Effect of Herpes Simplex Virus-2 Infection in Vitro on the Expression of HLA Class II Antigen of Monocytes

Objectives: In order to investigate the role of mono-cytes and human leukocyte antigen (HLA) class II an-tigen in herpes simplex virus-2 (HSV-2) infection, westudied the effect of HSV-2 infection in vitro on theexpression of HLA class II antigen on monocytes.Methods: Monocytes were infected with HSV-2(Strain 333). Culture cells were collected 1, 3, 5 and 7days after infection. The levels of expression of HLAclass II antigen were measured by using alkaline phos-phatase antialkaline phosphatase method (APAAP).Results: The levels of the expression of HLA class IIantigen on monocytes significantly decreased on thefirst day of post-infection, and then gradually returnedto levels found in the controls by the 7th day post-infection.Conclusion: HLA class II antigen expression onmonocytes was inhibited with HSV-2 infection, whichmight be one means of virus escape at an early phase.The expression of HLA class II antigen may play animportant role in herpes simplex viurs-2 pathogenic-ity and immunity.

A Study of Monocyte Excretion of TNF- α and IL-6 and Monocyte Expression of HLA Class Ⅱ Antigen In Genital Herpes

Objective: To study the role of monocytes in the pathogenesis of genital herpes. Methods: TNF- α and IL-6 levels in 27 cases of genital herpes were detected by enzyme linked immunosorbant assay (ELISA). HLA class Ⅱ antigen expression on monocytes were detected by an alkaline phosphatase anti-alkaline phosphatase method. Results: Compared with normal controls, levels of TNF- a and IL - 6 secreted by monocytes responding to LPS mitogen in vitro were significantly decreased [(3.13 ± 0.44ng/ml) vs (4.68 ± 0.54ng/ml), P<0.05 and (3.32 ± 1.06ng/ml) vs (6.46 ± 1.94ng/ ml), P<0.05, respectively]. HLA class Ⅱ antigen expression on monocytes in the genital herpes group was also significantly decreased [HLA-DR (67.48% ± 1.51%) vs (81.03% ± 1.32%), P<0.01 and HLA-DQ (29.54% ± 1.15%) vs (37.63% ± 1.79%), P <0.01 respectively]. Conclusion: These findings suggest that the decreased monocyte function may contribute to the pathogenesis of genital herpes. Augmenting or inducing monocyte function may be important in the prevention, treatment, and reduction of genital herpes cases.

IMPAIRED AUTOLOGOUS MIXED LYMPHOCYTE REACTION CORRELATED WITH DECREASED EXPRESSION OF HLA-Ⅱ ANTIGENS ON MONOCYTES IN PATIENTS WITH MYELOID LEUKEMIA

The proliferative response of T-cells to autolo-gous non-T-cells is referred to as the autologous mixed lymphocyte reaction (AMLR). Recent studies have suggested that AMLR represents a mechanism of immune regulation in vivo. We investigated AMLR in patients with acute- and chronic myeloid leukemia (AML and CML). AMLR was found to be significantly depressed (P<0.001) in AML patients (n=17, cpm=532±95) and CML patients (n=13, cpm=688±99) when compared with that of their healthy HLA-identical siblings serving as controls (n=17, cpm=4152±619 and n=13 cpm=4086±421, respectively). In order to understand the cellular basis of the defective AMLR in patients with AML end CML, we performed mitogen-treated T-cell cultures analysis of T-cell subsets and HLA-Ⅱ antigen detection on monocytes. The results indicated that the defect of AMLR in patients resided at the stimulator monocyte level rather than at the responder T-cell level. Enumeration of monocytes reactive with monoclonal antibody Tu22, which recognizes determinants of HLA-DQ, demonstrated that ML patients had a significantly decreased (P<0.091) number of circulating Tu22+ monocytes when compared with normal controls. These studies suggest that a deficiency of HLA-DQ+ monocytes contributes to the depression of AMLR in ML and possibly underlies the abnormalities of immune response present in this disease.

