Growth Responses During 3 Years of Growth Hormone Treatment in Children and Adolescents With Growth Hormone Deficiency: Comparison Between Idiopathic,Organic and Isolated Growth Hormone Deficiency,and Multiple Pituitary Hormone Deficiency

BackgroundThe study aimed to compare the growth responses to 3 years of growth hormone (GH) treatment in children and adolescents with GH deficiency (GHD) according to idiopathic, organic, isolated (IGHD), and multiple pituitary hormone deficiency (MPHD).MethodsTotal 163 patients aged 2–18 years (100 males and 63 females; 131 idiopathic and 32 organic GHD; 129 IGHD and 34 MPHD) were included from data obtained from the LG Growth Study. Parameters of growth responses and biochemical results were compared during the 3-year GH treatment.ResultsThe baseline age, bone age (BA), height (Ht) standard deviation score (SDS), weight SDS, mid-parental Ht SDS, predicted adult Ht (PAH) SDS, and insulin like growth factor-1 (IGF-1) SDS were significantly higher in the organic GHD patients than in the idiopathic GHD patients, but peak GH on the GH-stimulation test, baseline GH dose, and mean 3-year-GH dosage were higher in the idiopathic GHD patients than in the organic GHD patients. The prevalence of MPHD was higher in the organic GHD patients than in the idiopathic GHD patients. Idiopathic MPHD subgroup showed the largest increase for the ΔHt SDS and ΔPAH SDS during GH treatment, and organic MPHD subgroup had the smallest mean increase after GH treatment, depending on ΔIGF-1 SDS and ΔIGF binding protein-3 (IGFBP-3) SDS. The growth velocity and the parental-adjusted Ht gain were greater in the idiopathic GHD patients than the organic GHD patients during the 3-year GH treatment, which may have been related to the different GH dose, ΔIGF-1 SDS, and ΔIGFBP-3 SDS between two groups. Multiple linear regression analysis revealed that baseline IGF-1 SDS, BA, and MPH SDS in idiopathic group and baseline HT SDS in organic group are the most predictable parameters for favorable 3-year-GH treatment.ConclusionThe 3-year-GH treatment was effective in both idiopathic and organic GHD patients regardless of the presence of MPHD or underlying causes, but their growth outcomes were not constant with each other. Close monitoring along with appropriate dosage of GH and annual growth responses, not specific at baseline, are more important in children and adolescents with GHD for long-term treatment.Trial RegistrationClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT01604395","term_id":"NCT01604395"}}NCT01604395     

Isolation of a ''Speckled'' Nuclear Antigen Reactive with Autoantibodies in Patients with Cancer and Autoimmune Diseases

An antigenic substance reactive with autoantibodies found in patients with cancer and autoimmune diseases was isolated from calf thymus. The purification procedure included extraction of the tissues with acetone powder, batch and column chromatography on DEAE-resins, ammonium sulfate precipitation, gel filtration on Sephadex G-200, and affinity chromatography on antibody-Sepharose 4B. Indirect immunofluorescence examination of cultured human embryo cells, using the serum of patients with nasopharyngeal cancer, showed a speckled nuclear pattern. The antigenic factor was a soluble acidic protein with a pI of 5.0 and a molecular weight of 250,000. The antigenic activities of this purified substance from calf thymus, and of the material on the cultured human embryo cells, were destroyed by proteases, ribonuclease, and alkaline phosphatase. The determinants were also sensitive to periodate oxidation. Thermal stability to 60 degree C and pH stability between 2.6 and 8.5 were demonstrated. Cross-reactivity of the antigenic substance with antibodies isolated from individuals with cancer and autoimmune diseases was shown by immunofluorescence, with appropriate blocking and absorption controls.     

