High BAALC expression associates with other molecular prognostic markers, poor outcome, and a distinct gene-expression signature in cytogenetically normal patients younger than 60 years with acute myeloid leukemia: a Cancer and Leukemia Group B (CALGB) study

BAALC expression is considered an independent prognostic factor in cytogenetically normal acute myeloid leukemia (CN-AML), but has yet to be investigated together with multiple other established prognostic molecular markers in CN-AML. We analyzed BAALC expression in 172 primary CN-AML patients younger than 60 years of age, treated similarly on CALGB protocols. High BAALC expression was associated with FLT3-ITD (P = .04), wild-type NPM1 (P < .001), mutated CEBPA (P = .003), MLL-PTD (P = .009), absent FLT3-TKD (P = .005), and high ERG expression (P = .05). In multivariable analysis, high BAALC expression independently predicted lower complete remission rates (P = .04) when adjusting for ERG expression and age, and shorter survival (P = .04) when adjusting for FLT3-ITD, NPM1, CEBPA, and white blood cell count. A gene-expression signature of 312 probe sets differentiating high from low BAALC expressers was identified. High BAALC expression was associated with overexpression of genes involved in drug resistance (MDR1) and stem cell markers (CD133, CD34, KIT). Global microRNA-expression analysis did not reveal significant differences between BAALC expression groups. However, an analysis of microRNAs that putatively target BAALC revealed a potentially interesting inverse association between expression of miR-148a and BAALC. We conclude that high BAALC expression is an independent adverse prognostic factor and is associated with a specific gene-expression profile.      

High EVI1 levels predict adverse outcome in acute myeloid leukemia: prevalence of EVI1 overexpression and chromosome 3q26 abnormalities underestimated

Inappropriate expression of EVI1 (ecotropic virus integration-1), in particular splice form EVI1-1D, through chromosome 3q26 lesions or other mechanisms has been implicated in the development of high-risk acute myeloid leukemia (AML). To validate the clinical relevance of EVI1-1D, as well as of the other EVI1 splice forms and the related MDS1/EVI1 (ME) gene, real-time quantitative polymerase chain reaction was performed in 534 untreated adults with de novo AML. EVI1-1D was highly expressed in 6% of cases (n = 32), whereas 7.8% were EVI1⁺ (n = 41) when all splice variants were taken into account. High EVI1 predicted a distinctly worse event-free survival (HR = 1.9; P = .002) and disease-free survival (HR = 2.1, P = .006) following multivariate analysis. Importantly, we distinguished a subset of EVI1⁺ cases that lacked expression of ME (EVI1⁺ME^–; n = 17) from cases that were ME⁺ (EVI1⁺ME⁺; n = 24). The atypical EVI1⁺ME^– expression pattern exhibited cytogenetically detectable chromosomal 3q26 breakpoints in 8 cases. Fluorescence in situ hybridization revealed 7 more EVI1⁺ME^– cases that carried cryptic 3q26 breakpoints, which were not found in the EVI1⁺ME⁺ group. EVI1⁺ME^– expression predicts an extremely poor prognosis distinguishable from the general EVI1⁺ AML patients (overall survival [OS]: P < .001 and event-free survival [EFS]: P = .002). We argue that EVI1/ME quantitative expression analysis should be implemented in the molecular diagnostic procedures of AML.     

