Comparison of the sensitivity and specificity of p16/Ki-67 dual staining and HPV DNA testing of abnormal cervical cytology in the detection of histology proven cervical intraepithelial neoplasia grade 2 and above (CIN 2+).

INTRODUCTION: Human papillomavirus (HPV) testing is used as a means of triaging cervico-vaginal smears with low grade squamous abnormalities or as part of co-testing with cytology. While HPV testing has a high sensitivity, it has a low specificity in detecting cervical intraepithelial neoplasia grade 2 and above (CIN 2+) leading to unnecessary colposcopy referrals. We investigate the accuracy of the p16/Ki-67 dual immunocytochemical stain in determining the presence of CIN 2+ lesions on histology and its potential as a superior biomarker for triage. METHODS: Liquid based cervico-vaginal cytology specimens with squamous abnormalities and corresponding histology from 97 women with subsequent colposcopy and biopsy were included. The specimens were then subjected to the dual stain and Roche Cobas 4800 multiplex real time PCR HPV DNA testing. The sensitivity and specificity of the dual stain and HPV testing were calculated using CIN 2+ on histology as a reference standard. RESULTS: The sensitivity and specificity of the dual stain in detecting histology proven CIN 2+ was 93.7% and 76.5% while HPV testing was 85.7% and 14.7% respectively. Of the 44 women with ASCUS or LSIL on cytology, the dual stain also reduced the number of unnecessary colposcopy referrals from 27 to 7 when used as a triage marker compared to HPV testing. CONCLUSION: p16/Ki-67 dual stain was more sensitive and specific than HPV testing in determining the presence of CIN 2+ on histology. It could triage low grade cervico-vaginal specimens more effectively and potentially help women avoid unnecessary colposcopies. Future studies are needed to further evaluate its role in cervical cancer screening programmes.

Improving refractive outcomes at extreme axial lengths with the IOLMaster: the optical axial length and keratometric transformation.

AIMS: To optimise the relationship between the actual and predicted refractive outcomes following phacoemulsification and axial length of the eye. Four intraocular lens (IOL) power calculation formulae were compared: SKR-T, Holladay I, Hoffer-Q and Haigis. Optical axial length transformation based on the original calibration of the IOLMaster was tested to improve the predictability of outcomes. METHODS: The refractive outcomes of 155 eyes of 120 patients using the IOLMaster were reviewed following phacoemulsification. After optimising the IOL constants, the prediction error (PE; achieved spherical equivalent - calculated spherical equivalent) of each of the formulae was calculated for each eye and then correlated to the axial length of the eye with and without the optical transformation. Keratometry measurements of the IOLMaster were tested by transforming to that of standard autokeratometry. This was validated in a second group of 90 eyes. RESULTS: The PE of all but the Haigis triple optimised formula were found to be positively correlated to the axial length. The optical and keratometric transformation statistically significantly reduced this correlation, leading to fewer PE at all axial lengths. PE per millimetre axial length was 0.06 D/mm (SRK-T), 0.16 D/mm (Hoffer-Q), 0.14 D/mm (Holladay I), 0.11 D/mm (Haigis single) and -0.02 D/mm (Haigis triple). Following transformation, best case PE was reduced to -0.01 D/mm (SRK-T), 0.08 D/mm (Hoffer-Q), 0.01 D/mm (Holladay I), 0.01 D/mm (Haigis single) and -0.01 D/mm (Haigis triple). CONCLUSION: Transforming the IOLMaster measurement into the optical axial length while compensating for its keratometry measurement was able to improve the predictability of outcomes at extreme axial lengths without further modification to the standard IOL formulae.

Analysis of lolB gene sequence and its use in the development of a PCR assay for the detection of Vibrio cholerae.

A PCR assay has been developed based on a lolB (hemM) gene, which was found to be highly conserved among the Vibrio cholerae species but non-conserved among the other enteric bacteria. The lolB PCR detected all O1, O139 and non-O1/non-O139 serogroup and biotypes of V. cholerae. The analytical specificity of this assay was 100% while the analytical sensitivity was 10 pg/microL and 10(3) CFU/mL at DNA and bacterial level respectively. The diagnostic sensitivity and specificity was 98.5% and 100% respectively.

A new population-based measure of the economic burden of mental illness in Canada.

