Platelet-Associated IgG in Children - Values and Evaluation of PAIgG in Various Thrombocytopenias -

Platelet-associated IgG (PAIgG) levels were measured in 60 children with ITP (46-chronic, 14-acute) using Fab-anti Fab radioimmunoassay method described by McMillan et al. In some patients platelet binding IgG in serum (PBIgG) was also determined at the same time. Patients with ITP had significantly greater PAIgG levels than 30 normal subjects and 13 non-immune thrombocytopenic controls. Elevated PAIgG values did not correlate with parameters of platelet size (mean platelet volume; MPV and percentage of large platelet; PLP) and so these data indicated that high levels of PAIgG in ITP were not due to nonspecific adhesion of serum IgG to megathrombocytes usually increased in this disorder, but due to specific immunological reaction. PBIgG IgG values were also elevated in patients with pretreated chronic ITP, but high levels remained even after successful splenectomy. Furthermore, serial determination of PAIgG values were obtained in some patients with chronic ITP who underwent splenectomy and with acute ITP who achieved spontaneous remission. PAIgG returned to normal levels when thrombocytopenia disappeared. PAIgG seems to be the most reproducible indicator which reflects transition of the clinical picture in this disorder.     

儿童免疫相关性疾病的常规免疫学指标研究

目的比较特发性血小板减少性紫癜(ITP)、过敏性紫癜(HSP)及皮肤黏膜淋巴结综合征(KD)的常规免疫学指标变化及静脉注射免疫球蛋白(IVIG)的应用。方法用流式细胞仪测T细胞亚群,免疫比浊法测免疫球蛋白(Ig)及补体。常规加IVIG治疗。结果ITP患儿CD3 CD4 T细胞降低并IgG升高;HSP患儿IgA升高伴CD3 T细胞增高。KD患儿CD3 CD8 T细胞降低。IVIG可明显改善3种疾病临床症状,尤其有助KD患儿冠状动脉损害发生率减少。结论T细胞亚群、lg 应作为ITP、HSP及KD的常规检查项目。早期应用IVIG对改善预后及缩短病程有重要意义。     

Immunological study of childhood acute ITP at onset.

We attempted to search for any specific change in the immune system during the onset of childhood acute immune thrombocytopenic purpura (ITP) in order to clarify the pathophysiology of acute ITP by examining the lymphocyte subset, lymphocyte blastogenic response, serum complements, and immunoglobulins in 18 patients with childhood acute ITP and 18 controls (control values after normalization). At the onset of acute ITP, the levels of serum complements and IgG and IgA were found to be within the normal ranges, but serum IgM levels were greater than 200 mg/dL in six cases among 18 patients. Lymphocyte blastogenic response to phytohemagglutinin (PHA) and concanavalin A (ConA) was depressed in patients relative to controls (PHA: p less than 0.05, ConA: p less than 0.01). Lymphocyte blastogenic response to pokewood mitogen (PWM) was lower than that of the control, but no statistical significance was observed. There was no difference in the proportion of CD3, CD4, CD8, SmIg, SmIgG, SmIgM, SmIgA, and SmIgD. The CD4/CD8 ratio was not different from that of controls. The proportion of CD38 was higher than that of control, but no significant difference from the control was observed. Increase in the serum IgM level and proportion of CD38 and depressed lymphocyte blastogenic response may be the influence of preceding infection. It has been reported that the CD4/CD8 ratio is depressed due to an increase in the CD8 level in acute and convalescent phases of viral infection. However, the proportion of CD8 was not necessarily increased in our patient in whom preceding infection was obvious. The immunological status of the patients with acute ITP at onset differs from that after infection.     