不同种（株）利什曼原虫毒力相关基因的表达差异

目的 观察不同种（株）利什曼原虫前鞭毛体和无鞭毛体的毒力相关基因表达情况。 方法 制备杜氏利什曼原虫、婴儿利什曼原虫、热带利什曼原虫、硕大利什曼原虫和墨西哥利什曼原虫等5种7株利什曼原虫前鞭毛体和无鞭毛体的总RNA,采用半定量RT-PCR法,以α-微管蛋白基因和3-磷酸甘油醛脱氢酶基因（GAPDH）作为阳性对照,根据GenBank公布的GDP甘露糖焦磷酸酶基因（GDPMP）、A2抗原相关蛋白基因（A2rel）、脂磷酸多糖合成蛋白1基因（LPG1）、脂磷酸多糖合成蛋白2基因（LPG2）、动基体膜蛋白11基因（KMP-11）、胱氨酸蛋白酶C基因（CPC）、亲水性酰化表面蛋白B1基因（HASPB1）、胱氨酸蛋白酶2基因（CPB2）、胱氨酸蛋白酶B2.8基因（CPB2.8）和热激蛋白100基因（CLP b）等毒力相关基因的核苷酸序列,设计特异性引物进行RT-PCR扩增,分析以上各基因在各种（株）前鞭毛体和无鞭毛体中的表达情况。 结果 各毒力基因在不同种（株）利什曼原虫的前鞭毛体和无鞭毛体中的表达明显不同,HASPB1基因在7个种（株）利什曼原虫的无鞭毛体和杜氏利什曼原虫前鞭毛体中均表达,GDPMP、LPG1、LPG2、CPB2.8、CPB2、A2rel和CLP基因分别在特定种（株）的前鞭毛体和/或无鞭毛体中表达,CPC基因仅在杜氏利什曼原虫SC10株和硕大利什曼原虫无鞭毛体内表达,KMP-11基因在7个种（株）利什曼原虫前鞭毛体或无鞭毛体内均不表达。 结论 毒力相关基因的表达存在种特异性和期特异性。     

Anti-atherogenic and anti-inflammatory properties of high-density lipoprotein are affected by specific antibodies in systemic lupus erythematosus

Objective. To determine whether antibodies against high-densitylipoprotein (aHDL) and apolipoprotein A-I (aApo A-I) interferewith the anti-atherogenic functions of high-density lipoprotein(HDL) and relate to disease activity and damage in SLE. Methods. Seventy-seven SLE patients were compared with an age-and sex-frequency matched control group. Immunoglobulin G (IgG)aHDL, IgG aApoA-I, soluble vascular cell and intracellular celladhesion molecules (VCAM-1 and ICAM-1, respectively) were measuredby ELISA, paraoxonase (PON) activity by spectrophotometry, nitricoxide (NOx) metabolites by the Griess reaction, and total anti-oxidantcapacity (TAC) by chemiluminescence. Results. Compared with controls, SLE patients showed highertitres of IgG aHDL (P < 0.0001) and IgG aApo A-I (P <0.0001), lower PON activity (P < 0.0001), increased NOx (P< 0.0001), VCAM-1 (P < 0.0001) and ICAM-1 (P = 0.0008)and lower TAC (P = 0.0006). Titres of IgG aHDL positively correlatedwith IgG aApo A-I (r = 0.64, P < 0.0001), NOx (r = 0.32,P = 0.007), inversely correlated with PON activity (r = –0.34,P = 0.002) and TAC (r = –0.43, P = 0.0004) and were independentlyassociated with ICAM-1 (t = 3.509, P = 0.001). IgG aApo A-Ititres correlated positively with NO (r = 0.37, P = 0.007),inversely with PON activity (r = –0.31, P = 0.006), TAC(r = –0.47, P < 0.0001) and were independently associatedwith HDL (t = –2.747, P = 0.008) and VCAM-1 (t = 3.311,P = 0.002), the latter alongside NOx (T = 2.271, P = 0.02).Elevated titres of IgG aHDL and IgG aApo A-I and reduced PONactivity related to increased disease score (BILAG) and damageindex (SLICC/ACR DI). Conclusion. In SLE, IgG aHDL and aApo A-I associate with diseaseactivity and damage and interfere with the anti-oxidant andanti-inflammatory functions of HDL favouring atherogenesis. KEY WORDS: Systemic lupus, Antibodies against high-density lipoprotein, Antibodies against Apolipoprotein A-I, Paraoxonase, Nitric oxide, Endothelial dysfunction Submitted 6 March 2008; revised version accepted 15 September 2008.     