This paper presents a comprehensive measure of the incremental economic burden of mental illness in Canada which incorporates the use of medical resources and productivity losses due to long-term and short-term disability, as well as reductions in health-related quality of life (HRQOL), for the diagnosed and undiagnosed population with mental illness. The analysis was based on the population-based Canadian Community Health Survey Cycle 2.1 (2003). For all persons, we measured all health services utilization, longterm and short-term work loss, and health-related quality of life and their dollar valuations, with the economic burden being the difference in dollar measures between the populations with and without mental health problems. In total, the economic burden was $51 billion in 2003. Over one-half was due to reductions in HRQOL. The current accepted practice in economic assessments is to include changes in medical resource use, work loss, and reductions in HRQOL.

Central corneal thickness and its relationship to myopia in Chinese adults.

AIM: To investigate the association between central corneal thickness (CCT) and the degree of myopia among Chinese. METHODS: In this prospective observational study, 714 consecutive patients were recruited from a refractive surgery clinic. CCT was measured in both eyes of each patient using the Orbscan (Bausch and Lomb, Rochester, New York, USA), and data of the right eye were selected for analysis. CCT was correlated with the degree of myopia in dioptres (D) using Pearson's correlation coefficient and Dunnett's t test with multiple comparisons. RESULTS: The age of the patients ranged from 15 to 59 years. The mean CCT was 534.5 microm, with a standard deviation (SD) of 38.1 (range 305-684) microm. The mean (SD) myopic spherical equivalent was 5.30 (2.74) D, range -17.5--0.625 D. No correlation was found between CCT and the degree of myopia (r = -0.13, p = 0.719). CONCLUSIONS: Among Chinese with myopia, CCT was distributed over a large range but did not correlate with the degree of myopia.

Differential expression of splice variant and wild-type parkin in sporadic Parkinson's disease.

BACKGROUND: Altered splicing of parkin under cellular stress could lead to changes in gene expression and altered protein activity. The causative role of parkin in sporadic Parkinson's disease (PD) is unknown. OBJECTIVES: We described a parkin splice variant (SV) in the substantia nigra and leukocytes of sporadic PD patients. Using a case control methodology, we investigated the exon 4 SV (E4SV) and wild-type parkin expression in the leukocytes of sporadic PD patients and healthy individuals. METHODS/RESULTS: We identified a parkin E4SV in the substantia nigra and leukocytes of sporadic PD patients and controls by reverse transcriptase-polymerase chain reaction (PCR). The exon 4 (122 bp) deletion resulted in a reading frame shift over the junction of exons 3-5 and a stop codon (tga) 17 bp downstream from exon 3. The translated truncated protein was associated with a total loss of the two-RING finger functional domain. Utilizing TaqMan real-time PCR with probes located across the junction of exons 3-4 or 3-5, we demonstrated an over-expression of E4SV/wild-type parkin ratio in the leukocytes of sporadic PD patients compared to age-, gender-, and race-matched controls (p<0.0005). A multivariate regression analysis demonstrated that the ratio of E4SV/wild-type parkin expression increased with age in PD patients, but this was not observed in the controls (p<0.0005). CONCLUSION: The relative expression of E4SV/wild type parkin was increased in sporadic PD compared to healthy controls. Based on our observations, further functional studies to determine the pathophysiologic role of E4SV in sporadic PD patients will be of importance.

Parkin ubiquitinates the alpha-synuclein-interacting protein, synphilin-1: implications for Lewy-body formation in Parkinson disease.

Parkinson disease is a common neurodegenerative disorder characterized by the loss of dopaminergic neurons and the presence of intracytoplasmic-ubiquitinated inclusions (Lewy bodies). Mutations in alpha-synuclein (A53T, A30P) and parkin cause familial Parkinson disease. Both these proteins are found in Lewy bodies. The absence of Lewy bodies in patients with parkin mutations suggests that parkin might be required for the formation of Lewy bodies. Here we show that parkin interacts with and ubiquitinates the alpha-synuclein-interacting protein, synphilin-1. Co-expression of alpha-synuclein, synphilin-1 and parkin result in the formation of Lewy-body-like ubiquitin-positive cytosolic inclusions. We further show that familial-linked mutations in parkin disrupt the ubiquitination of synphilin-1 and the formation of the ubiquitin-positive inclusions. These results provide a molecular basis for the ubiquitination of Lewy-body-associated proteins and link parkin and alpha-synuclein in a common pathogenic mechanism through their interaction with synphilin-1.

