Autoimmunity Reviews 22 (2023) 103212

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Autoimmunity Reviews
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Anti-glomerular basement membrane vasculitis

Claudio Ponticelli a, Marta Calatroni b, c, *, Gabriella Moroni b, c
a
via Ampere 126, 20131 Milan, Italy
b
Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072, Pieve Emanuele, Milan, Italy
c
Nephrology and Dialysis Division, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089, Rozzano, Milan, Italy

A R T I C L E I N F O A B S T R A C T

Keywords: Antiglomerular basement membrane disease (anti-GBM) is a rare life-threatening autoimmune vasculitis that
Rapidly progressive glomerulonephritis involves small vessels and it is characterized by circulating autoantibodies directed against type IV collagen
Alveolar hemorrhage antigens expressed in glomerular and alveolar basement membrane. The typical clinical manifestations are the
Pulmonary-renal syndrome
rapidly progressive glomerulonephritis and the alveolar hemorrhage. The diagnosis is usually confirmed by the
Plasmapheresis
Anti-neutrophil cytoplasm antibody
detection of anti-GBM circulating antibodies. If not rapidly recognized, anti-GBM disease can lead to end stage
Goodpasture syndrome kidney disease (ESKD). An early diagnosis and prompt treatment with immunosuppressive therapies and plas­
mapheresis are crucial to prevent a poor outcome. In this review, we discuss the primary form of anti-GBM (the
so called Goodpasture syndrome) but also cases associated with other autoimmune diseases such as
antineutrophil-cytoplasmic-antibody (ANCA) vasculitis, membranous nephropathy, IgA nephritis and systemic
lupus erythematosus (SLE), as well as the few cases of anti-GBM vasculitis complicating kidney transplantation in
the Alport syndrome.

Antiglomerular basement membrane disease (anti-GBM) is a rare in Caucasian and rare in African, although it may occur in all racial
life-threatening autoimmune disorder, clinically characterized by the groups [7].
triad: rapidly progressive glomerulonephritis, pulmonary hemorrhage,
and circulating autoantibodies [1]. Anti GBM vasculitis can occur either 2. Outcome and prognosis
as a primary disease, as in the case of Goodpasture syndrome, or may be
secondary to different disorders, including antineutrophil-cytoplasmic- The clinical presentation of anti-GBM disease is characterized by a
antibody (ANCA) vasculitis, membranous nephropathy, IgA nephritis, rapidly progressive glomerulonephritis with hematuria, macroscopic in
systemic lupus erythematosus (SLE) and may complicate kidney trans­ 40% of cases, non-nephrotic proteinuria and increase in serum creati­
plantation in the Alport syndrome. nine. Hemoptysis and dyspnea of varying degrees are frequently present
at clinical onset or appear few days later. In a few cases, patients present
1. Anti-GBM disease with severe renal failure requiring immediate dialysis. The diagnosis is
usually confirmed by the detection of anti-GBM circulating antibodies.
In 1919, during a pandemic influenza, Doctor Ernest William However, atypical forms of anti-GBM disease can occur and lead to late
Goodpasture, an eminent pathologist and physician, described a patient or wrong diagnosis: kidney disease may precede pulmonary symptoms
whose infection was complicated by hemoptysis and acute glomerulo­ by several days or vice versa, anti-GBM antibodies may result negative,
nephritis [2]. For many years, this disorder has been called Goodpasture renal or more frequently pulmonary signs and symptoms may be absent
syndrome, but in the last years anti-GBM disease has been considered as [10–15].
a more specific term and is presently preferred [3–7]. Anti-GBM disease In most untreated or lately treated patients, the typical anti-GBM
is a rare disorder with a prevalence of 10 cases/million hospitalized disease can progress to end stage kidney disease (ESKD) or can cause
patients in the United States [8]. It may have a bimodal distribution, death from kidney or respiratory complications. However, rare cases of
with a peak at 30 years, when it mainly affects males, and a second peak spontaneous remission have been reported [16] and in patients with
at 60 years, when it preferentially affects females [9]. It is more frequent atypical anti-GBM disease the course may be indolent [17]. In most

* Corresponding author.
E-mail address: marta.calatroni@humanimed.it (M. Calatroni).

https://doi.org/10.1016/j.autrev.2022.103212
Received 15 September 2022; Accepted 11 October 2022
Available online 14 October 2022
1568-9972/© 2022 Published by Elsevier B.V.