Clinical impact of altered immunoglobulin levels in Henoch–Schönlein purpura

Background:  The aim of the present study was the identification of immunological features, present at the time of diagnosis, that would predict the severity of Henoch–Schönlein purpura and its outcome.
Methods:  A cohort study was carried out in a tertiary pediatric hospital of 69 children with Henoch–Schönlein purpura, in whom serum complement components C3, C4 and IgA, IgM, IgG were repeatedly determined.
Results:  During the acute phase of the disease in 54/69 patients (78.3%) immunological imbalances were observed. In 24/54 cases (44.4%) certain complications involving the kidneys and the gastrointestinal tract were noted as opposed to in 3/15 children (20%) without immunologic abnormalities. In 50/69 children (72.5%), elevated serum IgA was detected and 16 of them (32%) developed renal involvement while only 1/19 children (5.3%) with normal IgA concentration had renal involvement. Considering separately the group of 9/69 children (13%) with increased IgM and those with normal IgM levels (53/69; 76.8%), irrespective of IgA and IgG concentration, we found a comparable percentage of children who had both renal and intestinal involvement without, however, developing severe complications, which were exclusively seen in patients with increased IgA (5/7 children) and reduced IgM levels. Serum C3 fraction was elevated in 26 children (37.7%) and in 73% of cases it was associated with increased serum IgA values.
Conclusion:  Renal involvement was seen in 32% of children with increased IgA values. Most importantly, elevated IgA concentration along with reduced IgM levels was associated with higher prevalence of severe complications.     

Platelet proteins as autoantibody targets in idiopathic thrombocytopenic purpura

Idiopathic thrombocytopenic purpura (ITP), caused by autoantibodies directed against certain platelet antigens, is the most common entity of the immune thrombocytopenias. ITP is an acquired disorder and can affect both children and adults. However, the clinical syndromes of ITP are distinct between children and adults. Childhood (acute) ITP characteristically is acute in onset, occurs within 1-2 weeks of an infection, usually of viral origin, resolves spontaneously within 6 months. Adult (chronic) ITP has an insidious onset and rarely resolves spontaneously. Over the last decade considerable new information has accumulated as to the pathophysiological mechanisms of immune thrombocytopenias. In addition, most of the knowledge on this disorder has been obtained from studies of adult patients with chronic ITP. The present work gives an updated overview of the platelet autoantigens and the molecular immunological reactions in ITP.     

ITP患儿外周血T细胞T-bet/GATA-3基因的检测及意义

目的研究急慢性ITP患儿Th1、Th2类细胞因子和转录因子T-bet和GATA-3的相关性,探讨其在ITP发病机制。方法选择30例ITP患儿,运用T细胞分离富聚柱得纯化的T细胞,分别用ELISA法和RT-PCR技术检测ITP患儿血清中的IFN-γ、IL-4水平和外周血T细胞转录因子T-bet和GATA-3的表达状态,设30例健康儿童为对照组。结果慢性ITP患儿血清中IL-4水平较正常人降低,IFN-γ的水平升高,GATA-3 mRNA表达水平下降,T-be tmRNA表达水平升高;而急性ITP患儿外周血中IL-4水平较正常人升高,血清中IFN-γ水平及T-bet/GATA-3比值无显著性差异。结论慢性ITP患儿外周血Th1/Th2比例失衡,T-bet/GATA-3的表达失调,可能引起慢性ITP的免疫紊乱:而急性ITP患儿的发病机制可能与T-bet/GATA-3的表达无关。     

狼疮抗凝集物检测在系统性红斑狼疮、原发性血小板减少症中的临床应用

目的通过对系统性红斑性狼疮(SLE)310例和原发性血小板减少症(ITP)249例狼疮抗凝集物(LAC)和抗心磷脂抗体亚型(aCL-IgG、IgM、IgA)的测定,研究其与SLE临床表现的关系及LAC在ITP转归中的意义。方法采用脑磷脂-白陶土法(KCCT)及校正试验检测患儿血浆LAC;采用酶联免疫吸附试验(ELISA)测定息儿血清aCL-IgG,IgM、IgA。结果SLE 组中,66.1%显示体内存在高含量LAC,其中45.9%并狼疮肾炎;46.8?L抗体升高,其中90.2%为IgG和(或)IgM,分别有46.9%和11.7%是狼疮并中枢神经系统及血液系统病变。ITP组105例LAC阳性患儿中36.2%经抗核抗体(ANA)检测确诊为SLE,7.6%在2个月-2.4年后发展为SLE。结论LAC和aCL抗体亚型的水平与SLE临床表现密切相关,LAC在狼疮并肾脏病变中为优势病理性自身抗体;aCL抗体亚型的水平则与狼疮性血栓性血管炎性病变有相关关系。对单纯患有ITP的患儿应进行LAC动态观察,可及早确定疾病的转归。     

D-penicillamine-induced IgA deficiency in the therapy of Wilson's disease

Serum IgA deficiency was first noted in a 10 year old boy 8 months after the onset of D-penicillamine therapy. Special immunological examinations revealed a deficiency of the secretory component of IgA while cellular functions of T- and B-lymphocytes were normal. The patient showed discrete clinical signs compatible with IgA deficiency. Regular control of patients with Morbus Wilson and D-penicillamine treatment should include measurement of serum immunoglobulin levels.     

