Objective Autoantibodies are highly characteristic of primary Sjögren's syndrome (SS) and represent important tools for studying its pathogenesis. Nonetheless, thus far, no systematic investigations have assessed the presence of autoantibodies before diagnosis. This study was undertaken to analyze how early and in what order autoantibodies appear, how predictive they are of primary SS, and whether they identify disease subsets. Methods A nested case–control design linking data from the Malmö primary SS registry and 3 Swedish healthcare biobanks was applied. In all, 175 serum samples obtained from 117 individuals before diagnosis of primary SS and 1 serum sample from each of 117 matched controls were analyzed for antinuclear antibodies (ANAs), rheumatoid factor (RF), and antibodies against Ro 60/SSA, Ro 52/SSA, and La/SSB. Results Considering all patients with primary SS who were autoantibody positive after diagnosis, at least one autoantibody specificity was detected in 81% up to 20 years (median 4.3–5.1 years) before diagnosis. Those found most often were ANAs, followed by RF, anti–Ro 60/SSA, anti–Ro 52/SSA, and anti‐La/SSB. Anti‐Ro/SSA and anti‐La/SSB antibodies were strongly associated with the risk of developing primary SS, especially early‐onset disease and a severe disease course. When Bayesian prior prevalence estimates for primary SS were included in the calculation, prediagnostic anti–Ro 60/SSA and anti–Ro 52/SSA had the highest positive predictive values (25% and 100%, respectively). Conclusion Our findings indicate that autoantibodies are present for up to 18–20 years before the diagnosis of primary SS, but we cannot exclude even earlier seropositivity, since for most patients, the earliest sample analyzed was positive. In families with multiple cases of autoimmune disease, autoantibody profiling, along with assessment of genetic risk, enables identification of susceptible individuals in a predisease state.

Summary The possible role of leukotriene D4(LTD4)in nasal allergy was investigated in healthy volunteers. Nasal blood flow, nasal airway resistance, nasal discharge and nasal itching and sneezing were examined. LTD4 was found to induce a dose‐response related increase in nasal mucosal blood flow as measured by laser‐Doppler flowmetry. Histamine exhibited similar effects on blood flow in the same concentration range. Nasal airway resistance as recorded by rhinomanometry, increased in a dose‐related manner after topical LTD4. Nasal secretion was obtained by nasal lavage and estimated from a dilution principle. Topical LTD4 did not increase the amount of nasal secretion, whereas a dose‐related increase was found after topical histamine. LTD4 did not cause itching, sneezing or other irritative symptoms. In conclusion, LTD4 may play a role in nasal allergy by increasing blood flow and nasal airway resistance. Itching, sneezing and discharge, however, are apparently not caused by LTD4 but can be accounted for by the release of histamine or other mediators.

BackgroundAltered microbial composition of the intestine, commonly referred to as dysbiosis, has been associated with several autoimmune diseases including primary Sjögren’s syndrome (pSS). The aims of the current study were to study the intestinal microbial balance in pSS and to identify clinical features associated with dysbiosis.MethodsForty-two consecutive pSS patients and 35 age-matched and sex-matched control subjects were included in the study in an open clinic setting. Stool samples were analyzed for intestinal dysbiosis using a validated 16S rRNA-based microbiota test (GA-map™ Dysbiosis Test; Genetic Analysis, Oslo, Norway). Dysbiosis and severe dysbiosis were defined in accordance with the manufacturer’s instructions. Patients were evaluated with regard to disease activity (European League Against Rheumatism (EULAR) Sjögren’s Syndrome Disease Activity Index (ESSDAI) and Clinical ESSDAI (ClinESSDAI)). In addition, patients were examined for laboratory and serological features of pSS as well as fecal calprotectin levels.Furthermore, patients were investigated regarding patient-reported outcomes for pSS (EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI)) and irritable bowel syndrome (IBS)-like symptoms according to the Rome III criteria.ResultsSevere dysbiosis was more prevalent in pSS patients in comparison to controls (21 vs 3%; p = 0.018). Subjects with pSS and severe dysbiosis had higher disease activity as evaluated by the ESSDAI total score (13 vs 5; p = 0.049) and the ClinESSDAI total score (12 vs 5; p = 0.049), lower levels of complement component 4 (0.11 vs 0.17 g/L; p = 0.004), as well as higher levels of fecal calprotectin (110 vs 33 μg/g; p = 0.001) compared to the other pSS patients. In contrast, severe dysbiosis among pSS patients was not associated with disease duration, IBS-like symptoms, or the ESSPRI total score.ConclusionsSevere intestinal dysbiosis is a prevalent finding in pSS and is associated both with clinical and laboratory markers of systemic disease activity as well as gastrointestinal inflammation. Further studies are warranted to elucidate a potential causative link between dysbiosis and pSS.

No abstract

Recombinant Can f 4 brings the panel of available dog allergens closer to completion and will be important in component-resolved diagnostics in allergy to animal epithelial allergens.