Human leukocyte antigen compatibility and incidence of donorspecific antibodies in pediatric liver transplant recipients

BACKGROUND Antibody-mediated rejection following liver transplantation(LT)has been increasingly recognized,particularly with respect to the emergence of de novo donor-specific antibodies(DSAs)and their impact on graft longevity.While substantial evidence for adult populations exists,research focusing on pediatric LT outcomes remains limited.AIM To investigate the prevalence of human leukocyte antigen(HLA)mismatches and DSA and evaluate their association with rejection episodes after pediatric LT.METHODS A cohort of pediatric LT recipients underwent HLA testing at Santa Casa de Porto Alegre,Brazil,between December 2013 and December 2023.Only patients who survived for>30 days after LT with at least one DSA analysis were included.DSA classes I and II and cross-matches were analyzed.The presence of de novo DSA(dnDSA)was evaluated at least 3 months after LT using the Luminex®single antigen bead method,with a positive reaction threshold set at 1000 MFI.Rejection episodes were confirmed by liver biopsy.RESULTS Overall,67 transplanted children were analyzed;61 received grafts from living donors,85%of whom were related to recipients.Pre-transplant DSA(class I or II)was detected in 28.3%of patients,and dnDSA was detected in 48.4%.The median time to DSA detection after LT was 19.7[interquartile range(IQR):4.3-35.6]months.Biopsyproven rejection occurred in 13 patients at follow-up,with C4d positivity observed in 5/13 Liver biopsies.The median time to rejection was 7.8(IQR:5.7-12.8)months.The presence of dnDSA was significantly associated with rejection(36%vs 3%,P<0.001).The rejection-free survival rates at 12 and 24 months were 76%vs 100%and 58%vs 95%for patients with dnDSA anti-DQ vs those without,respectively.CONCLUSION Our findings highlight the importance of incorporating DSA assessment into pre-and post-transplantation protocols for pediatric LT recipients.Future implications may include immunosuppression minimization strategies based on this analysis in pediatric LT recipients.

Importance of human leukocyte antigen antibodies and leukocyte antigen/killer-cell immunoglobulin-like receptor genes in liver transplantation

Many mechanisms have been proposed to explain the hypothetical state of hepatic tolerance,which is described by eventual imbalances or deregulation in the balance of cytokines,mediators,effectors,and regulatory cells in the complex milieu of the liver.In this section,we will comment on the importance of donorspecific anti-human leukocyte antigen(HLA)antibodies(DSA)as well as the compatibility and pairings of HLA and killer-cell immunoglobulin-like receptor(KIR)genotypes in the evolution of liver transplantation.Thus,HLA compatibility,viral infections,and HLA-C/KIR combinations have all been linked to liver transplant rejection and survival.There have been reports of increased risk of acute and chronic rejection with ductopenia,faster graft fibrosis,biliary problems,poorer survival,and even de novo autoimmune hepatitis when DSAs are present in the recipient.Higher mean fluorescence intensity(MFI)values of the DSAs and smaller graft size were associated with poorer patient outcomes,implying that high-risk patients with preformed DSAs should be considered for selecting the graft placed and desensitization methods,according to the investigators.Similarly,in a combined kidney-liver transplant,a pretransplant with a visible expression of several DSAs revealed that these antibodies were resistant to treatment.The renal graft was lost owing to antibody-mediated rejection(AMR).The HLA antigens expressed by the transplanted liver graft influenced antibody elimination.Pathologists are increasingly diagnosing AMR in liver transplants,and desensitization therapy has even been employed in situations of AMR,particularly in patients with DSAs in kidney-hepatic transplants and high-class II MFI due to Luminex.In conclusion,after revealing the negative impacts of DSAs with high MFI,pretransplant virtual crossmatch techniques may be appropriate to improve evolution;however,they may extend cold ischemia periods by requiring the donor to be typed.

Association of human leukocyte antigen DQB1 and DRB1 alleles with chronic hepatitis B

AIM: To investigate the effect of human leukocyte antigen (HLA) DRB1 and DQB1 alleles on the inactive and advanced stages of chronic hepatitis B.