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patients, a prompt and aggressive treatment may substantially improve

the outcome. In a retrospective study on 964 patients with Goodpasture
syndrome, hospitalized in different structure in the USA, factors asso­
ciated with increased risk of mortality were age older than 70 years,
sepsis, the development of respiratory failure, circulatory failure, renal
failure, and liver failure. Instead, the factors associated with decreased
in-hospital mortality were more recent year of hospitalization and the
use of therapeutic plasmapheresis [8]. In a French multicenter cohort of
119 patients with anti-GBM disease the survival at 5 years was 92%. Risk
factors of death were age at onset, hypertension, dyslipidemia, and need
for mechanical ventilation. At 3 months, 46% of patients had ESKD.
They were older, more frequently females and had a higher serum
creatinine level at presentation than those without ESKD [18].
The renal prognosis largely depends on several risk-factors. A high
titer of autoantibody to the immunodominant epitopes is associated
with severe renal disease and worse prognosis [19]. The percentage [20]
and typology of glomerular lesions [21] may differ from case to case and
may result in benign (focal crescents) or ominous prognosis (sclerotic
crescents). A multicenter retrospective study of 123 patients with anti-
GBM disease showed that only one of 15 patients with ≥50% normal
glomeruli developed ESKD. Patients with ≥50% globally sclerotic
glomeruli and patients with 100% cellular crescents did not recover
from dialysis dependency at presentation [22]. The epithelial-
mesenchymal transition contributes to transformation of cellular cres­
cents to irreversible glomerular sclerosis [23,24]. Severe interstitial
fibrosis and tubular atrophy can also predict poor renal outcome
[25,26]. Patients requiring dialysis, only rarely may recover a partial
kidney function. In patients who recover, the recurrence of disease is
very rare but possible [27].

3. Pathology

At light microscopy, focal or diffuse crescentic or necrotizing

glomerulonephritis (GN) are typical findings at optic microscopy.
Proliferating crescents compress the glomerular tufts and the lesions are
all at the same stage of evolution. Various degrees of interstitial
inflammation are present. In advanced phase, crescents are fibrotic and
associated with glomerulosclerosis, interstitial fibrosis, and tubular at­
rophy. Other histologic renal patterns include prominent intracapillary
proliferation, focal glomerulosclerosis, minimal glomerular changes
(Fig. 1) [28,29]. At immunofluorescence, bright linear deposits of im­
munoglobulins (IgG 1 and IgG 3, rarely IgG4) and C3 on GBM can be Fig. 1. Light microscopy: Two glomeruli with tufts mostly compressed by
circumferential pluri-stratified cellular crescents mixed with inflammatory cells
seen along the inner aspect of the capillary wall [30]. At electron mi­
in the Bowman space.
croscopy, no electron-dense deposits are detected. In the lungs, alveolar
hemorrhage of various entity is frequent. Linear deposits of IgG along
the basement membrane of alveolar capillaries can be seen at trans (B-cell epitopes). Peptides in α3(IV)NC1 are B-cell epitopes which are
bronchial lung biopsy. recognized by nephrogenic antibodies that cause rapidly progressive
glomerulonephritis [36,37]. Experimental and clinical studies demon­
strated that also T cells play a critical role for antibody response
4. Pathophysiology
[38–41]. T cells not only can help the activation and maturation of B
cells but can also recognize the antigenic determinant and stimulate
Anti-GBM disease is an autoimmune disorder in which autoanti­
proliferation of Th1 and Th 17 cells (T-cell epitopes). T cell epitopes are
bodies are directed against the epitopes of an autoantigen located in
presented by molecules of the major histocompatibility complex that
collagen 4, the main component of the kidney and lung basement
trigger a T cell immune response [42]. In anti-GBM disease there is a
membranes. There are 6 subunit chains of collagen 4, called α 1-α 6.
strong association with DRB1*1501 and it has been showed that sus­
These chains assemble to form three different triple helices. The human
ceptibility to this allele may favor the presentation of T cell epitope to
GBM contains a triple helical formed by α3- α4 and α5. The antigen has
the immune system [43,44]. Even a single nephritogenic T cell epitope is
been identified as the non-collagenous domain 1 (NC1) of α3 chain of
sufficient to induce the clinical spectrum of anti-GBM disease [45]. On
type IV collagen (α3(IV)NC1). This antigen can be detected not only in
the other hand, peptides of B cell epitopes may also induce proliferation
anti-GBM disease but also in the general population [31,32]. In normal
of T cells [46].
conditions, the epitopes are hidden; however, conformational changes
Antibodies against GBM cause inflammation, release of reactive ox­
induced by infection [33], hydrocarbon exposure [34], smoking or other
ygen species and activation of complement that cause vascular necrosis
environmental factors may induce a conformational change, unveil
and breaks in the GBM. The leakage of plasma in the Bowman space
epitopes, and render them accessible to antibodies [35]. There are two
triggers the activation and proliferation of parietal epithelial cells and
categories of epitopes: linear epitopes which have a linear sequence of
their loss of polarity [47]. These changes together with macrophage and
amino acids, and conformational epitopes which have a discontinuous
lymphocyte infiltration lead to the formation of cellular crescents
amino acid sequence. Both forms can be targeted by specific antibodies

