Demographic associations for autoantibodies in disease-free individuals of a European population

The presence of autoantibodies usually precedes autoimmune disease, but is sometimes considered an incidental finding with no clinical relevance. The prevalence of immune-mediated diseases was studied in a group of individuals from the Estonian Genome Project (n = 51,862), and 6 clinically significant autoantibodies were detected in a subgroup of 994 (auto) immune-mediated disease-free individuals. The overall prevalence of individuals with immune-mediated diseases in the primary cohort was 30.1%. Similarly, 23.6% of the participants in the disease-free subgroup were seropositive for at least one autoantibody. Several phenotypic parameters were associated with autoantibodies. The results suggest that (i) immune-mediated diseases are diagnosed in nearly one-third of a random European population, (ii) 6 common autoantibodies are detectable in almost one-third of individuals without diagnosed autoimmune diseases, (iii) tissue non-specific autoantibodies, especially at high levels, may reflect preclinical disease in symptom-free individuals, and (iv) the incidental positivity of anti-TPO in men with positive familial anamnesis of maternal autoimmune disease deserves further medical attention. These results encourage physicians to evaluate autoantibodies in addition to treating a variety of patient health complaints to detect autoimmune-mediated disease early.Peer reviewe

Autoantikehade esinemine täiskasvanutel (TÜ Eesti geenivaramu põhine uuring)

http://tartu.ester.ee/record=b2655892~S1*es

Roles of GM-CSF in the Pathogenesis of Autoimmune Diseases: An Update.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) was first described as a growth factor that induces the differentiation and proliferation of myeloid progenitors in the bone marrow. GM-CSF also has an important cytokine effect in chronic inflammatory diseases by stimulating the activation and migration of myeloid cells to inflammation sites, promoting survival of target cells and stimulating the renewal of effector granulocytes and macrophages. Because of these pro-cellular effects, an imbalance in GM-CSF production/signaling may lead to harmful inflammatory conditions. In this context, GM-CSF has a pathogenic role in autoimmune diseases that are dependent on cellular immune responses such as multiple sclerosis (MS) and rheumatoid arthritis (RA). Conversely, a protective role has also been described in other autoimmune diseases where humoral responses are detrimental such as myasthenia gravis (MG), Hashimoto\u27s thyroiditis (HT), inflammatory bowel disease (IBD), and systemic lupus erythematosus (SLE). In this review, we aimed for a comprehensive analysis of literature data on the multiple roles of GM-CSF in autoimmue diseases and possible therapeutic strategies that target GM-CSF production

Äsja diagnoositud 1. tüüpi diabeeti põdevatel täiskasvanutel ja lastel on IgA-tüüpi enteroviirustevastaste antikehade hulk suurenenud

Eesti Arst 2023; 102(4):23

Quality of Precise Point Positioning based on the measurements of the 1st order geodetic reference network of Estonia in 1997 and 2008

Antud töös käsitletakse GPS täpse positsioneerimise (PPP) järeltöötluse teenust, mis võimaldab ühe vastuvõtjaga mõõdetud andmete põhjal leida punktide koordinaadid hinnanguliselt kuni ±1 cm täpsusega ja on kõigile vabalt kättesaadav. Magistritöö eesmärgiks on hinnata PPP- meetodi täpsust riikliku geodeetilise põhivõrgu 1. klassi punktide 1997. a ja 2008. a GPS- mõõtmisandmete põhjal relatiivse andmetöötluse teel saadud koordinaatidega võrdlemise teel. Maa-ameti arhiivist saadud 1997. a ja 2008. a mõõtmisandmete RINEX failid on kokku liidetud 24-tunnisteks failideks ning järeltöödeldud CSRS ja APPS on-line kalkulaatoritega. Lõpptulemusena on arvutatud sessioonide kaalutud keskmine koordinaat, mille määramatust on hinnatud lahenduste korduvusest leitud standardhälbe põhjal. Hinnatud on kahe PPP-kalkulaatori lahenduste erinevusi ning PPP-lahenduste erinevust relatiivsest diferentseeritud lahendusest saadud koordinaatide suhtes. Tulemuste kohta on tabelid ja joonised. Uuringus selgus, et PPP-meetodil saadud koordinaatide erinevus võrreldes klassikalise relatiivse staatilise lahendusega jääb ±1 cm piiridesse nagu eeldati ning kahe PPP-lahenduse koordinaatide erinevus võib tulla on-line kalkulaatorite erinevatest parameetritest.In current thesis, the GPS precise point positioning (PPP) post-processing service is discussed, basing on measurement data found with one receiver, GPS precise positioning post-processing allows to find the coordinates of points with estimably up to ±1 cm accuracy and furthermore, the service is freely accessible for everyone. The aim of this master’s thesis is to assess the accuracy of PPP-method, basing on comparing the geodetic reference network 1st order points coordinates of 1997th and 2008th years’ GPS-measurements’ data, which have been found with relative data analysis. The 1997 and 2008 years’ measurement data RINEX files, obtained from Estonian Land Board, are added together to 24h files and post-processed with CSRS and APPS on-line calculators. As an end result, the weighted arithmetic mean of sessions is calculated, which’ uncertainty is assessed basing on standard deviation of solutions’ repeatability. The differences of two PPP-calculator solutions and PPP-solutions difference from coordinates found with relative differential solutions are being assessed. Tables and figures relating to results have been made. It came out, that the difference of coordinates found with PPP-method compared with classical relative statistical solutions remains in ±1 cm limits, as presumed. Furthermore, it came out, that the difference between coordinates of two PPP-solutions can be originated from different parameters of on-line calculators