Comment on: The candidate lupus susceptibility gene Ifi202a is largely dispensable for B-cell function

SIR, We read with interest the letter by Bupp et al. [1] concerningthe candidate lupus susceptibility gene Ifi202a. They concludethat the Ifi202a gene is largely dispensable for B-cell function.However, we feel that Bupp et al. provided incomplete informationin their letter concerning Ifi202 genes. Moreover, before weconclude that the Ifi202a gene is largely dispensable for B-cellfunction, we feel there are a number of observations that needto be considered. A study by Wang et al. [2] revealed that Ifi202a gene     

Multiple myocardial abscesses successfully treated with medical management in an immunosuppressed patient

Myocardial abscess is usually resulted from the septicemia ofvarious microorganisms such as Candida, Staphylococcus, Aspergillus,Streptococcus, and Salmonella species. Since     

Lack of association of SLC22A4, SLC22A5, SLC9A3R1 and RUNX1 variants in psoriatic arthritis

SIR, Psoriatic arthritis (PsA) is an inflammatory arthritisassociated with various extra-articular features, includingpsoriasis (which is seen in the majority of subjects with PsA)and, occasionally, inflammatory bowel disease. Recently, therehave been major advances in the genetics of psoriasis (SLC9A3R1)[1], rheumatoid arthritis (SLC22A4 and RUNX1) [2], and Crohn'sdisease (a haplotype of SNPs in SLC22A4 and SLC22A5) [3]. AsSLC22A4, SLC22A5, SLC9A3R1 and RUNX1 have a proposed     

Identification of somatic JAK1 mutations in patients with acute myeloid leukemia

Somatic mutations in JAK2 are frequently found in myeloproliferative diseases, and gain-of-function JAK3 alleles have been identified in M7 acute myeloid leukemia (AML), but a role for JAK1 in AML has not been described. We screened the entire coding region of JAK1 by total exonic resequencing of bone marrow DNA samples from 94 patients with de novo AML. We identified 2 novel somatic mutations in highly conserved residues of the JAK1 gene (T478S, V623A), in 2 separate patients and confirmed these by resequencing germ line DNA samples from the same patients. Overexpression of mutant JAK1 did not transform primary murine cells in standard assays, but compared with wild-type JAK1, JAK1^T478S, and JAK1^V623A expression was associated with increased STAT1 activation in response to type I interferon and activation of multiple downstream signaling pathways. This is the first report to demonstrate somatic JAK1 mutations in AML and suggests that JAK1 mutations may function as disease-modifying mutations in AML pathogenesis.     

Calcitonin receptor-like receptor guides arterial differentiation in zebrafish

The calcitonin receptor-like receptor (crlr) is a major endothelial cell receptor for adrenomedullin, a peptide vasodilator involved in cardiovascular development, homeostasis, and disease. Here, we used the zebrafish (Danio rerio) model to characterize the role of crlr in vascular development. Crlr is expressed within somites from the 4- to the 13-somite stage and by arterial progenitors and axial vessels during zebrafish development. Loss of crlr results in profound alterations in vascular development and angiogenesis, including atrophic trunk dorsal aorta and interruption of anterior aortic bifurcation, delay in intersomitic vessel development, and lack of blood circulation. Remarkably, crlr morphants are characterized by the loss of arterial endothelial cell identity in dorsal aorta, as shown by the lack of expression of the arterial markers ephrin-B2a, DeltaC, and notch5. Down-regulation of crlr affects vascular endothelial growth factor (vegf) expression, whereas vegf overexpression is sufficient to rescue arterial differentiation in crlr morphants. Finally, genetic and biochemical evidences indicate that somitic crlr expression is under the control of sonic hedgehog. These data demonstrate that crlr plays a nonredundant role in arterial differentiation, representing a novel element of the sonic hedgehog–vegf-notch signaling cascade that controls arterial/venous fate.      

