Aspects on Immune Complex Handling and Complement Deficiency in Relation to Pathogenic Mechanisms in Systemic Lupus Erythematosus

Detta är en avhandling från Dept. of Laboratory Medicine, section of MIG; Sölvegatan 23; SE-223 62 Lund; Sweden

Sammanfattning: The autoimmune disease Systemic Lupus Erythematosus is associated with hereditary deficieny of early components from the classical pathway of complement activation, but not with deficiency of complement component C3 or of the alternative pathway components. The classical pathway is involved in elimination of pathological immune complexes from the circulation by transport via complement receptor type 1 (CR1). Here it is shown that immune complex adherence to CR1 is dependent on the presence of sufficient amounts of C3, suggesting that impaired immune complex elimination is not the major mechanism of SLE disease pathogenesis. In the absence of complement component C2, but with C1q and C4 present, the alternative pathway could be enhanced to activate C3 sufficiently for CR1 adherence. This mechanism was sensitive to the physiological concentration of alternative pathway component factor B. Selective C4A isotype deficiency was shown to be of minor importance in immune complex adherence to CR1 compared to activation of C3. Phosphorylation of C3 by a protein kinase released from activated platelets could be shown to have an effect on immune complex adherence to CR1, but it was not established whether the effect resulted from differences in C3 deposition or in immune complex solubilisation. The complement system is also involved in phagocytosis of apoptotic cells. It was shown here that SLE patient sera induced apoptosis in monocytes from healthy donors in vitro. Induction of apoptosis correlated with complement activation in the sera. Soluble HLA class I molecules (sHLA-I) are known to induce apoptosis in T-cells. Serum level of sHLA-I was elevated in SLE patient sera and correlated with complement activation, but no connection was found between sHLA-I level and induction of apoptosis in monocytes.

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