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The Effect of Some Drugs Used in Treatment of Vasculitis on the Complement System in Children

2018-10-09 09:35:14 | BioPortfolio

Summary

Vasculitis denotes affection of small to medium sized vessels by polyangitis. Antineutrophil cytoplasmic antibodies (ANCA) are immunoglobulin G (IgG) autoantibodies directed against constituents of neutrophil granules leading to neutrophil degeneration which results in cell apoptosis known as "Natoptosis" (NaTosis) of the cells. These lead to vessel endothelial cell damage. So that, ANCA formation seems to be the basic reaction in vasculitis.

Complement activation at C3 and C4 was thought to be involved in renal damage ANCA associated vasculitis (AAV).

Description

Vasculitis syndromes include: Henoch-Schonlein Purpura (HSP), connective tissue disorders e.g. Systemic Lupus Erythematosus (SLE), Rheumatoid arthritis...etc; where small vessels are mainly involved in the process of vasculitis. Vasculitis syndromes also include Kawasaki disease where also medium sized vessels are also included. Other vasculitis syndromes are also reported.

ANCA associated vasculitis may be due complex interplay of genetic risks, environmental or infection trigger or adaptive immunity leading to insufficient regulation of B cells with pathogenic ANCA generation and neutrophil activation (AAV).

Complement activation at C3 and C4 was involved in organ damage, especially renal, in AAV at the alternative complement pathway, factor B and properdin component colocalized with C3 complement in the endothelium of the blood vessels.

Furthermore, the common complement pathway was activated as reflected by increased C5a levels. This suggests that both the alternative and common complement pathways are involved in some cases of vasculitis. Furthermore a decrease in these activation factors was observed during remission of vasculitis. This may denote clearance of the degradation of cell component that were blocking inactive vasculitis. In addition, many studies noticed strong increased plasma levels of the anaphlatoxin C5a that has a strong proinflammatory activity on the endothelium of vessels that may be related to disease severity. So much so, that inhibition of C5a levels by immunologic inhibitors may have a therapeutic role in some forms of ANCA positive vasculitis.

Various treatment forms have been used for vasculitis syndromes.

- Drugs used in treatment of Juvenile Idiopathic Arthritis (JIA) are:

1. Non-steroidal Anti-inflammatory Drugs (NSAIDs) such as Salicylates e.g. Aspirin, Selective COX-2 inhibitors e.g. Celecoxib & Non-Selective COX-2 inhibitors e.g. Naproxen.

2. Non-biologic Disease-Modifying Anti-rheumatic drugs such as Methotrexate.

3. Biologic Disease-Modifying Anti-rheumatic Drugs such as Infliximab.

4. Oral or parenteral Glucocorticoids such as Methylprednisolone (According to American College of Rheumatology).

- In cases of SLE, the American College of Rheumatology (ACR) recommended corticosteroids in the 1st place and change to or add Biologic Disease-Modifying Anti-rheumatic Drugs Agents such as Rituximab.

- Regarding Henoch-Schonlein Purpura vasculitis, 70% of cases are self-limited. only cases with suspected renal involvement e.g. hematuria, hypertension, headache or proteinuria are to be treated with sreroids.

Study Design

Conditions

Vasculitis

Intervention

Ibuprofen, Prednisone, Methotrexate

Status

Not yet recruiting

Source

Assiut University

Results (where available)

View Results

Links

Published on BioPortfolio: 2018-10-09T09:35:14-0400

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