Aortic valve orifice equation independent of valvular flow intervals: application to aortic valve area computation in aortic stenosis and comparison with the Gorlin formula

An orifice equation is derived relating the effective aorticvalve area, A, the average aortic valve pressure gradient, dP,the stroke volume,SV, and the heart frequency, FH, through considerationsof momentum conservation across the aortic valve. This leadsto a formula consistent with Newton's second law of motion.The form of the new equation is A =(7.5 x 10^–5) SV F_H²/P_d, where A, V_s, F_H and P_d are expressed in cm², ml, s^–1and mmHg, respectively. Aortic valve areas computed with thenew orifice equation are found to correlate with those computedby the Gorlinformula in conditions of resting haemodynamic statesat a level of r = 0.86, SE=0.25 cm², N= 120. The results suggestthat the new formula may be considered as an independent orificeequation having a similar domain of validity as the Gorlinformula.The new equation offers the possibility of deriving additionaluseful haemodynamic relationships through combination with establishedcardiological formulas and applying it in a noninvasive Dopplerultrasonic or echocardiographic context.     

Evaluation of the cytogenetic aberration pattern in amyloid light chain amyloidosis as compared with monoclonal gammopathy of undetermined significance reveals common pathways of karyotypic instability

Chromosomal aberrations (CAs) have emerged as important pathogenetic and prognostic factors in plasma cell disorders. Using interphase fluorescence in situ hybridization (FISH) analysis, we evaluated CAs in a series of 75 patients with amyloid light chain amyloidosis (AL) as compared with 127 patients with monoclonal gammopathy of unknown significance (MGUS). We investigated IgH translocations t(11;14), t(4;14), and t(14;16) as well as gains of 1q21, 11q23, and 19q13 and deletions of 8p21, 13q14, and 17p13, detecting at least one CA in 89% of the patients. Translocation t(11;14) was the most frequent aberration in AL, with 47% versus 26% in MGUS (P = .03), and was strongly associated with the lack of an intact immunoglobulin (P < .001), thus contributing to the frequent light chain subtype in AL. Other frequent aberrations in AL included deletion of 13q14 and gain of 1q21, which were shared by MGUS at comparable frequencies. The progression to multiple myeloma (MM) stage I was paralleled by an increased frequency of gain of 1q21 (P = .001) in both groups. Similar branching patterns were observed in an oncogenetic tree model, indicating a common mechanism of underlying karyotypic instability in these plasma cell disorders.     

Thrombelastographic observations on the characteristics of hemophilic,thrombocytopenic and heparinized blood

1. Thrombelastographic determinations were made in cases of AHG-, PTC- and PTA-deficiencies, in thrombocytopenias and in normal plasmas after theaddition, in vitro, of heparin and synthetic heparin-like substances.

2. The components of the thrombelastogram (TEG) were correlated withrespect to the reaction time (r), the rate of clot formations (k), and the maximalamplitude (ma).

3. The differentiation of the hemophilic and thrombocytopenic syndromes wasmade on the basis of the typical variations of r, k and ma: prolonged r and k inhemophilia, prolonged k and decreased ma in thrombocytopenias.

4. The behavior of heparinized blood was characterized by a hemophilia-likeprolongation of r and k and a thrombocytopenic-like decrease of ma, with variations depending on the compound used.

