Lupus nephritis
It is worth address Lupus in general as a disease here, we will focus on the nephritis part of the condition a little bit later.
The current pathogenic model for understanding lupus is that of genetic susceptibility based on a threshold model involving multiple genes, environmental triggers (e.g. infection, sunlight and certain drugs) and altered immune function. Genes that account of increased lupus susceptibility include C1q, C2 and C4A coding genes (complement system). Additionally, regulation of interferon production (regulatory factor 5) and toll-like receptor pathways seem to be commonly affected. Other genetic pathways include MHC errors, HLA mutations, polymorphisms in Fc receptor genes and others. Viral environmental triggers are often cited as being important, especially the Epstein Barr virus. UV light can trigger flairs, the possible mechanism being a result of DNA damage.
The most characteristic lupus antibodies target intracellular particles of both nucleic acid and nucleic-binding proteins. Individuals with SLE present with positive antinuclear antibody (ANA) and anti-DNA antibodies.
Tissue damage in SLE is mediated by the deposition of immune complexes and subsequent complement activation and inflammation The classic pathway is the formation of antibody-antigen complexes which then initiate the complement pathway. So, consider this in the context of the risk factors above, let's say our patient gets a virus, this virus causes cellular lysis, exposing the DNA to the bodies immune system. Genetic susceptibility then means that there is the binding of antibodies to these parts of the self, giving us our Antibody-Antigen complexes which travel through the bloodstream and can be deposited causing damage. The damage caused by inflammation and activation of the complement system can be thought of as a Type III hypersensitivity disorder. However we can also get development of other specific antibodies that target red and white blood cells, and other tissues, via a Type II hypersensitivity mechanism.
The classic clinical presentation is:
- Fever
- Red skin rash
- Joint pain, all in a woman of a childbearing age
There are other genetic symptoms that appear as well however, and often additional layers of complexicity in diagnosis. As such, four of the below criteria must be met before we can give the diagnosis of SLE:
- Skin
- Malar (/butterfly) rash
- Discoid rash
- Photosensitivity of the skin
- Mucosa
- Ulcers (mouth or nose)
- Serosa
- Serositis (e.g. pleuritis, pericarditis)
- Joints
- Arthritis (2+ joints)
- Kidneys
- Renal disorders (abnormal urine protein, diffuse proliferative glomerulonephritis)
- Brain
- Seizures, psychosis
- Blood