21. SLE 的患者的血清有 BLyS 升高的情形
B 細胞
抗原在周邊組織或血液出現 單核球與巨噬細胞受抗原活化
,開始分泌大量的 BLyS
B cell 的存活、分化與特異性抗體的大量
生成
BLyS 分泌出來後
,進一步活化 B 細
胞去辨認抗原,並
且大量產生抗體
22. BLyS 加強了自體抗體的製造與作用
有自體免疫作用的
B cells
Dark zone
Light zone
細胞自然凋亡
正常情況 自體免疫疾病
Dark zone
Light zone
過度的
BLyS 表現
Autoantibody
自體抗體生成
IgG
IgM
B cell 的篩檢與選擇
存活
有自體免疫作用的
B cells
Treatment for SLE varies according to the individual and disease severity.1
Mild SLE can be managed with:
Sunscreens: topical sunscreens with sun protection factor ≥15 may treat ultraviolet-induced cutaneous or systemic disease flares.
NSAIDs: for fever, arthritis, mild serositis.
Antimalarials (hydroxychloroquine): for skin and joint manifestations, and to prevent flares.
Glucocorticoids (GCs): topical GCs can be applied to affected rash areas; low-dose oral GCs may have HRQoL benefits.
Serious SLE manifestations (organ or life-threatening) can be managed with:
High-dose GCs (prednisone, methylprednisolone): dosage and mode of administration varies according to nature and severity of condition; associated with significant toxicity.
Immunosuppressive/cytotoxic agents: drug choice depends on nature and severity of condition: eg, methotrexate for severe arthritis; and MMF, cyclophosphamide, and GCs for SLE nephritis.2
Severe SLE without renal involvement can be managed with:
IV gamma globulin or cyclosporine A, apheresis (cytopenias, cryoglobulinemia, CNS disease), plasmapheresis (thrombotic thrombocytopenic purpura), dapsone (refractory skin lesions), retinoid derivatives (resistant skin lesions), anticoagulants and combinations of therapeutic agents and experimental therapies.
To date, there is no accepted SLE treatment algorithm. Consequently, current therapeutic approaches are primarily reactive until significant disease activity is observed and patients are at high risk for developing major organ system disease.
Reference
ACR Ad Hoc Committee on Systemic Lupus Erythematosus Guidelines. Arthritis Rheum. 1999;42:1785-96.
2. Kalunian K, Merrill JT. New directions in the treatment of systemic lupus erythematosus. Curr Med Res Opin. 2009;25:1501-14.
All current treatments for SLE are accompanied by AEs.
The pain-reducing and immunosuppressive therapies currently used in SLE treatment have potentially serious Aes; none are optimal for chronic use. The table lists the most common AEs associated with different classes of treatment.1-4
Practitioners must attempt to balance the need for aggressive therapy and risk of AEs.
On a patient-by-patient basis, achieving this balance may involve utilizing different agents or limited titrating of current modalities.
References
ACR Ad Hoc Committee on Systemic Lupus Erythematosus Guidelines. Arthritis Rheum. 1999;42:1785-96.
Ioannou Y, Isenberg DA. Current concepts for the management of systemic lupus erythematosus in adults: a therapeutic challenge. Postgrad Med J. 2002;78:599-606.
Rheumatrex Prescribing Information. DAVA Pharmaceuticals, Inc, 2009. Fort Lee, NJ.
Kalunian K, Merrill JT. New directions in the treatment of systemic lupus erythematosus. Curr Med Res Opin. 2009;25:1501-14.
Some autoreactive B cells that survive negative selection processes in the bone marrow may mature in the germinal centers of peripheral lymphoid tissues by somatic hypermutation1
during somatic hypermutation, alterations in antibody structures fine-tune the recognition of antigen, ultimately resulting in the proliferation of B cells that produce high-affinity antibodies1
certain patterns of somatic mutation have been associated with antibody binding to self antigens, including DNA.2
Although autoreactive B cells can be deleted at this stage,1 excess BLyS, which activates the anti-apoptotic genes Bcl-2 and Bcl-xl, may override the induction of apoptosis and promote the survival of autoreactive B cells.3–5
References
Delves PJ, Roitt IM. N Engl J Med 2000;343:37–50.
Silverman GJ. Bull NYU Hosp Jt Dis 2006;64:51–56
Kanakaraj P, et al. Cytokine 2001;13:25–31.
Do RK, et al. J Exp Med 2000;192:953–64.
Amanna IJ, et al. J Immunol 2003;170:4593–600.
Patients with SLE have abnormal activation of B cells, which leads to tissue and organ damage.1,2
In healthy people, developing autoreactive B cells are purged at different stages of development. In patients with SLE, these cells—which are normally destined for apoptosis—survive, leading to autoantibody production.
These autoantibodies are directed against self molecules of the nucleus, cytoplasm, and cell surface, and also soluble molecules (ie, IgG and coagulation factors).3
Elevated levels of circulating immune complexes, deposition of these complexes, and low levels of complement are additional hallmarks of SLE.4,5
Immune complexes containing autoantibodies require complement for clearance, but in SLE, complement is compromised. These complexes build up and can cause additional tissue/organ damage and inflammation.4
This lack of clearance of immune complexes often occurs in the kidney, resulting in lupus nephritis.
References
ACR Ad Hoc Committee on SLE Guidelines. Guidelines for referral and management of systemic lupus erythematosus in adults. Arthritis Rheum. 1999;42:1785-96.
Hoffman IEA et al. Specific antinuclear antibodies are associated with clinical features in systemic lupus erythematosus. Ann Rheum Dis. 2004;63:1155-8.
Mok CC et al. Pathogenesis of systemic lupus erythematosus. J Clin Pathol. 2003;56:481-90.
Janeway CA et al, eds. Immunobiology: the Immune System in Health and Disease. 6th ed. New York, NY: Garland Publishing; 2005.
Muñoz LE et al. SLE: a disease of clearance deficiency? Rheumatology. 2005;44:1101-7.
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