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Increased binding of D-penicillamine to monocytes in rheumatoid arthritis
Abstract:
Long-term therapy of D-penicillamine (D-Pen) for rheumatoid arthritis (RA) is associated with a fall in rheumatoid factor, but many patients develop autoantibodies. In vitro binding of D-Pen to human peripheral blood monocytes was examined in 37 patients with RA and 75 healthy subjects. Mononuclear cells were reacted with D-Pen coupled to a fluorescein isothiocyanate-bovine serum albumin (BSA) conjugate in the presence of sodium azide and BSA, and analyzed by flow cytometry. Patients showed significantly higher D-Pen binding to monocytes than did healthy subjects. The proportion of monocytes binding D-Pen increased with age in the patients but not in healthy subjects. None of 6 patients who had D-Pen-induced autoimmune side effects was associated with increased D-Pen binding though patients with therapeutic responses showed high D-Pen binding. These results suggest that D-Pen binding to monocytes may be important in mediating therapy and inducing autoimmune side effects.
Insights
D-penicillamine (D-Pen) therapy for rheumatoid arthritis (RA) shows increased binding to monocytes in patients. This binding may influence therapeutic effects and autoimmune side effects in RA patients.
Area of Science:
- Immunology
- Rheumatology
- Pharmacology
Background:
- Long-term D-penicillamine (D-Pen) treatment for rheumatoid arthritis (RA) can lead to autoantibody development.
- Understanding the interaction between D-Pen and immune cells is crucial for managing RA therapy.
Purpose of the Study:
- To investigate the in vitro binding of D-penicillamine to monocytes in patients with rheumatoid arthritis.
- To explore the relationship between D-Pen monocyte binding, patient age, therapeutic response, and side effects.
Main Methods:
- Flow cytometry was used to analyze D-Pen binding to peripheral blood monocytes.
- Mononuclear cells from 37 RA patients and 75 healthy subjects were incubated with a D-Pen-fluorescein isothiocyanate-bovine serum albumin conjugate.
Main Results:
- Rheumatoid arthritis patients exhibited significantly higher D-penicillamine binding to monocytes compared to healthy individuals.
- Monocyte binding of D-Pen increased with age in RA patients, but not in controls.
- Patients with therapeutic responses showed high D-Pen binding, while those with D-Pen-induced autoimmune side effects did not show increased binding.
Conclusions:
- D-penicillamine binding to monocytes appears to play a role in both the therapeutic efficacy and the induction of autoimmune side effects in rheumatoid arthritis.
- Further research is warranted to elucidate the precise mechanisms of D-Pen immunomodulation in RA.