the disease caused by autoantibodies with specificity for the nc1 domain of the 3-chain of type iv collagen , often referred to as anti - glomerular basement membrane disease ( anti - gbm disease ) or goodpasture 's disease , is characterized by rapidly progressive glomerulonephritis ( gn ) often accompanied by lung haemorrhage .
disease progression is usually dramatic , and a substantial proportion of patients in recently published series present with oliguric or anuric acute renal failure [ 24 ] .
detectable amounts of anti - gbm antibodies usually do not remain in the circulation for > 612 months , even without the use of cytotoxic drugs .
after that time , the recurrence of anti - gbm antibodies as well as relapse of glomerulonephritis ( gn ) is rare [ 35 ] . here
, we report a case of a clinically and histologically mild form of gn , associated with low levels of anti - gbm antibodies but complicated by a protracted relapsing course .
a 71-year - old woman with a medical history that included a peripheral facial paresis and an irritable colon sought medical attention in august 2000 after a 6-month period of general malaise , intermittent subfebrility and myalgia .
blood tests indicated a mild renal failure with a serum creatinine of 100 mol / l and an erythrocyte sedimentation rate of 80 mm / h . a week later
her creatinine had risen to 130 mol / l and serology was positive for anti - gbm with 61 and myeloperoxidase - antineutrophil cytoplasmic anitbody ( mpo - anca ) > 320 elisa units ( above 10 is considered as positive in both the assays ) .
she was transferred to the lund university hospital , where she received apheresis with protein a adsorption columns .
a renal biopsy showed focal necrotizing glomerulonephritis with crescents in 6 of 16 glomeruli and a typical linear immunofluorescence pattern for igg , kappa and lambda .
after 5 months , the medication was switched to azathioprine 50 mg daily , which was continued for 12 months .
serum creatinine remained stable at a level of 90 mol / l and anti - gbm antibodies were below the detection limit ( figure 1 ) . 

1.the solid line represents levels of anti - gbm antibodies measured by the enzyme - linked immunosorbent assay ( elisa ) and expressed in arbitrary elisa units as indicated by the right vertical axis .
the serological relapses coincided with clinical relapses ; start ( and restart ) of immunosuppressive treatment is indicated by arrows .
method * was used until june 2007 , then method * * was used until november the same year when method * * * , using international units , was introduced .
elisa units for mpo - anca are indicated on the left vertical axis , levels differ between the three assays .
the solid line represents levels of anti - gbm antibodies measured by the enzyme - linked immunosorbent assay ( elisa ) and expressed in arbitrary elisa units as indicated by the right vertical axis .
the serological relapses coincided with clinical relapses ; start ( and restart ) of immunosuppressive treatment is indicated by arrows .
method * was used until june 2007 , then method * * was used until november the same year when method * * * , using international units , was introduced .
elisa units for mpo - anca are indicated on the left vertical axis , levels differ between the three assays .
two years later in the fall of 2004 , she experienced a relapse with re - emergence of anti - gbm antibodies , return of microscopic haematuria and a slight elevation of serum creatinine ( maximum 108 mol / l ) .
anti - gbm remained positive at low level , but turned negative in april 2006 .
, she experienced her second minor relapse with return of anti - gbm antibodies , microscopic haematuria and a slight elevation of creatinine ( maximum 131 mol / l ) .
treatment with pulse cyclophosphamide therapy was initiated , resulting in disappearance of anti - gbm antibodies and haematuria .
, both haematuria and anti - gbm antibodies returned , like at previous relapses there was no malaise or other symptoms of general inflammation .
this third relapse was curbed with an increase in azathioprine doses to 150 mg and reinstitution of a moderate prednisolone dose .
once again , there was a response with vanishing haematuria and autoantibodies . at the most recent follow - up in october 2011 ,
anti - gbm was negative , there was no haematuria , and creatinine was 106 mol / l .
the clinical course in this case was benign , with preserved renal function for more than a decade .
most cases of anti - gbm disease are diagnosed at a more advanced stage . in our series of 75 cases ,
it is impossible to discern whether the benign clinical course was due to the inherent nature of the case or a direct result of the swift initiation of aggressive autoantibody lowering therapy .
a finding in favour of a mild inherent nature in this case is the relatively low levels of anti - gbm antibodies , 61 elisa units , compared with a median level of anti - gbm antibodies in positive cases at the laboratory of 112 units ( interquartile range 39197 ) .
previous studies have indicated that levels of anti - gbm antibodies at diagnosis are predicative of long - term outcome [ 2 , 3 ] . however , it is probable that without treatment , levels of anti - gbm would have increased along with an accelerated intensity of the glomerulonephritis .
the most remarkable feature of this case is the three mild relapses . in all instances ,
the return of anti - gbm antibodies was associated with the return of microscopic haematuria , strongly indicating a pathogenic capacity of the autoantibodies . however ,
there are only a few reports of late relapses of anti - gbm disease [ 57 ] .
reported two cases with relapses among 71 patients in his long - term follow - up study   and we found one among 75 . in the present case ,
this combination is common and was found in 30% of the patients in our swedish cohort , and other studies have found similar frequencies .
the mpo - anca levels fluctuated , and even though four peaks can be identified , the mpo - anca and anti - gbm curves were not parallel . a temporal separation of anti - gbm and mpo - anca in the form a sequential appearance of the autoantibodies has previously been reported [ 9 , 10 ] . the combination of anca and anti - gbm could indicate some sort of overlap syndrome between goodpasture 's disease and anca - associated vasculitis , but while there was a strict correlation between anti - gbm and microscopic haematuria , there was no obvious correlation between the mpo - anca levels and clinical findings .
also in the case described by serratrice et al . , the flare of anti - gbm disease was preceded by a rise in mpo - anca levels that had peaked several months earlier . in summary
, this case shows that anti - gbm antibodies might be present in cases with relatively mild renal failure , and that high vigilance is necessary as mild disease might be at hand only during a relatively short window of opportunity .
even though this case might represent an overlap syndrome with anca - associated vasculitis , the return of the anti - gbm antibodies several years after successful treatment demonstrates that long - term surveillance is warranted . how the follow - up should be organized with respect to frequency of visits and anti - gbm test
however , the present case suggests that negative dipstick tests for haematuria might be sufficient to rule out recurrence of anti - gbm nephritis .
 anti - glomerular basement membrane disease ( anti - gbm ) is usually characterized by rapidly progressive glomerulonephritis , and when autoantibody production has ceased , relapses are rare . here , we report a 71-year - old women diagnosed at a stage of mild renal insufficiency . over a period of 10 years , she experienced three mild relapses with return of anti - gbm antibodies , haematuria and slight elevations in serum creatinine level . 
 all three relapses responded to immunosuppressive therapy , and all were preceded by peaks of myeloperoxidase - antineutrophil cytoplasm antibodies ( mpo - anca ) . 
 this case shows that long - term follow - up is warranted in patients treated for anti - gbm - mediated disease , but urinary dipsticks may be sufficient for early detection of relapses . 
Background
Case report
Discussion
Conflict of interest statement