The complement system and human autoimmune diseases.

Area of Science:

• Immunology
• Genetics
• Autoimmunity

Background:

• Genetic deficiencies in early classical complement pathway components (C1q, C1r, C1s, C4) are strongly associated with systemic lupus erythematosus (SLE).
• While rare, specific complement deficiencies such as C4A isotype deficiency and acquired C1q deficiency via autoantibodies are frequently observed in SLE patients.
• Complement system plays a crucial role in immune regulation and the development of autoimmune diseases.

Purpose of the Study:

• To review the genetic basis of complement deficiencies in autoimmune diseases.
• To discuss the association between complement C4 genetic diversity and autoimmune conditions.
• To provide clinical guidance for suspecting and testing complement deficiencies and to outline mechanisms linking these deficiencies to autoimmunity.

Main Methods:

• Literature review focusing on genetic complement deficiencies and autoimmune diseases.
• Analysis of existing data on complement C4 genetic diversity and its autoimmune associations.
• Synthesis of current understanding regarding mechanisms of complement deficiency-induced autoimmunity.

Main Results:

• Early classical complement pathway deficiencies are potent monogenic causes of SLE, though rare.
• C4A isotype deficiency and acquired C1q deficiency are prevalent in SLE patients.
• Complement deficiencies are implicated in the pathogenesis of SLE, inflammatory arthritis, and myositis.

Conclusions:

• Complement deficiencies, particularly C4A and C1q, are significant factors in SLE development and progression.
• Understanding complement C4 genetic diversity is crucial for assessing autoimmune disease risk.
• Clinical suspicion and testing for complement deficiencies are warranted in specific autoimmune contexts to elucidate pathogenic mechanisms.