Analysis of the impact of sex and age on the variation in the prevalence of antinuclear autoantibodies in Polish population: a nationwide observational, cross-sectional study

The detection of antinuclear autoantibody (ANA) is dependent on many factors and varies between the populations. The aim of the study was first to assess the prevalence of ANA in the Polish adult population depending on age, sex and the cutoff threshold used for the results obtained. Second, we estimated the occurrence of individual types of ANA-staining patterns. We tested 1731 patient samples using commercially available IIFA using two cutoff thresholds of 1:100 and 1:160. We found ANA in 260 participants (15.0%), but the percentage of positive results strongly depended on the cutoff level. For a cutoff threshold 1:100, the positive population was 19.5% and for the 1:160 cutoff threshold, it was 11.7%. The most prevalent ANA-staining pattern was AC-2 Dense Fine speckled (50%), followed by AC-21 Reticular/AMA (14.38%) ANA more common in women (72%); 64% of ANA-positive patients were over 50 years of age. ANA prevalence in the Polish population is at a level observed in other highly developed countries and is more prevalent in women and elderly individuals. To reduce the number of positive results released, we suggest that Polish laboratories should set 1:160 as the cutoff threshold.

Development of fibrosis and impairment of lung function in patients with a new coronavirus disease

The aim: review scientific research to find out whether the new coronavirus infection (NCI) causes fibrotic changes in the lungs and, if any, how long they persist and whether functional disorders of the respiratory system accompany them. Disruption of the functional state of the lungs in patients with severe novel coronavirus disease (COVID-19) is still seen 6 months after completion of inpatient treatment. High-resolution computed tomography (HRCT) demonstrates persistent pathological changes in the lungs, some of which are fibrosis-like. Pathomorphological features of the COVID-19 course, as well as the ability of the virus to activate connective tissue growth factor (CTGF) and enhance the signaling of transforming growth factor-beta (TGF-β), can contribute to lung tissue fibrosis. Increased titers of antinuclear autoantibodies and specific autoantibodies indirectly reveal dysregulation of the immune response leading to the progression of organizing pneumonia and fibrotic changes in the lung tissue. These increased titers can also indicate the need to prescribe immunosuppressive and antifibrotic drugs. Researchers are considering the possibility of including antifibrotic drugs in combination therapy for severe COVID-19 in the early stages of treatment in patients with risk factors for developing pulmonary fibrosis. However, further monitoring and determination of the role of antifibrotic drugs are required. Sometimes patients with COVID-19 develop severe, irreversible fibrotic lung disease, and lung transplantation is the only treatment option.Conclusion. There is no unequivocal opinion among researchers concerning the clinical significance and further prognosis of COVID-19 so far, which is a reason for further studies.

Functional IKK/NF-κB Signaling in Pancreatic Stellate Cells is Essential to Prevent Autoimmune Pancreatitis

Pancreatic stellate cells (PSCs) are resident cells in the exocrine pancreas which contribute to pancreatic fibrogenesis and inflammation. Studies on NF-κB in pancreatitis so far focused mainly on the parenchymal and myeloid compartments. Its function in PSCs during chronic pancreatitis has not been investigated. Here we show a protective immunomodulatory function of NF-κB in PSCs. Conditional deletion of NEMO(IKKγ) in PSCs leads to spontaneous pancreatitis with elevated circulating IgM, IgG and antinuclear autoantibodies (ANA) within 18 weeks. When further challenged with experimental chronic pancreatitis, NEMOΔCol1a2 mice show an exacerbated autoimmune phenotype characterized by increased infiltration of eosinophils, B and T lymphocytes with extremely reduced latency period. These mice fail to recover even 18 weeks after the induction of pancreatitis but show sustained fibrosis and elevated eosinophil infiltration. Transcriptomic profiling shows that NEMOΔCol1a2 mice display molecular signatures resembling autoimmune pancreatitis patients. Mechanistically, we show that PSCΔNEMO cells have higher fibrogenic activities (upregulated Col1a1 and Col3a1) and produce high levels of eotaxin-2 (CCL24) which contributes to eosinophil recruitment. Corticosteroid treatment strongly attenuates the autoimmune phenotype in NEMOΔCol1a2 mice. Our findings uncover an important and unexpected immunomodulatory role specifically of NF-κB in PSCs and its deregulation may be a trigger of autoimmune pancreatitis.

Prevalence of anti-nuclear autoantibodies (ANA) in the general Polish population - analysis of the influence of sex and age on the variability of ANA.