Occurrence of human leukocyte antigen B51-related ankylosing spondylitis in a family:Two case reports

BACKGROUND Ankylosing spondylitis(AS)is strongly associated with the human leukocyte antigen(HLA)B27 haplotype.In regions where conventional polymerase chain reaction for HLA typing is available for antigens such as HLA B27 or HLA B51,it is common to perform the HLA B27 test for evaluation of AS.While HLA B27-associated clustered occurrences of AS have been reported in families,we report the first case series of HLA B51-related occurrences of AS in a family.CASE SUMMARY A father and his daughters were diagnosed with AS and did not have the HLA B27 haplotype.Although they were positive for HLA B51,they exhibited no signs of Behçet’s disease(BD).Of the five daughters,one had AS,and three,including the daughter with AS,were positive for HLA B51.The two daughters with the HLA B51 haplotype(excluding the daughter with AS)exhibited bilateral grade 1 sacroiliitis,whereas the daughters without the HLA B51 haplotype did not have sacroiliitis.Thus,this Korean family exhibited a strong association with the HLA B51 haplotype and clinical sacroiliitis,irrespective of the symptoms of BD.CONCLUSION It is advisable to check for HLA B51 positivity in patients with AS/spondyloarthropathy who test negative for HLA B27.

Relationship of human leukocyte antigen class II genes with the susceptibility to hepatitis B virus infection and the response to interferon in HBV-infected patients

AIM： To study the relationship of human leukocyte antigen （HLA）-DRB1 and -DQB1 alleles with the genetic susceptibility to HBV infection and the response to interferon （IFN） in HBV-infected patients. METHODS： Low-resolution DNA typing kit was used to determine HLA-DR-1 and -DQB1 genes in 72 patients with chronic hepatitis B （CHB） and HLA-DRB1 in 200 healthy people ready to donate their bone marrow in Shanghai. Among CHB patients, 35 were treated with IFNα-1b for 24 wk. RESULTS： The frequencies of HLA-DRBI＊06, DRBI＊08 and DRB1＊16 alleles in 72 patients were higher than in 200 healthy people （2.08% vs0%, OR = 3.837, P= 0.018; 11.11% vs5.50%, OR = 2.148, P= 0.034; and 6.94% vs 3.00%, OR = 0.625, P = 0.049, respectively）; whereas that of DRBI＊07 allele was lower （2.78% vs 7.75%, OR = 0.340, P= 0.046）. The frequency of HLA-DRBI＊ 14 allele was higher in 11 responders to IFN compared with 24 non-responders （18.18% vs2.08%, OR = 10.444, P = 0.031）, whereas that of DQBI＊07 allele was inverse （9.09% vs37.50%, OR = 0.167, P= 0.021）. CONCLUSION： The polymorphism of HLA class II may influence the susceptibility to HBV infection and the response to IFN in studied CHB patients. Compared with other HLA-DRB1 alleles, HLA-DRBI＊06, DRBI＊08, and DRB1＊16 may be associated with chronicity of HBV infection, HLA-DRBI＊07 with protection against HBV infection, and HLA-DRB1＊14 allele may be associated with a high rate of the response of CHB patients to IFN treatment. Compared with other HLA-DQB1 alleles, HLA-DQBI＊07 may be associated with low response rate to IFN. 2005 The WJG Press and Elsevier Inc. All rights reserved

Impact of human leukocyte antigen mismatching on outcomes of liver transplantation:A meta-analysis