甲状腺球蛋白抗体和甲状腺过氧化物酶抗体在儿童免疫性血小板减少症中的表达及临床意义北大核心CSCD

目的观察免疫性血小板减少症(immune thrombocytopenia,ITP)患儿血清甲状腺球蛋白抗体(thyroglobulin antibody,TGAb)、甲状腺过氧化物酶抗体(thyroid peroxidaseantibody,TPOAb)的表达情况。方法前瞻性选择2019年10月至2021年10月收治的120例ITP患儿作为ITP组,另选择60例非ITP患儿作为非ITP组。根据ITP临床分型将ITP组患儿分为新诊断ITP(n=53)、持续性ITP(n=42)与慢性ITP(n=25)。比较ITP组与非ITP组、不同ITP临床分型患儿临床资料,分析ITP患儿血清TGAb、TPOAb表达情况,及其与ITP临床分型的关系。结果ITP组CD_(3)^(+)、CD_(4)^(+)比例及血小板计数低于非ITP组,CD_(8)^(+)比例及TGAb、TPOAb水平高于非ITP组(P<0.05);慢性ITP患儿CD_(3)^(+)、CD_(4)^(+)比例及血小板计数低于新诊断ITP、持续性ITP患儿,CD_(8)^(+)比例及TGAb、TPOAb高于新诊断ITP、持续性ITP患儿(P<0.05)。经logistic回归分析结果显示,CD_(3)^(+)、CD_(4)^(+)、CD_(8)^(+)、TGAb、TPOAb表达水平变化与慢性ITP的发生密切相关(P<0.05);绘制决策曲线,结果显示,在高风险阈值0.0~1.0范围内TGAb联合TPOAb评估儿童ITP临床分型的净收益率始终>0,有临床意义。结论TGAb、TPOAb在ITP患儿中呈异常表达,且与患儿ITP临床分型有关。     

IgA deficiency in children: A clinical study with special reference to intestinal findings

Clinical, immunological, and intestinal studies on 26 children with IgA deficiency in the age range 2 to 16 years are reported. 9 of these children were suffering from autoimmune disease, namely thyroiditis (5), thyrotoxicosis (1), rheumatoid arthritis (2), and probable Sjögren''s syndrome (1). The last-mentioned patient had defective cellular immunity. Altogether 11 patients were subject to recurrent respiratory tract infections. The symptomatology of the remaining patients was variable. In a boy with growth retardation, a chromosome anomaly was found, and endocrinological studies indicated total absence of growth hormone.In 21 patients IgA was undetectable, while 5 had trace amounts of IgA in their sera. IgG was raised in 11 patients, and one patient had low serum IgG. IgM levels were mostly normal. Precipitating antibodies to cow''s milk proteins were present in all but one serum.Small intestinal biopsy was performed on all patients. In 3 cases total villous atrophy was detected and these probably had coeliac disease, though malabsorption symptoms were not always evident. Disaccharidase assay of biopsy specimens revealed 2 cases of isolated lactase deficiency among 8 tested.Results show that the increased incidence of autoimmune disease reported in IgA deficiency in adults also holds true in children; i.e. that there is a raised incidence of coeliac disease with or without symptoms in IgA deficiency.     

静注免疫球蛋白及地塞米松对特发性血小板减少性紫癜患儿免疫功能的影响

探讨大剂量地塞米松 (DEX)及静注免疫球蛋白 (IVIG)治疗 ,对特发性血小板减少性紫癜 (ITP)患儿外周血 T淋巴细胞亚群及免疫球蛋白的影响 ,在以DEX、IVIG治疗 ITP患儿 ,治疗前后各抽血一次 ;以 APAAP法测定 T淋巴细胞亚群 ,以单向琼脂免疫扩散法测定免疫球蛋白。结果表明 1.ITP患儿外周血 CD4+ 降低 ,CD8+增高 CD4+ /CD8+ ,显著降低。单纯 DEX组治疗后 ,CD4+、CD8+均显著降低 ,CD4+ /CD8+升高 ,Ig A、Ig G、Ig M降低 ;单纯 IVIG组治疗后 ,CD8+显著降低 ,CD4+ /CD8+升高 ,Ig G显著升高。2 .单纯 DEX组治疗后 ITP患儿外周血白细胞计数显著高于治疗前 ,单纯 IVIG组与 IVIG加 DEX组治疗前后无显著差异。治疗过程中院内交叉感染率单纯 DEX组为 31.43% ,单纯 IVIG治疗组为 2 5 % ,IVIG加 DEX组为2 8.5 7%。因此 ,本文认为 ITP患儿外周血 T淋巴细胞亚群表达异常 ,IVIG及 DEX治疗均干扰了 ITP患儿机体的免疫状态     