Objectives: Diagnosis of Systemic Autoimmune Rheumatic Diseases using antinuclear autoantibodies (ANA) is dependent on many factors and varies between populations, such that the screening dilution used for indirect immunofluorescence assay (IIFA) should be defined locally for each population. The aim of the study was firstly, to assess the prevalence of ANA in the Polish adult population depending on age, sex and the cut-off threshold used for the results obtained. Second, we estimated the occurrence of individual types of ANA staining patterns.Methods: The tested material included serum samples from 1731 participants (1043 women and 688 men) that were tested with the commercially available IIFA using two cut-off thresholds 1:100 and 1:160.Results: We found ANA in 260 participants (15.0%), but the percentage of positive results strongly depended on the cut-off level. For a cut-off threshold 1:100, the positive population was 19.5% and for the 1:160 cut-off threshold, it was 11.7%. The most prevalent ANA staining pattern was AC-2 Dense Fine speckled (50%), followed by AC-21 Reticular/AMA (14.38%) ANA were more common in women (72%); 64% of ANA positive patients were over 50 years of age.Conclusion: ANA prevalence in the Polish population is at a level observed in other highly developed countries. ANA were more prevalent in women and elderly individuals. In order to reduce the number of positive results released, we suggest that Polish laboratories should set 1:160 as the cut-off threshold.

Antinuclear Autoantibodies in Health: Autoimmunity Is Not a Synonym of Autoimmune Disease

The incidence of autoimmune diseases is increasing. Antinuclear antibody (ANA) testing is a critical tool for their diagnosis. However, ANA prevalence in healthy persons has increased over the last decades, especially among young people. ANA in health occurs in low concentrations, with a prevalence up to 50% in some populations, which demands a cutoff revision. This review deals with the origin and probable physiological or compensatory function of ANA in health, according to the concept of immunological clearance, theory of autoimmune regulation of cell functions, and the concept of functional autoantibodies. Considering ANA titers ≤1:320 as a serological marker of autoimmune diseases seems inappropriate. The role of anti-DFS70/LEDGFp75 autoantibodies is highlighted as a possible anti-risk biomarker for autoimmune rheumatic disorders. ANA prevalence in health is different in various regions due to several underlying causes discussed in the review, all influencing additive combinations according to the concept of the mosaic of autoimmunity. Not only are titers, but also HEp-2 IFA) staining patterns, such as AC-2, important. Accepting autoantibodies as a kind of bioregulator, not only the upper, but also the lower borders of their normal range should be determined; not only their excess, but also a lack of them or “autoimmunodeficiency” could be the reason for disorders.

Antinuclear Autoantibodies in Health: Autoimmunity Is Not a Synonym of Autoimmune Disease

Incidence of autoimmune diseases increases. Antinuclear antibodies (ANA) testing is a critical tool for their diagnosis. However, ANA prevalence in health increased over last decades, especially among young people. ANA in health occur in low concentrations, with prevalence up to 50% in some populations, which demands a cutoff revision. The review deals with origin and probable physiological or compensatory function of ANA in health, according to the concept of immunological clearance, theory of autoimmune regulation of cell functions and the concept of functional autoantibodies. Considering ANA titers ≤1:320 as a serological marker of autoimmune diseases seems inappropriate. The role of anti-DFS70/LEDGFp75 autoantibodies is highlighted as possible anti-risk biomarker for autoimmune rheumatic disorders. ANA prevalence in health is different in various regions due to several underlying causes discussed in the review, all influencing in additive combinations according to the concept of the mosaic of autoimmunity. Not only titer, but the HEp-2 IFA staining patterns, like AC-2, is also important. Accepting autoantibodies as a kind of bioregulators, not only upper, but also lower borders of their normal range should be determined. Not only their excess, but also lack of them or “autoimmunodeficiency” could be a reason of disorders.

The Roles of Autoimmunity and Biotoxicosis in Sick Building Syndrome as a “Starting Point” for Irreversible Dampness and Mold Hypersensitivity Syndrome

Background: The terminology of “sick building syndrome” (SBS), meaning that a person may feel sick in a certain building, but when leaving the building, the symptoms will reverse, is imprecise. Many different environmental hazards may cause the feeling of sickness, such as high indoor air velocity, elevated noise, low or high humidity, vapors or dust. The Aim: To describe SBS in connection with exposure to indoor air dampness microbiota (DM). Methods: A search through Medline/Pubmed. Results and Conclusions: Chronic course of SBS may be avoided. By contrast, persistent or cumulative exposure to DM may make SBS potentially life-threatening and lead to irreversible dampness and mold hypersensitivity syndrome (DMHS). The corner feature of DMHS is acquired by dysregulation of the immune system in the direction of hypersensitivities (types I–IV) and simultaneous deprivation of immunity that manifests as increased susceptibility to infections. DMHS is a systemic low-grade inflammation and a biotoxicosis. There is already some evidence that DMHS may be linked to autoimmunity. Autoantibodies towards, e.g., myelin basic protein, myelin-associated glycoprotein, ganglioside GM1, smooth muscle cells and antinuclear autoantibodies were reported in mold-related illness. DMHS is also a mitochondropathy and endocrinopathy. The association of autoimmunity with DMHS should be confirmed through cohort studies preferably using chip-based technology.