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The role of complement in the aetiopathogenesis of systemic lupus erythematosus
1Department of Clinical Immunology, Royal Prince Alfred Hospital, NSW, Australia.
Insights
Deficiencies in classical complement pathways, crucial for managing immune complexes in systemic lupus erythematosus (SLE), can lead to this autoimmune disease. Genetic factors beyond the major histocompatibility complex (MHC) also play a significant role in SLE.
Area of Science:
- Immunology
- Genetics
- Rheumatology
Background:
- Classical complement pathway components are vital for immune complex (IC) homeostasis.
- Deficiencies in these components or their regulators can precipitate IC-mediated diseases like systemic lupus erythematosus (SLE).
- Genetic associations, including those with the major histocompatibility complex (MHC), are implicated in SLE pathogenesis.
Purpose of the Study:
- To review the role of classical complement pathway components in SLE.
- To discuss the interplay between MHC and non-MHC genes in SLE.
- To explore the contribution of complement deficiencies to SLE etiology.
Main Methods:
- Literature review of classical complement pathway functions in SLE.
- Analysis of genetic associations between MHC/non-MHC genes and SLE.
- Examination of complement C4's role in drug-induced lupus.
Main Results:
- Deficiencies in classical complement components (e.g., C2, C4) are linked to SLE.
- MHC class II genes show associations with SLE occurrence.
- Complement C4 is implicated in drug-induced lupus due to drug interactions.
Conclusions:
- Complement deficiencies and non-MHC genetic factors are significant contributors to SLE pathogenesis.
- Further research into non-MHC encoded complement deficits is warranted for understanding SLE.
- Understanding complement's role is crucial for SLE management and therapeutic strategies.
Abstract:
The role of classical pathway complement components in systemic lupus erythematosus (SLE) is reviewed. Their importance in maintaining immune complexes (IC) in soluble form and in enhancing clearance of IC through binding to red cell CR1 is such that deficiency, complete or partial, of these components or some of their controlling enzymes can lead to IC mediated disease like SLE. C2 and C4 are encoded within the class III region of the major histocompatibility complex (MHC). There are certain well described associations between class II MHC genes and the occurrence of SLE and the relative importance of the two sets of gene products and their potential interactions are discussed. Complement C4 plays a role in drug induced lupus as many of the lupus associated drugs bind to C4 and interfere with its protective functions. Classical genetic studies provide clear evidence that non MHC genes are important in the aetiopathogenesis of SLE. Non MHC encoded complement deficiencies and functional deficits may well represent some of these other genetic factors and is clearly a fertile area for future research.