Serum tumor markers (carcinoembryonic antigen, carbohydrate antigen 19-9, carbohydrate antigen 72-4, carbohydrate antigen 24-2, ferritin) and gastric cancer prognosis correlation

BACKGROUND Gastric cancer is a kind of malignant tumor which is prevalent all over the world.Although some progress has been made in the treatment of gastric cancer,its prognosis is still not optimistic,so it is of great significance to find reliable prog-nostic indicators to guide the treatment and management of patients with gastric cancer.AIM To explore the relationship between serum levels of five biomarkers[carcinoem-bryonic antigen(CEA),carbohydrate antigen(CA)19-9,CA72-4,CA24-2,and ferritin]and prognosis in patients with gastric cancer.METHODS This study included 200 patients with gastric adenocarcinoma,and conducted an in-depth analysis of their baseline characteristics,relationship between tumor markers and staging,and prognosis.The study found that CA19-9 has a signi-ficant correlation with tumor stage,the average levels of CA24-2,CEA,CA72-4 and ferritin were slightly increased disregarding the stage of tumor.Survival analysis showed that increases in CEA,CA19-9,CA24-2,and ferritin were all associated with shortened overall survival of patients.Further multivariate ana-lysis revealed that elevated serum CA72-4 levels were an inde-pendent adverse prognostic factor.RESULTS This study reveals that there is a significant correlation between the expression levels of serum tumor markers CEA,CA19-9,CA72-4,CA24-2 and ferritin in patients with gastric cancer and prognosis,and can be used as important indicators for prognostic evaluation of gastric cancer.In particular,markers that appear abnormally elevated initially may help identify gastric cancer patients with poor prognosis.CONCLUSION Serum CEA and CA19-9 play an important role in the prognosis assessment of gastric cancer,and are effective tools to guide clinical practice and optimize individualized treatment strategies for gastric cancer patients.

Immunohistochemical Study of HLA-DR Antigen in Endometrial Tis-sue of Patients with Endometriosis

In order to evaluate the expression of HLA DR antigen in glandular cells in eutopic and ectopic endometrium in patients with endometriosis, 19 infertile patients with endometriosis were analyzed immunohistochemically by labelled streptavidin biotin (LSAB) method. Nineteen infertile patients without endometriosis were studied as controls. The results showed that the expression of HLA DR antigen in the glandular cells in both eutopic and ectopic endometrium was increased significantly as compared with that in the controls ( P <0.01). It is likely that aberrant expression of HLA DR antigen in endometriotic tissue is involved in abormal immunogenesis of endometriosis.

Prevalence of Human Leukocyte Antigen HLA-B*5701 in HIV-1 Infected Individuals in Brazil

This study was designed to establish the prevalence of HLA-B*5701 at HIV-1 infected individuals in Brazil. A total of 517 consecutive individuals were followed in this study from February 2009 through July 2011. The presence of HLA-B*5701 was determined by Nested-PCR with HLA-B*57 and HLA-B*5701 sequence-specific primers (PCR-SSP). The expression of HLA-B*57 was negative in the 385 (74.5%) and positive in the 103 (19.9%) of infected individuals. Among these, the expression of HLA-B5701 was positive in the 29 (5.6%) of individuals. No demographic or ethnic differences were found between HLA-B*57/HLA-B*5701 HIV-1 negative patients, with a prevalence of Caucasians (57.1%) individuals. During the period of study, 68 patients were submited to an abacavir contain- ing regimen. The HLA-B*5701 allele was observed in 7 (10.3%) patients, with a significant incidence of Hypersensitivity reactions at 4 of them (p < 0.001). Conclusions: Although Brazilian population consists of a mixture of individuals of Caucasian, African and Native American genetic background, prevalence of HLA-B*5701 in this population is similar to the one found in pure Caucasians.

An Immunohistochemical Study of Langerhans Cells,T-Cells and the HLA Antigen in Human Cornea

The distribution of Langerhans cells (LC),T-cell subsets andHLA antigen in 12 normal and 7 morbid corneas,including 4 of suppurativecorneal ulcer and 3 of uveogenic endophthalmitis,was investigated withmonoclonal antibodies.The results revealed that a small amount of LC andT-cell subsets were present in the limbal region of normal corneas,whilelarge numbers of LC and OKT_4^+ were observed in the corneas of suppurativeulcer.HLA-A,B,C antigens were expressed on the epithelial cells keratocytes of the normal corneas, while the HLA-DRantigens wereexpressed on the surface of LC at the limbus.

