Research by Becker Y, et al.
The production of antibodies to components of the cell nucleus (i.e., ANAs) is the most characteristic immunologic feature of SLE, although autoantibodies to cytoplasmic antigens also occur. Recognition of autoantibodies to cytoplasmic antigens is important because antibodies to ribosomal P proteins, for example, are highly associated with SLE. Thus, the use of the term ANA can be misleading for serologic testing, especially if a laboratory calls a sample with cytoplasmic staining negative; the term anti-cellular antibody may be preferred to ANA to be more inclusive and call attention to autoreactivity against cytoplasmic targets.
Recently, investigators have identified antibodies to mitochondria in the sera of patients with SLE, an interesting finding because mitochondria, a cellular organelle, have intrinsic immunostimulatory properties due to molecular similarities to bacteria (e.g., DNA with unmethylated CpG motifs). The anti-mitochondrial antibodies in SLE differ, however, from those in primary biliary cholangitis.
As the study by Becker et al. demonstrates, the complement component 1Q subcomponent binding protein (C1qBP) and mitofusin 1 (Mfn1) are members of the mitochondrial proteasome that can serve as autoantigens in SLE and show associations with serological markers for the antiphospholipid antibody syndrome.
Studies like this are important to expand and clarify the serological profile of SLE, as well as focus attention on the mitochondria as a unique source of autoantigens that can drive SLE.
Abstract 0888—Disease flares in lupus are concordant with Ruminococcus blautia gnavus blooms within unstable gut microbiota communities11
Research by Azzouz D, et al.
The study by Azzouz et al. provides new insights into the role of the microbiome in the pathogenesis of SLE. The microbiome represents the huge collection of bacteria, fungi and viruses that inhabit locales around the body, with the gut microbiome attracting the most investigative interest because of its size and role in metabolism and immune regulation. Dysbiosis is a disturbance in the usual composition of the microbiome, potentially contributing to disease susceptibility.
Among disturbances documented in this study, longitudinal instability of organisms in the gut in SLE is notable, with transient spikes of potentially pathogenic organisms, such as Ruminococcus blautia gnavus, occurring, especially in patients with renal disease. As the molecular analyses of the ribosomal genes of the bacteria indicated, blooms of Ruminococcus blautia gnavus can coincide with disease flares. This finding could suggest that blooms impair the gut barrier function allowing translocation of bacterial products into the circulation to drive inflammation.