Inborn errors of immunity and related microbiome.

Inborn errors of immunity (IEI) are characterized by diverse clinical manifestations that are dominated by atypical, recurrent, chronic, or severe infectious or non-infectious features, including autoimmunity, lymphoproliferative disease, granulomas, and/or malignancy, which contribute substantially to morbidity and mortality. Some data suggest a correlation between clinical manifestations of IEI and altered gut microbiota. Many IEI display microbial dysbiosis resulting from the proliferation of pro-inflammatory bacteria or a decrease in anti-inflammatory bacteria with variations in the composition and function of numerous microbiota. Dysbiosis is considered more established, mainly within common variable immunodeficiency, selective immunoglobulin A deficiency, severe combined immunodeficiency diseases, Wiskott-Aldrich syndrome, Hyper-IgE syndrome, autoimmune polyendocrinopathy-candidiasis-ectodermal-dystrophy (APECED), immune dysregulation, polyendocrinopathy, enteropathy X-linked (IPEX) syndrome, IL-10 receptor deficiency, chronic granulomatous disease, and Kostmann disease. For certain IEIs, the specific predominance of gastrointestinal, respiratory, and cutaneous involvement, which is frequently associated with dysbiosis, justifies the interest for microbiome identification. With the better understanding of the relationship between gut microbiota, host immunity, and infectious diseases, the integration of microbiota modulation as a therapeutic approach or a preventive measure of infection becomes increasingly relevant. Thus, a promising strategy is to develop optimized prebiotics, probiotics, postbiotics, and fecal microbial transplantation to rebalance the intestinal microbiota and thereby attenuate the disease activity of many IEIs.

Anti-double stranded DNA antibodies: A rational diagnostic approach in limited-resource settings.

Context: Anti-double-stranded deoxyribonucleic acid antibodies (dsDNA Abs) are highly specific markers of systemic lupus erythematosus (SLE). Multiple methods are employed for their detection in routine diagnostics. Objectives: The aim of this study was to evaluate a diagnostic approach for anti-dsDNA Abs using DNA-ELISA and Crithidia luciliae fluorescence test (CLIFT), in combination with antinuclear antibody (ANA) screening. Methods: We enrolled 113 patients-53 with SLE, 50 with other systemic autoimmune rheumatic diseases (OSARD), and 10 with non-autoimmune clinical conditions (NAICC).Patients' samples were tested for anti-dsDNA Abs using an enzyme-linked immunosorbent assay (ELISA) and CLIFT, combined to ANA screening by indirect immunofluorescence assay (ANA-IIFA). Results: The mean age of patients was 39.94 ± 15 years (ranges: 11-85 years). Overall, specimens from 77.3%, 11.7%, and 20% of patients with SLE, OSARD and NAICC respectively were ELISA-positive; and those from 54.7% to 4% of patients with SLE and OSARD, respectively, were CLIFT-positive. CLIFT positivity was significantly associated with high ELISA titers (p = 0.002) and homogeneous ANA-IIF pattern (p = 0.0002). Conclusion: For better clinical relevance of anti-dsDNA antibodies, we suggest a combined detection strategy based on ELISA, CLIFT and ANA-IIFA, considering the clinical criteria of SLE.