Nephrol Dial Transplant (2007) 22: 1233–1235
doi:10.1093/ndt/gfl841
Advance Access publication 3 February 2007
Case Report
Linear anti-glomerular basement membrane IgG but no glomerular
disease: Goodpasture’s syndrome restricted to the lung
Sanjeev Sethi1, Matthew Lewin1, Lauren Lopez2 and Donna Lager1
1
Department of Laboratory Medicine and Pathology, Mayo Clinic, 55905 Rochester, MN and 2Department of Medicine,
Elmbrook Memorial Hospital, Brookfield, WI, USA
Keywords: goodpasture’s syndrome; anti-GBM
antibodies; IgG4
Introduction
We present an unusual case of Goodpasture’s
syndrome with pulmonary manifestations and no
renal function abnormalities and normal urinalysis,
although there was intense linear staining for antiglomerular basement membrane (GBM) antibodies.
Case presentation
C.V. is a 22-year-old woman, who presented to the
emergency room (ER) with shortness of breath,
coughing and frank haemoptysis. She had been seen
in the ER twice over the previous 3 weeks for similar
symptoms, but with only mild blood-tinged sputum.
Chest X-ray showed bilateral infiltrates. She was
treated with Zithromax and subsequently Biaxin for
a presumed pneumonia. There was no history of fevers,
chills or weight loss. However, the haemoptysis
persisted with increasing shortness of breath, forcing
her back to the ER. Her history was significant in that
she is a smoker and works as a bartender in a smoky
restaurant. Laboratory investigations at admission:
haemoglobin 10 gm/dl, platelet count 309 103/ml,
sodium 138 mEq/l, potassium 3.8 mEq/l, serum creatinine 0.7 mg/dl, blood urea nitrogen 11 mg/dl, total
bilirubin 1.5 mg/dl, PCO2 34, PO2 48. Urinalysis was
unremarkable. Chest X-rays showed worse diffuse
alveolar infiltrates compared with the previous
X-rays. The clinical diagnosis was that of acute
interstitial lung disease with haemoptysis and included
a differential diagnosis Wegner’s granulomatosis,
lupus, sarcoidosis, pneumonitis, Goodpasture’s
disease, etc. Titres for anti-GBM antibodies returned
high positive (>32 U/ml, normal <3 U/ml). Remaining
serological tests were negative. A renal biopsy was
done to confirm Goodpasture’s disease and to document whether renal disease was present or not.
Renal biopsy findings
The renal biopsy showed an essentially normalappearing renal parenchyma on light microscopy.
There were five glomeruli present, none were sclerosed.
The glomeruli did not show any evidence of crescents,
fibrinoid necrosis or karyorrhexis (Figure 1). The
mesangium was not expanded, the capillary loops
were patent and there was no evidence of endocapillary
proliferation. There was also no evidence of thrombosis, emboli or double contours. The interstitium was
well preserved and the vessels were unremarkable.
Five glomeruli were present for immunofluorescence
studies. The glomeruli show bright linear staining (3þ)
for IgG, and k light chains along the glomerular
basement membranes (Figure 2A). There was mild
linear staining for C3 (1þ). Staining for IgA, IgM and
C1q was negative. Staining for subtypes of IgG showed
predominantly bright linear staining for IgG4 subclass
(Figure 2C) with milder staining for IgG1 subclass
(Figure 2B), while IgG2 and IgG3 were negative.
Electron microscopy was unremarkable.
Renal biopsy diagnosis
Linear IgG deposition along the GBMs, with no
evidence
of
a
crescentic
or
necrotizing
glomerulonephritis.
Clinical follow-up
Correspondence and offprint requests to: Sanjeev Sethi, MD, PhD,
Department of Laboratory Medicine and Pathology, Mayo Clinic,
200 1st Street SW, Rochester, MN 55905, USA.
Email: [email protected]
She was treated with steroids and plasmapheresis.
