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Background <p>Levamisole is a commonly used steroid-sparing medication in pediatric nephrotic syndrome. While use of this agent is associated with development of antineutrophil cytoplasmic antibodies (ANCA), there is limited data on their prevalence and antigen specificity.</p> Methods <p>This cross-sectional study, conducted from October 2020 to June 2022, included 117 patients, aged 2–18&#xa0;years, with steroid-sensitive nephrotic syndrome&#xa0;and&#xa0;receiving levamisole at a dose of 2–2.5&#xa0;mg/kg on alternate days for ≥ 6-months. All patients were screened for ANCA by indirect immunofluorescence and conventional ELISA. Patients positive on screening underwent&#xa0;profile ELISA&#xa0;to determine its antigen specificity.</p> Results <p>Twenty (17.1%) patients tested positive for ANCA by either screening method. On profile ELISA, antibodies showed specificity to myeloperoxidase (n = 13), human neutrophil elastase (n = 6), proteinase-3 (n = 4), and/or&#xa0;their combination (n = 3). Risk factors independently associated with presence of ANCA included female sex [adjusted odds ratio (aOR) 3.1; 95% CI 1.0–9.3; <i>P</i> = 0.044] and cumulative prednisolone intake in the last 6-months&#xa0;[aOR 0.0041; 0.0001–0.21; <i>P</i> = 0.006]. Following levamisole discontinuation, ANCA was negative in all 16 patients who were retested at 40.6 (3–67.2) months. Antinuclear and anticardiolipin antibodies were present in 19 and 8 patients, respectively, and leukopenia in 4 patients.</p> Conclusions <p>A significant proportion of patients with steroid-sensitive nephrotic syndrome receiving &gt; 6-months’ therapy with levamisole show positive ANCA, with antigen specificity against myeloperoxidase, neutrophil elastase and/or proteinase-3. The risk was higher in girls and lower in those receiving concurrent therapy with prednisolone in the past 6-months.&#xa0;Stopping levamisole therapy was associated with resolution of ANCA.</p> Graphical abstract <p></p>

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Prevalence and types of anti-neutrophil cytoplasmic antibodies in patients with nephrotic syndrome treated with levamisole

  • 期刊论文

  • 发表日期：

    2025年12月1日

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  • Puneet Singh,
  • Aditi Sinha,
  • Uma Kumar,
  • Vineeta Batra,
  • Pankaj Hari,
  • Arvind Bagga

摘要

Background

Levamisole is a commonly used steroid-sparing medication in pediatric nephrotic syndrome. While use of this agent is associated with development of antineutrophil cytoplasmic antibodies (ANCA), there is limited data on their prevalence and antigen specificity.

Methods

This cross-sectional study, conducted from October 2020 to June 2022, included 117 patients, aged 2–18 years, with steroid-sensitive nephrotic syndrome and receiving levamisole at a dose of 2–2.5 mg/kg on alternate days for ≥ 6-months. All patients were screened for ANCA by indirect immunofluorescence and conventional ELISA. Patients positive on screening underwent profile ELISA to determine its antigen specificity.

Results

Twenty (17.1%) patients tested positive for ANCA by either screening method. On profile ELISA, antibodies showed specificity to myeloperoxidase (n = 13), human neutrophil elastase (n = 6), proteinase-3 (n = 4), and/or their combination (n = 3). Risk factors independently associated with presence of ANCA included female sex [adjusted odds ratio (aOR) 3.1; 95% CI 1.0–9.3; P = 0.044] and cumulative prednisolone intake in the last 6-months [aOR 0.0041; 0.0001–0.21; P = 0.006]. Following levamisole discontinuation, ANCA was negative in all 16 patients who were retested at 40.6 (3–67.2) months. Antinuclear and anticardiolipin antibodies were present in 19 and 8 patients, respectively, and leukopenia in 4 patients.

Conclusions

A significant proportion of patients with steroid-sensitive nephrotic syndrome receiving > 6-months’ therapy with levamisole show positive ANCA, with antigen specificity against myeloperoxidase, neutrophil elastase and/or proteinase-3. The risk was higher in girls and lower in those receiving concurrent therapy with prednisolone in the past 6-months. Stopping levamisole therapy was associated with resolution of ANCA.

Graphical abstract