AIM:To assess the effect of human leukocyte antigen(HLA) mismatching on liver graft outcome and acute rejection from a meta-analysis of available cohort studies.METHODS:Articles in PubMed/MEDLINE,EMBASE and the Cochrane database from January 1970 to June 2009,including non-English literature identified in these databases,were searched.Only studies comparing HLA or sub-phenotype matching with mismatching were extracted.The percentage of graft survival was extracted by "Engauge Digitizer" from survival curves if the raw data were not displayed.A meta-analysis was performed when at least 3 studies provided data.RESULTS:Sixteen studies met the inclusion criteria.A lower number of HLA mismatches(0-2 vs 3-6) did reduce the incidence of acute rejection(relative risk:0.77,P = 0.03).The degree of HLA mismatching(0-2 vs 3-6) had no significant effect on 1-year [hazard ratio(HR):1.04,P = 0.68] and 5-year(HR:1.09,P = 0.38) graft survival.In sub-phenotype analysis,the degree of HLA-A,B and DR mismatching(0 vs 1-2) had no significant effect on 1-year and 5-year graft survival,either.The HRs and P-values were 0.95,0.71(HLA-A,1-year);1.06,0.60(HLA-A,5-year);0.77,0.16(HLA-B,1-year);1.07,0.56(HLA-DR,1-year);1.18,0.23(HLADR,5-year),respectively.CONCLUSION:The results of this systematic review imply that good HLA compatibility can reduce the incidence of acute rejection in spite of having no influence on graft outcomes.To obtain a short recovery time and minimize rejection post transplantation,HLA matching studies should be considered before the operation.

Association of cytomegalovirus infection with human leukocyte antigen genotypes in recipients after allogeneic liver transplantation

BACKGROUND: Cytomegalovirus (CMV) infection is the important cause affecting the survival rate and function of the transplanted organ after transplantation. The occurrence of CMV infection after liver transplantation (LT) is associated with many factors. Lots of studies suggest that genetic mutation between hosts and CMV may play a role in the occurrence and development of CMV infection. CMV exists in an incubative state, affect or destroy the expression of human leukocyte antigen (HLA) molecules in the host cell surface, and interfere antigen's submission. This mechanism is the key of CMV to avoid immune defense mechanism of the host. To detect HLA and CMV antibody (CMV-Ab), CMV antigen (CMV-Ag) of transplantation recipients, we evaluated the association of CMV infection and the particular HLA genotypes in recipients after LT. METHODS: 277 blood samples were collected from 39 LT recipients. CMV antibody and antigen were detected by ELISA or immunohistochemical methods. The HLA types of the recipients were determined by PCR. To analyze the association of HLA alleles and the occurrence of CMV antigenemia in the patients, relative risk degree (RR) was used as the parameter for the Chi-square test. RESULTS: The LT recipients were serum CMV IgG positive (100%), but none of them was CMV IgM positive (0%). Thirty-three LT recipients (84.6%) were CMV antigenic positive with 1-50 positive leukocytes per 50000 leukocytes in extent and 7.2±4.2 positive leukocytes per 50000 leukocytes on average. Thirteen patients developed CMV pneumonia, with CMV antigenic positive (100%) and 17.7±5.5 positive leukocytes per 50000 leukocytes on average. Some HIA alleles were associated with the occurrence and extent of CMV antigenemia. HLA-A2 was the higher frequency allele for patients with antigenemia (P<0.05), and 7 patients carrying HLA-DR11 allele developed antigenemia (P<0.05). In the lower antigenemia group, HLA-A11 was higher in frequency than others (P<0.05). Besides, none of the patients carrying HLA-B16 allele developed clinical symptoms of CMV infection (P<0.05). CONCLUSIONS: The variability of HLA alleles might modulate immune response to CMV infection. HLA examination before transplantation should be made for prevention and treatment of CMV infection aider operation.

Impact of human leukocyte antigen matching on hepatitis B virus recurrence after liver transplantation

