thus, a strong caries prediction formula was derived through which probability of caries occurrence in the child could be determined prematurely. Conclusion: Thus, it can be concluded that using the clinical and genetic factors, the caries prediction can be done for the child and preventive protocol can be started before disease occurrence.

HLA-G y su función en trasplantes de órganos sólidos / HLA-G and its role in solid organ transplants

RESUMEN El trasplante de órganos sólidos se ha considerado el fin último para algunas enfermedades crónicas en estadio terminal, sin embargo, las incompatibilidades del HLA entre el donante y el receptor pueden permitir que la alorespuesta se convierta en nociva para el órgano trasplantado, respuesta que puede ser tanto innata como adaptativa. Se ha identificado el HLA-G como una molécula natural inductora de tolerancia (28) principalmente en el embarazo y se considera una molécula del HLA clase I no clásico, sin embargo, comparte algunas características estructurales con el HLA clásico. Los genes HLA-G se caracterizan por tener un limitado polimorfismo y una distribución celular y tisular restringida al trofoblasto fetal y células del epitelio tímico entre otras. La búsqueda persistente de la tolerancia en los trasplantes de órganos ha permitido un estudio específico del HLA-G, como posibilidad terapéutica para aumentar la sobrevida tanto de los injertos como de los pacientes trasplantados, es por tal motivo que se realiza una revisión en dicha molécula para estimular la investigación y entendimiento de sus funciones.

ABSTRACT Solid organ transplantation has been considered the ultimate goal for some end-stage chronic diseases, however, HLA incompatibilities between the donor and the recipient may allow the alloresponse to become deleterious for the transplanted organ, a response that can be both innate and adaptive. HLA-G has been identified as a natural tolerance-inducing molecule (28) mainly in pregnancy and is considered a non-classical HLA class I molecule; however, it shares some structural characteristics with classic HLA. HLA-G genes are characterized by having a limited polymorphism and a cellular and tissue distribution restricted to the fetal trophoblast and thymic epithelial cells, among others. The persistent search for tolerance in organ transplants has allowed a specific study of HLA-G, as a therapeutic possibility to increase grafts and transplant patient's survival; for this reason we carried out a review ofthis molecule to stimulate research and understanding of its functions.

A retrospective comparative study of haplotype hematopoietic stem cell transplantation and human leukocyte antigen-matched sibling donor hematopoietic stem cell transplantation in the treatment of acute B-lymphocyte leukemia / 中华血液学杂志

Objective: To investigate whether haplotype hematopoietic stem cell transplantation (haplo-HSCT) is effective in the treatment of pre transplant minimal residual disease (Pre-MRD) positive acute B lymphoblastic leukemia (B-ALL) compared with HLA- matched sibling donor transplantation (MSDT) . Methods: A total of 998 patients with B-ALL in complete remission pre-HSCT who either received haplo-HSCT (n=788) or underwent MSDT (n=210) were retrospectively analyzed. The pre-transplantation leukemia burden was evaluated according to Pre-MRD determinedusing multiparameter flow cytometry (MFC) . Results: Of these patients, 997 (99.9% ) achieved sustained, full donor chimerism. The 100-day cumulative incidences of neutrophil engraftment, platelet engraftment, and grades Ⅱ-Ⅳ acute graft-versus-host disease (GVHD) were 99.9% (997/998) , 95.3% (951/998) , and 26.6% (95% CI 23.8% -29.4% ) , respectively. The 3-year cumulative incidence of total chronic GVHD was 49.1% (95% CI 45.7% -52.4% ) . The 3-year cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) of the 998 cases were 17.3% (95% CI 15.0% -19.7% ) and 13.8% (95% CI 11.6% -16.0% ) , respectively. The 3-year probabilities of leukemia-free survival (LFS) and overall survival (OS) were 69.1% (95% CI 66.1% -72.1% ) and 73.0% (95% CI 70.2% -75.8% ) , respectively. In the total patient group, cases with positive Pre-MRD (n=282) experienced significantly higher CIR than that of subjects with negative Pre-MRD [n=716, 31.6% (95% CI 25.8% -37.5% ) vs 14.3% (95% CI 11.4% -17.2% ) , P<0.001]. For patients in the positive Pre-MRD subgroup, cases treated with haplo-HSCT (n=219) had a lower 3-year CIR than that of cases who underwent MSDT [n=63, 27.2% (95% CI 21.0% -33.4% ) vs 47.0% (95% CI 33.8% -60.2% ) , P=0.002]. The total 998 cases were classified as five subgroups, including cases with negative Pre-MRD group (n=716) , cases with Pre-MRD<0.01% group (n=46) , cases with Pre-MRD 0.01% -<0.1% group (n=117) , cases with Pre-MRD 0.1% -<1% group (n=87) , and cases with Pre-MRD≥1% group (n=32) . For subjects in the Pre-MRD<0.01% group, haplo-HSCT (n=40) had a lower CIR than that of MSDT [n=6, 10.0% (95% CI 0.4% -19.6% ) vs 32.3% (95% CI 0% -69.9% ) , P=0.017]. For patients in the Pre-MRD 0.01% -<0.1% group, haplo-HSCT (n=81) also had a lower 3-year CIR than that of MSDT [n=36, 20.4% (95% CI 10.4% -30.4% ) vs 47.0% (95% CI 29.2% -64.8% ) , P=0.004]. In the other three subgroups, the 3-year CIR was comparable between patients who underwent haplo-HSCT and those received MSDT. A subgroup analysis of patients with Pre-MRD<0.1% (n=163) was performed, the results showed that cases received haplo-HSCT (n=121) experienced lower 3-year CIR [16.0% (95% CI 9.4% -22.7% ) vs 40.5% (95% CI 25.2% -55.8% ) , P<0.001], better 3-year LFS [78.2% (95% CI 70.6% -85.8% ) vs 47.6% (95% CI 32.2% -63.0% ) , P<0.001] and OS [80.5% (95% CI 73.1% -87.9% ) vs 54.6% (95% CI 39.2% -70.0% ) , P<0.001] than those of MSDT (n=42) , but comparable in 3-year NRM [5.8% (95% CI 1.6% -10.0% ) vs 11.9% (95% CI 2.0% -21.8% ) , P=0.188]. Multivariate analysis showed that haplo-HSCT was associated with lower CIR (HR=0.248, 95% CI 0.131-0.472, P<0.001) , and superior LFS (HR=0.275, 95% CI 0.157-0.483, P<0.001) and OS (HR=0.286, 95% CI 0.159-0.513, P<0.001) . Conclusion: Haplo HSCT has a survival advantage over MSDT in the treatment of B-ALL patients with pre MRD<0.1% .