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involvement, skin, and lung involvement but crescentic GN is rare

[48,49]. Blood tests can allow to classify the different diseases. Circu­
lating anti-GBM antibodies are positive in about 95% of untreated pa­
tients with Goodpasture syndrome. The titer of the anti-GBM antibody
may be correlated with the severity of the renal disease. About 30% of
patients with anti-GBM disease may also present with concomitant
ANCA (usually MPO-ANCA) and about 5% of those with ANCA vasculitis
have concomitant anti-GBM antibodies [50,51]. Although the histologic
picture at light microscopy may be similar in all the types of crescentic
GN, fibrinoid necrosis is frequent in ANCA-associated vasculitis and rare
in anti-GBM disease. Granuloma may be seen in granulomatosis with
polyangiitis, eosinophil infiltration can occur in eosinophilic gran­
ulomatosis with polyangiitis while granulomas and eosinophil infiltra­
tion are absent in Goodpasture syndrome. The findings at
immunofluorescence are decisive. Linear deposits of immunoglobulins G
along GBM are typical of anti-GBM disease. Instead, in ANCA associated
vasculitis immunoglobulin deposits are absent or faint. However, the
presence of overlapping diseases, such as thrombotic microangiopathy,
membranous nephropathy or IgA nephritis [52,53] or mild kidney
injury and scarce lung hemorrhage [54] may render difficult the
diagnosis.