BACKGROUND: Liver transplantation (LT) is an effective therapy for end-stage hepatitis B virus (HBV) infection. Recurrence of HBV is one of the frequent complications. In the present study, we investigated whether human leukocyte antigen (HLA) matching influences the incidence of HBV recurrence, and the time point of HBV recurrence after LT. METHODS: One hundred and two recipients of LT with end-stage chronic HBV infection were reviewed. The triple-drug immunosuppression regimen consisted of tacrolimus, mycophenolate, and prednisone. All patients were subjected to prophylaxis with hepatitis B immunoglobulin and lamivudine. HLA typing was performed using a sequence-specific primer-polymerase chain reaction kit. Serology for hepatitis B and HBV DNA was examined using a commercial kit. RESULTS: The incidence of recurrent HBV infection post-LT was 6.86%. The recurrent infection of HBV was independent of the degree of H LA matching (P>0.05). The time point of HBV recurrence, however, was prolonged in HLA-A matched patients compared with matchless patients (P=0.049). The recurrence of HBV infection was independent of H LA compatibility. CONCLUSIONS: This retrospective analysis showed that more HLA-A locus compatibility is associated with a prolonged time of recurrence of HBV in patients after LT for end-stage HBV infection. The incidence of HBV recurrence is independent of HLA compatibility. (Hepatobiliary Pancreat Dis Int 2010; 9: 139-143)

Human leukocyte antigen class II DQB1*0301, DRB1*1101 alleles and spontaneous clearance of hepatitis C virus infection: A meta-analysis

AIM： To assess the associations of human leukocyte antigen （HI_A） class Ⅱ DQB1＊0301 and/or DRB1＊1101 allele with spontaneous hepatitis C virus （HCV） clearance by meta-analysis of individual dataset from all studies published till date. METHODS： To clarify the impact of HLA class Ⅱ polymorphisms on viral clearance, we performed a metaanalysis of the published data from 11 studies comparing the frequencies of DQB1＊0301 and DRB1＊1101 alleles in individuals with spontaneous resolution to those with persistent infection. As we identified the heterogeneity between studies, summary statistical data were calculated based on a random-effect model. RESULTS： Meta-analyses yielded summary estimatesodds ratio （OR） of 2.36 [95%CI （1.62, 3.43）, P〈0.00001] and 2.02 [95%CI （1.56, 2.62）, P〈0.00001] for the effects of DQB1＊0301 and DRB1＊1101 alleles on spontaneous clearance of HCV, respectively. CONCLUSION： These results support the hypothesis that specific HLA class Ⅱ alleles might influence the susceptibility or resistance to persistent HCV infection. Both DQB1＊0301 and DRB1＊1101 are protective alleles and present HCV epitopes more effectively to CD4^＋T lymphocytes than others, and subjects with these two alleles are at a lower risk of developing chronic HCV infection. Large, multi-ethnic confirmatory and welldesigned studies are needed to determine the host genetic determinants of HCV infection.

Up-regulation of Human Leukocyte Antigen G Expression in Primary Cutaneous Malignant Melanoma Associated with Host-vs-tumor Immune Response

Human leukocyte antigen G （HLA-G） is one of the molecules implicated in immunotolerance. To investigate the role of HLA-G in primary cutaneous malignant melanoma （CMM）, a series of 47 skin melanocytic lesions were immunohistochemically evaluated. The correlation between HLA-G expression and CMM clinicohistopahtological data and Bcl-2 expression was also analyzed. HLA-G expression was detected in a variety of cell types. No significant difference in HLA-G expression was observed between malignant and non-malignant melanocytic lesions. HLA-G expression was significantly correlated with the inflammatory infiltration and Bcl-2 expression, whereas no significant correlation with ulceration, tumor thickness, clinical stage, histopathological subtypes were observed. HLA-G expression may be the result of host immune reaction in tumor microenvironment rather than a malignant feature of CMM.

Association between human leukocyte antigen gene polymorphisms and multiple EPIYA-C repeats in gastrointestinal disorders