系统性红斑狼疮患者自身抗体检测及意义

目的：探讨自身抗体在系统性红斑狼疮（SLE）中的意义。方法：采用放射免疫分析检测50例SLE患者血清中的抗双链DNA（dsDNA）抗体,采用德国IMTEC公司抗核抗体谱线性印迹法检测抗核小体抗体（AnuA）、抗组蛋白抗体（AHA）、抗StuD1等其他自身抗体。结果：抗StuD1阳性率最高（82％）,其次是抗R060KD抗体（80％）和AunA（72％）;抗dsDNA、AHA、抗U1-RNP、抗R052KD、抗SSB的阳性率分别为44％、32％、58％、48％、24％。其他三种自身抗体阳性率很低。结论：SLE患者血清中可出现大量的自身抗体,同时检测多种自身抗体能提高对SLE的鉴别诊断。     

Autoantibodies in Patients with Rheumatoid Arthritis

Aim:  The aim of this study is to examine the diagnostic value of autoanitbodies in patients suffering from rheumatoid arthritis. We evaluated the presence of the following autoantibodies: rheumatoid factor (RF), antinuclear antibodies (ANAs), antibodies against cadiolipin (a-CL) and antibodies against cyclic citrullinated peptide (anti-CCP).
Methods:  We studied the presence of RF, ANA, a-CL and anti-CCP in 40 patients with rheumatoid arthritis. Rheumatoid factor was measured using nephelometric method, while ANAs were examined by indirect immunofluorescence technique using Hep-2 cells as substrate. Sera that reacted at 1/80 dilution were classified as ANA positive. Positive sera were studied up to 1/1280 dilution. A-CL and anti-CCP were measured by enzyme-linked immunosorbent assay.
Results:  RF was positive in 30 patients (75%), ANA in 15 (37%), a-CL in 10 (25%) and anti-CCP in 36 (90%). Predominant pattern of nuclear staining of ANA-positive sera was homogenous and speckled type. ANA titres were particularly low; most patients (6) had ANA titre equal to 1/80, and five patients had a titre of 1/160, while only four out of 40 had an ANA titre of 1/320.
Conclusions:  Autoimmune disorders such as RA are characterized by various autoantibodies that usually are not specific, as they are present in many other diseases. However, RF and especially anti-CCP are very often and show higher specificity for RA, being useful diagnostic serological markers. On the other hand, ANA and a-CL are less common in RA paitents; they may be useful in terms of prognosis and treatment, but they always should be evaluated in correlation with the clinical features and the rest of the laboratory findings of each patient.     

生长激素释放激素和胰高血糖素对成人及生长激素缺乏患者生长激素分泌的影响

本文报告正常成人和成年生长激素缺乏(GHD)患者血清生长激素(GH)对GH释放激素(GHRH)和胰高血糖素(G1u)的反应。肌注G1u后血糖失升高后降低,血糖下降是兴奋GH分泌的因素。联合注射G1u/GHRH后的血清GH峰值部GH反应曲线下面积等于单独注射G1u和GHRH的和。二例对GHRH有GH分泌反应的GHD患者,对单独注射G1u无GH分泌反应。他们的GH分泌对联合注射G1u/GHRH与单独注射GHRH的反应相同。作者认为注射G1u引起的血糖下降可能是通过抑制下丘脑释放生长抑素从而引起GH的分泌。     

自身抗体与血浆炎症因子联合检测对肝硬化合并肝功能衰竭的诊断价值

目的 探讨和分析自身抗体、血浆炎症指标联合检测在肝硬化合并肝功能衰竭患者中的诊断价值.方法 选取2014年10月至2016年8月我院收治的62例肝硬化合并肝功能衰竭患者作为试验组,并选取同一时段于我院治疗的42例慢性肝炎患者作为疾病对照组,以及42例健康体检志愿者作为健康对照组.分别采用电化学发光法(ECLIA)检测3组的血清PCT水平,采用免疫散射比浊法(INA)检测血清CRP水平,以及酶联免疫标记法(ELISA)检测其血清AMA-M2和抗-gp210水平.结果 试验组血清PCT、CRP表达水平与疾病对照组和健康对照组相比,差异具有统计学意义(P<0.05);而对疾病对照组和健康对照组的血清PCT、CRP表达水平比较发现,同样呈现显著性差异(P<0.05);试验组血清AMA-M2、抗-gp210、PCT及CRP检测的阳性率均明显高于两对照组,差异有统计学意义(P<0.05);血清AMA-M2、抗-gp210、PCT及CRP检测的灵敏度分别为82.3%、71.0%、74.1%和58.1%,特异性分别为91.7%、80.9%、76.2%和67.9%,准确度分别为76.7%、79.5%、78.8%和72.6%,而四者联合检测的灵敏度、特异度及准确度分别为43.5%、96.9%和92.7%,与各指标单独检测相比,灵敏度下降、特异度和准确度提升,差异有统计学意义(P<0.05).此外AMA、抗-gp210和PCT或CRP三者联合检测同样会显著降低灵敏度,提升特异性,但准确度变化不大.结论 AMA-M2、抗-gp210、PCT及CRP单独检测在肝硬化合并肝功能衰竭的诊断中具有一定的价值,但也存在着误诊及漏诊的情况,而自身抗体与血浆炎症指标的联合检测可有效提高检测特异度及准确度,增加疾病的检测率,值得临床推广运用.     