Calmodulin binds to and inhibits the activity of the membrane distal catalytic domain of receptor protein-tyrosine phosphatase alpha.

cDNA expression library screening revealed binding between the membrane distal catalytic domain (D2) of protein-tyrosine phosphatase alpha (PTPalpha) and calmodulin. Characterization using surface plasmon resonance showed that calmodulin bound to PTPalpha-D2 in a Ca(2+)-dependent manner but did not bind to the membrane proximal catalytic domain (D1) of PTPalpha, to the two tandem catalytic domains (D1D2) of PTPalpha, nor to the closely related D2 domain of PTPepsilon. Calmodulin bound to PTPalpha-D2 with high affinity, exhibiting a K(D) approximately 3 nm. The calmodulin-binding site was localized to amino acids 520-538 in the N-terminal region of D2. Site-directed mutagenesis showed that Lys-521 and Asn-534 were required for optimum calmodulin binding and that restoration of these amino acids to the counterpart PTPepsilon sequence could confer calmodulin binding. The overlap of the binding site with the predicted lip of the catalytic cleft of PTPalpha-D2, in conjunction with the observation that calmodulin acts as a competitive inhibitor of D2-catalyzed dephosphorylation (K(i) approximately 340 nm), suggests that binding of calmodulin physically blocks or distorts the catalytic cleft of PTPalpha-D2 to prevent interaction with substrate. When expressed in cells, full-length PTPalpha and PTPalpha lacking only D1, but not full-length PTPepsilon, bound to calmodulin beads in the presence of Ca(2+). Also, PTPalpha was found in association with calmodulin immunoprecipitated from cell lysates. Thus calmodulin does associate with PTPalpha in vivo but not with PTPalpha-D1D2 in vitro, highlighting a potential conformational difference between these forms of the tandem catalytic domains. The above findings suggest that calmodulin is a possible specific modulator of PTPalpha-D2 and, via D2, of PTPalpha.

Isolation of a novel protein tyrosine phosphatase inhibitor, 2-methyl-fervenulone, and its precursors from Streptomyces.

High-throughput screening identified an extract from Streptomyces sp. IM 2096 with inhibitory activity toward several protein tyrosine phosphatases (PTPs). Four 1,2,4-triazine compounds 2096A-D (1-4) were isolated from this extract and their structures elucidated by interpretation of spectroscopic data and confirmed by degradation and synthesis. The novel glycocyamidine derivatives 1 and 2 are diastereomers and may interconvert. Both are inactive in the PTP inhibition assay. Compounds 1 and 2 are unstable and partially decompose to 3 and glycocyamidine (5) at room temperature. Compound 3, known as MSD-92 or 2-methyl-fervenulone, is a broad-specificity PTP inhibitor with comparable potency to vanadate. The imidazo[4, 5-e]-1,2,4-triazine (4), inactive in the PTP-inhibition assay, may be a degradation product of 3.

Catalytic activation of the membrane distal domain of protein tyrosine phosphatase epsilon, but not CD45, by two point mutations.

Most, if not all, of the catalytic activity of the tandem catalytic domain-containing receptor-like protein tyrosine phosphatases (PTPs) resides in the membrane proximal domains (D1), with little to no activity associated with the membrane distal domains (D2). Two point mutations in the D2 domain of PTPalpha, which restore invariant amino acids found in the KNRY motif and WPD loop of all active D1 domains, synergistically confer D1-equivalent kinetic properties towards the phosphotyrosine analogue pNPP, and activate PTPalpha-D2 catalysed phosphopeptide hydrolysis (Lim et al., J. Biol. Chem. 273 (1998) 28986-28993; Buist et al., Biochemistry 38 (1999) 914-922). As all D2 domains lack these two D1-invariant amino acids, we have investigated whether other D2 domains are activated by such point mutations. Mutant PTPepsilon-D2, closely related to PTPalpha-D2 and belonging to a subgroup of D2 domains with minimal and conservative substitutions of D1-invariant amino acids, exhibits synergistic activation towards pNPP but not towards a phosphopeptide substrate. CD45-D2, belonging to another subgroup of D2 domains with considerable substitutions in D1-invariant amino acids, is not activated by these mutations, even in the context of a third mutation which restores the minimal essential active site sequence C(X(5))R, indicating that additional defects are sufficient to preclude catalysis. The ability of the KNRY and WPD replacements to activate PTPepsilon-D2 and PTPalpha-D2, but not CD45-D2, in conjunction with the extent and nature of their wild-type amino acid substitutions, suggests that these D2 domains are representative of two functionally distinct groups of D2 domain.