Celiac Disease in Children, Particularly with Accompanying Type 1 Diabetes, Is Characterized by Substantial Changes in the Blood Cytokine Balance, Which May Reflect Inflammatory Processes in the Small Intestinal Mucosa

Cytokines play a pivotal role in the maintenance of intestinal homeostasis inducing pro- or anti-inflammatory response and mucosal barrier function in celiac disease (CD) and type 1 diabetes (T1D). We aimed to compare the levels of pro- and anti-inflammatory cytokines in CD patients without and with coexisting T1D, as well as to evaluate its association with the presence of enteroviruses (EV), regulatory T cells (Tregs), and dendritic cells (DCs) in small bowel mucosa. Altogether, 72 patients (median age 10.1 years) who had undergone small bowel biopsy were studied. The study group consisted of 24 patients with CD (median age 6.5 years), 9 patients with CD and concomitant T1D (median age 7.0 years), two patients with T1D (median age 8.5 years), and 37 patients (median age 14.0 years) with functional gastrointestinal disorders (FGD) and a normal small bowel mucosa as controls. The levels of 33 cytokines in serum were measured by multiple analysis using the Milliplex® MAP Magnetic Bead assay. The densities of FOXP3+ Tregs, CD11c+ DC, indoleamine 2,3-dioxygenase+ (IDO+) DC, langerin+ (CD207+) DCs, and EV were evaluated by immunohistochemistry as described in our previous studies. Circulating anti-EV IgA and IgG were evaluated using ELISA. The most important finding of the study is the significant increase of the serum levels of IL-5, IL-8, IL-13, IL-15, IL-17F, IL-22, IL-27, IP-10, MIP-1β, sIL-2Rα, sTNFRII, and TNFα in CD patients compared to controls and its correlation with the degree of small bowel mucosa damage graded according to the Marsh classification. The leptin level was higher in females in all study groups. The levels of IL-2, IL-6, IL-12 (P70), IL-15, IP-10, and IFNγ correlated significantly with the density of FOXP3+ Tregs in lamina propria of the small bowel mucosa, which supports the evidence about the signaling role of these cytokines in the peripheral maintenance of FOXP3+ Tregs. At the same time, a significant negative correlation occurred between the level of IL-4 and density of FOXP3+ Tregs in controls. Another important finding of our study was the correlation of IL-17F, IP-10, sTNFRII, MCP-1, and GM-CSF with the density of EV-positive cells in the lamina propria of the small bowel mucosa. Correlation of MIP-1 (CCL-4) with CD103+ DC and langerin+ DC densities may point to their significance in the recruitment of immune cells into the lamina propria and in driving the inflammatory response in CD patients. Our results suggest the predominance of Th1 and Th17 immune responses over EV VP1 protein in CD and T1D patients. The significant elevation of Th2 cytokines, like IL-5 and IL-13, but not IL-4, in CD patients and its correlation with the degree of small bowel mucosa damage could reflect the role of these cytokines in gut defense and inflammation

Changes in Blood B Cell-Activating Factor (BAFF) Levels in Multiple Sclerosis: A Sign of Treatment Outcome.

Multiple sclerosis (MS) is mediated primarily by autoreactive T cells. However, evidence suggesting the involvement of humoral immunity in brain diseases has increased interest in the role of B cells and their products during MS pathogenesis. The major survival factor for B cells, BAFF has been shown to play a role in several autoimmune conditions. Elevated BAFF levels have been reported in MS animal model and during MS relapse in patients. Moreover, disease-modifying treatments (DMT) reportedly influence blood BAFF levels in MS patients, but the significance of these changes remains unclear. The present study addresses how blood BAFF levels are associated with the clinical course of relapsing-remitting MS and the effectiveness of DMT and short-term steroid treatment. During a prospective longitudinal follow-up of 2.3 years, BAFF was measured in the blood of 170 MS patients in the stable phase and within 186 relapses. BAFF levels were significantly higher in MS patients compared to healthy controls. However, stable MS patients without relapses exhibited significantly higher BAFF levels than relapsing patients. Treatment with interferon-β and immunosuppressants raised BAFF blood levels. Interestingly, a similar effect was not seen in patients treated with glatiramer acetate. Short-term treatment with high doses of intravenous methylprednisolone did not significantly alter plasma BAFF levels in 65% of relapsing-remitting MS patients. BAFF were correlated weakly but significantly with monocyte and basophil counts, but not with other blood cell types (neutrophils, lymphocytes, or eosinophils) or inflammatory biomarkers. To our knowledge, this is the first report demonstrating that higher blood BAFF levels may reflect a more stable and effective MS treatment outcome. These results challenge hypotheses suggesting that elevated blood BAFF levels are associated with more severe disease presentation and could explain the recent failure of pharmaceutical trials targeting BAFF with soluble receptor for MS treatment