BACKGROUND Polymorphisms of human leukocyte antigen(HLA)genes are suggested to increase the risk of gastric cancer(GC).AIM To investigate the HLA allele frequencies of patients with GC relative to a control group in terms of CagA+multiple(≥2)EPIYA-C repeats.METHODS The patient group comprised 94 patients[44 GC and 50 duodenal ulcer(DU)patients],and the control group comprised 86 individuals[(50 non-ulcer dyspepsia patients and 36 people with asymptomatic Helicobacter pylori(H.pylori)].Polymerase chain reaction was performed for the amplification of the H.pylori cagA gene and typing of EPIYA motifs.HLA sequence-specific oligonucleotide(SSO)typing was performed using Lifecodes SSO typing kits(HLA-A,HLA-B HLA-C,HLA-DRB1,and HLA-DQA1-B1 kits).RESULTS The comparison of GC cases in terms of CagA+multiple(≥2)EPIYA-C repeats showed that only the HLA-DQB1*06 allele[odds ratio(OR):0.37,P=0.036]was significantly lower,but significance was lost after correction(Pc=0.1845).The HLA-DQA1*01 allele had a high ratio in GC cases with multiple EPIYA-C repeats,but this was not significant in the univariate analysis.We compared allele frequencies in the DU cases alone and in GC and DU cases together using the same criterion,and none of the HLA alleles were significantly associated with GC or DU.Also,none of the alleles were detected as independent risk factors after the multivariate analysis.On the other hand,in a multivariate logistic regression with no discriminative criterion,HLA-DQA1*01(OR=1.848),HLA-DQB1*06(OR=1.821)and HLA-A*02(OR=1.579)alleles were detected as independent risk factors for GC and DU.CONCLUSION None of the HLA alleles were detected as independent risk factors in terms of CagA+multiple EPIYA-C repeats.However,HLA-DQA1*01,HLA-DQB1*0601,and HLA-A*2 were independent risk factors with no criterion in the multivariate analysis.We suggest that the association of these alleles with gastric malignancies is not specifically related to cagA and multiple EPIYA C repeats.

Inhibition of host immune response in colorectal cancer:Human leukocyte antigen-G and beyond

Colorectal cancer (CRC) is one of the most diffuse cancers worldwide and is still a clinical burden. Increasing evidences associate CRC clinical outcome to immune contexture represented by adaptive immune cells. Their type, density and location are summarized in the Immune Score that has been shown to improve prognostic prediction of CRC patients. The non-classical MHC class&#x02005;I&#x02005;human leukocyte antigen-G (HLA-G), is a crucial tumor-driven immune escape molecule involved in immune tolerance. HLA-G and soluble counterparts are able to exert inhibitory functions by direct interactions with inhibitory receptors present on both innate cells such as natural killer cells, and adaptive immune cells as cytotoxic T and B lymphocytes. HLA-G may play a prominent role in CRC strategies to avoid host immunosurveillance. This review highlights the current knowledge on HLA-G contribution in CRC, in related inflammatory diseases and in other type of cancers and disorders. HLA-G genetic setting (specific haplotypes, genotypes and alleles frequencies) and association with circulating/soluble profiles was highlighted. HLA G prognostic and predictive value in CRC was investigated in order to define a novel prognostic immune biomarker in CRC.

ASSOCIATION BETWEEN PEMPHIGUS VULGARIS AND HUMAN LEUKOCYTE ANTIGEN IN HAN NATION OF NORTHEAST CHINA

Objective To investigate the relationship between pemphigus vulgaris （PV） and human leukocyte antigen （HLA） in Han nation of northeast China. Mothods Standard microcytotoxicity test and polymerase chain reaction-sequence specific primers method were used to detect the HLA class Ⅰ antigens and HLA-DRBI and DQBI alleles in 27 patients with PV and results were compared with control group. Gene and phenotype frequencies of HLA-A3, A26（10）, B60（40）, and B13 （27.99%, 48%; 16.11%, 30%; 23.02%, 41%; 16.11%, 30%, respectively） increased significantly in PV group compared with control （1.01%, 2%; 0.5%, 1%; 4.61%, 9%; 5,13%, 10%, respectively）. After P value correction, the difference of A3, A26 （10）, and B60 （40） between the two groups was still significant. The gene frequencies of HLA-DRB 1^＊ 140x （1401, 1404, 1405, 1407, 1408）, DRBI^＊I20x, and DQBI＊0503 alleles in PV group （42.26%, 25.46%, and 23.02%） were significantly higher than control group （5.09%, 7.74%, and 1.89%）. After P value correction, the difference was still significant between the two groups. Collusion PV significantly relates with HLA in PV patients of Han nation of northeast China.