5. The correlations between the r, k and ma values of TEG are suggested forthe evaluation of thrombelastography.

Submitted on April 8, 1955 Accepted on August 26, 1955     

The Cellular Basis of the Genetically Determined Hemopoietic Defect in Anemic Mice of Genotype Sl/Sld

The proliferation and function of hemopoietic cells derived from geneticallyanemic Sl/Sl^d mice have been studied by the use of cell transplantationtechnics. It was found that marrow cells derived from anemic Sl/Sl^d or Sl^d/Sl^dmice, when implanted into heavily irradiated mice of genotype +^sl/+^sl, arecapable of forming macroscopic spleen colonies, with approximately the samefrequency as cells derived from normal +^sl/+^sl mice. Marrow cells derivedfrom Sl/Sl^d animals were tested for their capacity to cure the anemia of W/W^rmice and were found to implant as rapidly and to have as long-lasting abeneficial effect as did marrow cells from +^sl/+^sl mice. The radiosensitivityof the colony-forming ability of marrow cells from Sl/Sl^d mice was found tobe similar to that found previously for +^sl/+^sl marrow cells, although theanemic animals are known to be more sensitive to total-body irradiation thanare their normal littermates. Marrow cells from +^sl/+^sl mice were found toproliferate more slowly in irradiated mice of genotype Sl/Sl^d than in irradiated+^sl/+^sl littermates, even when the anemic and the normal mice were joinedin parabiosis. These observations indicate that the hemopoietic colony-formingcells in mice of genotype Sl/Sl^d are normal, but fail to function adequately because the tissues of mice of this genotype are unable to provide sufficient support for proliferation and differentiation of these progenitor cells.

Submitted on November 25, 1964 Accepted on December 25, 1964     

Vascular dysfunction in a murine model of severe hemolysis

Spectrin is the backbone of the erythroid cytoskeleton; sph/sph mice have severe hereditary spherocytosis (HS) because of a mutation in the murine erythroid -spectrin gene. sph/sph mice have a high incidence of thrombosis and infarction in multiple tissues, suggesting significant vascular dysfunction. In the current study, we provide evidence for both pulmonary and systemic vascular dysfunction in sph/sph mice. We found increased levels of soluble cell adhesion molecules in sph/sph mice, suggesting activation of the vascular endothelium. We hypothesized that plasma hemoglobin released by intravascular hemolysis initiates endothelial injury through nitric oxide (NO) scavenging and oxidative damage. Likewise, electron paramagnetic resonance spectroscopy showed that plasma hemoglobin is much greater in sph/sph mice. Moreover, plasma from sph/sph mice had significantly higher oxidative potential. Finally, xanthine oxidase, a potent superoxide generator, is decreased in subpopulations of liver hepatocytes and increased on liver endothelium in sph/sph mice. These results indicate that vasoregulation is abnormal, and NO-based vasoregulatory mechanisms particularly impaired, in sph/sph mice. Together, these data indicate that sph/sph mice with severe HS have increased plasma hemoglobin and NO scavenging capacity, likely contributing to aberrant vasoregulation and initiating oxidative damage.     

A PRELIMINARY STUDY OF MAGNETIC RESONANCE RELAXATION TIMES (T1 AND T2) IN INFLAMMATORY AND DEGENERATIVE SYNOVIAL FLUIDS

Multiple synovial fluid samples from 21 patients were analysedusing standard synovial analysis techniques and by nuclear magneticresonance spectroscopy. Significant negative correlations werenoted between both T₁ (P<0.01) and T₂ (P<0.0006) relaxationtimes and synovial fluid total protein. No differences in T₁or T₂ relaxation times were noted in synovial fluid between16 patients with inflammatory forms of arthritis and five patientswith degenerative arthritis. In a single rheumatoid arthritispatient with concurrent staphylococcal arthritis, T₁ and T₂relaxation times did not vary between the active phase and therecovery phase. The lack of any significant differences in themeasured relaxation times as a function of joint condition suggestthat in vivo magnetic resonance measurements of T₁ or T₂ forjoint analysis may not reveal information of either a diagnosticor pathophysiological nature. KEY WORDS: Magnetic resonance spectroscopy, Arthritis, Synovial fluid     

Modulation of murine embryonic stem cell-derived CD41+c-kit+ hematopoietic progenitors by ectopic expression of Cdx genes

