Flashcards in Lupus Deck (14):
What is systemic lupus erythematosus?
This is an autoimmune disease characterized by inflammation that may affect many tissues and organs within the body with patients often developing skin rashes and joint pain in the early stages along with fever in some patients
There may also be haematological involvement with reduced leucocyte and lymphocyte counts
They may also have pleuric chest pain due to inflammation of the pleura or pericardium
What are the autoantibodies seen in systemic lupus?
They typically have antibodies which are reactive against a wide range of antigens in various tissues with the most famous being antinuclear antibodies which react to various proteins normally found in cell nuclei
These are commonly found in low titre but in disease sufferers they are at a high titre
What is the important type of antinuclear antibody seen in lupus?
The antinuclear antibody to double stranded DNA, these are highly specific for a diagnosis of lupus and are present at high titre for those with kidney involvement
These will form circulating antibody complexes which may deposit adjacent to or within the basement membrane of the glomerulus and promote complement activation and inflammation
How can lupus patients develop thrombocytopenia?
Sometimes autoantibodies from to antigens on the surface of white blood cells or red blood cells or platelets resulting in premature destruction of these cells
If they form against platelets then these will be phagocytosed by macrophages which may cause thrombocytopenia if done on a large scale
What is the role of B cells in lupus?
Traditionally lupus has been described to be due to a lack of T cell regulation of B cell activity however this does not explain the effectiveness of B cell deleting therapies like rituximab (antiCD20)
There is B cell hyperactivity causing spontaneous proliferation and differentiation into plasma cells and antibody secretion, this hyperactivity may be mediated by the B cells themselves
What B cell signalling occurs in lupus?
There is increased calcium flux and increased serum levels of the B lymphocyte stimulator (Blys or BAFF)
What is the role of T cells in lupus?
T cells express less of the key cytokine IL-2
There are lower numbers of Treg cells
There is a reduction in the action of CD8 T cells
T cells express increased CD44 allowing faster migration to inflammation
Increased T cell expression of CD40L causing an increase the help they proved B cells
There is an increased proportion of the TH17 subset
What are the cytokines which play a key role in lupus?
Plasmacytoid dendritic cells are major produced of IFN-alpha which promotes B cell differentiation into plasma cells
IFN-alpha levels correlate with disease severity and anti-dsDNA titre
Sunburn and viruses increase IFN-alpha levels which can lead to lupus flares
What is the role of toll-like receptors in lupus?
They allow recognition of PAMPs and initiate the signalling which leads to TNF-alpha secretion
What is the role of complement activation in lupus?
Complement proteins may prevent lupus by binding to apoptotic cells and promoting clearance while complement consumption occurs in active lupus with low levels of C3 and C4
What are the clinical manifestations of lupus?
Haematological and immunological disorders
Anti nuclear antibodies
What are the methods which allow management of lupus?
Immunosuppressive therapies like Hydroxychloroquinine which stabilizes lysosomal membranes
Steroids which may be given orally or through IV
New biologics like Rituximab and belimumab
What are the epidemiological features of lupus?
It has a prevalence of 50:100000 with a female to male ratio of 9:1 it is more common in African americans/Maori/Pacific people but affects all races
The mean age of onset is 28 years
Tends to occur in women of child bearing years
It is also increased in Kleinfelter’s males suggesting a hormonal influence