Reflections on the prevalence of human leukocyte antigen-B27 and human leukocyte antigen-B51 co-occurrence in patients with spondylarthritis

We performed a literature mini-review of the clinical profile of patients with spondylarthritis who are also human leukocyte antigen(HLA)-B51-positive.It seems to us that patients with HLA-B27 and HLA-B51 are more common in men,Asians and between the third and ninth decades of life.They are more likely to develop peripheral joint conditions,with cutaneous manifestations(e.g.,oral ulcers)and uveitis.Therefore,more robust epidemiological studies with more accurate methodology and multicenter locations are needed to better map the role of the interaction between HLA-B51 in patients with spondylarthritis.

Soluble Human Leukocyte Antigen-G Expression in Pregnancy Success and Early Pregnancy Loss in Korle-Bu Teaching Hospital

Introduction: Human leukocyte antigen G (HLA-G) is a non-classical major histocompatibility complex (MHC) class Ib antigen characterized by a limited polymorphism. The expression of HLA-G at immune privileged sites and its ability to inhibit the effectors functions of immune cells has set HLA-G as a molecule of immune tolerance. This expression pattern is unique among HLA genes and suggests that HLA-G may be involved in interactions that are critical in establishing and/or maintaining pregnancy. Methods: Soluble HLA-G (sHLA-G) levels were measured using a BioVendor sHLA-G ELISA kit following the manufacturer’s protocol. The study participants include women undergoing spontaneous abortion, non-pregnant women, males and an archive sample of women who had normal vaginal deliveries without any complications and any history of malaria infection from gestation to delivery. Results: Soluble HLA-G levels were higher among women undergoing spontaneous abortion as compared to women who had normal vaginal delivery and non-pregnant women. Soluble HLA-G levels were also higher in second trimester as compared to first trimester in both women who had spontaneous abortions and women who had normal delivery. Conclusion: Although sHLA-G levels were higher among women undergoing spontaneous abortion as compared to non-pregnant women and women who had normal delivery, this may be playing a role in the maintenance of maternal immune tolerance to fetal antigen, since plasma sHLA-G levels increased with increasing trimester in both women who had normal delivery and women undergoing spontaneous abortion.

Psoriatic arthritis: clinical patterns, rheumatoid factor, anti-cyclic citrullinated peptide and human leukocyte antigen risk alleles

