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Cytokine Analysis of Eosinophilic Ascites in Systemic Lupus Erythematosus

  • Mamoru HondaEmail author
  • Takako Asano
  • Daiji Takajo
  • Kosei Takada
  • Mari Nakamura
  • Kanako Sekinaka-Mitsui
  • Hajime Wakamatsu
  • Shigeaki Nonoyama
Scientific Letter
  • 76 Downloads

To the Editor: A 13-y-old girl developed recurrent abdominal pain, diarrhea and massive ascites at disease onset. Abdominal computed tomography and ultrasonography showed ascites and edematous intestine of serosal side. Abdominal puncture revealed eosinophilic ascites (eosinophils 312 /μL). Although eosinophilic gastroenteritis (EGE) was the most suspected diagnosis, systemic lupus erythematosus (SLE) was also suspected because mild leukopenia, proteinuria, and hypocomplementemia were noted intermittently (Supplementary Fig. 1). Anti-nuclear antibody (speckled type) was elevated (1:320), whereas anti-dsDNA and anti-Sm antibodies were within the normal range. Further, she presented with oral ulcer and fulfilled the American College of Rheumatology 1997 Revised Classification Criteria for SLE [1]. Prednisolone (PSL) (1 mg/kg/d) was initiated at 51st d of illness. Her abdominal manifestations and proteinuria gradually diminished after starting the PSL. Renal biopsy findings obtained at the 71st d of illness were consistent with those for lupus nephritis (Supplementary Fig. 2).

We conducted a multi-cytokine analysis of the patient’s serum and ascites using the Luminex system to clarify the pathophysiology of eosinophilic ascites in the present case. Serum samples in the active phase and during remission, and ascites sample in the active phase were investigated, which revealed elevated interleukin (IL)-5, IL-6, and tumor necrosis factor (TNF)-α levels in ascites and serum IL-6 and TNF-α levels in the active phase. On the other hand, serum IL-6 and TNF-α levels were decreased in remission (Supplementary Fig. 3).

Previous studies have reported that serum IL-6, IL-10, IL-17, TNF-α, and IFN-γ levels are elevated in patients with SLE [2, 3]. In the present case, the IL-6 and TNF-α levels were elevated in both the serum and ascites samples. Moreover, the IL-5 level was elevated only in ascites, which is characteristic for this case. IL-5, the growth and differentiation factor of eosinophils, is associated with the onset of EGE and eosinophilic infiltration into the gastrointestinal (GI) tract [4]. Our study suggests that eosinophilic ascites in this patient with SLE is the result of IL-5 production of abnormal T lymphocytes in ascites. Atypical cytokine production from abnormal T lymphocytes in this patient can cause this atypical clinical course similar to that of EGE.

Notes

Compliance with Ethical Standards

Conflict of Interest

None.

Supplementary material

12098_2019_3092_MOESM1_ESM.docx (45 kb)
Supplementary Fig. 1 Clinical course of the patient. Recurrent abdominal pain and ascites concurrent with mild leukopenia, proteinuria, and hypocomplementemia were the first manifestations of this patient. Colon fibroscopy (CF) revealed only edematous mucosa of the ileocecum, but no signs of eosinophil infiltration. Ascites test revealed eosinophils in ascites. Both eosinophilic gastroenteritis and systemic lupus erythematosus (SLE) were suspected. Montelukast and epinastine were initiated at first, with no effect. Then, oral ulcer was observed, which fulfilled the SLE diagnostic criteria. Prednisolone was effective; abdominal manifestations and proteinuria (max 12.8 g/gCr) disappeared. Mycophenolate mofetil (1200 mg/m2/d) and tapering of PSL was started at 82nd d of illness. Presently, the patient maintains remission at 2 y after the disease onset.CF Colon fibroscopy; GIF Gastrointestinal fibroscopy; PSL Prednisolone; MMF Mycophenolate mofetil (DOCX 45 kb)
12098_2019_3092_MOESM2_ESM.docx (2.8 mb)
Supplementary Fig. 2 Renal biopsy findings. (a) Light microscopy revealed 71 glomeruli, among which 24 showed mesangial proliferation and matrix expansion. (b) Electronic microscopy showed paramesangial electron-dense deposits. (c–i) Immunofluorescence staining demonstrated a “full-house pattern” with granular staining of capillary wall and mesangial deposits by C1q (c), C3 (d), C4 (e), IgA (g), IgG (h), and IgM (i), except for fibrinogen (f). These findings were consistent with those for lupus nephritis (World Health Organization classification class IIa, ISN/RPS classification class II). (DOCX 2873 kb)
12098_2019_3092_MOESM3_ESM.docx (20 kb)
Supplementary Fig. 3 Cytokine analysis. (a) Serum cytokine analysis in the active phase and remission. The interleukin (IL)-6 (16.61 pg/ml) and tumor necrosis factor (TNF) -α (30.34 pg/ml) levels were elevated in the active phase (at 33rd d of illness) but decreased in remission (at 8 mo after the onset). (b) Ascites cytokine profiles in the active phase (at 31st d of illness). The IL-5 (171 pg/ml), IL-6 (495 pg/ml) and TNF-α (40.79 pg/ml) levels were elevated. (DOCX 20 kb)

References

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Copyright information

© Dr. K C Chaudhuri Foundation 2019

Authors and Affiliations

  1. 1.Department of PediatricsNational Defense Medical CollegeTokorozawaJapan

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