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.

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.

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.

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.

Anti-human leukocyte antigens and anti-major histocompatibility complex class I-related chain A antibody expression in kidney transplantation during a four-year follow-up

Background Humoral immunity is an important factor for long-term survival of renal allograft. Here we performed a four-year follow-up to explore the clinical significance of monitoring anti-human leukocyte antigens （HLA） and anti-major histocompatibility complex class I-related chain A （MICA） antibody expression after kidney transplantation. Methods We obtained serial serum samples from 84 kidney transplant patients over a four-year period. All patients were followed up at least 6 months after transplantation and had at least two follow-up points. Anti-HLA and anti-MICA antibody titres and serum creatinine （SCr） levels were evaluated at each follow-up. Patients were divided into 4 groups： HLA（＋） MICA（-）, HLA（-）MICA（＋）, HLA（＋）MICA（＋） and HLA（-）MICA（-）. The impact of post-transplant antibody level on kidney allograft function was evaluated. Results Antibodies were detected in 38.1% （32/84） of the renal allograft recipients. HLA, MICA and HLA＋MICA expression was observed in 18.89%, 14.44% and 5.93% of the recipients respectively. The most frequent anti-HLA and anti-MICA specific antibodies identified were All, A24, A29, A32, A33, A80; B7, B13, B37; DR17, DR12, DR18, DR52, DR53, DR1, DR4, DR9, DR51; DQ7, DQ4, DQ8, DQ2, DQ9, DQ5, DQ6 and MICA02, MICA18, MICA19, MICA07, MICA27. As the time after transplantation elapsed, more recipients developed de novo antibody expression. Total 11.91% （10/84） of the recipients had de novo antibody expression during the follow up. The average level of SCr and the percentage of recipients with abnormal allograft function were significantly higher in recipients with anti-HLA and/or anti- MICA antibody expression than those without. The appearance of anti-HLA and anti-MICA antibody expression always preceded the increase in SCr value. Conclusions Anti-HLA and anti-MICA antibody expression has predictive value for early and late allograft dysfunction. The presence of donor specific antibody is detrimental to graft function and graft survival.

Impact of preformed donor-specific antibodies against HLA class Ⅰ on kidney graft outcomes:Comparative analysis of exclusively anti-Cw vs anti-A and/or-B antibodies

AIM To analyze the clinical impact of preformed antiH LA-Cw vs antiH LA-A and/or-B donor-specific antibodies(DSA) in kidney transplantation.METHODS Retrospective study, comparing 12 patients transplanted with DSA exclusively antiH LA-Cw with 23 patients with preformed DSA antiH LA-A and/or B.RESULTS One year after transplantation there were no differencesin terms of acute rejection between the two groups(3 and 6 cases, respectively in the DSA-Cw and the DSA-A-B groups; P = 1). At one year, eG FR was not significantly different between groups(median 59 mL /min in DSA-Cw group, compared to median 51 mL /min in DSA-A-B group, P = 0.192). Moreover, kidney graft survival was similar between groups at 5-years(100% in DSA-Cw group vs 91% in DSA-A-B group, P = 0.528). The sole independent predictor of antibody mediated rejection(AMR) incidence was DSA strength(HR = 1.07 per 1000 increase in MFI, P = 0.034). AMR was associated with shortened graft survival at 5-years, with 75% and 100% grafts surviving in patients with or without AMR, respectively(Log-rank P = 0.005).CONCLUSION Our data indicate that DSA-Cw are associated with an identical risk of AMR and impact on graft function in comparison with "classical" class I DSA.

Donor-specific antibodies,glomerulitis,and human leukocyte antigen B eplet mismatch are risk factors for peritubular capillary C4d deposition in renal allografts

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

Pathogenetic mechanisms of antiphospholipid antibody production in antiphospholipid syndrome

Antiphospholiipid syndrome(APS) is an autoimmune disease characterized by the pathological action of antiphospholipid antibodies(a PL),that leads to recurrent pregnancy loss and thrombosis.Despite limited evidence,it is clear that there are both inherited and acquired components of the ontogeny of these antibodies.Animal genetic studies and human familial and population studies highlight the influence of genetic factors in APS,particularly human leukocyte antigen associations.Similarly,both animal and human studies have reported the importance of acquired factors in APS development and infectious agents in particular have a great impact on a PL production.Bacterial and viral agents have been implicated in the induction of autoimmune responses by various mechanisms including molecular mimicry,cryptic autoantigens exposure and apoptosis.In this review we highlight the latest updates with regards to inherited and acquired factors leading to the manufacturing of pathogenic antibodies and APS.