四种自身抗体联检对SLE诊断的临床价值

目的：探讨抗核抗体（ANA）、抗双链DNA（ds-DNA）抗体、抗Sm抗体和抗核糖体P蛋白（r-RNP）抗体联检对系统性红斑狼疮（SLE）诊断的临床价值。方法：检测49例SLE患者、33例其他结缔组织病患者（对照组）和40名正常人血清ANA、抗ds-DNA抗体、抗Sm抗体和抗r-RNP抗体。结果：ANA、抗ds-DNA抗体、抗Sm抗体和抗r-RNP抗体在SLE患者中的阳性率明显高于对照组和正常人组（P〈0.01）;ANA与抗ds-DNA抗体的敏感性显著高于其他两种自身抗体（P〈0.05）;SLE活动期患者与非活动期患者抗ds-DNA抗体阳性率有显著性差别（P〈0.01）;抗ds-DNA抗体滴度与SLE-DAI呈正相关（r=0.57,P〈0.01）;ANA、抗ds-DNA抗体、抗Sm抗体和抗r-RNP抗体联检的敏感性可达98.0%。结论：自身抗体联检提高了SLE诊断的敏感性,对SLE的诊断和治疗有重要意义。     

慢性丙型肝炎患者自身抗体的检测分析

采用荧光抗体间接法（ＩＦＡ）对３９例慢性丙型肝炎患者血清进行了自身抗体检测。结果显示慢活肝（ＣＡＨ）抗核抗体（ＡＮＡ）和抗平滑肌抗体（ＳＭＡ）检出率均高于健康人（Ｐ＜０．０５，Ｐ＜０．０１）。自身抗体阳性的慢性丙型肝炎患者血清转氨酶显著高于自身抗体阴性患者。因此认为自身免疫可能是丙型肝炎病毒（ＨＣＶ）慢性感染后肝组织损伤的重要因素。     

Anti-Tribbles Homolog 2 Autoantibodies in Japanese Patients with Narcolepsy

Study Objectives:

Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness and cataplexy. The association with human leukocyte antigen (HLA)-DQB1*0602 and T-cell receptor alpha locus suggests that autoimmunity plays a role in narcolepsy. A recent study reported an increased prevalence of autoantibodies against Tribbles homolog 2 (TRIB2) in patients with narcolepsy. To replicate this finding, we examined anti-TRIB2 autoantibodies in Japanese patients with narcolepsy.

Design:

We examined anti-TRIB2 autoantibodies against a full-length [³⁵S]-labeled TRIB2 antigen in Japanese patients with narcolepsy-cataplexy (n = 88), narcolepsy without cataplexy (n = 18), and idiopathic hypersomnia with long sleep time (n = 11). The results were compared to Japanese healthy controls (n = 87). Thirty-seven healthy control subjects were positive for HLA-DRB1*1501-DQB1*0602. We also examined autoantibodies against another Tribbles homolog, TRIB3, as an experimental control.

Measurements and Results:

Autoantibodies against TRIB2 were found in 26.1% of patients with narcolepsy-cataplexy, a significantly higher prevalence than the 2.3% in healthy controls. We found that anti-TRIB3 autoantibodies were rare in patients with narcolepsy and showed no association with anti-TRIB2 indices. No significant correlation was found between anti-TRIB2 positivity and clinical information.

Conclusions:

We confirmed the higher prevalence and specificity of anti-TRIB2 autoantibodies in Japanese patients with narcolepsy-cataplexy. This suggests a subgroup within narcolepsy-cataplexy might be affected by an anti-TRIB2 autoantibody-mediated autoimmune mechanism.

