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Immune complexes and the pathogenesis of neutropenia in Felty's syndrome
Abstract:
The effect of the injection of serum from patients with rheumatoid arthritis (RA) and Felty's syndrome (FS) into mice on the number of circulating polymorphonuclear cells (PMN) was studied. The number of circulating PMN dropped to 61% (range 34-98%) of the initial counts after the injection of FS serum. This phenomenon was observed less frequently after injection of RA serum. In contrast, injection of serum from healthy controls always resulted in an immediate increase in the number of circulating PMN. No decrease in PMN counts was found after injection of FS sera pretreated with polyethylene glycol to precipitate immune complexes (IC). Gel filtration of FS sera on Sepharose 4B showed that the effect on the PMN counts in mice did not coincide with the 7S peak but occurred only in fractions containing larger material. Serum fractions from FS patients that contained IC were more active in producing neutropenia than the corresponding fractions from patients with RA. Microscopic and immunohistochemical examination of the organs from mice injected with FS serum showed sequestration of PMN and deposition of human IgG, IgA, and IgM in the vascular bed of the lungs. These results indicate that the interaction between PMN and IC of patients with FS leads to sequestration of PMN in mice and suggests that this interaction in humans may have a role in the pathogenesis of FS.
Insights
Serum from patients with Felty's syndrome (FS) significantly reduced circulating polymorphonuclear cells (PMN) in mice. This effect, linked to immune complexes (IC), suggests a role for PMN-IC interactions in FS pathogenesis.
Area of Science:
- Immunology
- Rheumatology
- Hematology
Background:
- Rheumatoid arthritis (RA) and Felty's syndrome (FS) are autoimmune conditions.
- Polymorphonuclear cells (PMN) play a role in immune responses.
- The pathogenesis of FS involves complex immune system dysregulation.
Purpose of the Study:
- To investigate the effect of serum from FS and RA patients on circulating PMN counts in mice.
- To determine the role of immune complexes (IC) in this effect.
- To explore the potential mechanism of PMN sequestration in FS.
Main Methods:
- Injection of patient serum (FS, RA, healthy controls) into mice.
- Quantification of circulating PMN counts.
- Treatment of serum with polyethylene glycol to precipitate IC.
- Gel filtration of serum.
- Microscopic and immunohistochemical examination of mouse organs.
Main Results:
- FS serum caused a significant drop in mouse PMN counts, unlike RA serum or control serum.
- Precipitating IC from FS serum abolished the PMN-lowering effect.
- The effect was associated with larger molecular weight fractions containing IC.
- PMN sequestration and deposition of human immunoglobulins (IgG, IgA, IgM) were observed in mouse lungs.
Conclusions:
- Interaction between PMN and IC in FS serum leads to PMN sequestration in mice.
- This PMN-IC interaction may contribute to the pathogenesis of Felty's syndrome in humans.