Nada Čikeš

Non-MS autoimmune demyelination

Connective tissue diseases can be characterised by central nervous system (CNS) involvement, in some patients manifested by demyelination areas in the white matter of the brain and spinal cord, which are difficult to differentiate from multiple sclerosis (MS) and other demyelinating processes, such as transverse myelitis and optic neuritis. Demyelinating process may be the feature of nervous impairment in systemic lupus erythematosus, Behcets disease (BD), Sjoegrens syndrome (SS), systemic sclerosis (SSc) or very rarely other systemic autoimmune diseases. An acute isolated neurological syndrome, as the most common symptom of MS can sometimes be the only feature or even first manifestation of nervous impairment in connective tissue disease, hence presenting the diagnostic problem. Although the white matter abnormalities seen by magnetic resonance imaging may be similar in non-MS autoimmune demyelination and MS, it is the most important diagnostic tool in the differential diagnosis of the mentioned conditions. Investigating the presence of various autoantibodies potentially involved in the pathogenesis of demyelinating lesions as well as cerebrospinal fluid (CSF) analysis can be helpful.

Antiphospholipid antibodies and atherosclerosis: Insights from Rheumatoid arthritis – A five-year follow-up study

OBJECTIVES Life expectancy in rheumatoid arthritis (RA) patients is reduced by 3-10 years, probably due to cerebrovascular and cardiovascular diseases associated with atherosclerosis. In the present study, we wanted to verify if previously reported IgA anti-beta 2-glycoprotein I (2GPI) antibodies possibly represented an independent risk factor for atherosclerosis in RA patients during a longer period of follow up. METHODS The follow-up study (after 5.5 years) comprised all initially included patients and controls (premenopausal women, non-diabetic, normotensive at the start of the study), except for two RA patients (one died and one not available). The same clinical, laboratory and ultrasound assessments were performed. RESULTS Patients and controls were divided into three categories: Intima-media thickness (IMT) progressors, plaque progressors, IMT and plaque progressors. In controls, 55% represented IMT progressors and 5% IMT and plaque progressors. No statistically significant differences were detected comparing the progressors with delta (Δ=difference between follow-up and baseline study for each group in a time span of 5.5 years) LDL cholesterol, homocysteine and IgA anti-β2GPI. In patients, there were 48.5% IMT progressors, 5.8% plaque progressors and 19.1% IMT and plaque progressors. The progression was statistically significant associated with the levels of Δ homocysteine and Δ apolipoprotein B but not with LDL cholesterol and IgA anti-β2GPI. CONCLUSIONS The follow-up study showed advanced atherosclerosis in RA patients compared to sex and age matched controls. However, we were not able to confirm our initial impression that IgA anti-β2GPI might represent an independent risk factor for atherosclerosis.

Differences and similarities in rheumatology specialty training programmes across European countries

Objectives To analyse the similarities and discrepancies between the official rheumatology specialty training programmes across Europe. Methods A steering committee defined the main aspects of training to be assessed. In 2013, the rheumatology official training programmes were reviewed for each of the European League Against Rheumatism (EULAR) countries and two local physicians independently extracted data on the structure of training, included competencies and assessments performed. Analyses were descriptive. Results 41 of the 45 EULAR countries currently provide specialist training in rheumatology; in the remaining four rheumatologists are trained abroad. 36 (88%) had a single national curriculum, one country had two national curricula and four had only local or university-specific curricula. The mean length of training programmes in rheumatology was 45 (SD 19) months, ranging between 3 and 72 months. General internal medicine training was mandatory in 40 (98%) countries, and was performed prior to and/or during the rheumatology training programme (mean length: 33 (19) months). 33 (80%) countries had a formal final examination. Conclusions Most European countries provide training in rheumatology, but the length, structure, contents and assessments of these training programmes are quite heterogeneous. In order to promote excellence in standards of care and to support physicians’ mobility, a certain degree of harmonisation should be encouraged.

Antibodies to Tamm-Horsfall Protein in Patients with Acute Pyelonephritis

The role of antibodies to Tamm-Horsfall protein in the diagnosis of acute pyelonephritis was studied. Antibodies to Tamm-Horsfall protein were also determined in a group of normal subjects. Patients with acute pyelonephritis were divided into subgroups according to the concurrent presence of vesicoureteral reflux or nephrolithiasis. No statistically significant differences (p > 0.05) were observed for any class of antibodies (IgG, IgA and IgM) between the groups of healthy subjects and patients with acute pyelonephritis, regardless of the presence or absence of vesicoureteral reflux or nephrolithiasis. Values for different antibody classes showed that IgM antibodies were the most abundant in all the groups examined. A difference in the values of IgM relative to IgA and IgG antibodies was found to be statistically significant in the patient group only (p < 0.05). In patients with vesicoureteral reflux, there was no statistically significant difference (p > 0.05) between the values of IgM and of other antibody classes. In these patients, however, the highest values of all the three antibody classes were obtained, although these differences were also not statistically significant (p > 0.05). The results pointed to the need of further studies of the role of antibodies to Tamm-Horsfall protein in the diagnosis and pathogenesis of tubulointerstitial nephritis.

Binding of Anti-Double Stranded (ds) DNA-Positive Sera to Denatured (d) DNA and Synthetic Poly[dA-dT] x Poly[dA-dT] Double Stranded Copolymer in an ELISA Format

Using an ELISA assay anti-nuclear antibody-positive sera from 300 patients with various immune-related diseases and 64 anti-nuclear antibody-negative sera were analysed for binding to S1-nuclease-treated double stranded (ds) DNA. In addition, the pattern of reactivity of 50 selected anti-dsDNA-positive sera was established using denatured (d) DNA and poly[dA-dT] X poly[dA-dT] double-stranded alternating copolymer (dAT) as additional DNA antigens. None of the 64 anti-nuclear antibody-negative sera and 76 of the 300 anti-nuclear antibody-positive sera (25%) were anti-dsDNA-positive. Of the anti-nuclear antibody-positive and anti-dsDNA-positive sera, 48 (63%) were from systemic lupus erythematosus patients, and 7 (9%) from rheumatoid arthritis patients, whereas 21 patients (27.6%) suffered from various immune and non-immune related diseases. Anti-dsDNA-positive reactivity was highly correlated with dDNA and dAT reactivity (r = 0.906, p < 0.0001 and r = 0.93, p < 0.0001, respectively). Although the majority of the 50 selected (37 systemic lupus erythematosus and 13 non-systemic lupus erythematosus) anti-dsDNA-positive sera concomitantly bound to both additional antigens, 7 of these (14%) did not bind to dAT, and 2 (4%) did not bind to dDNA. Anti-dsDNA-positive sera (n = 37) showed a similar pattern, in which 8.1% and 2.7% of sera did not bind to dAT and to dDNA, respectively. In contrast, anti-dsDNA-negative sera from various immune-related diseases bound either ssDNA (12.5%) or dDNA and dAT (12.5%). These data suggest that dsDNA and dAT-based assays detect similar but not identical specificities in the sera of patients suffering from systemic lupus erythematosus and in a proportion of non-systemic lupus erythematosus patients.