急性特发性血小板减少性紫癜患儿免疫功能变化及其临床意义

目的检测特发性血小板减少性紫癜(ITP)患儿的免疫功能并探讨ITP的发病机制。方法抗血小板抗体(PAIgG)测定采用放射免疫法,IgA、IgG、IgM测定采用WL-快速免疫消浊比浊法,T淋巴细胞亚群测定采用APAAP法,血清IL-2、sIL-2R和IL-6测定采用ELISA法。结果 ITP患儿的IL-2、IL-6,IgA、IgM、CD8及IL-2R表达均明显升高(P<0.01),CD4+、CD4+/CD8+细胞均明显减少(P<0.01)。结论细胞免疫及体液免疫异常共同参与ITP致病机制,调节淋巴细胞亚群平衡有助于寻找ITP治疗的新途径。     

儿童特发性血小板减少性紫癜患儿Th2相关细胞因子IL-4、IL-10与血小板相关抗体的检测及意义研究

探讨Th2相关细胞因子IL 4、IL 1 0与血小板相关抗体PAIgG、PAIgM在儿童ITP的发病机理中的作用。方法是采用双抗体夹心酶联免疫吸附试验 [ELISA]技术检测 30例ITP患儿血浆中IL 4、IL 1 0水平 ,同时检测PAIgG、PAIgM的水平 ,研究IL 4、IL 1 0对PAIgG、PAIgM的调节作用。结果显示 :( 1 )急性期ITP患儿IL 4、PAIgG、PAIgM水平均高于对照组 (P <0 .0 5)。( 2 )慢性ITP病例半年后IL 4、PAIgG、PAIgM仍然高于对照组 (P <0 .0 5) ,IL 4与血小板相关抗体水平呈显著正相关。 ( 3)病程中IL 1 0与对照组无明显变化。结论 :ITP患儿IL 4表达增加 ,提示Th2相关细胞因子比例失调 ,使血小板相关抗体增高为重要的致病因素之一。     

Selective IgA deficiency with unusual features: Development of common variable immunodeficiency,Sjögren's syndrome,autoimmune hemolytic anemia and immune thrombocytopenic purpura

We report on a girl with selective IgA deficiency and persistently low complement component 4 (C4) levels compatible with heterozygous C4 deficiency. Deterioration of her serum immunoglobulin levels and transition to common variable immunodeficiency were observed within a 5 year follow-up. She also developed Sjögren's syndrome, autoimmune hemolytic anemia and immune thrombocytopenic purpura While these abnormalities have been described before in various combinations, to our knowledge, they have not been reported in a single individual.     

Immune dysfunction in the presence of residual splenic tissue.

Immunological function was examined in children who had undergone splenectomy, in 8 for trauma, and in 11 for haematologic/oncologic reasons. Particular emphasis was placed on the effects of residual splenic tissue on immune function. Children in the elective group had no evidence of splenosis but 6 of the 8 trauma patients showed residual splenic activity. A general trend indicated that immunological dysfunction was associated with the presence of residual splenic tissue. Three patients with significant post-traumatic splenosis showed low IgM levels, one also had a low IgG level and another a low IgA and impaired lymphocyte response to mitogens. The trauma patients with little or no splenic tissue had normal immune functions. Immunological abnormalities were found in 8 of the 11 haematologic/oncologic patients with no splenosis suggesting the abnormalities were possibly due to the primary disease. In contrast to the popular belief that splenosis confers protection against overwhelming sepsis, the present findings suggest that patients with residual splenic tissue are at a greater risk of infection because of a lower level of immune response.     