Expression and function of HLA-G in human T-cell leukemia virus type 1-positive T cells / 中华微生物学和免疫学杂志

Objective:To analyze the expression of human leukocyte antigen G (HLA-G) in human T-cell leukemia virus type 1 (HTLV-1)-positive T cells, and to investigate its role in the occurrence and development of HTLV-1 infection.Methods:The expression of HLA-G in HTLV-1-positive T cell lines (MT2 and MT4) was detected by Western blot and real-time PCR. HLA-G gene in MT2 and MT4 cells was knocked down by siRNA, and the effects of HLA-G on the expression of HTLV-1 Tax and P19 at mRNA and protein levels were detected by Western blot and real-time PCR. Moreover, the changes in cytokine expression in MT2 and MT4 cells were monitored at RNA level after HLA-G gene silencing. The proliferation ability of MT2 and MT4 cells was analyzed by CCK8. Signal transducer and activator of transcription 3 (STAT3) pathway-related proteins were detected by Western blot.Results:Compared with HTLV-1-negative T cells (Jurkat and MOLT4), the expression of HLA-G increased significantly in MT2 and MT4 cells. After knocking down the HLA-G gene with siRNA in MT2 and MT4 cells, the expression of HTLV-1 Tax and P19 at mRNA and protein levels was decreased, and the expression of antiviral cytokines IFN-γ and TNF-α was increased. The proliferation of MT2 and MT4 cells and STAT3 phosphorylation in these cells were decreased.Conclusions:HTLV-1 could induce T cells to overexpress the immune tolerance molecule HLA-G. Silencing HLA-G gene in HTLV-1-positive T cells could promote the production of antiviral cytokines and reduce IL-6 expression and STAT3 phosphorylation, thereby effectively inhibiting the replication of HTLV-1.

Association analysis of high level of BK virus viruria and HLA site after kidney transplantation / 中华器官移植杂志

Objective:To explore the temporal distribution of high level of BK virus(BKV) viruria after kidney transplantation(KT)and the association of high level of viruria with clinical factors and specific human leukocyte antigen(HLA)sites in donors and recipients.Methods:From January 1, 2017 to December 31, 2019, clinical data were retrospectively reviewed for 212 recipients of cadaveric KT.A high level of urinary BKV viruria was defined as urinary BKV-DNA quantification>10 7(copies/ml)after KT while 212 recipients with the same gender composition below the threshold during the same period were selected as low-level controls.Clinical data and HLA sites of two groups were statistically analyzed and risk factors for high level of viruria screened by univariate and multifactorial Logistic regressions. Results:The median time to initial high-level BKV infection in urine after RT was 125.5 days.Based upon univariate Logistic analysis, delayed graft function(DGF)and HLA-A24 of recipient were risk factors for high-level BKV infection in urine while HLA-DQ9 of donor acted as a protective factor.Through multivariate Logistic analysis, DGF( OR=2.18, 95% CI 1.18~4.01, P=0.012)and HLA-A24( OR=1.63, 95% CI 1.06~2.53, P=0.027)of recipient were independent risk factors for high-level BKV infection in urine.And HLA-DQ9 of donors( OR=0.58, 95% CI 0.36~0.91, P=0.019)was an independent protective factor. Conclusions:High level of BKV viruria after RT is associated with donor/recipient-specific HLA sites.Early risk factor stratification and protective factors of recipients can aid in tailoring postoperative immunosuppression and screening program and developing T cell-associated vaccines.