Pepsinogen--an immunoglobulin binding artefact in 'collagen' preparations

Area of Science:

• Immunology
• Biochemistry
• Rheumatology

Background:

• Human articular cartilage extracts, often containing type II collagen, are known to interact with immune complexes and aggregated immunoglobulins.
• Sera from patients with rheumatoid arthritis and psoriatic arthritis exhibit reactivity with these cartilage extracts, unlike sera from patients with inflammatory bowel disease.

Purpose of the Study:

• To investigate the nature of the aggregate-binding activity found in digested human articular cartilage extracts.
• To determine if this activity is related to collagen or represents a distinct factor.

Main Methods:

• Extraction of human articular cartilage and subsequent pepsin digestion.
• Testing reactivity with heat-aggregated immunoglobulin and artificial immune complexes.
• Analysis of binding patterns in patient sera (rheumatoid arthritis, psoriatic arthritis, inflammatory bowel disease).
• Salt solubility tests and SDS-PAGE for purification and characterization of the aggregate-binding factor.

Main Results:

• The aggregate-binding activity in digested cartilage extracts showed different salt solubility compared to collagen.
• Further purification via SDS-PAGE revealed the aggregate-binding factor to be an artifact.
• This artifact resulted from the binding of small immune complexes to pepsinogen, a component of the pepsin preparation.

Conclusions:

• The previously identified aggregate-binding factor in digested human articular cartilage extracts is not an intrinsic component of the cartilage.
• The observed reactivity is an artifact of the experimental procedure, specifically the interaction between immune complexes and pepsinogen.
• This finding clarifies the nature of immune complex binding to cartilage components in the context of certain autoimmune diseases.