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Expression of CD64 on polymorphonuclear neutrophils in patients with familial Mediterranean fever
K Migita1, K Agematsu, K Yamazaki
1Clinical Research Center, Nagasaki Medical Center, Omura, Japan. migita@nmc.hosp.go.jp
Abstract:
Familial Mediterranean fever (FMF) is an autoinflammatory disease characterized by recurrent episodes of fever and serosal or synovial inflammation. We examined the utility of CD64 (FcγRI) expression in polymorphonuclear neutrophils (PMNs) as clinical and biological parameters in patients with FMF. We studied 12 Japanese FMF patients (mean age; 22·8 ± 15·5 years, male/female: 2/10), along with rheumatoid arthritis patients (RA, n = 38 male/female: 6/32, mean age; 52·2 ± 15·3 years), systemic lupus erythematosus (SLE, n = 15 male/female: 0/15, mean age; 38·5 ± 15·9 years) and 12 healthy subjects (male/female: 3/9, mean age; 37·9 ± 17·2 years). CD64 expression on PMNs was determined using flow cytometry. The quantitative expression of CD64 in patients with FMF (2439·6 ± 2215·8 molecules per PMN) was significantly higher than in healthy subjects (547·8 ± 229·5, P = 0·003) or in patients with RA (606·5 ± 228·2, P < 0·0001) and SLE (681·3 ± 281·1, P = 0·004). The increased CD64 expression on PMNs isolated from untreated FMF patients was down-regulated by colchicine treatment. NACHT-LRR-PYD-containing protein 3 (NLRP3) activation using MurNAc-L-Ala-D-isoGln (MDP) resulted in increased CD64 expression on PMNs from healthy subjects. Our results suggest that quantitative measurement of CD64 expression on PMNs can be a valuable tool to discriminate between FMF and autoimmune diseases.
Insights
Familial Mediterranean fever (FMF) is an autoinflammatory disease. Measuring CD64 expression on polymorphonuclear neutrophils (PMNs) can help distinguish FMF from other autoimmune conditions like RA and SLE.
Area of Science:
- Immunology
- Rheumatology
- Genetics
Background:
- Familial Mediterranean fever (FMF) is a chronic autoinflammatory disorder.
- Recurrent episodes of fever and inflammation characterize FMF.
- Distinguishing FMF from other inflammatory conditions can be challenging.
Purpose of the Study:
- To evaluate the diagnostic utility of CD64 expression on polymorphonuclear neutrophils (PMNs) in patients with FMF.
- To compare CD64 expression levels in FMF patients with those in patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and healthy individuals.
- To assess the effect of colchicine treatment on CD64 expression in FMF patients.
Main Methods:
- Flow cytometry was used to quantify CD64 expression on PMNs.
- Patient cohorts included FMF, RA, SLE, and healthy controls.
- NLRP3 inflammasome activation was induced using MDP in healthy subjects' PMNs.
Main Results:
- CD64 expression on PMNs was significantly elevated in FMF patients compared to healthy subjects, RA patients, and SLE patients.
- Colchicine treatment reduced elevated CD64 expression in untreated FMF patients.
- MDP stimulation increased CD64 expression on PMNs from healthy subjects, suggesting a role for NLRP3 inflammasome.
Conclusions:
- Quantitative measurement of CD64 expression on PMNs serves as a valuable biomarker for differentiating FMF from other autoimmune diseases.
- CD64 expression levels reflect disease activity and treatment response in FMF.
- The findings support the role of inflammasome activation in FMF pathogenesis.