Targeted disruption of the tyrosine phosphatase PTPalpha leads to constitutive downregulation of the kinases Src and Fyn.

A role for the receptor-like protein tyrosine phosphatase alpha (PTPalpha) in regulating the kinase activity of Src family members has been proposed because ectopic expression of PTPalpha enhances the dephosphorylation and activation of Src and Fyn [1] [2] [3]. We have generated mice lacking catalytically active PTPalpha to address the question of whether PTPalpha is a physiological activator of Src and Fyn, and to investigate its other potential functions in the context of the whole animal. Mice homozygous for the targeted PTPalpha allele (PTPalpha-/-) and lacking detectable PTPalpha protein exhibited no gross phenotypic defects. The kinase activities of Src and Fyn were significantly reduced in PTPalpha-/- mouse brain and primary embryonic fibroblasts, and this correlated with enhanced phosphorylation of the carboxy-terminal regulatory Tyr527 of Src in PTPalpha-/- mice. Thus, PTPalpha is a physiological positive regulator of the tyrosine kinases Src and Fyn. Increased tyrosine phosphorylation of several unidentified proteins was also apparent in PTPalpha-/- mouse brain lysates. These may be PTPalpha substrates or downstream signaling proteins. Taken together, the results indicate that PTPalpha has a dual function as a positive and negative regulator of tyrosine phosphorylation events, increasing phosphotyrosyl proteins through activation of Src and Fyn, and directly or indirectly removing tyrosine phosphate from other unidentified proteins.

Interconversion of the kinetic identities of the tandem catalytic domains of receptor-like protein-tyrosine phosphatase PTPalpha by two point mutations is synergistic and substrate-dependent.

The two tandem homologous catalytic domains of PTPalpha possess different kinetic properties, with the membrane proximal domain (D1) exhibiting much higher activity than the membrane distal (D2) domain. Sequence alignment of PTPalpha-D1 and -D2 with the D1 domains of other receptor-like PTPs, and modeling of the PTPalpha-D1 and -D2 structures, identified two non-conserved amino acids in PTPalpha-D2 that may account for its low activity. Mutation of each residue (Val-536 or Glu-671) to conform to its invariant counterpart in PTPalpha-D1 positively affected the catalytic efficiency of PTPalpha-D2 toward the in vitro substrates para-nitrophenylphosphate and the phosphotyrosyl-peptide RR-src. Together, they synergistically transformed PTPalpha-D2 into a phosphatase with catalytic efficiency for para-nitrophenylphosphate equal to PTPalpha-D1 but not approaching that of PTPalpha-D1 for the more complex substrate RR-src. In vivo, no gain in D2 activity toward p59(fyn) was effected by the double mutation. Alteration of the two corresponding invariant residues in PTPalpha-D1 to those in D2 conferred D2-like kinetics toward all substrates. Thus, these two amino acids are critical for interaction with phosphotyrosine but not sufficient to supply PTPalpha-D2 with a D1-like substrate specificity for elements of the phosphotyrosine microenvironment present in RR-src and p59(fyn). Whether the structural features of D2 can uniquely accommodate a specific phosphoprotein substrate or whether D2 has an alternate function in PTPalpha remains an open question.

Physical and functional interactions between receptor-like protein-tyrosine phosphatase alpha and p59fyn.

We have examined the in vivo activity of receptor-like protein-tyrosine phosphatase alpha (PTPalpha) toward p59(fyn), a widely expressed Src family kinase. In a coexpression system, PTPalpha effected a dose-dependent tyrosine dephosphorylation and activation of p59(fyn), where maximal dephosphorylation correlated with a 5-fold increase in kinase activity. PTPalpha expression resulted in increased accessibility of the p59(fyn) SH2 domain, consistent with a PTPalpha-mediated dephosphorylation of the regulatory C-terminal tyrosine residue of p59(fyn). No p59(fyn) dephosphorylation was observed with an enzymatically inactive mutant form of PTPalpha or with another receptor-like PTP, CD45. Many enzyme-linked receptors are complexed with their substrates, and we examined whether PTPalpha and p59(fyn) underwent association. Reciprocal immunoprecipitations and assays detected p59(fyn) and an appropriate kinase activity in PTPalpha immunoprecipitates and PTPalpha and PTP activity in p59(fyn) immunoprecipitates. No association between CD45 and p59(fyn) was detected in similar experiments. The PTPalpha-mediated activation of p59(fyn) is not prerequisite for association since wild-type and inactive mutant PTPalpha bound equally well to p59(fyn). Endogenous PTPalpha and p59(fyn) were also found in association in mouse brain. Together, these results demonstrate a physical and functional interaction of PTPalpha and p59(fyn) that may be of importance in PTPalpha-initiated signaling events.