Psoriatic arthritis is an inflammatory arthritis associated with psoriasis.Both rheumatoid factor and anti-cyclic citrullinated peptide antibodies positive psoriatic arthritis patients may be in risk for development of symmetrical polyarthritis pattern.Symmetrical polyarthritis pattern was predominant(42%)among clinical pattern of psoriatic arthritis.Among 10 rheumatoid factor positive patients,8(80%)patients had symmetrical polyarthritis pattern and out of 7 anti-cyclic citrullinated peptide antibody positive patients,7(100%)patients had symmetrical polyarthritis pattern.Association of anti-cyclic citrullinated peptide(P=0.008)and rheumatoid factor(P=0.006)showed statistical significance with symmetrical polyarthritis pattern.Human leukocyte antigen-B*07,*38 and human leukocyte antigen-C*07 were predominantly found in rheumatoid factor and anti-cyclic citrullinated peptide positive psoriatic arthritis patients.Background:Psoriatic arthritis is an inflammatory arthritis associated with psoriasis.It is usually seronegative in nature but a small percentage of patients may be positive for rheumatoid factor and anti-cyclic citrullinated peptide antibodies.Anti-cyclic citrullinated peptide and rheumatoid factor are highly specific for rheumatoid arthritis but their role is not clear in psoriatic arthritis.The prevalence and prognostic value of anti-cyclic citrullinated peptide antibody and rheumatoid factor in psoriatic arthritis patients is not well known.The aim of this study was therefore to investigate the prevalence of anti-cyclic citrullinated peptide antibodies and rheumatoid factor in psoriatic arthritis patients and assess their clinical associations and also to see the distribution of human leukocyte antigen-B and human leukocyte antigen-C locus antigens in anti-cyclic citrullinated peptide antibody and rheumatoid factor positive psoriatic arthritis patients.Methods:Fifty patients with psoriatic arthritis were tested for the presence of rheumatoid factor and anti-cyclic citrullinated peptide antibodies.Polymerase chain reaction was done with sequence specific primer for detection of human leukocyte antigen-B and human leukocyte antigen-C locus antigens in rheumatoid factor and anti-cyclic citrullinated peptide positive psoriatic arthritis patients.Data on five clinical patterns of rheumatological manifestations of psoriatic arthritis patients were collected prospectively on all patients and statistically compared between anti-cyclic citrullinated peptide,rheumatoid factor positive and negative patients by chi-square test.We also see the distribution of human leukocyte antigen-B and human leukocyte antigen-C locus antigens in anti-cyclic citrullinated peptide antibody and rheumatoid factor positive psoriatic arthritis patients.Results:Among 50 psoriatic arthritis patients,rheumatoid arthritis test was positive in 10(20%)patients and anti-cyclic citrullinated peptide was positive in 7(14%)patients.Symmetrical polyarthritis pattern is predominant among clinical pattern of psoriatic arthritis which was found in 21(42%)patients.Among 7 anti-cyclic citrullinated peptide positive psoriatic arthritis patients,symmetrical polyarthritis pattern is predominant and it was found in 7(100%)patients.Among 10 rheumatoid factor positive psoriatic arthritis patients,symmetrical polyarthritis pattern is predominant and it was found in 8(80%)patients.In this study,symmetrical polyarthritis pattern is statistically associated with anti-cyclic citrullinated peptide positive psoriatic arthritis patients(P=0.008)and rheumatoid factor positive psoriatic arthritis patients(P=0.006).Human leukocyte antigen-B*07,*38 and human leukocyte antigen-C*07 were predominantly found in rheumatoid factor and anti-cyclic citrullinated peptide positive psoriatic arthritis patients.Conclusion:Both rheumatoid factor and anti-cyclic citrullinated peptide positive psoriatic arthritis patients may be in risk for development of symmetrical polyarthritis pattern.Among rheumatoid factor and anti-cyclic citrullinated peptide positive psoriatic arthritis patients,Human leukocyte antigen-B*07,*38 and human leukocyte antigen-C*07 alleles were more frequently found alleles.

Clinical significance of donor-specific human leukocyte antigen antibodies in liver transplantation

Antibody-mediated rejection(AMR) caused by donorspecific anti-human leukocyte antigen antibodies(DSA) is widely accepted to be a risk factor for decreased graft survival after kidney transplantation. This entity also plays a pathogenic role in other solid organ transplants as it appears to be an increasingly common cause of heart graft dysfunction and an emerging issue in lung transplantation. In contrast, the liver appears relatively resistant to DSA-mediated injury. This "immune-tolerance" liver property has been sustained by a low rate of liver graft loss in patients with preformed DSA and by the intrinsic liver characteristics that favor the absorption and elimination of DSA; however, alloantibody-mediated adverse consequences are increasingly being recognized, and several cases of acute AMR after ABO-compatible liver transplant(LT) have been reported. Furthermore, the availability of new solid-phase assays, allowing the detection of low titers of DSA and the refinement of objective diagnostic criteria for AMR in solid organ transplants and particularly in LT, have improved the recognition and management of this entity. A cost-effective strategy of DSA monitoring, avoidance of class Ⅱ human leukocyte antigen mismatching, judicious immunosuppression attached to a higher level of clinical suspicion of AMR, particularly in cases unresponsive to conventional antirejection therapy, can allow a rational approach to this threat.

