Propylthiouracil-associated rapidly progressive crescentic glomerulonephritis with double positive anti-glomerular basement membrane and antineutrophil cytoplasmic antibody: the first case report

Abstract

We report a case of propylthiouracil (PTU)-induced double antineutrophil cytoplasmic antibody (ANCA) and anti-glomerular basement membrane antibody (anti-GBM antibody) disease causing pulmonary-renal syndrome in a 35-year-old Thai woman with 10-year history of PTU treatment for thyrotoxicosis. She developed clinical symptoms of vasculitis upon receiving long-term PTU treatment. Prednisolone treatment and the switching from PTU to methimazole resulted to short-term clinical improvement. Nevertheless following termination of steroid treatment, she developed recurrent pulmonary hemorrhage and rapidly progressive glomerulonephritis. The kidney biopsy showed crescentic glomerulonephritis with linear IgG deposit on the glomerular basement membrane although transbronchial lung biopsy showed no immune deposit along the alveolar basement membrane. Serum testing for p-ANCA was positive and western blot showed positive antibody to the alpha-3 chain of collagen type IV. Both ANCA and anti-GBM antibody may play a role in the development of end organ damage. To facilitate early and specific intervention, clinicians should be aware of the propensity of PTU to cause lupus-like syndromes with renal involvement. In patients with PTU-induced ANCA-associated glomerulonephritis, serum anti-GBM antibody test may be useful in the early diagnosis of double positive antibodies disease and plasmapheresis should be performed without delay.

Keywords: Anti-glomerular basement membrane antibody; Antineutrophil cytoplasmic antibody; Crescentic glomerulonephritis; Propylthiouracil.

Fig. 1

Chest X-ray. a Chest X-ray at first presentation shows mild cardiomegaly and diffuses alveolar infiltration. b Chest X-ray upon recurrence of clinical symptoms showed marked cardiomegaly and bilateral diffuse alveolar infiltration

Fig. 2

Kidney pathology. a The low magnification of the biopsy shows cellular crescents in 3 glomeruli with interstitial inflammation and tubular injury (PAS staining ×100). b The high magnification of the glomerulus shows circumferential cellular crescent (H&E staining ×200). c The glomerulus shows circumferential cellular crescent. Discontinuation and fragments of the glomerular basement membrane (arrow head) are observed. Discontinuation/rupture of Bowman’s capsule is noted (arrow). d Immunofluorescence staining shows linear deposits of immunoglobulin G (IgG)

Fig. 3

Western blot of serum against alpha 3 collagen type IV. Western blotting was performed with native type IV collagen antigens purified from bovine testis (Bov) and with recombinant human type IV collagen alpha-3 (rA3) and alpha-5 chain (rA5) NC1 domains [20]. Samples were run on 12.5 % 8 × 10 cm SDS-PAGE gels in non-reducing conditions and electroblotted to nitrocellulose membranes, using a wet system (Sigma), overnight at 30 mA. Negative controls obtained from pooled normal human serum (control negative serum) and putative low-titer samples were used at 1:20. The positive control serum (control positive serum) obtained from patients diagnosed with anti-glomerular basement membrane disease were used at 1:40–1:100. The positive band of 41 kDa monomer of recombinant human alpha-3 antigen was detected in positive control (control positive serum) and the patient’s serum (rA3 lane), which confirmed the presence of autoantibodies against the alpha 3 chain of collagen type IV [21]. These serums also bind alpha 3 chain of collagen type IV purified from bovine testis (Bov lane). They recognize the 45 and 28 kDa bands corresponding to dimers and monomers of the NC1 domain of type IV collagen purified from bovine testis seminiferous basement membrane [22, 23]. There was no band detected in the negative control incubated with the type IV collagen purified from bovine testis