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Friday, 29 November 2013

.Cerebritis, Lupus, and Lupus Cerebritis- The Causes

Cerebritis is defined as an inflammation of the cerebrum, a structure associated with memory, speech, etc., as a result of the formation of an abscess within the brain itself, found commonly in patients with lupus.

Systemic lupus erythematosus (SLE) or Lupus is a chronic, autoimmune disease as as a result of the development of autoantibodies that attack the systems and organs in the body.researchers at the indicated that saturated fatty acid palmitate, but not unsaturated oleate, induces the activation of the NLRP3-ASC inflammasome, causing caspase-1, IL-1β and IL-18 production.

Lupus cerebritis is a disorder of nervous system problems (an autoimmune inflammatory disorder) caused by lupus as as a result of the development of autoantibodies that attack the systems and organs in the body. It causes migraine headache, if the duration of the central nervous system involvement last for a few minutes, or causes dementia that can lead to neurological deficits as a transient attacks or permanently.
B. Causes
Cerebritis can be caused by an infection due to bacteria, viruses invasion and pathogens invasion into
the brain through the sinuses or as a result of trauma
1. Gene
Research at the Oklahoma Medical Research Foundation, published in the April 6 issue of the American Journal of Human Genetics describes three lupus genes discovered by OMRF researchers as part of a massive international collaboration, by Using samples from a wide range of ethnic backgrounds, scientists found the genes IRF8 and TMEM39a were associated with lupus in European-American, African-American, Gullah and Asian patients. A third gene named IKZF3 was only significant in African-American and European-American samples."Identifying and characterizing these genetic risk factors in lupus will undoubtedly lead to improved diagnostics and therapeutics for this complex disease," said senior author and OMRF scientist Kathy Moser, Ph.D.(18)

2. Klebsiella pneumoniae
Klebsiella pneumoniae is defined as a form of bacterial pneumonia associated with Klebsiella pneumoniae. In a report of a case of Klebsiella cerebritis in an adult patient with a proven extracranial focus of infection, researchers suggested considering cerebritis as a differential diagnosis for altered level of consciousness in patients of severe sepsis, even if an extracranial source of infection is proven.(2)

3. Autoimmune system dysfunction
Some researchers found that the interactions between elevations of serum prolactin (PRL)[1], cytoquines[2], autoantibodies[3] and organ involvement[4] suggest that PRL participates in local and generalized immune and inflammatory processes and acts as a bridge between the neuroendocrine and immune systems in SLE. Understanding the interactions between these systems in systemic lupus erythematosus (SLE), will help us to understand and treat this important autoimmune disease(3)

[1]. Elevations of serum prolactin (PRL)
In a study of conducted by Centro Medico Nacional La Raza, showed that elevated PRL and interleukin (IL)-6[5] have been found in the urine of patients with active lupus nephritis and in cerebrospinal fluid (CSF) of patients with active central nervous system (CNS) SLE. PRL may therefore participate in the pathogenesis of lupus nephritis and cerebritis, and the presence of PRL may reflect an abnormal communication between the immune system and the neuroendocrine system in active SLE. Lymphocytes from patients with active SLE produce increased amounts of PRL, and this extrapituitary PRL may participate in aberrant immune processes in SLE.(3)

[2]. Cytoquines
Cytoquines is a small protein released by cells that has a specific effect on the interactions between cells, on communications between cell, or on the behavior of cells. There a report that the final mechanism of lupus cerebritis involves the cytokines. The cytokines trigger edema, endothelial thickening, and infiltration of neutrophils in brain tissue. Two cytokines, interferon alpha and interleukin-6, have been found in the CSF of SLE patients with psychosis(4)

[3}. Antibodies
In the study to investigate the possibility that idiotypes (Ids) defined on anti-double stranded DNA (dsDNA) antibodies during active and inactive stages of lupus (1/84 Id and 4/90 Id, respectively) were expressed on anti-DNA antibodies during a subsequent active period (9/90) of the disease, researchers at the St. Luke's Hospital showed that they are of related clonal origin. The present study suggests the idiotypic heterogeneity of anti-DNA antibodies and the shift of antigen specificity within an idiotypically related anti-DNA population during exacerbation of the disease.(7)

[4] Organ involvement
In the report there are few data on the relationship between the onset of new organ involvement and lupus serologies, especially in children, found that in managing two children with lupus nephritis, both developed life-threatening extrarenal complications (cerebritis and carditis) soon after receiving high-dose immunosuppressive therapy and despite normalizing serologies. This lack of concordance between serologies and the development of carditis and cerebritis needs to be recognized so that health care professionals treating children with SLE can promptly intensify immunosuppressive medications and avoid life-threatening delays from seeking alternative explanations for symptomatology.(5)

[5]. Interleukin (IL)-6
Interleukin (IL)-6 secreted by T cells and macrophages to stimulate immune response has the function to act  both a pro-inflammatory and anti-inflammatory cytokine.[see Cytoquines]

[6]. DNA and anti-DNA complexes
Circulating immune complexes, consist of DNA and anti-DNA, cause an inflammatory response as well as a disruption of the blood-brain barrier. There is a report that the number of patients with the SLE manifestations was not higher in the group with the high amount of DNA in immune complexes. Elevated levels of DNA in immune complexes was found only in sera of SLE patients with the active, as well as quiescent form, of the disease and not in sera of healthy donors. The presence of increased amounts of DNA antigen in circulating immune complexes could indicate the presence of SLE pathology even if no manifestations of SLE are found.(6)

[7]. Etc.

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Sources
(1) http://www.cerebritis.net/
(2) http://www.ncbi.nlm.nih.gov/pubmed/19881180 
(3) http://www.ncbi.nlm.nih.gov/pubmed?term=Autoimmune%20systems%20and%20Cerebritis
(4) http://www.ncbi.nlm.nih.gov/pubmed/606451 
(5) http://www.ncbi.nlm.nih.gov/pubmed/12634943
(6) http://www.ncbi.nlm.nih.gov/pubmed/9802934