Correlation between expression of HLA class Ⅱ antigen on hepatocyte membrane and viral replication in chronic hepatitis B virus carriers

In order to study the relationship between replicative status and human leucocyte antigens(HLA),HLA class Ⅱ antigen on hepatocyte membrane was analyzed in liver biopsies from 49 pa-tients with chronic hepatitis B virus infection.The results revealed that expression of HLA classⅡ antigen on hepatocyte membrane was observed in 57% (13/23) of hepatitis B e antigen (HBeAg)positive,only in 15% (4/26) of anti-HBe positive carriers.The display of HLA class Ⅱ antigen onhepatocyte membrane yeas found in 65% (11/17) hepatitis B core antigen (HBcAg) positive and in19% (6/32) HBcAg negative patients with chronic hepatitis B virus infection.There was nosignificant difference in the expression of HLA class Ⅱ antigen on hepatocyte membrane between mi-nor hepatic diseases and active liver diseases.These findings suggested that display of HLA classⅡ antigen on hepatocyte membrane might be associated with viral replication in the chronic hepati-tis B virus carriers.

Immunohistochemical assessments of HLA-DR antigen expression in autoimmune thyroid diseases

40 thyroid specimens from Tru-cut needle biopsy and surgerywere analyzed by APAAP immunohistochemical technique.It was shown thatthe expression of HLA-DR antigen on thyroid follicular cells (TFC) wasinvolved in almost every patient.The degree of DR expression was signifi-cantly higher in autoimmune thyroiditis (AIT) than in Graves’ disease (GD)and in nontoxic goiter (NTG),The level of DR expression on TFC not onlycorrelated markedly with degree of MNC infiltration,but more so with degreeof DR expression on intrathyroidal infiltrates,suggesting that aberrant DR ex-pression in vivo may be related to the activation of intrathyroidal T cells.

Expression of HLA-DR antigen in hepatocellular carcinoma and its up-regulation by interferon

Objective:To observetheexpressionof humanleukocyticantigenDR(HLA-DR)inprimaryhepatocellular carcinoma(HCC)anditsup-regulationby interferon(IFN).Methods:The expressionof HLA-DRin46specimensof humanHCCtissues,4humanHCCcelllines(SMMC-7721,HCC-9204,BEL-7402andHHCC)anda humanhepatocyte celllineQZGwas respectivelydetectedby immunohistochemicalABCstainingandflowcytometry.Theexpressionof HLA-DRinthe5celllineswasdetectedby ELISAbeforeandafterthecellsweretreatedwithIFN-γor IFN-α.Results:Eighteenoutof46HCCtissues(39.1%)expressedHLA-DR,whereasallthenormallivertissuesimmediatelyadjacentto HCCtissueswereHLA-DR-negative.No obviousHLA-DR-positivestainingwas foundin allthe5celllines.The expressionof HLA-DRwas up-regulatedin allthe5celllinesafterIFN-γor IFN-αtreatment.The up-regulationof HLA-DRinQZGcellswaslessobviousthanthatinHCCcelllines.Theeffectof IFN-γwasmoresignificantthanthatof IFN-α.Conclusion:HCCtissuescanexpressHLA-DRto someextent,butHCCcelllinesdo notexpressdetectable HLA-DR.IFNcanup-regulateHLA-DRexpressioninHCCcells.

