Lupus review
Dr. Mohammad Saeed’s Review on Lupus published in the journal “Immunogenetics”
‘The challenge will be more robust clinical classification of SLE. As more antibodies are discovered, such as MDA5 and PLA2R, and genetic tests seep into clinical practice, it is likely that SLE classification may change further. Perhaps, SLE clinical definition may incorporate a mandatory presence of nuclear antibodies (ANA and its subsets) and the nuclear-antibody negative SLE may be classified according to the specific antibodies or mutation findings.’…..’On the other hand, expert panels may take a more inclusive approach by subclassifying SLE into more refined phenotypes. Whatever the course SLE classification takes in the future, genetic exploration of this complex disease has not only enhanced its own pathobiology but opened doors to understanding autoimmune disease in general as well.’
Lay Summary of the Lupus Review
- Lupus is a syndrome rather than a single disease. 330 types of lupus are possible. Therefore, every lupus patient is unique.
- Lupus is initiated with aberrant processing of DNA (and RNA) during apoptosis. This means the clearance system of the body is defective and unable to remove properly the debris of dying cells.
- This nuclear material is picked up by cells of the immune system specifically plasmacytoid dendritic cells (pDCs) and B-cells which react to it (through intricate cellular pathways) by releasing high levels of interferon-alpha.
- These cells may be further activated by viral and bacterial infections or conditions like pregnancy.
- Both pDCs and B-cells present the nuclear material in immunoreactive forms (antigens) to T-cells which coordinate the formation of antibodies by the B-cells.
- The cells and antibodies attack the ‘self’-antigens in tissues such as the kidney and brain.
- This sets up a perpetual cycle of immunologic abnormalities that defines lupus – aberrant apoptosis followed by immune complex formation and deposition.
- Antibodies are often present in lupus but do not necessarily cause lupus. They however do indicate a dysfunctional immune system. SLE can result even without any detectable antibodies.
- SLE treatment has so far largely been guided by clinical experience. With the recent advent of targeted biologic therapies, this paradigm has started to change.
- Molecular analysis has shown the similaries and differences between various SLE drugs.
- Biologic medications such as Rituximab, Belimumab (both anti-B cell) and the upcoming Anifrolumab (designed against the interferon alpha receptor – anti-pDC and B-cell) are powerful lupus treatment medications.
- Given more than 100 genes now known for lupus and a plethora of antibodies, it is expected that the clinical disease definition of lupus will change as well. The new definition may be more clinically robust.
‘Lupus pathobiology based on genomics’