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THU0378 Interleukin-6 blocking therapy by tocilizumab in patients with multicentric castleman’s disease results in a significant decrease in serum levels of IgG4 and IGE
  1. M. Murakami,
  2. T. Matsutani,
  3. C. Aoki,
  4. H.-M. Lee,
  5. Y. Li,
  6. N. Nishimoto
  1. Laboratory of Immune Regulation, Wakayama Medical University, Ibaraki, Osaka, Japan

Abstract

Background Multicentric Castleman disease (MCD) is a rare lymphoproliferative disorder characterized by systemic lymphadenopathy, constitutional inflammatory symptoms, and abnormal laboratories such as hyper-γ-globulinemia, increases in various auto-antibodies as well as acute phase proteins. While the symptoms are closely associated with dysregulated overproduction of interleukin (IL)-6, an increase in serum IgG4 and/or IgE levels in MCD patients is frequently observed. Blocking IL-6 with anti-IL-6 receptor antibody, tocilizumab (TCZ), ameliorates not only systemic inflammatory symptoms but also abnormal laboratories including hyper-γ-globulinemia.

Objectives 1) To clarify differences in clinical features between MCD patients with high serum IgG4 and those with normal serum IgG4. 2) To analyze changes in serum IgG subclasses as well as IgE levels of MCD patients with TCZ treatment.

Methods Serum levels of total IgG and four IgG subclasses as well as IgE of 18 MCD patients were measured. Eleven of 18 patients were treated with TCZ. Serum IgG subclass levels (n=11) and serum IgE levels (n=9) were compared before and after the treatment.

Results Serum IgG4 levels at baseline were elevated in 12 of 18 MCD patients (542.2±387.7 mg/dl, n=12 vs. 45.2±39.8 mg/dl, n=6; the normal range is less than 105 mg/dl). Clinical features between MCD patients with high serum IgG4 and those with normal serum IgG4 were not distinct. Serum IgE levels at baseline were elevated in 12 of 16 MCD patients (3414.0±7198.2 IU/ml, n=12 vs. 95.8±66.4 IU/ml, n=4). All the 12 patients with high serum IgG4 showed elevated levels of IgE while only 2 out of 4 patients with normal IgG4 showed high IgE levels. IgG4 and IgE levels were significantly correlated. The mean absolute numbers of all IgG subclasses were significantly decreased after TCZ treatment. Furthermore, the mean ratio of IgG4 to total IgG was significantly decreased (7.4% vs. 5.5%, p<0.05, n=11), while those of the other subclasses did not change. The mean absolute number of IgE levels was also significantly decreased by TCZ treatment (1316.7 IU/ml vs. 481.0 IU/ml, p<0.05, n=9).

Conclusions Decreases in the serum IgG4/IgG ratios and IgE levels after TCZ treatment suggests that IL-6 may be involved in the class switch to IgG4 and IgE.

Disclosure of Interest M. Murakami: None Declared, T. Matsutani: None Declared, C. Aoki: None Declared, H.-M. Lee: None Declared, Y. Li: None Declared, N. Nishimoto Grant/Research support from: Chugai and Roche group, the product company of TCZ., Consultant for: Chugai and Roche group, the product company of TCZ.

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