6. Treatment

A vigorous treatment should be initiated as soon as possible in pa­

tients with rapidly progressive GN, even before knowing the cause and
classification [55]. The usual approach is based on a combination of
corticosteroids and cytotoxic drugs. Treatment is often initiated with
intravenous methylprednisolone pulses (0.5–1 g each) repeated every
day for 3 days, followed by oral prednisone 1 mg/kg/24 h progressively
reduced over the time, plus cyclophosphamide, either intravenously at a
dosage of 0.5–1 g/m2 or orally at a dose 2–3 mg/kg/24 h. These doses
should be reduced in old or frail patients. Patients with anti-GBM disease
respond well to corticosteroids and cyclophosphamide if treatment is
initiated early. The use of plasma exchange was associated with better
survival in two large retrospective studies [8,54]. The use of plasma­
pheresis or immunoadsorption is particularly indicated in patients with
Fig. 2. Pathophysiology of anti-GBM disease in the kidney. Anti-GBM disease is massive alveolar hemorrhage. In a recent phase II trial Imlifidase, an IgG
caused by circulating autoantibodies against an antigen intrinsic to the GBM, degrading enzyme of Streptococcus pyogenes capable to cleave IgG within
principally the domain 1 (NC1) of the alpha-3 chain of the type IV collagen. hours, has been tested with excellent results in 15 patients with severe
Binding of the Auto-Ab to its target antigen results in activation of complement, Goodpasture disease [56]. Rituximab has also been used in anti-GBM
release of reactive oxygen species and lytic enzyme that cause tissue damage, disease. In a small study on 5 patients, it proved to be effective in
with capillary injury and breaks of the GBM. The leakage of plasma in the managing pulmonary manifestations with no major serious adverse
Bowman space triggers the activation and proliferation of proliferation of pa­
events. However, renal outcomes were not significantly improved [57].
rietal epithelial cells and, together with immune cells infiltration, leads to the
In another study on 8 patients, rituximab was started within two months
formation of cellular crescents.
GBM, glomerular basement membrane; AG, antigen; AB, antibody; ROS, reac­ after diagnosis when patients were already treated with corticosteroids,
tive oxygen species. cyclophosphamide, and plasmapheresis. Complete remission was
observed in 7 out of 8 patients, mostly 3 months after rituximab therapy.
After a mean follow-up of 26 months, patient and renal survival were
(Fig. 2).
100% and 75% respectively but rituximab use did not improve kidney
function. Anti-GBM antibodies remained negative for all patients during
5. Diagnosis
follow-up. One patient developed a severe bacterial infection, but no
opportunistic or viral infections were reported [58]. Usually, treatment
An early diagnosis is of paramount importance to prevent a poor
of Goodpasture syndrome is discontinued at 3 months, when circulating
outcome. The recognition of a rapidly progressive GN is easy and mainly
antibodies are undetectable. Late recurrence is very rare and usually
based on rapid increase in serum creatinine. However, crescentic GN
responds to treatment. Patients with ESKD may be treated with dialysis
may complicate other diseases and may be associated with pulmonary
and transplantation. It should be noted that a few patients on regular
complications, particularly in ANCA-associated vasculitis. In micro­
dialysis may unexpectedly recover kidney function [59–61]. Thus,
scopic polyangiitis (MPA), crescentic GN may affect 65% of patients.
caution is needed before considering renal failure irreversible. The
However, at difference with anti-GBM disease, infiltrates can be present
outcome of kidney transplantation in Goodpasture syndrome is similar
together with skin ulcers and arthralgias. In granulomatosis with poly­
to that of other causes of ESKD. Linear deposits of IgG may be seen in
angiitis (GPA), crescentic GN may occur in 70% of cases, lung cavita­
allografts, particularly if circulating anti-GBM antibodies are present at
tions and noduli are frequent but the diagnosis may be facilitated by the
the time of transplantation. However, clinical disease consequent to the
presence of mononeuritis, sinusitis, otitis media, and/or episcleritis.
glomerular deposits of anti-GBM antibodies occurs in <10% of cases and
Eosinophilic granulomatosis with polyangiitis (EGPA) has also a com­
only rarely leads to graft loss. In patients in whom antibodies cannot be
plex presentation with asthma, sinusitis, peripheral neuropathy, cardiac
detected, recurrent disease does not recur [62]. In the past, bilateral

