Overlap of coronary disease and pulmonary arterial hypertension in systemic sclerosis.

OBJECTIVES: Pulmonary arterial hypertension (PAH) is a common complication of systemic sclerosis (SSc). Symptoms of coronary artery disease (CAD) and PAH are closely related and cardiac catheterisation is needed to confirm their diagnosis. The aim of the present work was to investigate of the extent of overlap between CAD and PAH in patients with SSc. METHODS: Based on non-invasive investigations, 20 patients out of 120 were suspected to have PAH ("suspected PAH" group). Another 10 patients showed signs of coronary disease ("suspected CAD" Group). In these 30 patients, right heart catheterisation and coronary angiography were performed, and the coronary flow reserve (CFR) was assessed by thermodilution technique. RESULTS: In the "suspected PAH" and the "suspected CAD" groups, PAH was found in 12/20 and 2/10 cases, and coronary artery stenosis in 9/20 and 6/10 cases, respectively. Severely reduced CFR was revealed in 7/20 and 3/10 cases, respectively. CONCLUSIONS: PAH, CAD and reduced CFR all show a considerable overlap in symptomatic patients with SSc. The current non-invasive investigations are neither sensitive nor specific enough to make an appropriate distinction between these different disease manifestations. A more invasive approach, such as coronary angiography at the initial catheterisation, is required to properly characterise and treat the different forms of cardiac involvement in SSc.

Comprehensive investigation of novel serum markers of pulmonary fibrosis associated with systemic sclerosis and dermato/polymyositis.

OBJECTIVE: To investigate the association between serum levels and clinical signs of lung fibrosis in patients with systemic sclerosis and inflammatory myopathies. METHODS: ELISA tests for a mucin-like glycoprotein KL-6, von Willebrandt factor (vWF), soluble E-selectin (sES) and surfactant protein D (SP-D) were performed in sera of 104 patients with systemic sclerosis, 31 patients with poly/dermatomyositis) and 24 patients with Raynaud's phenomenon as controls. The clinical and laboratory data were evaluated by a simple standard protocol including chest x-ray, lung function tests, echocardiography and, in selected cases, high resolution computer tomography (HRCT). Clinically significant pulmonary fibrosis (PF) defined as a simultaneous presence of radiological sign of pulmonary fibrosis and restrictive impairment. Severe PF was established if HRCT scans showed diffuse interstitial lung disease with low diffusing capacity. End stage PF was determined as severe PF with very low diffusing capacity. RESULTS: Patients with pulmonary fibrosis on chest x-ray showed significantly elevated serum levels of KL-6, SP-D and vWF. Inverse correlation was found between serum levels of KL-6/SP-D and lung function parameters, such as DLCO% and FVC. With regard to HRCT findings, patients with elevated serum level of KL-6 showed significantly more frequently ground glass opacity, diffuse and honeycombing fibrosis than patients with normal level of KL-6. The sensitivity of KL-6 for PF in SSc is increased with the severity of PF (PF on chest x-ray < severe PF < end stage of PF). Lung fibrosis occurred more frequently in patients with simultaneously elevated KL-6 and sES compared to cases with a single positivity of either KL-6 or sES. CONCLUSION: KL-6, SP-D, vWF and ES are good surrogate factors of pulmonary fibrosis but can not replace conventional diagnostic procedures. However, these markers are suitable for the assessment of progression and severity of pulmonary fibrosis in systemic autoimmune disorders once the diagnosis is established.

Functional variants of interleukin-23 receptor gene confer risk for rheumatoid arthritis but not for systemic sclerosis.

OBJECTIVES: Recently, an association was found between Crohn's disease and the interleukin-23 receptor (IL-23R) gene. Since the IL-23/IL-17 pathway is known to associate with other autoimmune diseases, including rheumatoid arthritis (RA) and systemic sclerosis (SSc), we hypothesised that IL-23R could be a shared susceptibility gene. METHODS: Groups of patients with rheumatoid arthritis (n = 412), systemic sclerosis (n = 224), Crohn's disease (n = 190) and healthy controls (n = 220) were genotyped for rs10889677 (exon-3'UTR C2370A), rs2201841, and rs1884444 variants; the first two have been shown to confer risk for Crohn's disease. RESULTS: We observed an increased prevalence of the homozygous rs10889677 AA and homozygous rs2201841 CC genotypes both in the Crohn's disease and in the RA groups as compared to the controls (12.1%, 11.9% vs 5.91%, p<0.05; and 13.2%, 13.1% vs 5.91%, p<0.05), but not in the SSc patients. Logistic regression analysis revealed that bearing these alleles represent risk for the development of rheumatoid arthritis (chi(2) = 5.58, p = 0.018, OR = 2.15, 95% CI 1.14-4.06 for rs10889677; and chi(2) = 7.45, p = 0.006, OR = 2.40, 95% CI 1.28-4.51 for rs2201841). The rs1884444 allele, which has been previously reported as neutral for development of Crohn's disease, was also found neutral for all studied groups in the present study. CONCLUSIONS: The data reported here provide direct evidence that some allelic variants or haplogroups of IL-23R represent independent risk factors for rheumatoid arthritis as well as Crohn's disease, but not for scleroderma.

Association between early onset and organ manifestations of systemic lupus erythematosus (SLE) and a down-regulating promoter polymorphism in the MBL2 gene.

The serum concentration of mannose-binding lectin (MBL) is genetically determined by a series of allelic polymorphisms in the MBL2 gene. Since several polymorphisms of the MBL2 gene have been suggested to be risk locus for systemic lupus erythematosus (SLE), we investigated MBL2 polymorphisms in 315 SLE patients from Hungary and 182 geographically matched healthy controls. Within the group of patients, we found that homozygotes for an MBL2 down-regulating promoter polymorphism at position -221 (YA to XA) (rs7096206) were significantly (p=0.017) younger at diagnosis than the other patients. The frequency of juvenile-onset SLE (