为提升IPTR患者血小板输注后CCI值建立分级规避HLA抗体对应抗原方法及HLAMatchmaker的应用研究

目的:建立分级规避HLA抗体MFI阈值对应抗原方法,联合应用HLAMatchmaker表位计算法,选择供患者表位最小错配评分值,评估两种方法为免疫性血小板输注无效(Immune platelet transfusion refractoriness,IPTR)患者选择HLA相容性血小板供者,在提升血小板输注后校正增加值(CCI)的应用价值。方法:采用SPRCA法完成51例IPTR患者的7807次血小板交叉配型实验,判断其免疫反应阴/阳性结果。采用Luminex单抗原流式微珠法检测患者的HLA-I类抗体,获得不同特异性抗体对应HLA-I类抗原MFI值,并将其分组及分级,强阳性组(MFI>4000,1级)、中阳性组(1000中阳性组>弱阳性组)。强阳性和中阳性组与阴性对照组之间的SPRCA实验免疫反应阳性结果检出数存在统计学差异(P<0.001),弱阳性位组和阴性对照组之间的SPRCA实验免疫反应阳性结果检出数无统计学差异(P>0.05)。设置强阳性组为相应特异性HLA位点对应抗原1级规避阈值,中阳性组为2级规避阈值,弱阳性组为3级规避阈值,在供者血小板紧缺情况下,可以不需要规避弱阳性组。规避1和2级HLA-I类抗体对应供者抗原及选择HLAMatchmaker表位错配评分数≤7血小板供者策略,24 h内CCI值均>4.5×109/L,均可获得临床血小板输注有效。结论:在为IPTR患者选择HLA-I类相容性供者时,分级规避HLA-I类抗体对应供者抗原,综合选择供受者HLAMatchmaker表位错配评分数≤7,经血小板交叉配型实验确认为阴性结果的供者选择策略,对提升IPTR患者血小板计数具有一定实际应用价值。

先兆流产患者保胎结局影响因素及与血清sHLA-G、ACA水平关系

目的:探索先兆流产患者保胎结局的影响因素,并分析其与血清可溶性人白细胞抗原-G(sHLA-G)、抗心磷脂抗体(ACA)的关系。方法:回顾性收集2021年6月-2023年6月本院收治的80例先兆流产患者临床资料,根据保胎结局分为保胎失败组与保胎成功组,对比两组一般资料,酶联免疫吸附法检测两组sHLA-G、ACA水平,经单因素及Pearson相关性分析法探讨先兆流产保胎结局的影响因素及与血清sHLA-G、ACA水平关系。结果:两组年龄、既往流产史、合并阴道炎、生殖道感染、妊娠期糖尿病、接触有毒化学物质等方面有差异;保胎失败组sHLA-G(7.43±1.20 U/ml)水平低于保胎成功组(50.14±4.56 U/ml),ACA阳性率(74.1%)高于保胎成功组(20.8%)(均P<0.05)。logistic回归分析,高龄、既往流产史、合并阴道炎、生殖道感染、妊娠期糖尿病、接触有毒化学物质、sHLA-G水平低、ACA阳性率高均是影响先兆流产患者保胎结局的重要因素;Pearson相关性分析,年龄、既往流产史、合并阴道炎、生殖道感染、妊娠期糖尿病、接触有毒化学物质与血清sHLA-G水平呈负相关,与ACA阳性率呈正相关(均P<0.05)。结论:先兆流产患者保胎结局可能与高龄、既往流产史、合并阴道炎、生殖道感染、妊娠期糖尿病、接触有毒化学物质、sHLA-G水平及ACA阳性率有关,临床可针对上述因素给予密切关注,并通过监测sHLA-G水平及ACA阳性率的变化来指导临床早期干预,以确保母婴安全。

HLA配型、群体反应性抗体与肾移植术后早期急性排斥反应的关系

目的 :研究人类白细胞抗原 (HLA)配型、群体反应性抗体 (PRA)与肾移植术后早期急性排斥反应的关系。方法 :应用单克隆抗体板、微量序列特异性引物、混合抗原板进行供受者HLA I类抗原分型、HLA II类基因分型、PRA检测。结果 :PRA为低、中、高三组受者的早期急性排斥反应发生率分别为 16 %、2 7%、6 6 6 %。HLA位点错配数 (MM)为 0 1组明显比 5 6组早期急性排斥反应率低。结论 :良好的组织配型、低水平的PRA ,可降低早期急性排斥反应的发生。

