Our data attribute a clinical relevance to both IgG and IgM aPS/PT antibodies. In particular, the significant prevalence of aPS/PT in APS-ne patients suggests including them as additional laboratory criterion for APS.
Positivity to IgA anti-β2GPI antibody detected using FEIA was found to be clinically relevant in PAPS patients. Moreover the prevalence of isolated IgA anti-β2GPI antibody positivity was significant in the seronegative patients.
Despite a lower comparative sensitivity, CLIA showed a higher comparative specificity for some aPL and a good level of agreement and correlation with a homemade ELISA. CLIA also detected some aCL and anti-β2GPI antibodies in the seronegative patients not usually identified by homemade ELISA.
Triggering of autoimmunity that leads to rheumatic disease has been suggested to depend upon gene-environment interactions occurring in epithelial barriers and associated immune cells. Genetic studies have identified associations of the FAM167A-BLK locus with rheumatoid arthritis, systemic lupus erythematosus (SLE) and Sjögren's syndrome. While BLK (B lymphocyte kinase) has a well-established role in B cells, family with sequence similarity to 167 member A (FAM167A) and its gene family remain uncharacterized. To begin to understand the role of FAM167A in rheumatic disease pathogenesis, we explored this gene family and cloned and investigated the gene products. Expression of quantitative trait locus analysis was performed in immune cells. FAM167A and FAM167B were cloned from human peripheral blood mononuclear cells (PBMC). Gene conservation and protein properties were analysed by online tools, mRNA expression measured in mouse organs by quantitative polymerase chain reaction (qPCR) and protein expression investigated in human tissues by immunohistochemistry. We found that autoimmune risk genotypes within the FAM167A-BLK locus lead to increased expression of FAM167A. The FAM167 gene family includes two members, FAM167A and FAM167B, which are not homologous to any other annotated gene but are evolutionarily conserved. The encoded proteins, which we denote 'disordered autoimmunity' (DIORA)-1 and DIORA-2, respectively, are characterized by a high content of intrinsic disorder. Notably, DIORA-1 has its highest expression in the lung, detectable in both bronchial epithelium and alveolar macrophages with an endosomal localization pattern. In summary, the FAM167A gene is associated with several rheumatic diseases and encodes a novel disordered protein, DIORA-1, which is expressed highly in the lung, consistent with a potential role in disease pathogenesis.
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