A case of a 6-year-old girl with anti-neutrophil cytoplasmic autoantibody-negative pauci-immune crescentic glomerulonephritis

Abstract

A 6-year-old girl was admitted to our hospital with proteinuria, hematuria, skin rash and joint pain of the lower limbs. Due to rapid progression of renal insufficiency, hemodialysis and peritoneal dialysis were performed. She was diagnosed with rapidly progressive glomerulonephritis. Kidney biopsy showed severe crescent formation (50% of glomeruli) and no deposition of any immunoglobulins or complements. Serologically, anti-neutrophil cytoplasmic autoantibody (ANCA) was negative not only by ELISA against proteinase-3 and myeloperoxidase-ANCA but also by indirect immunofluorescent assay against cytoplasmic and perinuclear ANCA. Anti-glomerular basement membrane antibody was also negative. In the acute phase, proinflammatory cytokines such as soluble tumor necrosis factor receptor 1 (sTNFR1), soluble interleukin (IL)-2 receptor (sIL2R), IL-6 and chemokine IL-8 were elevated. The patient was diagnosed with ANCA-negative pauci-immune crescentic glomerulonephritis (CrGN). Intensive treatment with methylprednisolone pulse therapy, plasma exchange, and multiple drug therapy including prednisolone and cyclophosphamide resulted in histopathological improvement and complete remission of proteinuria. There was a possibility that sTNFR1, sIL2R, IL-6 and IL-8 might be involved in the initiation and progression of ANCA-negative pauci-immune CrGN, and to remove and suppress these cytokines might be an effective way to treat ANCA-negative pauci-immune CrGN.

AP-VAS 2012 case report: a case of ANCA-negative pauci-immune crescentic glomerulonephritis associated with IL-6-producing adenosquamous cell carcinoma of the lung

“…Shimizu et al [5] observed neutrophil infiltration in the glomerular lesion and elevated IL-6 and IL-8 levels in the acute phase of ANCA-negative CrGN. Moreover, there have been a few reports of Th17 cells and IL-17 in patients with ANCAnegative CrGN.…”

“…ANCA also plays a crucial role in the initiation and progression of ANCA-associated CrGN, but a significant number patients with pauci-immune CrGN are negative for ANCA. ANCA-negative pauci-immune CrGN has been demonstrated in only a limited number of case reports [3][4][5][6]. The prevalence of this disease is approximately 10-30 % [3,4].…”

“…Most patients with pauci-immune CrGN have anti-neutrophil cytoplasmic antibodies (ANCAs) in the circulation, so-called ANCAassociated CrGN [2]. However, some patients with this form of glomerulonephritis have no ANCAs [3][4][5][6]. The pathogenesis of ANCA-negative pauci-immune CrGN has not been fully clarified [4].…”

Anca-Negative Pauci-Immune Crescentic Glomerulonephritis Linked With Non Small Cell Carcinoma of the Lung

“…Shimizu et al [8] observed neutrophil infiltration in the glomerular lesion and elevated IL-6 and IL-8 levels in the acute phase of ANCA-negative CrGN. Morikawa et al [5] reported a large amount of neutrophil infiltration in the glomerulus, with crescent formation, and significant elevated levels of IL-6, TGF-β, and IL-8 in the blood in their report of ANCA-negative pauci-immune CrGN patients associated with adenosquamous cell carcinoma of the lung.…”

Problems in the Diagnosis and Treatment of Anca-Associated Systemic Vasculitis: In the Focus of Anca-Negative Pauci-Immune Glomerulonephritis

“…Отмечено, что острая фаза сопровождается нейтро-фильной инфильтрацией в клубочках [15,53], повышени-ем концентрации интерлейкинов 6 и 8 в крови [53]. Проду-кты дегрануляции нейтрофилов обнаруживают в сыворот-ке крови у АНЦА-негативных пациентов с рauci-иммун-ным ГН даже в более высокой концентрации, чем в АНЦА-позитивных случаях [21].…”