小儿血型不合活体肝移植的临床疗效分析

目的探讨小儿血型不合活体肝移植的临床疗效。方法回顾性分析242例小儿活体肝移植受者的临床资料。根据供、受者血型相合情况分为A组(供、受者血型相同,165例)、B组(供、受者血型相合,42例)、C组(供、受者血型不合,35例)。观察并比较3组受者的术后并发症发生情况、术后供体特异性抗体(DSA)产生情况;分析C组供、受者血型分布及红细胞抗体产生情况;比较3组受者肝移植术后的生存情况。结果3组受者并发症发生率比较,差异均无统计学意义(均为P>0.05)。肝移植术后DSA以人类白细胞抗原(HLA)Ⅱ类抗体为主,多为抗HLA-DR和抗HLA-DQ。C组肝移植受者术后红细胞抗体多为IgM,所有抗体滴度均为≤12。3组受者术后生存率差异均无统计学意义(均为P>0.05)。结论小儿血型不合活体肝移植是一种安全有效的治疗方式,可有效扩大肝移植供者来源,挽救患儿生命。

肾移植受者抗HLA抗体监测的临床意义

目的探讨动态监测肾移植受者抗HLA抗体的临床意义。方法采用酶联免疫吸附试验(ELISA)对1517例肾移植受者进行手术前、后血清群体反应性抗体(panel reactive antibody,PRA)强度动态监测,对PRA阳性受体进一步行抗HLA抗体分型并进行随访,观察PRA水平对移植物长期存活和移植肾功能的影响。结果1517例中,术前PRA阴性者1336例,阳性者181例。术前PRA阳性受者和阴性受者的移植物功能延迟恢复(DGF)发生率分别为34.8%、11.9%,两组比较差异有统计学意义(P<0.01)。术前PRA阳性受者的移植肾1、3、5、8年存活率分别为94%、85%、73%和63%,术前PRA阴性受者相应为96%、87%、72%和65%,两组比较差异均无统计学意义(P>0.05)。移植前及移植6个月后PRA均为阴性的265例受者中,血清肌酐水平异常者仅占19.6%,而术后PRA转为阳性的57例受者中,血清肌酐异常者高达61%,两者比较差异有统计学意义(P<0.01);移植前PRA阳性的53例受者中,有24例移植后PRA转为阴性,术后血清肌酐全部正常。结论术前筛查PRA可科学评估肾移植患者的体液致敏状态,为致敏患者选配合适供者;术后监测PRA可及时了解移植肾的免疫状态,有利于防治排斥反应。

血小板捐献者血型资料数据库的建设与应用展望

供受者血小板配合输注可有效解决免疫性血小板输注无效问题。由于受HLA和HPA基因系统多态性、人群中CD36抗原缺乏个体比例及临床应用需求时限性等因素的影响,需要提前建立有一定规模的血小板捐献者血型资料库,才可能在临床需要时及时提供配合性血小板。血小板捐献者血型资料库涉及HLA-A,-B基因型资料库、HPA基因型资料库和CD36抗原阴性资料库;国内部分血站已建立200—4 000(人)份捐献者血小板血型资料库。建库中献血者选择、HLA-C位点覆盖问题、HPA系统最适检测范围和检测方法选择仍有待标准化。血小板捐献者血型资料库具有良好的应用前景,但仍需要通过扩大血小板捐献者基因型资料库规模、缩短配合血小板制备发放流程所需时间和加强临床沟通等措施,来提升基因型配合血小板的临床应用。

双重膜滤过式血浆置换清除肾移植受者供体特异性抗体的临床观察

目的探讨双重膜滤过式血浆置换(DFPP)对高致敏肾移植受者的供体特异性抗体(DSA)的清除效果。方法 4例肾移植高致敏受者共进行了7例次DFPP治疗,采用Luminex技术监测DSA的变化,观察治疗效果、急性排斥反应发生情况及其不良反应。结果治疗后DSA的MFI[1 036(0~4 113)]较治疗前[6 446(2 999~12 905)]明显下降(Z=-2.503,P=0.012)。4例高致敏肾移植受者均未发生超急性排斥反应,仅有1例发生急性排斥反应且通过术后DFPP治疗及调整免疫抑制剂得到逆转。受者随访至今移植肾功能良好,未发生排斥反应。DFPP治疗引起白蛋白水平下降。结论 DFPP可以有效清除受者体内的DSA,可以安全、有效地预防高致敏人群肾移植术后急性排斥反应。