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nephrectomy of the native kidneys was performed to allow disappear­ vessel vasculitis is played by complement, which is mainly activated by
ance of antibodies. This intervention is not recommended today. Most the alternative pathway [82].
clinicians prefer to check the titer of circulating anti-GBM antibodies The fundamental renal lesion of ANCA associated vasculitis is the
periodically and wait for 6–12 months before transplantation until anti- presence of glomerular crescents. The clinical presentation of AAV is
GBM antibodies disappear. With such a policy, the recurrence of anti- characterized by a rapid progressive decline in renal function, associated
GBM disease has virtually disappeared. However, rare cases of recur­ with dysmorphic hematuria, erythrocyte casts, and modest glomerular
rent disease accompanied by reappearance of anti-GBM antibodies have proteinuria. Nephrotic syndrome and hypertension are relatively un­
been reported 4–8 years after transplantation in patients in whom anti- common. In the absence of specific treatment, the disorder may rapidly
GBM antibodies had disappeared. In these cases, the prognosis is severe. progress to ESKD. Treatment is similar to that already described for
Most patients lost their allograft [63–66]. rapidly progressive GN.
As reported above, about 30% of patients with anti-GBM disease may
7. Secondary anti-GBM antibodies also present with concomitant ANCA (usually MPO-ANCA) and about
5% of those with ANCA vasculitis have concomitant anti-GBM anti­
7.1. Alport syndrome bodies [50,51]. Patients with double positivity have severe renal disease
and lung hemorrhage at presentation. Half of surviving patients with
Alport syndrome (AS) is a hereditary disorder, characterized by double positive disease had recurrent disease during a median follow-up
sensorineural hearing loss, ocular abnormalities, and progressive renal of 4.8 years [83]. Renal survival in patients with double positivity is
failure. These disorders depend on the abnormal composition of similar to that of anti-GBM disease and is worse compared with patients
collagen 4, the main collagen component of basement membranes. The with MPO-ANCAs only [84] but the risk of progression to ESKD in
synthesis of collagen 4 is regulated by the genes COL4A3, COL4A4, double positive disease may be aggravated by the frequent relapses [85].
which reside on chromosome 2, and by the gene COL4A5, which is Intensive and prolonged treatment is required. Patients with dual dis­
located on the X chromosome. There are three types of Alport syndrome: ease have an increased risk of malignancy related to the high doses of
X-linked dominant AS in which the affected gene is COL4A5, autosomal cyclophosphamide. Instead, a retrospective study found that rituximab-
dominant or recessive forms due to mutations of COL4A3 or COL4A4, treated patients had the same risk of malignancy than general popula­
and digenic AS due to mutations of COL4A3 and COL4A4 in cis or trans tion [86]. In summary, patients with dual positivity for ANCA and anti-
or COLA3, COLA4 and COL4A5 [67]. Males with X-linked dominant AS GBM antibodies demonstrate an intermediate phenotype that lies be­
will develop Alport syndrome and eventually ESKD, while females, with tween that of Goodpasture syndrome and AAV.
two chromosomes X, will have asymptomatic hematuria and rarely se­ In about 10% of cases, anti-GBM antibodies can develop later in
vere renal disease [68,69]. A multicenter randomized controlled trial in patients with pANCA vasculitis [87,88]. In these cases, one may hy­
Germany showed that the renin-angiotensin system inhibitors (RASi) pothesize that the attack of anti-MPO antibodies to capillary endothe­
ramipril decreased the risk of progression, diminished the slope of lium may cause GBM injury and increased the expression of GBM
albuminuria progression and the decline in glomerular filtration [70]. epitopes that trigger the development of anti-GBM antibodies.
However, the use of RASi can slow down but cannot eliminate pro­
gression to ESKD. 7.3. Membranous nephropathy and anti GBM disease
Male patients with ESKD are young adults and have superior patient
survival while undergoing dialysis and superior patient and graft sur­ Membranous nephropathy (MN) is a glomerular disease clinically
vival after deceased-donor kidney transplantation compared with pa­ characterized by proteinuria, usually in a nephrotic range, and histo­
tients with other causes of ESKD [71]. A major issue may be represented logically marked by an apparent thickening of the GBM, caused by
by the fact that in Alport’ patients there is an abnormal expression of subepithelial deposits of immune complexes. The etiology of MN is
alpha 5. Different isophorms of alpha 5(IV)NC1 epitope may be recog­ unknown, and the disease is called primary but in 20%–30% of cases
nized as antigen and initiate the immune response of the recipient with membranous nephropathy is secondary being associated with chronic
production of specific antibodies [72,73]. In the Alport syndrome the infection, systemic diseases, cancer, exposure to drugs or toxic agents
different alpha chains may associate to form a hexamer during the [89]. Idiopathic MN is an autoimmune disease in which autoantibodies
biosynthesis, with altered expression of alpha 3 and possible production are directed against epitopes of podocyte antigens. In about 60%–70% of
of antibodies against its epitopes [74]. However, after kidney trans­ cases the antigen has been identified as the M-type of phospholipase A2
plantation, most patients with Alport syndrome either show isolated receptor (PLA2r) [90], but several new antigens have been discovered
microscopic hematuria or do not present any specific problem. In about [91,92]. The disease may enter spontaneous remission of proteinuria but
10% of cases, it is possible to find faint linear deposits of IgG at immu­ in the long-term half of patients may enter ESKD or die from disease-
nofluorescence. Only in 2–5% of males with X-linked AS a rapidly pro­ related complications [93]. For patients at risk of progression (persis­
gressive GN may develop [75–77]. This event usually develops in the tent nephrotic syndrome, reduced GFR, elevated levels of anti-PLA2r
first posttransplant year but may also occur after 6 years or later. It is antibodies, severe tubulointerstitial changes at kidney biopsy) treat­
more frequent in patients who receive a second kidney transplant. The ment based on rituximab, corticosteroids, and cyclophosphamide, or
prognosis is severe. Despite intensive therapy most patients with anti- calcineurin inhibitors are recommended [94].
GBM antibodies lost their graft [78–81]. Patients with anti-GBM disease may develop MN. This association is
well documented [95–97]. Double-positive patients have a broader
7.2. Anti-GBM antibodies in ANCA-associated vasculitis spectrum of anti-GBM antibodies and lower levels of antibodies against
alpha3(IV)NC1 compared with that of patients with anti-GBM disease
The term ANCA-associated vasculitis (AAV) encompasses three [98]. Anti-PLA2r antibodies are undetectable in anti-GBM patients with
different vasculitis granulomatosis with polyangiitis, microscopic poly­ MN, suggesting that patients with dual positivity have distinct clinical
angiitis, and eosinophilic granulomatosis with polyangiitis also known features and a different immunological profile of MN [99]. In addition,
as Churg-Strauss syndrome. In turn, ANCAs have been subdivided into most dual-positive patients with crescents develop a long-term decline
anti-proteinase 3 (PR3) or cANCA vasculitis, and anti-myeloperoxidase in renal function despite immunosuppressive therapy [100]. Experi­
(MPO) or pANCA vasculitis. The pathophysiology of AAV is multifac­ mental study suggested that the subnephritogenic anti-GBM antibodies
torial and includes the role of inflammation, innate immunity, predis­ may cause an inflammatory environment in glomeruli that is amplified
posing genetic and environmental factors, aberrant response of adaptive by ANCA and neutrophils [101]. It is also possible that alterations of
immunity, and complement system activation A prominent role in small GBM caused by anti-GBM antibodies may unveil cryptic antigens with