The combined detection of carcinoembryonic antigen,carcinogenic antigen 125,and carcinogenic antigen 19-9 in colorectal cancer patients

BACKGROUND Hepatic metastases are common and difficult to treat after colorectal cancer(CRC)surgery.The predictive value of carcinoembryonic antigen(CEA),cancer antigen(CA)125 and CA19-9 combined tests for liver metastasis is unclear.AIM To evaluate predictive value of combined tests for CEA,CA125,and CA19-9 levels in patients with liver metastases of CRC.METHODS The retrospective study included patients with CRC alone(50 cases)and patients with CRC combined with liver metastases(50 cases)who were hospitalized between January 2021 and January 2023.Serum CEA,CA125 and CA19-9 levels were compared between the two groups,and binary logistic regression was used to analyze the predictive value of the combination of these tumor markers in liver metastasis.In addition,we performed receiver operating characteristic(ROC)curve analysis to assess its diagnostic accuracy.RESULTS The results showed that the serum CEA,CA125 and CA19-9 levels in the CRC with liver metastasis group were significantly higher than those in the CRC alone group.Specifically,the average serum CEA level in the CRC with liver metastasis group was 162.03±810.01 ng/mL,while that in the CRC alone group was 5.71±9.76 ng/mL;the average serum CA125 levels were 43.47±83.52 U/mL respectively.and 13.5±19.68 U/mL;the average serum CA19-9 levels were 184.46±473.13 U/mL and 26.55±43.96 U/mL respectively.In addition,binary logistic regression analysis showed that CA125 was significant in predicting CRC liver metastasis(P<0.05).ROC curve analysis results showed that the areas under the ROC curves of CEA,CA125 and CA19-9 were 0.607,0.692 and 0.586.CONCLUSION These results suggest that combined detection of these tumor markers may help early detection and intervention of CRC liver metastasis,thereby improving patient prognosis.

Chimeric Antigen Receptors and Regulatory T Cells:The Potential for HLA-Specific Immunosuppression in Transplantation

Chimeric antigen receptors(CARs)are a breakthrough in genetic engineering that have revolutio nized the field of adoptive cellular therapy(ACT).Cells expressing these receptors are rerouted to a predefined target by the inclusion of an antigen-specific binding region within the synthetic CAR construct.The advantage of cells with programmed specificity has been demonstrated clinically in the field of oncology,and it is clear that such cells have greater accuracy,potency,and reduced off-target therapeutic effects compared with their unmodified counterparts.In contrast to conventional T cells(Tconvs),regulatory T cells(Tregs)play a major role in suppressing immune activation and regulating the host immune response.CAR expression within Tregs has been proposed as a therapy for autoimmune and inflammatory diseases,graft-versus-host disease(GVHD),and organ transplant rejectio n.In the latter,they hold immense potential as mediators of immune tolerance for recipients of allotransplants.However,current research into CAR-Treg engineering is extremely limited,and there is uncertainty regarding optimal design for therapeutic use.This review examines the rationale behind the development of CAR-Tregs,their significance for human transplantation,potential designs,safety considerations,and comparisons of CAR-Tregs in transplantation models to date.

STUDY ON MECHANISM OF MODIFICATION OF HLA ANTIGEN CAMOUFLAGED BY DIVERSE mPEGs

Objective To study mechanism of various effects of HLA antigen camouflaged by differentmPEGs. Methods Effects of the modification of HLA antigen camouflaged by various mPEGs were detected by microlymphocytotoxicity test. The ability of modification was detected by SDS-PAGE. The mechanism of the modification was depicted by the three-dimensional structure of HLA antigen. Results The specific reaction between HLA-A2 antigen and its antibody were completely blocked by mPEG-BTC and mPEG-SPA. mPEG-MAL did not camouflage HLA antigen. The diversity of the modification of HLA antigen camouflaged by varied mPEGs was closely associated with the amides displayed on the surface of HLA antigen. Conclusion Only the amides which were exposed to the surface of HLA antigen can be camouflaged by mPEG. The amides on the surface of three-dimensional structure of HLA-A2 antigen determine the effect of the modification by various mPEGs.

