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Scanty information is available concerning anti-neutrophil cytoplasmic autoantibodies (ANCAs) associated disease in children, and very few cases of familial vasculitis have been reported in the literature.1–3
We have observed two monozygotic twins developing ANCA necrotising glomerulonephritis (GN).
A 7 year old boy was hospitalised for normocomplementemic acute nephritis. Percutaneous renal biopsy revealed idiopathic crescentic GN with negative immunofluorescence. Dialysis was started because of a worsening in renal insufficiency. Despite several courses of daily plasma exchanges combined with intravenous methylprednisolone and cyclophosphamide, there was no improvement; one year later, the boy received a cadaveric renal transplant.
Persistent proteinuria appeared four years after transplantation, when a renal biopsy revealed focal necrotising GN.
At the age of 10 years, the identical male twin was found to have microscopic haematuria and proteinuria of >1 g/24 h with normal renal function. Renal biopsy showed focal necrotising GN with 20% cellular and segmental crescents. Perinuclear ANCAs were observed at a dilution of 1/160. The stored samples of the first twin were tested and pANCAs were detected by indirect immunofluorescence.
This second twin was given intravenous methylprednisolone and cyclophosphamide. The clinical course was characterised by acute episodes resolving with repeated courses of methylprednisolone pulses.
ANCA positivity in the second twin (also found retrospectively in the first twin's serum) allowed us to classify the disease as a renal limited vasculitis expressed by necrotising and crescentic GN.
The HLA antigen profiles of the two boys are A3,11; B27,35; DR12; DQ1.
Acute nephritis or urinary abnormalities were the initial onset symptoms in our patients. They occur in about 40% of children with ANCA associated GN.1 This emphasises the need for a precise diagnosis and aggressive treatment in such patients: ANCAs should be sought in the presence of acute nephritis or persistent urinary abnormalities of unclear aetiology, and not only in children with frank vasculitis or rapidly progressive GN.
We believe this to be the first report of the recurrence of paucimmune crescentic GN in a transplanted kidney in a child. Anti-rejection treatment with steroids and cyclosporine A seems to be a useful means of controlling disease flare ups.
Furthermore, as far as we are aware, this is the first report of pANCA GN in HLA-identical twins. The pathogenesis of ANCA-GN is unknown but likely implicates genetic and/or environmental influences.2
The onset of disease at different times in two identical twins seems to suggest a genetically determined susceptibility rather than environmental triggers. Review of the literature revealed few reports of familial vasculitis, with some evidence suggesting a genetic predisposition. Two of the HLA class I antigens present in our twins (A11, B35), and antigen B35 alone have also been found in two families.3,4
In conclusion, a pANCA test should always be performed in children with acute nephritis of unclear aetiology; a diagnosis of ANCA GN should not preclude renal transplantation. HLA B35 may play a role in the pathogenesis of ANCA GN.
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