Cdx1, Cdx2, and Cdx4 comprise the caudal-like Cdx gene family in mammals, whose homologues regulate hematopoietic development in zebrafish. Previously, we reported that overexpression of Cdx4 enhances hematopoietic potential from murine embryonic stem cells (ESCs). Here we compare the effect of ectopic Cdx1, Cdx2, and Cdx4 on the differentiation of murine ESC-derived hematopoietic progenitors. The 3 Cdx genes differentially influence the formation and differentiation of hematopoietic progenitors within a CD41⁺c-kit⁺ population of embryoid body (EB)–derived cells. Cdx1 and Cdx4 enhance, whereas Cdx2 strongly inhibits, the hematopoietic potential of CD41⁺ckit⁺ EB-derived cells, changes that are reflected by effects on hematopoietic lineage-specific and Hox gene expression. When we subject stromal cell and colony assay cultures of EB-derived hematopoietic progenitors to ectopic expression of Cdx genes, Cdx4 dramatically enhances, whereas Cdx1 and Cdx2 both inhibit hematopoietic activity, probably by blocking progenitor differentiation. These data demonstrate distinct effects of Cdx genes on hematopoietic progenitor formation and differentiation, insights that we are using to facilitate efforts at in vitro culture of hematopoietic progenitors from ESC. The behavior of Cdx genes in vitro suggests how derangement of these developmental regulators might contribute to leukemogenesis.      

Characteristics and clinical correlates of MPL 515W>L/K mutation in essential thrombocythemia

Among 994 patients with essential thrombocythemia (ET) who were genotyped for the MPLW515L/K mutation, 30 patients carrying the mutation were identified (3.0%), 8 of whom also displayed the JAK2V671F mutation. MPLW515L/K patients presented lower hemoglobin levels and higher platelet counts than did wild type (wt) MPL; these differences were highly significant compared with MPLwt/JAK2V617F–positive patients. Reduced hemoglobin and increased platelet levels were preferentially associated with the W515L and W515K alleles, respectively. MPL mutation was a significant risk factor for microvessel disturbances, suggesting platelet hyperreactivity associated with constitutively active MPL; arterial thromboses were increased only in comparison to MPLwt/JAK2wt patients. MPLW515L/K patients presented reduced total and erythroid bone marrow cellularity, whereas the numbers of megakaryocytes, megakaryocytic clusters, and small-sized megakaryocytes were all significantly increased. These data indicate that MPLW515L/K mutations do not define a distinct phenotype in ET, although some differences depended on the JAK2V617F mutational status of the counterpart.     

Lymphocyte responses to Chlamydia antigens in patients with coronary heart disease

AIMS: To clarify the relationship of Chlamydia pneumoniae infectionand coronary atherosclerosis we studied cell-mediated and humoralimmune responses to Chlamydia in 93 patients with angiographicallyconfirmed coronary heart disease and in 115 controls withoutangiographically demonstrable lesions. METHODS AND RESULTS: Cell-mediated responses were analysed by measuring lymphocyteproliferative reactivity to whole elementary body antigens ofC. pneumoniae. Control antigens included C. trachomatis andpurified protein derivative of tuberculin. Chlamydia-specificantibodies were measured using microimmunofluorescence assay.Marked C. pneumoniae-specific immune reactivity, demonstratedby the high incidence of elevated IgG and IgA antibodies andstrong lymphocyte proliferative response, was associated withcoronary heart disease in male but not in female patients orcontrols. In male patients, the cell-mediated responses werestrong to C. pneumoniae (median stimulation index 9,6) and toC. trachomatis (stimulation index 6,9). The females with coronaryheart disease showed significantly stronger cell-mediated responsesto C. pneumoniae (stimulation index 6,5) than to C. trachomatis(3,8; P<0·001) and were comparable to the controls. CONCLUSION: Marked cell-mediated and humoral immunity to C. pneumoniae inmales with coronary heart disease suggest that the immune mechanismstriggered by Chlamydia are a possible contributing factor inthe disease pathogenesis of coronary atherosclerosis in males.The Chlamydia-specific cell-mediated responses seem to be predominantlyinduced by antigenic structures that are similar among differentChlamydia-species.     