Human leukocyte antigen typing and crossmatch:A comprehensive review

Renal transplantation remains the best option for patients suffering from end stage renal disease(ESRD).Given the worldwide shortage of organs and growing population of patients with ESRD,those waitlisted for a transplant is ever expanding.Contemporary crossmatch methods and human leukocyte antigen(HLA) typing play a pivotal role in improving organ allocation and afford better matches to recipients.Understanding crossmatch as well as HLA typing for renal transplantation and applying it in clinical practice is the key step to achieve a successful outcome.Interpretation of crossmatch results can be quite challenging where clinicians have not had formal training in applied transplant immunology.This review aims to provide a worked example using a clinical vignette.Furthermore,each technique is discussed in detail with its pros and cons.The index case is that of a young male with ESRD secondary to Lupus nephritis.He is offered a deceased donor kidney with a 1-0-0 mismatch.His complement dependent cytotoxicity(CDC) crossmatch reported positive for B lymphocyte,but flow cytometry crossmatch(FCXM) was reported negative for both B and T lymphocytes.Luminex-SAB(single antigen bead) did not identify any donor specific antibodies(DSA).He never had a blood transfusion.The positive CDCcrossmatch result is not concordant with DSA status.These implausible results are due to underlying lupus erythematosus,leading to false-positive B-lymphocyte crossmatch as a result of binding immune complexes to Fc-receptors.False positive report of CDC crossmatch can be caused by the underlying autoimmune diseases such as lupus erythematosus,that may lead to inadvertent refusal of adequate kidney grafts.Detailed study of DSA by molecular technique would prevent wrong exclusion of such donors.Based on these investigations this patient is deemed to have "standard immunological risk" for renal transplantation.

Human leukocyte antigen DQ2/8 prevalence in non-celiac patients with gastrointestinal diseases

AIM: To investigate the prevalence of human leukocyte antigen (HLA) DQ2/8 alleles in Southern Italians with liver and gastrointestinal (GI) diseases outside of celiac disease. METHODS: HLA DQ2/8 status was assessed in 443 patients from three ambulatory gastroenterology clinics in Southern Italy (University of Federico Ⅱ, Naples, Loreto Crispi Hospital, Ruggi D'Aragona Hospital, Salerno). Patients were grouped based on disease status [pre-post transplant liver disease, esophageal/gastric organic and functional diseases, irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD)] and DQ2/8 alleles, which correspond to a celiac disease genetic risk gradient. Subject allele frequencies were compared to healthy Italian controls. RESULTS: One hundred and ninety-six out of four hundred and forty-three (44.2%) subjects, median age 56 years and 42.6% female, were DQ2/8 positive. When stratifying by disease we found that 86/188 (45.7%) patients with liver disease were HLA DQ2/8 positive, 39/73 (53.4%) with functional upper GI diseases and 19/41 (46.3%) with organic upper GI diseases were positive. Furthermore, 38/105 (36.2%) patients with IBS and 14/36 (38.9%) with IBD were HLA DQ2/8 positive (P = 0.21). Compared to healthy controls those with functional upper GI diseases disorders had a 1.8 times higher odds of DQ2/8 positivity. Those with liver disease had 1.3 times the odds, albeit not statistically significant, ofDQ2/8 positivity. Both those with IBS and IBD had a lower odds of DQ2/8 positivity compared to healthy controls. CONCLUSION: The proportion of individuals HLA DQ2/8 positive is higher in those with liver/upper functional GI disease and lower in IBS/IBD as compared to general population estimates.

Methodological aspects of anti-human leukocyte antigen antibody analysis in solid organ transplantation

Donor human leukocyte antigen(HLA)-specific antibodies(DSA) play an important role in solid organ transplantation. Preexisting IgG isotype DSA are considered a risk factor for antibody mediated rejection, graft failure or graft loss. The post-transplant development of DSA depends on multiple factors including immunogenicity of mismatched antigens, HLA class Ⅱ typing of the recipient, cytokine gene polymorphisms, and cellular immunoregulatory mechanisms. De novo developed antibodies require special attention because not all DSA have equal clinical significance. Therefore, it is important for transplant clinicians and transplant immunologists to accurately characterize DSA. In this review, the contemporary immunological techniques for detection and characterization of anti-HLA antibodies and their pitfalls are described.