Kinetic analysis of two closely related receptor-like protein-tyrosine-phosphatases, PTP alpha and PTP epsilon.

Among transmembrane protein-tyrosine-phosphatases, the membrane distal catalytic domain (D2) of protein-tyrosine-phosphatase alpha (PTP alpha) is unusual in having low but detectable activity in the absence of the membrane proximal catalytic domain (D1). To investigate the catalytic properties of PTP alpha D2 in association with D1, kinetic parameters of activity were established for PTP alpha D1D2 proteins containing an inactivating point mutation in D1 and/or D2. In this context, D2 activity was unchanged by the presence (N-terminal or C-terminal) or absence of inactive D1, and the presence or absence of inactive D2 affected the velocity but not the Km of D1 catalysis. While D1 appears to be the major catalytic contributor to PTP alpha activity, D2 possesses a significantly higher substrate-specific activity relative to wild-type D1D2 than the D2 domains of other protein-tyrosine-phosphatases. Also, PTP alpha D2 is an active phosphatase with comparable or better efficiency, on the basis of k(cat)/Km criteria, to some of the dual specificity phosphatases. Kinetic parameters of a closely related receptor-like protein-tyrosine-phosphatase, PTP epsilon, were determined. PTP epsilon D1 is the major, if not the only, catalytic moiety of PTP epsilon, and has much higher turnover numbers than D1 of PTP alpha. The PTP epsilon D2 activity is insignificant compared to that of PTP epsilon-D1D2, with lower turnover numbers than PTP alpha D2. Thus, the intrinsic activity of PTP alpha D2 is high compared to other D2 domains and, more outstandingly, its activity relative to D1 appears unique. These are also apparent upon in vitro assay of full-length PTP alpha catalytic mutants expressed in mammalian cells. Together. these results suggest potential catalytic and regulatory roles for PTP alpha D2, and that PTP alpha may be an optimal model transmembrane protein-tyrosine-phosphatase for investigating the former within the cell.

Correlation between CD29 density on CD8+ lymphocytes and serum IgG in systemic lupus erythematosus.

The purpose of this paper is to establish whether there is increased lymphocyte adhesion molecule density in systemic lupus erythematosus (SLE), which could alter the migration pathways and activation thresholds of lymphocytes and thus contribute to the pathogenesis of the disease. We analysed the CD11a, CD29 and CD2 bound antibody molecule (bam) density on the CD4+ and CD8+ CAMhigh (primed) lymphocytes of 28 SLE patients (8 active and 20 inactive by BILAG), using reproducible flow cytometric measurements, standardized with fluorescent beads and antibodies of known fluorescein: protein ratios. In a second patient cohort (17 patients), we investigated whether CD29 density on CD8+ cells correlated with measures of humoral (serum IgG) or cellular (urine neopterin) activation. In the first cohort, 36% of patients had elevated CD29 (beta 1 integrin) density on CD8+ cells. In the second cohort, CD29 density on CD8+ cells was found to be closely associated with total plasma IgG (r = 0.71, P = 0.001), but not with urine neopterin, disease activity (BILAG) or drug treatment. We conclude that CD29 on CD8+ cells is associated with B cell activation in SLE.

Rat fibroblast cells overexpressing kinase-inactive human insulin receptors are insulin responsive: influence of growth conditions.