MPL mutations in myeloproliferative disorders: analysis of the PT-1 cohort

Activating mutations of MPL exon 10 have been described in a minority of patients with idiopathic myelofibrosis (IMF) or essential thrombocythemia (ET), but their prevalence and clinical significance are unclear. Here we demonstrate that MPL mutations outside exon 10 are uncommon in platelet cDNA and identify 4 different exon 10 mutations in granulocyte DNA from a retrospective cohort of 200 patients with ET or IMF. Allele-specific polymerase chain reaction was then used to genotype 776 samples from patients with ET entered into the PT-1 studies. MPL mutations were identified in 8.5% of JAK2 V617F^– patients and a single V617F⁺ patient. Patients carrying the W515K allele had a significantly higher allele burden than did those with the W515L allele, suggesting a functional difference between the 2 variants. Compared with V617F⁺ ET patients, those with MPL mutations displayed lower hemoglobin and higher platelet levels at diagnosis, higher serum erythropoietin levels, endogenous megakaryocytic but not erythroid colony growth, and reduced bone marrow erythroid and overall cellularity. Compared with V617F^– patients, those with MPL mutations were older with reduced bone marrow cellularity but could not be identified as a discrete clinicopathologic subgroup. MPL mutations lacked prognostic significance with respect to thrombosis, major hemorrhage, myelofibrotic transformation or survival.     

ALTERED LEVELS OF SOLUBLE ADHESION MOLECULES IN RHEUMATOID ARTHRITIS, VASCULITIS AND SYSTEMIC SCLEROSIS

We compared the levels of soluble adhesion molecules E-selectin(sE-selectin), intercellular adhesion molecule-1 (sICAM-1) andvascular cell adhesion molecule-1 (sVCAM-1) alongside von Willebrandfactor (vWf), CRP and rheumatoid factor in 40 patients withRA, 38 with systemic sclerosis (SSc), 35 with vasculitis andin 80 asymptomatic controls. Adhesion molecules were measuredin serum by ELISA, rheumatoid factor by sheep red blood cellagglutination and CRP by immunonephelometry. Compared to controls,increased sE-selectin was found in patients with RA (P = 0.0015),vasculitis (P = 0.0003) and SSc (P = 0.0126), whilst raisedsICAM-1 was found in RA (P < 0.0003), vasculitis (P <0.0003) and SSc (P < 0.0378). sVCAM was lower in RA thanin controls (P = 0.0102), but was unchanged in vasculitis orin SSc. vWf was raised in RA (P = 0.0102), vasculitis (P <0.0003) and SSc (P < 0.0003). In a Spearman's rank analysisof all the data, vWf correlated with sVCAM-1 and sICAM-1 (bothP < 0.001), sE-selectin with sICAM-1 (P < 0.001) and sVCAMwith sICAM-1 (P < 0.005). Levels of rheumatoid factor correlatedwith those of sE-selectin (P = 0.003) and sVCAM-1 (P < 0.012),but there were no correlations between any index and CRP. Thestrongest correlations within the RA group were between sICAMand sVCAM (P = 0.001), in vasculitis it was between sE-selectinand sICAM (P < 0.001), and in SSc it was between sE-selectinand sVCAM (P = 0.019). These data suggest that the differinglevels of vWf, sE-selectin and sICAM-1 in the inflammatory vasculitidesmay be useful in establishing a rolefor leucocyte/endothelialadhesion in these diseases. KEY WORDS: Vasculitis, Rheumatoid arthritis, Systemic sclerosis, von Willebrand factor, Soluble E-selectin, Soluble ICAM-1, Soluble VCAM-1