The Effects of Triptolide on HLA Antigens Expression of Corneal Epithelial Cells Induced by Interferon-γ in Vitro

Objective:To observe the effects of immunosuppressants triptolide(TL)and cyclosporineA(CSA)on HLA antigens expression induced by interferon-γ（INF-γ）in vitro.Method:By using an indirect immunofluorescent method and analysing with ACAS-570,the abnormal HLA antigen expression of cultured corneal epithelial cells was induced by INF-γ，After incubation with one of the immunosuppressants(CSA,TL) for72hrs.the amount of HLA-ABCand HLA-DRantigens was measured.Result:There was no significant difference(P>0.05)between the group with CAS and the positive control group without CAS.In contrast to CSA,TL dramatically inhibited INF-γinduced expression of HLA antigens of corneal epithelial cells(P<0.001),compared with the control group withoutTL.Conclusion:TL had direct inhibition on the expression of HLA-ABCand HLA-DRantige ns induced by INF-γin vitro,while CSAhad no obvious inhibition,Eye Science2000;16:34-37.

Recurrence and influencing factors of hepatitis B surface antigen seroclearance induced by peginterferon alpha-based regimens

BACKGROUND The long-term stability of hepatitis B surface antigen(HBsAg)seroclearance following peginterferon alpha(peg-IFN-α)-based therapy has not been extensively studied,leaving the full potential and limitations of this strategy unclear.AIM To assess HBsAg recurrence after seroclearance achieved by peg-IFN-αregimens.METHODS This prospective,multicenter,observational study was conducted from November 2015 to June 2021 at three Chinese hospitals:The Second Affiliated Hospital of Xi’an Jiaotong University,Ankang Central Hospital,and The Affiliated Hospital of Yan’an University.Participants who achieved HBsAg seroclearance following peg-IFN-α-based treatments were monitored every 4-12 weeks post-treatment for hepatitis B virus(HBV)markers,HBV DNA,and liver function.The primary outcome was HBV recurrence,defined as the reemergence of HBsAg,HBV DNA,or both,at least twice within 4-8 weeks of follow-up.RESULTS In total,121 patients who achieved HBsAg seroclearance were enrolled.After a median follow-up of 84.0(48.0,132.0)weeks,four subjects were lost to follow-up.HBsAg recurrence was detected in 16 patients.The cumulative HBsAg recurrence rate in the intention-to-treat population was 15.2%.Multivariate logistic regression analysis demonstrated that consolidation time<12 weeks[odds ratio(OR)=28.044,95%CI:4.525-173.791]and hepatitis B surface antibody disappearance during follow-up(OR=46.445,95%CI:2.571-838.957)were strong predictors of HBsAg recurrence.HBV DNA positivity and decompensation of liver cirrhosis and hepatocellular carcinoma were not observed.CONCLUSION HBsAg seroclearance following peg-IFN-αtreatment was durable over 84 weeks of follow-up with a cumulative recurrence rate of 15.2%.

Prostate cancer with elevated free prostate-specific antigen density:A case report

BACKGROUND Prostate cancer is the second most common cancer among men worldwide,and prostate-specific antigen(PSA)is often used in clinical practice to screen for prostate cancer.Normal total PSA(tPSA)level initially excludes prostate cancer.Here,we report a case of prostate cancer with elevated free PSA density(fPSAD).CASE SUMMARY A patient diagnosed with benign prostatic hyperplasia underwent prostatectomy,and the postoperative pathological results showed acinar adenocarcinoma of the prostate.The patient is currently undergoing endocrine chemotherapy.CONCLUSION We provide a clinical reference for diagnosis and treatment of patients with normal tPSA but elevated fPSAD.

Hepatitis B surface antigen-negative but hepatitis B envelope antigen-positive false occult hepatitis B virus infection:A case report

BACKGROUND Occult hepatitis B infection(OBI)is characterized by the detection of hepatitis B virus(HBV)DNA in serum(usually HBV DNA<200 IU/mL)or the liver but negativity for hepatitis B surface antigen(HBsAg).The diagnosis of OBI relies on the sensitivity of assays used in the detection of HBV DNA and HBsAg.HBsAg assays with inadequate sensitivity or inability to detect HBV S variants may lead to misdiagnosis of OBI in people with overt HBV infection.CASE SUMMARY We report a HBsAg-negative but hepatitis B envelope antigen-positive patient who had a significant HBV DNA level.The patient was initially diagnosed as having OBI.However,sequence analysis revealed a unique insertion of amino acid residues at positions 120-124 in the S protein,which affects the formation of a disulfide bond that is associated with the formation of a loop.It is well known that there is an overlap between the S protein and Pol protein.We found that this new insertion site occurred in polymerase/reverse transcriptase domain,indi-cating that this insertion might be involved in HBV pathogenicity.The patient was finally diagnosed with a false OBI.CONCLUSION An insertion of amino acid residues at positions 120-124 of the S protein affects the formation of immunodominant epitopes and results in negative HBsAg levels.

