Clinical and serological associations of autoantibodies to the Ku70/Ku80 heterodimer determined by a novel chemiluminescent immunoassay.

BACKGROUND: Autoantibodies targeting Ku, an abundant nuclear protein with DNA helicase activity, have been reported in patients with systemic autoimmune rheumatic diseases. Little is known about the clinical associations of anti-Ku antibodies, especially when novel diagnostic technologies are used. The objective of the present study was to analyse the prevalence of anti-Ku antibodies in different medical conditions using a novel chemiluminescent immunoassay. PATIENTS AND METHODS: Serum samples from adult patients with systemic lupus erythematosus (SLE, n=305), systemic sclerosis (SSc, n=70) and autoimmune myositis patients (AIM, n=109) were the primary focus of the study. Results were compared with disease controls (rheumatoid arthritis, RA, n=30; infectious diseases, n=17) and healthy individuals (n=167). In addition, samples submitted for routine autoantibody testing from patients referred to a rheumatology clinic (n=1078) were studied. All samples were tested for anti-Ku antibodies by QUANTA Flash Ku chemiluminescent immunoassay (research use only, Inova Diagnostics, San Diego, USA) using full length recombinant human Ku. SLE patient samples were also tested for other autoantibodies. Clinical data of anti-Ku antibody positive patients (high titres) were obtained by retrospective chart review. RESULTS AND FINDINGS: In the disease cohorts, 30/305 (9.8%) SLE, 3/70 (4.3%) systemic sclerosis and 4/109 (3.7%) autoimmune myositis (AIM) patients were positive, respectively. The four positive AIM patients had an overlap myositis syndrome that included two patients with SLE. The three systemic sclerosis (SSc) positive samples had diagnoses of SSc/SLE overlap, diffuse cutaneous SSc, and early edematous phase SSc. In the control cohorts, 2/170 (1.2%) healthy individuals (all low titre), 0/30 (0.0%) (RA) and 0/17 (0.0%) infectious disease patients were positive. The area under the curve values were: 0.75 for SLE vs. controls, 0.68 for SSc vs. controls and 0.37 for AIM vs. CONTROLS: In the rheumatology clinic referral cohort, 12/1078 (1.1%) were positive for anti-Ku antibodies, nine showing low and three high titres. The diagnoses of the three high positive anti-Ku positive patients were: probable SLE, mixed connective tissue disease (MCTD) and ANA positive RA. CONCLUSION: Anti-Ku antibodies detected by chemiluminescent immunoassay are most prevalent in SLE. When found in AIM and SSc, they were associated with overlap syndrome and early SSc.

In vivo evaluation of brain damage in the course of systemic lupus erythematosus using magnetic resonance spectroscopy, perfusion-weighted and diffusion-tensor imaging.

Twenty-two neuropsychiatric (NPSLE) and 13 systemic lupus erythematosus (SLE) patients with a normal appearing brain on plain magnetic resonance (MR) as well as 20 age-matched healthy controls underwent MR spectroscopy (MRS), perfusion-weighted (PWI) and diffusion-tensor imaging (DTI). In MRS NAA/Cr, Cho/Cr and mI/Cr ratios were calculated from the posterior cingulate cortex and left parietal white matter. In PWI, values of cerebral blood volume (CBV) were assessed from 14 regions, including gray and white matter. In DTI fractional anisotropy (FA) values were obtained from 14 white matter tracts including projection, commissural and association fibers. All MR measurements were correlated with clinical data. SLE and NPSLE patients showed significantly (p < 0.05) lower NAA/Cr ratios within both evaluated regions and FA values within the cingulum, as well as a tendency to cortical hypoperfusion. Compared to SLE, NPSLE subjects revealed lower FA values within a wide range of association fibers and corpus callosum. Advanced MR techniques are capable of in vivo detection of complex microstructural brain damage in SLE and NPSLE subjects regarding neuronal loss, mild hypoperfusion and white matter disintegrity. MRS and DTI seem to show the highest usefulness in depicting early changes in normal appearing gray and white matter in SLE patients.

Antinuclear and antiphospholipid antibodies in patients with multiple sclerosis.