Citation:

Toyoda H; Tanaka S; Miyagawa T; Honda Y; Tokunaga K; Honda M. Anti-Tribbles homolog 2 autoantibodies in Japanese patients with narcolepsy. SLEEP 2010;33(7):875-878.     

Efficacy and Safety of Sustained-Release Recombinant Human Growth Hormone in Korean Adults with Growth Hormone Deficiency

Purpose

The administration of recombinant human growth hormone in adults with growth hormone deficiency has been known to improve metabolic impairment and quality of life. Patients, however, have to tolerate daily injections of growth hormone. The efficacy, safety, and compliance of weekly administered sustained-release recombinant human growth hormone (SR-rhGH, Declage™) supplement in patients with growth hormone deficiency were evaluated.

Materials and Methods

This trial is 12-week prospective, single-arm, open-label trial. Men and women aged ≥20 years with diagnosed growth hormone deficiency (caused by pituitary tumor, trauma and other pituitary diseases) were eligible for this study. Each subject was given 2 mg (6 IU) of SR-rhGH once a week, subcutaneously for 12 weeks. Efficacy and safety at baseline and within 30 days after the 12th injection were assessed and compared. Score of Assessment of Growth Hormone Deficiency in Adults (AGHDA score) for quality of life and serum IGF-1 level.

Results

The IGF-1 level of 108.67±74.03 ng/mL was increased to 129.01±68.37 ng/mL (p=0.0111) and the AGHDA QoL score was decreased from 9.80±6.51 to 7.55±5.76 (p<0.0001) at week 12 compared with those at baseline. Adverse events included pain, swelling, erythema, and warmth sensation at the administration site, but many adverse events gradually disappeared during the investigation.

Conclusion

Weekly administered SR-rhGH for 12 weeks effectively increased IGF-1 level and improved the quality of life in patients with GH deficiency without serious adverse events.     

IgE Antibodies in Sera from Patients with Bullous Pemphigoid Are Autoantibodies Preferentially Directed Against the 230-kDa Epidermal Antigen (BP230)

Bullous pemphigoid (BP) is unique among autoimmune skin diseases in which a high serum IgE level has been detected. We sought to determine the antigenic specificity of these IgE antibodies in 39 BP sera by immunofluorescence microscopy, immunoblot, and ELISA. The patient's sera contained IgG antibodies to 230-kDa (BP230) (n = 20), 180-kDa (BP180) (n = 9), and both BP230 and BP180 (n = 10) antigens. Serum IgE levels varied from 29 to 5000 kIU/L (mean ± SD, 856 ± 1426 kIU/L), among which sera containing IgG antibodies to BP230 had an IgE level on average 4.3 times higher than anti-BP180 sera. IgE antibodies in 18 sera were found to be autoantibodies reactive either with an epidermal component of basement membrane zone by immunofluorescence microscopy on 1 M NaCl-split skin or with a 230-kDa antigen by immunoblots of cultured human keratinocytes.⁷ The 230-kDa epidermal antigen recognized by IgE antibodies comigrated with the BP230 as labeled by a specific human monoclonal antibody. IgE anti-BP230 antibodies in patients' sera were always associated with IgG autoantibodies. No sera contained IgE antibodies to BP180 or to any other epidermal or dermal antigens as verified by immunoblot and ELISA. A good correlation was found between the presence of IgE circulating autoantibodies and the level of serum IgE (P < 0.004). IgE antibodies to BP230, like IgG autoantibodies, were mapped primarily to the C-terminal end of the protein, as they labeled rBP55, a BP230 recombinant protein encoded by a cDNA for the C-terminal end of BP230.     

HL-A Antigen Changes in Patients Treated with Chloramphenicol

HL–A antigens were determined by the microlymphocytotoxicity test in patients treated with chloramphenicol and compared with appropriate controls. A reversible loss of antigenicity was found to be associated with chloramphenicol treatment. Possible mechanisms of action and clinical implications are discussed.     

