Pulmonary arterial hypertension and interstitial lung fibrosis in systemic sclerosis: One-stop shop assessment with cardiac and chest ultrasound

Background: Interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) are common complications of systemic sclerosis (SSc). Echocardiography evaluates PAH, and chest sonography detects even mild ILC as ultrasound lung comets (ULC), i.e. multiple comet-tails fanning out from the lung surface and originating from subpleural interlobular septa thickened by fibrosis. Aim: to assess ILD and PAH by integrated cardiac and chest ultrasound in SSc. Materials and methods: We enrolled 30 consecutive SSc patients (age=54?13 years, 23 females) in the Rheumatology Clinic of Pisa University. In all, we assessed Systolic Pulmonary Arterial Pressure (SPAP), from maximal velocity of tricuspid regurgitation flow, and ULC score with chest sonography (summing the number of ULC from each scanning space of anterior and posterior right and left chest, from second to fifth intercostal space). All patients underwent plasma assay for anti-topoisomerase antibodies (anti-Scl70), associated with development of pulmonary fibrosis. Twenty-eight patients also underwent High Resolution Computed Tomography, HRCT (from 0=no fibrosis to 3=honey combing). Results: ULC number - but not SPAP - was correlated to HRCT fibrosis and presence SSc-70 antibodies (see figure). ULC number was similar in localized or diffuse forms (16?20 vs. 21?19, p=ns) and was unrelated to SPAP (r=0.216, p=ns). Conclusions: Cardiac and chest sonography assessment of SPAP and ULC allow a complete, simple, radiation-free characterization of vascular and interstitial lung involvement in SSc - all in one setting and with the same instrument, same transducer and the same sonographer. In particular, ULC number, but not SPAP, is associated with HRCT evidence of lung fibrosis and presence of Scl-70 antibodies

The Role of Osteopontin (OPN/SPP1) Haplotypes in the Susceptibility to Crohn's Disease

Osteopontin represents a multifunctional molecule playing a pivotal role in chronic inflammatory and autoimmune diseases. Its expression is increased in inflammatory bowel disease (IBD). The aim of our study was to analyze the association of osteopontin (OPN/SPP1) gene variants in a large cohort of IBD patients. Genomic DNA from 2819 Caucasian individuals (n = 841 patients with Crohn's disease (CD), n = 473 patients with ulcerative colitis (UC), and n = 1505 healthy unrelated controls) was analyzed for nine OPN SNPs (rs2728127, rs2853744, rs11730582, rs11739060, rs28357094, rs4754 = p.Asp80Asp, rs1126616 = p.Ala236Ala, rs1126772 and rs9138). Considering the important role of osteopontin in Th17-mediated diseases, we performed analysis for epistasis with IBD-associated IL23R variants and analyzed serum levels of the Th17 cytokine IL-22. For four OPN SNPs (rs4754, rs1126616, rs1126772 and rs9138), we observed significantly different distributions between male and female CD patients. rs4754 was protective in male CD patients (p = 0.0004, OR = 0.69). None of the other investigated OPN SNPs was associated with CD or UC susceptibility. However, several OPN haplotypes showed significant associations with CD susceptibility. The strongest association was found for a haplotype consisting of the 8 OPN SNPs rs2728127-rs2853744-rs11730582-rs11439060-rs28357094-rs112661-rs1126772-rs9138 (omnibus p-value = 2.07×10⁻⁸). Overall, the mean IL-22 secretion in the combined group of OPN minor allele carriers with CD was significantly lower than that of CD patients with OPN wildtype alleles (p = 3.66×10⁻⁵). There was evidence for weak epistasis between the OPN SNP rs28357094 with the IL23R SNP rs10489629 (p = 4.18×10⁻²) and between OPN SNP rs1126616 and IL23R SNP rs2201841 (p = 4.18×10⁻²) but none of these associations remained significant after Bonferroni correction. Our study identified OPN haplotypes as modifiers of CD susceptibility, while the combined effects of certain OPN variants may modulate IL-22 secretion

ACTIVATION OF MURINE AUTOREACTIVE B-CELLS BY INTERLEUKIN 1-LIKE FACTORS RELEASED FROM SYNOVIAL INFLAMMATORY CELLS OF RHEUMATOID-ARTHRITIS PATIENTS

The effect of interleukin 1 (IL-1)-like factor(s), produced by cells isolated from the synovial fluids of rheumatoid arthritis (RA) patients, on an in vitro murine model of spontaneous autoimmunity, i.e., the development of plaque-forming cells (PFC) to bromelain-treated mouse red blood cells (Br-MRBC) in mouse peritoneal cell (PC) cultures, has been investigated. It has been found that IL-1-containing culture supernatants from cells isolated from joint fluids of RA patients, as well as recombinant IL-1, determine a marked increase in anti-Br-MRBC PFC development. Moreover, factor(s) of 10-20 KD molecular weight, with IL-1-like biological activity, capable of increasing the anti-Br-MRBC PFC development in mouse PC cultures, have been demonstrated in joint fluids from RA patients. The finding that synovial inflammatory cells produce factors that activate autoreactive B cells further supports the role of autoimmunity in the pathogenesis of rheumatoid arthritis, as self-perpetuing disorder

Xenotropic Murine Leukemia Virus-Related Virus Infection in Italian Patients with Chronic Fatigue Syndrome, Fibromyalgia or Rheumatoid Arthritis

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