The effects of insulin to stimulate metabolic and mitogenic responses were examined in Rat 1 fibroblast cells that overexpressed either normal (HIRc) or kinase-deficient human insulin receptors. When studied at the optimal growth stage for each cell line, insulin-stimulated responses measured in cells containing kinase-defective receptors with a Lys1018-Ala1018 substitution in the ATP-binding site of the kinase domain (A/K1018). Maximal insulin responsiveness for all these effects, measured as fold-increase over basal, was comparable in parental and HIRc cells (1.8- to 2.4-fold increases). Relative insulin responsiveness for all effects was greatest in A/K 1018 cells. One clone (AK-I) expressing a similar number of kinase-inactive receptors as in the HIRc cells displayed maximal responsiveness of 3.6- to 5.5-fold increases. A second A/K cell line containing 1/10 the number of kinase-inactive receptors displayed responsiveness intermediate between AK-I and parental or HIRc cells (1.5- to 4.8-fold increases). Both clones of kinase-deficient A/K1018 cells displayed impaired insulin sensitivity compared with HIRc cells. These findings suggest that expression of insulin receptor kinase activity is a determinant of insulin sensitivity but not necessarily of the final biological responsiveness of cells to insulin.

Skeletal muscle lymphocytic vasculitis in systemic lupus erythematosus: relation to disease activity.

Lymphocytic vasculitis (LV) characterises systemic lupus erythematosus (SLE) and this potentially reversible lesion, which may be subclinical, may imply overt systemic disease activity. Needle quadriceps muscle biopsy was performed in 26 unselected patients with SLE and the presence of LV in these muscle specimens was compared with SLE disease activity scored using the British Isles Lupus Assessment Group Index (BILAG). Ten of the 22 patients with active disease showed evidence of LV compared with none of the four patients with inactive disease. In the patient group with LV, significantly higher ESR and urine neopterin values were found with P = 0.002 and P = 0.02, respectively compared with patients without LV. Features of vasculitis (as defined by BILAG) were also significantly more common in these patients (P = 0.005). None of the other parameters, including creatine kinase, were significantly different between the two patient subgroups. Thus, LV in needle quadriceps muscle biopsy specimens is a further valuable marker of disease activity in patients with SLE and might provide histological evidence of a systemic vasculitic process in a group of patients with diverse clinical manifestations.

Investigation of the prevalence and clinical associations of antibodies to human fibronectin in systemic lupus erythematosus.

OBJECTIVES: To assess the prevalence of antibodies to human fibronectin (anti-Fn) in sera of patients with certain connective tissue diseases and to determine their association with disease activity and the pattern of organ involvement in patients with systemic lupus erythematosus (SLE). METHODS: A capture enzyme linked immunosorbent assay (ELISA) was developed to quantify anti-Fn antibodies in serum samples from 65 patients with well characterised SLE, 50 with rheumatoid arthritis (RA), 15 with Behçet's disease (BD), 15 with systemic vasculitis and 36 healthy subjects. An anti-Fn antibody titre greater than mean + 3SD of the healthy control log values after back transformation to the normal scale was considered positive. Disease activity in SLE patients was scored using the British Isles Lupus Assessment Group (BILAG) Index. Erythrocyte sedimentation rate (ESR), concentrations of anti-dsDNA antibody, soluble interleukin-2 receptors (sIL-2R), C3, C4, C3 degradation products (C3dg) and immunoglobulin, and antinuclear antibody (ANA) titres were measured in blood samples from SLE patients; neopterin concentration was measured in corresponding urine samples. RESULTS: Anti-Fn antibodies were found in 22 of 65 SLE patients (33.8%), seven of 50 with RA (14%), one of 15 with BD (6.6%) and none of the 15 subjects with vasculitis. Thirty SLE patients had active disease and 35 had inactive disease; their median anti-Fn concentrations were 117 u/ml (range 47-450) and 68 u/ml (range 17-334), respectively (p = 0.0001). The presence of anti-Fn did not correlate with immunoglobulin concentrations or ANA titres in these sera. No significant difference was found between SLE patients with disease activity in one major organ system compared with multiple organ involvement, as defined by BILAG (p = 0.19). However, patients with musculoskeletal manifestations had consistently greater anti-Fn concentrations compared with patients with other clinical manifestations. There were significant correlations between amounts of anti-Fn in SLE sera and ESR (rs = 0.25, p = 0.045), sIL-2R (rs = 0.28, p = 0.024) and urine neopterin (rs = 0.3, p = 0.016) but not with serum anti-dsDNA antibody titres, plasma C3, C3dg or C4. However multiple regression analysis showed a low significant correlation only with sIL-2R and BILAG score (p = 0.047 and 0.042, respectively). CONCLUSION: Anti-Fn antibodies were detected in 34% of SLE patients and in small proportions of RA and BD patients. An association between serum anti-Fn and disease activity in SLE has been identified and most SLE patients with musculoskeletal involvement had increased anti-Fn antibody concentrations.