RFLP OF HLA CLASS I GENES IN CHINESE POPULATION AND ITS CORRELATION WITH SEROLOGICALLY DEFINED ANTIGEN SPECIFICITIES

The restriction fragnent length polymorphisms （RFLPs） of HLA class I genes in 104 unrelated healthy Chinese individuals were analyzed with Southern blot assay. The DNAs from peripheral blood leucocytes were digested with EcoRI, EcoRV and XbaI respectively, and hybridized with 32P-labeled HLA class I probe （ 1.4Kb, B7 cDNA ）. The results showed that 3 EcoRI fragments （13.7, 8.1 and 5.2 Kb ）, 3 EcoR V fragments （11.3, 7.8 and 4.1 Kb） and 7 Xbal fragmnents （21.9, 19.2, 16.3, 6.0, 3.8, 1.8 and 1.5 Kb） were polymorphic. Ten of the fragments were found to be correlated significantly with the serologically de fined antigen specificities. The significance of this kind of correlation is discussed.

The Effects of Triptolide on HLA Antigens Eapression of Corneal Epithelial Cells Induced by Interferon－γ in Vitro

Objective:To observe the effects of immunosuppressants triptolide(TL) and cyclosporine A(CSA) on HLA antigens expression induced by interferon-γ(INF-γ)in vitro.Method:By using an indirect immunofluorescent method and analyzing with ACAS-570,the abnormal HLA antigen expression of cultured corneal epithelial cells was induced by INF-γ.After incubation with one of the immunosuppressants(CSA,TL) for 72 hrs,the amount of HLA-A BC and HLA-DR antigens was measured.Result:There was no significant difference(P>0.05) between the group with CSA and the positive control group without CSA.In contrast to CSA, TL dramatically inhibited IFN-γ induced expression of HLA antigens of corneal epithelial cells (P<0.001),compared with the control group without TL.Conclusion:TL had direct inhibition on the expression of HLA-ABC and HLA-DR antigens induced by INF-γ in vitro,while CSA had no obvious inhibition.Eye Science 2000;16:34-37.

Total IgA and IgA reactivity to antigen I/II epitopes in HLA-DRB1*04 positive subjects

Bacterial adherence to the acquired dental pellicle, important in dental caries (caries), is mediated by receptor-adhesins such as salivary agglutinin binding to Streptococcus mutans antigen I/II (I/II). Ten selected I/II epitopes were chosen to determine their reactivity to human salivary IgA. Previous studies suggested that a specific HLA biomarker group (HLA-DRB1*04) may have differential influence of immune responses to I/II. However, it was not known whether secretory IgA (SIgA) responses to the selected epitopes from HLA-DRB1*04 positive subjects were different compared to controls, or across other caries-related factors such as total IgA (TIgA). Thirty-two total subjects were matched according to HLA type, gender, ethnicity and age. HLA genotyping, oral bacterial, immunoglobulin and antibody analyses were performed. A large observed difference emerged with regard to the natural immune reservoir of TIgA in HLA-DRB1*04 positive subjects, specifically, a 27.6% reduction compared to controls. In contrast to all other epitopes studied, HLA-DRB1*04 positive subjects also exhibited reduced reactivity to I/II epitope 834-853. HLA-DRB1*04 positive subjects exhibited lower specific SIgA activity/TIgA to 834-853 and also a lower specific reactivity to 834-853/whole cell S. mutans UA159. Furthermore, HLA-DRB1*04 positive subjects exhibited lower responses to I/II in its entirety. The large observed difference in TIgA and the 834-853 reactivity pattern across multiple measures suggest potentially important connections pertaining to the link between HLA-DRB1*04 and caries.