Identification of Four Novel Mutations in Patients with Carnitine Palmitoyltransferase II (CPT II) Deficiency

Carnitine palmitoyltransferase II (CPT II) deficiency, an autosomal recessive disorder of fatty-acid oxidation, presents as three distinct phenotypes (neonatal, infantile, and adult onset). In order to investigate the molecular basis of these three phenotypes, six patients with CPT II deficiency have been studied. All six unrelated patients in this study experienced the clinical symptoms of CPT II deficiency. Three patients had the neonatal form, one had the milder infantile form, and the remaining two had the adult-onset form with “muscular” symptoms only. Their diagnoses were based uponin vitroanalysis of the mitochondrial β-oxidation pathway in fibroblasts and standard enzyme assays. We devised a method to screen the entire coding sequence and flanking splice junction of the CPT II gene. A total of six different mutations have been identified, including four novel mutations. Among them, the previously reported common mutation, S113L, was only found in 3 of 12 variant alleles. Three of the six mutations have been identified in a few unrelated patients, while the remaining three have been found in single families. This study, as well as those by others, indicates genetic heterogeneity in this disease. In addition to tabulating the mutations, the correlation of mutant genotype to clinical phenotype is briefly discussed.     

外周血中血管生成素样蛋白2联合CEA、CA242检测对胃癌诊断的临床价值

目的 探讨外周血中血管生成素样蛋白2(ANGPTL2)、癌胚抗原(CEA)和糖类抗原242(CA242)联合检测对胃癌患者的临床诊断价值.方法 选取我院确诊的60例胃癌患者作为实验组,以及60例其他类型胃病患者作为对照组,酶联免疫吸附试验检测两组患者血清中 CEA、CA242和ANGPTL2水平,采用 Logistic 回归结合受试者工作特征(receiver operating characteristic,ROC)曲线评价单独或联合检测血清CEA、CA242和ANGPTL2水平对胃癌诊断的临床价值.结果与对照组比较,实验组血清中CEA、CA242和ANGPTL2水平显著升高(P<0.05).血清CEA、CA242和ANGPTL2单独和联合诊断胃癌的ROC曲线下面积分别为0.796,0.787,0.795和0.930,Youden指数最大值分别为0.433,0.500,0.550和0.717,对应的灵敏度为0.617,0.567,0.717和0.867,特异性为0.817,0.933,0.833和0.850.结论 血清中CEA、CA242和ANGPTL2均具有一定的胃癌诊断价值,三者联合诊断对于辅助临床胃癌诊断的价值较高.     

B-lymphocyte Subpopulations in Patients with Selective IgA Deficiency

Introduction

Selective deficiency IgA (IgAD) is the most common primary abnormality of immunoglobulin production with unknown pathophysiology. It is genetically related to common variable immunodeficiency (CVID), where besides IgA also IgG and frequently IgM serum levels are decreased. In this study we focused on determination of B-lymphocyte developmental stages and searching for similarities between CVID and IgAD.

Materials and Methods

Using flow cytometry we determined major lymphocyte subpopulations and B-lymphocyte subsets: na?ve (CD27^-IgD⁺), marginal zone cells (CD27⁺IgD⁺), class-switched memory cells (CD27⁺IgD^-), ??double-negative?? B cells (CD27^-IgD^-), transitional cells (IgM⁺⁺CD38⁺⁺), plasmablasts (CD38⁺⁺⁺IgM⁺ or IgM^-), and CD21^lowCD38^low cells in 80 patients with IgAD, 48 patients with CVID, and 80 control persons.

Results

Compared to healthy controls, a decrease in the absolute number and frequency of CD4+ cells (both?P?P?=?0.035) as well as plasmablasts (P?lowCD38^low subset (P?=?0.007) was observed in IgAD patients compared to control persons. No significant differences were observed in the remaining B-cell developmental subsets. A decrease in CD27⁺IgD^- (<0.4% of peripheral blood lymphocytes), frequently observed in CVID patients and also previously reported in IgAD, was found in only five patients (6%) with IgAD, two of them being first-degree relatives of CVID patients.

Conclusion

Our results show a decrease of terminally differentiated B-lymphocyte subsets in patients with IgAD, similar as previously found in patients with CVID, but these results are less expressed than in CVID patients.     

Mannose-Binding Lectin Deficiency in Brazilian Patients with Spondyloarthritis

Background: Infections are usually involved in the pathogenesis of spondyloarthritis (SpA). Mannose-binding lectin (MBL) is a component of the innate immune system with an important role in microbial defense.

Objective: To study the prevalence of MBL deficiency in SpA patients as well as its influence in the clinical profile of these diseases.

