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AB1169 Compensatory increase in fcΓriib expression on b cells in patients with systemic sclerosis
  1. N Yagi,
  2. T Matsushita,
  3. Y Hamaguchi,
  4. K Takehara
  1. Department of Dermatology, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan

Abstract

Background Systemic sclerosis (SSc) is a systemic autoimmune disease that is characterized by excessive fibrosis and microvascular damage. The contribution of B cells to the pathology of SSc has been mainly recognized as polyclonal B cell activation and autoantibody production. The receptor for the Fc region of IgG (FcγRs) is member of the Ig superfamily, the members of which modulate the activation and inhibition of immune responses. FcγRIIB is the only FcγR that has an inhibitory function. Previous studies revealed that a decrease in the expression of FcγRIIB on B cells induced excessive immune responses and resulted in the development of autoimmunity. However, the expression levels of FcγRIIB on B cells in SSc currently remain unknown.

Objectives We aimed to clarify how the abnormal activation of B cells involves inhibitory FcγRIIB on B cells in SSc patients.

Methods Blood samples were collected from 76 SSc patients (38 limited cutaneous SSc [lcSSc], 38 diffuse cutaneous SSc [dcSSc]) and 59 healthy subjects. We evaluated the expression of FcγRIIB, CD80, CD86, and CD95 on B cell subsets. B cells were classified into five subsets depending on their surface molecular expression by flow cytometry: naïve B cells (CD19+IgD+CD27-), preswitched memory B cells (CD19+IgD+CD27+), double negative (DN) memory B cells (CD19+IgD-CD27-), switched memory B cells (CD19+IgD-CD27mid), and plasmablasts (CD19+IgD-CD27high). The mRNA expression of FcγRIIB was measured using real-time PCR. We examined the relationship between FcγRIIB expression and clinical features.

Results The expression of FcγRIIB on SSc naïve B cells and DN memory B cells was significantly stronger than that on the B cells of healthy subjects (Figure 1) (p<0.05 and p<0.001, respectively). FcγRIIB mRNA expression on SSc B cells was also significantly stronger than that on the B cells of healthy subjects (p<0.01). The expression of CD80, CD86, and CD95, activation markers on B cells, was stronger in all 5 B cell subsets, except for CD80 in switched memory B cells and plasmablasts. Patients with the stronger expression of FcγRIIB on DN memory B cells more frequently had interstitial lung disease than those with normal levels (p<0.05). Cyclophosphamide pulse therapy significantly reduced the expression of FcγRIIB on preswitched memory B cells and switched memory B cells (p<0.05 and p<0.05, respectively).

Conclusions Our results suggest that SSc B cells exhibit compensatory increases in the expression of FcγRIIB in order to suppress the abnormal activation of B cells, and the expression of FcγRIIB may be an indicator of the clinical severity of SSc.

Disclosure of Interest None declared

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