亲属肾移植患者术后肾功能与HLA配型和PRA相关性研究

目的研究活体亲属肾移植受者人类白细胞抗原(human leukocyte antigen,HLA)配合率、群体反应性抗体(panelreactive antibody,PRA)的产生和肾功能变化对移植肾存活的影响。方法将336例活体亲属肾移植患者分为5组:①父母给子女供肾组(118例)。②子女给父母供肾组(12例)。③兄弟姐妹间供肾组(107例)。④其他亲属供肾组(92例)。⑤夫妻间供肾组(7例)。进行HLA供受者配合率分析,并于肾移植术后1-4年追踪肾功能变化和PRA产生的情况。HLA分型检测采用美国One lanmbda公司提供的HLA-PCR-SSP分型试剂盒。PRA采用美国莱姆德公司和美国GTI公司提供的酶联免疫吸附试剂盒检测。结果第1组的118例肾移植供受者HLA-A、B、DR、DQ抗原单体型半相合,其中有22例抗原配合率高于单体型半相合。肾移植术后有36例患者出现肾功能下降,其中8例为PRA阳性。第2组的12例肾移植供受者HLA-A、B、DR、DQ抗原单体型半相合,其中有7例HLA抗原配合率高于单体型半相合。肾移植术后1例患者肾功能下降,且为再次肾移植患者。第3组的107例兄弟姐妹间HLA-A、B、DR、DQ配型完全相配合有18例,73例为单体型半相合或大于单体型半相合,其余为低于单体型半相合或不相合。肾移植术后中有13例患者肾功能下降,其中3例PRA阳性。第4组的92例其他亲属移植的供受者间HLA-A、B、DR、DQ等于或大于单体型半相合的有24例,完全不相合的有9例,虽然HLA抗原配合率大于4个抗原,但并不是单体型半相合抗原的有8例,等于或小于3个抗原配合的有51例。肾移植术后有11例患者肾功能下降,其中6例患者PRA阳性。第5组的7例夫妻间肾移植患者,HLA配合率均≤3个抗原。肾移植术后有2例患者肾功能下降,且为PRA阳性。结论父母、子女及兄弟姊妹等直系亲属肾移植供受者中HLA配合率高于其他亲属间移植供受者,但兄弟姊妹间HLA配型完全相同的则较低。HLA配型与近期移植肾存活无关,而与供者的年龄有关。良好的HLA配型与肾移植术后PRA生成的概率低有关。

安徽汉族免疫性不育症与HLA-DQA1基因的相关性研究

目的:探讨抗精子抗体阳性的免疫性不育症患者与HLA-DQA1基因的相关性。方法:采用聚合酶链反应-序列特异性引物(PCR-SSP)技术,对50例抗精子抗体阳性的免疫性不育症患者和60例正常健康者的HLA-DQA1基因进行分型研究。结果:2组均未发现DQA1I0104和DQA1I0302两种基因型。免疫性不育症组DQA1I0401等位基因频率明显高于正常对照组(RR=5.5,P<0.05)。结论:DQA1I0401可能是安徽汉族免疫性不育症的易感基因。

抗环瓜氨酸肽抗体检测与类风湿性关节炎早期诊断

目的 :探讨抗环瓜氨酸肽抗体 (抗CCP抗体 )对类风湿性关节炎 (RA)早期诊断的意义。方法 :采用酶联免疫吸附法 (ELISA) ,了解抗CCP抗体在诊断RA中的敏感性和特异性 ;以及抗CCP抗体在类风湿性关节炎、系统性红斑狼疮、强直性脊柱炎中阳性率的关系。结果 :5 6例RA患者 (RF >30 .0IU/ML) ,抗CCP抗体的阳性率为 5 0 .0 % ;6 8例RA患者 (RF2 0 .0～ 30 .0IU/ML) ,抗CCP抗体阳性率为 4 4 .1%。抗CCP抗体对RA的敏感性和特异性分别为 5 0 .0 %和 95 .8%。 30例系统性红斑狼疮 (SLE)且ANA阳性患者 ,抗CCP抗体的阳性率为 10 .0 % ,2 5例强直性脊柱炎 (AS)且HLA -B2 7阳性患者 ,抗CCP抗体的阳性率为 4 .0 %。结论 :抗CCP抗体对RA具有很好的敏感性和特异性 ,且在RF2 0 .0～ 30 .0IU/ML患者中抗CCP抗体的阳性率为4 4 .1% ,结合临床症状能早期诊断RA ,故抗CCP抗体可作为RA血清学早期诊断指标。

