alpha 1-Antitrypsin and reactive systemic amyloidosis.

Area of Science:

• Biochemistry
• Immunology
• Rheumatology

Background:

• Serum contains amyloid A-degrading activity, crucial for preventing amyloidosis.
• This activity is significantly reduced in rheumatoid arthritis (RA) patients who develop amyloidosis.
• Alpha 1-antitrypsin is known to inhibit this amyloid A-degrading activity.

Purpose of the Study:

• To investigate the role of alpha 1-antitrypsin in regulating serum amyloid A-degrading activity in RA patients.
• To determine if differences in alpha 1-antitrypsin concentration, activity, or phenotype account for reduced amyloid A-degrading activity in RA-associated amyloidosis.

Main Methods:

• Quantified alpha 1-antitrypsin concentrations and elastase-inhibitory activity in RA patients with and without amyloidosis.
• Determined protease inhibitor (Pi) phenotypes of alpha 1-antitrypsin in these patient groups.
• Compared these parameters between RA patients with amyloidosis, RA patients without amyloidosis, and control subjects.

Main Results:

• Alpha 1-antitrypsin concentrations and biological activity were elevated in both RA patient groups compared to controls.
• No significant differences in alpha 1-antitrypsin levels or activity were observed between RA patients with and without amyloidosis.
• All RA patients who developed amyloidosis possessed the common Pi MM phenotype.

Conclusions:

• The reduced serum amyloid A-degrading activity in RA patients with amyloidosis is not explained by variations in alpha 1-antitrypsin concentration, activity, or phenotype.
• Other regulatory mechanisms likely influence amyloid A degradation and the development of amyloidosis in RA.