The prevalence of autoantibodies in multiple sclerosis (MS) patients and their clinical associations differ between various studies. This study investigated antiphospholipid and antinuclear antibodies in 85 patients with multiple sclerosis (MS) and clinically isolated syndrome (CIS) with regard to their association with demographic features, MS specific clinical features and symptoms of connective tissue diseases. Autoantibodies tested included antinuclear antibodies (ANA) with their specificities and anticardiolipin (aCL) and anti-beta-2-glycoprotein I (anti-ß2GPI) antibodies. Antinuclear antibodies were more prevalent in MS patients than in controls (63.5% vs. 3.3%; p < 0.01) and in 19% of patients specific antinuclear antibodies were detected. Anti-ß2GPI IgM antibodies were more frequent in MS patients than in the control group (20% vs. 3.3%; p < 0.05). The frequency of anticardiolipin antibodies did not differ between MS patients and controls. MS patients seropositive for ANA and extractable nuclear antigens (ENA) had significantly shorter disease duration than seronegative patients (p < 0.05) and a lower disability score (Expanded Disability Status Score; EDSS) (p < 0.05). Anti-ß2GPI antibodies were more frequent in patients with secondary progressive MS (SP-MS) and specific ANA antibodies were more frequent in patients with clinically isolated syndrome (CIS) (p < 0.05). The presence of autoantibodies was not associated with the predominant site of neurological involvement or the clinical features of connective tissue diseases.

The development of a simple questionnaire to screen patients with SLE for the presence of neuropsychiatric symptoms in routine clinical practice.

AIM: The creation of a physician-administered questionnaire to screen patients with Systemic Lupus Erythematosus (SLE) for the presence of symptoms suggestive of neuropsychiatric involvement (NPSLE). METHODS: The development of the questionnaire followed three phases. First, a list of manifestations was prepared based on the ACR case definitions for NPSLE. A first questionnaire was constructed including 119 items. To reduce their number, a Delphi analysis was carried out and a second questionnaire with 62 questions was developed. This questionnaire was administered to 139 patients with SLE (58 with NPSLE: 29 active, 29 inactive; and 81 without NPSLE: 39 active, 42 inactive). Questions relevant to the screening of patients were selected on the basis of the receiver operating characteristic (ROC) curve analysis. RESULTS: Twenty-seven questions concerning central nervous system and psychiatric manifestations were found to be relevant; the remaining could be eliminated without significantly affecting AUC. The area under the ROC curve (AUC) was 0.69 (95% CI 0.61-0.78). A score above 17 was considered as suggestive of the presence of NPSLE with a sensitivity of 92.9% (95% CI 85.1-97.3 %) and specificity of 25.4% (95% CI 14.7-39.00 %). CONCLUSIONS: This questionnaire could represent a 'core set' of questions that could help in clinical practice to identify patients with neuropsychiatric symptoms requiring further evaluation.

Rheumatoid arthritis in a patient with common variable immunodeficiency: difficulty in diagnosis and therapy.

Common variable immunodeficiency (CVID) is the most frequent primary immunodeficiency syndrome in adults with equal sex prevalence. The syndrome typically presents as recurrent infections, with onset in childhood or young adulthood (between 20 and 30 years). CVID patients also have a higher prevalence of autoimmune diseases. A 38-year-old woman presented to the Rheumatology Department with polyarthralgia and fever of 39 degrees C of several months' duration. She had recurrent respiratory and gastrointestinal tract infections and pernicious anemia. Immunological studies showed decreased levels of IgG, IgM, complete IgA deficiency, increased percentage of CD8 lymphocytes, and a reduced CD4:CD8 ratio. HLA-DR typing was performed and we identified HLA-DRB1*01. Adequate intravenous immune globulin substitution as well as antibiotic and anti-inflammatory treatment resulted in the remission of arthritis. Hand radiograms repeated after 12 months showed narrowing of the intra-articular space in the right metacarpophalangeal and radiocarpal joints with multiple bone cysts and erosions. Erosions were found in both humeral heads as well. This prompted the diagnosis of rheumatoid arthritis. Arthritis can be a presenting symptom of primary immunodeficiency in adults, especially when accompanied by recurrent infections or autoimmune diseases. These patients require more advanced diagnostic procedures and therapeutic cooperation of different specialists.

Familial inflammatory Sneddon's syndrome-case report and review of the literature.

Sneddon's syndrome (SNS) which originally was a clinical diagnosis, is now regarded as a common clinical manifestation of different disease entities. It has been divided into idiopathic, autoimmune and thromboembolic subsets or in systemic lupus erythematosus (SLE)-associated, antiphospholipid syndrome (APS)-associated and primary forms. Familial occurrence of Sneddon's syndrome is rare. We present a familial case of Sneddon's syndrome with inflammatory disease pattern, early disease onset and association with autoimmune thyroid disease and anticardiolipin antibodies. Although most authors reporting on adult cases of SNS consider it a non-inflammatory, thromboembolic process, the study of cases with early onset brings attention to the possible inflammatory origin of the syndrome.