Directions for research in autoimmune thrombocytopenic purpura (ITP)

All attendees participated in a round-table discussion regarding directions for research in autoimmune thrombocytopenic purpura (ITP). Suggested areas for study were grouped into five main areas: (i) improved classification of ITP identifying subsets of patients with differing clinical syndromes and response to treatment, and those more likely to have serious bleeding manifestations; identification of patients with reduced thrombopoiesis was emphasized; (ii) studies aimed at elucidating the aetiology and pathophysiology of ITP, with emphasis on distinctions between acute and chronic ITP and between patients responsive or refractory to therapy; these studies focused on measures of humoral and cellular immune dysregulation; (iii) studies of platelet function in ITP, with the intent of defining these abnormalities and correlating them with the clinical manifestations of the disease; (iv) new approaches to treatment, particularly of refractory patients; and (v) a miscellaneous group, which included development of an ITP registry, evaluation of the "burden" of disease, investigation of mood changes in ITP, etc. The discussion was not intended to be all-inclusive, but focused on the content of other talks in this symposium. It is hoped that some of thesesuggestions will be further developed for investigation in multicentre co-operative studies to improve the diagnosis, understanding and treatment of ITP.     

Chronic, episodic thrombocytopenia. A case report with long-term observation

A male patient with chronic idiopathic thrombocytopenic purpura (ITP) did not fit into any of the known risk groups for chronic ITP. He was unique in that he manifested a cyclic increase of platelet counts each winter followed by a nadir in the summer, without having other hematologic abnormalities.     

特发性血小板减少性紫癜患儿血清和骨髓激活素A的变化及意义

目的探讨血清和骨髓激活素A在急性特发性血小板减少性紫癜(ITP)患儿的变化意义。方法收集91例ITP患儿治疗前后及20例相对正常儿童血清和骨髓上清,采用酶联免疫吸附法(ELISA)测定血清和骨髓激活素A浓度。结果急性ITP患儿治疗前血清和骨髓激活素A浓度均高于正常对照组(P<0.05)和治疗后组(P<0.05),治疗后组与正常对照组相比均无显著性差异(P>0.05)。慢性ITP患儿无效组治疗前后血清和骨髓激活素A浓度相比,差异均无统计学意义(P>0.05)。有效组治疗后血清和骨髓激活素A与治疗前相比,差异均有统计学意义(P<0.01)。结论激活素A的变化可能与ITP患儿的病情变化有关。     

婴儿期特发性血小板减少性紫癜与人巨细胞病毒感染的关系

目的探讨婴儿期特发性血小板减少性紫癜(ITP)与人巨细胞病毒(HCMV)感染及免疫功能的关系。方法对54例ITP患儿(病例组)及30例正常婴儿(对照组)采用酶联免疫吸附法(ELISA)行HCMV抗体检测,PCR法行HCMV DNA检测,并对病例组采用直接免疫荧光染色法行血T细胞亚群检测,比较两组差异。结果两组HCMV抗体、DNA阳性数比较,差异有显著性意义(P均<0.01)。病例组HCMV-IgM阳性与阴性者T细胞亚群CD4 、CD8 及CD4 /CD8 比较,差异有显著性意义(P均<0.01)。结论婴儿期HCMV感染可能为ITP发病的重要因素之一。免疫功能紊乱与ITP发生、发展密切相关。     

特发性血小板减少性紫癜巨核系祖细胞巨细胞病毒感染的临床研究

目的特发性血小板减少性紫癜（ITP）是儿童常见的出血性疾病,其病因尚不十分清楚。很多研究表明,该病的发生与病毒感染密切相关。探讨人类巨细胞病毒（HCMV）感染巨核系祖细胞致ITP血小板减少的发病机制及其有效的治疗方法。方法HCMV相关ITP骨髓巨核细胞集落形成单位（CFU-MK）体外培养技术收集集落细胞,采用逆转录-聚合酶链反应（RT-PCR）检测HCMV晚期抗原基因mRNA,并给予更昔洛韦治疗。结果46例血清HCMV-DNAPCR阳性或血清HCMV-IgM阳性的ITP骨髓巨核细胞集落形成单位（CFU-MK）集落细胞HCMV晚期抗原基因mRNA阳性19例,更昔洛韦治疗有效16例;mRNA阴性27例,更昔洛韦治疗有效4例。阳性组疗效高于阴性组,P〈0．01,差异有统计学意义。结论HCMV可感染CFU—MK而成为1TP血小板减少的原因之一。巨核系祖细胞HCMV晚期抗原基因mRNA检测阳性者更昔洛韦治疗有效,能使血小板上升或恢复正常。