C1 inactivator-C1s complexes in inflammatory joint disease.

Area of Science:

• Immunology
• Rheumatology
• Biochemistry

Background:

• Inflammatory joint diseases, such as rheumatoid arthritis (RA), involve complex immunological processes.
• Complement system activation, particularly the classical pathway, is implicated in RA pathogenesis.
• Quantifying specific complement activation markers is crucial for understanding disease mechanisms.

Purpose of the Study:

• To investigate the activation of the classical pathway of complement in inflammatory joint diseases.
• To quantify C1 inhibitor (C1In)-C1s complexes in synovial fluid (SF) and serum (S) from patients with various arthritides.
• To correlate complement activation markers with immune complex levels and disease characteristics.

Main Methods:

• Development and application of a novel enzyme-linked immunosorbent assay (ELISA) for C1In-C1s complex quantitation.
• Analysis of synovial fluid and paired serum samples from patients with rheumatoid arthritis, other arthritides, and non-inflammatory joint effusions.
• Measurement of immune complexes (IC) using a staphylococcal binding assay.

Main Results:

• C1In-C1s complexes were significantly higher in RA SF compared to paired RA serum (P < 0.01).
• Immune complexes were elevated in RA SF compared to non-RA SF.
• A significant inverse correlation was observed between SF C1In-C1s complexes and SF total hemolytic complement, suggesting complement consumption.
• While a correlation between IC and C1In-C1s complexes existed in all SF samples, it was not significant in RA SF alone.
• No correlation was found between rheumatoid factor titre and C1In-C1s complexes.

Conclusions:

• Activation of the classical complement pathway is a hallmark of rheumatoid synovitis.
• The findings suggest functional heterogeneity of both circulating and intra-articular immune complexes in RA.
• The developed ELISA is a valuable tool for studying complement activation in inflammatory joint diseases.