恶性血液病患者血小板HLA-Ⅰ抗体产生与HLA-A、B基因之间的相关性分析

目的:探讨恶性血液病患者血小板HLA-Ⅰ抗体产生与HLA-A、B基因之间的相关性和血小板HLA-Ⅰ抗体产生的易感基因。方法:选择本院血液科需多次输注血小板治疗的恶性血液病患者作为研究对象,采用ELISA法对患者进行HLA-I类抗体检测,根据抗体检测结果将患者分为抗体阳性组和抗体阴性组,提取患者基因组DNA后进行HLA-A、B基因测序,比较两组之间HLA-A、B基因频率的差异。结果:患者HLA-I类抗体阳性率为22.95%。对100例研究对象进行HLA-A、B基因测序,共获得HLA-A等位基因13个,HLA-B等位基因14个,其中HLA-A*24、HLA-A*30、HLA-B*13等位基因频率在抗体阳性组与阴性组之间存在统计学差异(P<0.05)。抗体阳性组HLA-A*30、HLA-B*13等位基因频率低于抗体阴性组(RR=0.107,0.387),HLA-A*24等位基因频率高于抗体阴性组(RR=1.412)。HLA-A*24、HLA-A*30、HLA-B*13基因高分辨基因分型显示等位基因HLA-A*24∶02、HLA-A*30∶01、HLA-B*13∶02在抗体阳性组和阴性组间存在差异,RR值分别为1.412、0.107、0.125,95%CI分别为0.961-2.075、0.016-0.721、0.300-0.515。结论:恶性血液病患者HLA-A*24∶02等位基因可能是血小板HLA-Ⅰ抗体产生的易感基因,而HLA-A*30∶01、HLA-B*13∶02等位基因可能是保护基因。

滋肾育胎丸对抗心磷脂抗体阳性复发性流产患者可溶性人白细胞抗原G、抗子宫内膜抗体水平的影响

目的:探讨滋肾育胎丸对抗心磷脂抗体(ACA)阳性复发性流产患者可溶性人白细胞抗原G(sHLA-G)、抗子宫内膜抗体(Em Ab)水平的影响。方法:选取2017年8月至2020年10月河北省人民医院收治的ACA阳性复发性流产患者102例,按照分层抽样法分为对照组和滋肾育胎丸组,每组51例。对照组患者采用常规治疗,滋肾育胎丸组患者采用滋肾育胎丸治疗。采用酶联免疫吸附试验法检测两组患者肿瘤坏死因子相关蛋白12(CTRP12)、sHLA-G、抗缪勒管激素(AMH)、前列腺素E2(PGE2)、环氧化酶2(COX-2)、β人绒毛膜促性腺激素(β-HCG)水平和抗精子抗体(As Ab)、EmAb及ACA表达水平,采用全自动生化分析仪测定孕酮(P)、黄体生成激素(LH)及睾酮(T)水平,观察两组患者的临床疗效。结果:与对照组相比,滋肾育胎丸组患者治疗后的CTRP12、sHLA-G水平明显升高,AMH水平明显降低,差异均有统计学意义(P<0.05)。与对照组相比,滋肾育胎丸组患者治疗后的P水平明显升高,T、LH水平明显降低,差异均有统计学意义(P<0.05)。与对照组相比,滋肾育胎丸组患者治疗后的PGE2、COX-2及β-HCG水平明显升高,差异均有统计学意义(P<0.05)。与对照组相比,滋肾育胎丸组患者治疗后的EmAb、ACA及As Ab阳性率明显降低,差异均有统计学意义(P<0.05)。滋肾育胎丸组患者的治疗总有效率为94.12%(48/51),与对照组的78.43%(40/51)相比,差异有统计学意义(P<0.05)。结论:滋肾育胎丸治疗ACA阳性复发性流产患者,可有效提高患者s HLAG水平,降低EmAb阳性率,改善患者性激素水平,效果显著。