Systemic lupus erythematosus (SLE or lupus) is a chronic Type III Hypersensitivity (Systemic Immune Complex Disease) with potential Type II Hypersentivity involvement, potentially debilitating and sometimes fatal autoimmune disease in which the immune system attacks the body?s cells and tissue, resulting in inflammation and tissue damage. SLE can affect any part of the body, but often harms the heart, joints (rheumatological), skin, lungs, blood vessels and brain/nervous system. Lupus is treatable, mainly with immunosuppression, though there is currently no cure for it.
Abnormalities in apoptosis
* Apoptosis is increased in monocytes and keratinocytes
* Expression of Fas by B cells and T cells is increased
* There are correlations between the apoptotic rates of lymphocytes and disease activity
Tingible body macrophages (TBMs) are large phagocytic cells in the germinal centers of secondary lymph nodes. They express CD68 protein. These cells normally engulf B cells which have undergone apoptosis after somatic hypermutation. In some patients with SLE, significantly fewer TBMs can be found, and these cells rarely contain material from apoptotic B cells. Also, uningested apoptotic nuclei can be found outside of TBMs. This material may present a threat to the tolerization of B cells and T cells.
Dendritic cells in the germinal center may endocytose such antigenic material and present it to T cells, activating them. Also, apoptotic chromatin and nuclei may attach to the surfaces of follicular dendritic cells and make this material available for activating other B cells which may have randomly acquired self-specificity through somatic hypermutation.
Common initial and chronic complaints are fever, malaise, joint pains, myalgias and fatigue. Because they are so often seen with other diseases, these signs and symptoms are not part of the diagnostic criteria for SLE. When occurring in conjunction with other signs and symptoms, however, they are considered suggestive.
Dermatological manifestations: As many as 30% of patients present with some dermatological symptoms (and 65% suffer such symptoms at some point), with 30% to 50% suffering from the classic malar rash (or butterfly rash) associated with the disease. Patients may present with discoid lupus (thick, red scaly patches on the skin). Alopecia, mouth, nasal, and vaginal ulcers, and lesions on the skin are also possible manifestations.
Musculoskeletal manifestations: Patients most often seek medical attention for joint pain, with small joints of the hand and wrist usually affected, although any joint is at risk. Unlike rheumatoid arthritis, SLE arthropathy is not usually destructive of bone, however, deformities caused by the disease may become irreversible in as many as 20% of patients.
Hematological manifestations: Anemia and iron deficiency may develop in as many as half of patients. Low platelet and white blood cell counts may be due to the disease or a side-effect of pharmacological treatment. Patients may have an association with antiphospholipid antibody syndrome (a thrombotic disorder) where autoantibodies to phospholipids are present in the patient's serum. Abnormalities associated with antiphospholipid antibody syndrome include a paradoxical prolonged PTT (which usually occurs in hemorrhagic disorders) and a positive test for antiphospholipid antibodies, the combination of such findings have earned the term "lupus anticoagulant positive". Another autoantibody finding in lupus is the anticardiolipin antibody which can cause a false positive test for syphillis.
Cardiac manifestations: Patients may present with inflammation of various parts of the heart: pericarditis, myocarditis and endocarditis. The endocarditis of SLE is characteristically non-infective (Libman-Sacks endocarditis), and involves either the mitral valve or the tricuspid valve. Atherosclerosis also tends to occur more often and advance more rapidly in SLE patients than in the general population. (Asanuma et al 2003, Hahn 2003, Roman et al 2003).
Pulmonary manifestations: Lung and plura inflammation can cause pleuritis, pleural effusion, lupus pneumonitis, chronic diffuse interstitial lung disease, pulmonary hypertension, pulmonary emboli, pulmonary hemorrhage.
Renal involvement: Painless hematuria or proteinuria may often be the only presenting renal symptom. Acute or chronic renal impairment may develop with lupus nephritis, leading to acute or end stage renal failure. Because of early recognition and management of SLE, end stage renal failure occurs in less than 5% of patients.
Histologically, a hallmark of SLE is membranous glomerulonephritis with "wire loop" abnormalities. This finding is due to immune complex deposition along the glomerular basement membrane leading to a typical granular appearance in immunofluorescence testing.
Neurological manifestations: About 10% of patients may present with seizures or psychosis. A third may test positive for abnormalities in the cerebrospinal fluid.
Other rarer manifestations: Lupus gastroenteritis, lupus pancreatitis, lupus cystitis, autoimmune inner ear disease, parasympathetic dysfunction, retinal vasculitis, and systemic vasculitis.
T-cell abnormalities: Abnormalities in T cell signaling are associated with SLE, including deficiency in CD45 {phosphatase, increased expression of CD40 ligand.
Also associated with SLE is increased expression of Fc?RI?, which replaces the TCR ? chain, which is deficient in some SLE patients.
Other abnormalities include:
* increased and sustained calcium levels in T cells
* moderate increase of inositol triphosphate
* reduction in PKC phosphorylation
* reduction in Ras-MAP kinase signalling
And deficiencies in protein kinase A I activity
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