Plasmapheresis was continued until anti-GBM titres
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S. Sethi et al.
returned negative. The steroids were continued for
6 months. The steroids are being tapered off at the time
of submission of the manuscript. At this time, she is
essentially asymptomatic. Chest X-rays are negative
and anti-GBM antibody titres are negative. Throughout
the course the renal function remained normal.
Discussion
Goodpasture’s syndrome is due to anti-GBM antibodies
against antigens in the basement membranes. Hudson
et al. [1,2] have identified a3 NCI domain of collagen IV
as the target antigen. The antigen is present in both
pulmonary and GBMs and patients usually present with
the pulmonary-renal syndrome. The a3 (IV) NCI
epitope is hidden within the a3.a4.a5 (IV) protomer
and for binding of the anti-GBM antibody, exposure to
an environmental agent (such as cigarette smoke,
hydrocarbons, etc.) is often required in order to reveal
these epitopes[3]. Renal biopsy in patient’s with
Goodpasture’s syndrome shows a necrotizing and
crescentic glomerulonephritis, the diagnosis is confirmed
Fig. 1. Light microscopy showing hematoxylin and eosin-stained
sections (20).
on immunofluorescent microscopy which demonstrates
linear IgG antibody staining along the GBMs.
We present a case of young lady with Goodpasture’s
syndrome restricted to the lung. The patient was a
heavy smoker, and as stated earlier, cigarette smoking
and working in a smoke-filled environment may have
led to the onset of Goodpasture’s syndrome. The case
is unusual in that the renal biopsy showed bright linear
staining for anti-IgG on immunofluorescent microscopy, yet there were no morphological changes of
anti-GBM glomerulonephritis on light microscopy.
In addition, urinalysis and renal function was essentially normal throughout the course. From the clinical
standpoint, the patient was treated with steroids and
plasmapheresis, given the high anti-GBM antibody
titres and the acute pulmonary symptoms from
pulmonary haemorrhage. The patient is doing well,
has quit smoking, symptoms have resolved and
anti-GBM titres have gradually become negative.
From the pathology standpoint, the case was perplexing in that, although there was bright linear anti-GBM
staining of the GBMs, there was no evidence of a
crescentic or necrotizing glomerulonephritis. A possible explanation is that while the anti-GBM antibodies
were pathogenic in the lung, they did not have the
same pathogenic characteristics in the kidney. In a
study of the subtypes of anti-GBM IgG antibodies in
Goodpasture’s syndrome, Noel et al. [4] found that the
most predominant was IgG1 (91%), followed by IgG4
(73%). IgG1, unlike IgG4, can fix complement and
activate macrophages. Sub-typing of the anti-GBM
IgG antibodies of our case showed predominantly
IgG4 linear staining, with much milder staining
for IgG1. Therefore, in our case, since the predominant
IgG sub-type was IgG4, it likely that the binding
of the IgG4 antibodies to the GBM did not result in
significant complement activation and renal injury.
This is supported by the finding of only very mild
complement deposition along the GBMs.
A search of the literature revealed few reports
of similar biopsy findings, although in most cases,
while renal function was normal in the setting of
Goodpasture’s syndrome, the urinary sediment showed
haematuria [5–8]. It is also possible that kidneys with
C
A
B
Fig. 2. Immunofluorescence microscopy showing linear GBM staining for anti- (A) IgG, (B) mild linear staining for IgG1 and (C) bright
linear staining for IgG4.
Goodpasture’s syndrome restricted to the lung
normal renal histology and normal renal function may
represent an early form of Goodpasture’s syndrome,
and early recognition and treatment results in no
significant renal injury. The case also illustrates the
fact that Goodpasture’s syndrome should be in
differential diagnosis of haemoptysis, even in the setting
of normal renal function.
Conflict of interest statement. None declared.
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Received for publication: 30.11.06
Accepted in revised form: 26.12.06