Methods: We studied 89 SpA patients and 89 healthy individuals, paired for age and gender. MBL serum levels were measured by ELISA test. Individuals with levels ≤100 ng/mL were considered deficient. SpA patients had determination of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP, Bath Ankylosing Spondylitis Functional Index (BASFI), C reactive protein (CRP), erythrocyte sedimentation rate (ESR), and review of their clinical profile.

Results: SpA patients had MBL levels ranging from 100 to 4100 ng/mL (median = 375 ng/mL); controls levels ranged from 100 to 4703 ng/mL (median = 1204 ng/mL; p < 0.0001). The prevalence of MBL deficiency was 27/89 (30.3%) in SpA patients and 12/89 (13.5%) in controls, with p = 0.01; OR = 2.5 (95% IC = 1.2–5.3). No association/correlation was found between MBL levels with BASDAI, BASFI, age at disease onset, ASDAS-CRP, ESR, CRP, presence of uveitis, HLAB27, peripheral arthritis, or SpA subtype (all p = NS).

Conclusion: MBL levels may be linked with the occurrence of SpA but do not influence its phenotype.     

Deficiency of Biotinyl-AMP Synthetase Activity in Fibroblasts of Patients with Holocarboxylase Synthetase Deficiency

A simple, rapid assay was developed to diagnose holocarboxylase synthetase deficiency. Holocarboxylase synthetase first catalyzes the formation of biotinyl-AMP from biotin and ATP, an activity designated as biotinyl-AMP synthetase. In the second step of the reaction, biotin is transferred from biotinyl-AMP to the enzymatically inactive apocarboxylase to form an active holocarboxylase. The assay for holocarboxylase synthetase activity therefore requires a protein apocarboxylase substrate which is not readily available. In the assay for biotinyl-AMP synthetase, hydroxylamine reacts nonenzymatically with the product of the enzymatic reaction, biotinyl-AMP, to form biotinylhydroxamate. At the end of the reaction, unreacted radioactive biotin substrate, which is negatively charged at neutral pH, is bound to an anion-exchange resin and a neutral radioactive biotinylhydroxamate product in the supernatant is counted. In fibroblasts from 11 patients with proven holocarboxylase synthetase deficiency, the mean biotinyl-AMP synthetase activity at 25 nM biotin was 4% of the control mean with a range of 0.2 to 8%. This is an improved assay because it does not require preparation of an apocarboxylase substrate and is suitable for the diagnosis of patients with holocarboxylase synthetase deficiency.     

Pathophysiology of Antigen 85 in Patients with Active Tuberculosis: Antigen 85 Circulates as Complexes with Fibronectin and Immunoglobulin G

Antigen 85 (Ag85) complex proteins are major secretory products of Mycobacterium tuberculosis and induce strong cellular and humoral immune responses in infected experimental animals and human beings. We have previously shown that nanogram doses of these 30- to 32-kDa fibronectin-binding proteins inhibit local expression of delayed hypersensitivity by a T-cell fibronectin-dependent mechanism. Circulating levels of Ag85 might be expected to be elevated in patients with active tuberculosis and possibly to play a role in systemic anergy in these patients. To test this hypothesis, Ag85 was measured in serum and urine by a monoclonal antibody-based dot immunobinding assay in 56 patients and controls with known skin test reactivity. Median serum Ag85 levels were 50- to 150-fold higher in patients with active tuberculosis than in patients with active M. avium-intracellulare disease or other nontuberculous pulmonary disease or in healthy controls (P < 0.001). The median and range of serum Ag85 in patients with active tuberculosis was not significantly different between skin test-positive and -negative subjects. Patients with active M. avium disease could be distinguished from those with disease due to M. tuberculosis by monoclonal anti-Ag85 antibodies of appropriate specificities. No increases in urinary Ag85 were detected in any patient, regardless of the Ag85 level in serum. Chromatographic analysis and immunoprecipitation studies of serum revealed that Ag85 existed in the serum of these patients complexed to either fibronectin or immunoglobulin G (IgG). Uncomplexed circulating Ag85 was demonstrable in serum from fewer than 20% of patients with active tuberculosis. In patients with active tuberculosis, Ag85 is therefore likely to circulate primarily as complexes with plasma fibronectin and IgG rather than in unbound form. The existence of Ag85 complexes with plasma proteins would account for its lack of urinary clearance.