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development of MN. GBM serum levels were correlated with the anti-double-stranded DNA
More rarely, patients affected by idiopathic or secondary MN may antibodies and with anti-nucleosome antibodies. Alveolar hemorrhage
develop anti-GBM disease [102–104]. One may speculate that abnor­ was significantly more frequent in lupus patients with anti-GBM anti­
malities of GBM in MN may favor conformational changes of α3(IV)NC1 bodies than in those without anti GBM antibodies. In addition, histo­
that stimulates the production of anti-GBM antibodies. logical damage and prognosis were worse in patients with anti-GBM
antibodies than in those without anti-GBM. In Europe, anti GBM anti­
7.4. IgA nephropathy and anti-GBM disease bodies were tested retrospectively in 100 SLE and in 100 Lupus nephritis
sera collected from 2011 to 2014 from a Franco-German European
Immunoglobulin A nephropathy (IgAN) is a primary glomerular biobank. The results were compared with that of 100 healthy people.
disease characterized by diffuse, and generalized mesangial deposition Most patients were Caucasians. None of the 300 tested sera at fluores­
of IgA, typically of the IgA1 subclass. IgA1 molecules have an aberrant cence enzyme immunoassay was positive for anti-GBM antibodies at
structure of O-glycans that can cause the production of autoantibodies titer >10 U/ml. Three cases with a titer >7 U/m were re-tested by in­
and circulating immune complexes that localize in the glomerular direct immunofluorescence assays but were found to be negative [126].
mesangium, with activation of mesangial cells, proliferation of extra­ The different results between European and Chinese study can be due
cellular matrix, and release of cytokines and chemokines acting to both to the different ethnicities and to the different methods for testing
initiate and perpetuate glomerular injury. Genetic factors are likely to anti-GBM antibodies. Indeed, the serum auto-antibody profiles and the
influence the pathogenesis of IgAN [105]. The disease is characterized frequency of proliferative lupus nephritis varies in the different ethnic­
principally by episodes of glomerular hematuria often with persistent ities [127,128]. On the other hand, the specificity of the commercial anti
proteinuria of a variable degree. The natural course of IgA may be GBM assays may vary considerably [129]. Altogether, these data suggest
indolent or slowly progressive leading to ESKD in 30%–50% of cases in that anti-GBM antibodies should not be included in the routinary
the long-term. In rare cases the disease may have a rapidly progressive immunological tests for SLE except in patient's whit rapidly progressive
course. Promising results have been obtained with use of corticosteroids renal failure and in those with signs of vasculitis such as intra-alveolar
in IgAN [106,107]. There is little evidence that additional immuno­ hemorrhage.
suppression is helpful [108].
Apart from rare cases of anti-GBM disease with IgG4 antibodies, Ethical statement
concurrent cases of both anti-GBM nephritis and IgAN have been re­
ported. Moulis et al. [109] described a case of IgA-mediated Good­ This article does not contain any studies with human participants or
pasture syndrome and reported the outcome for other 11 cases. Despite animals performed by any of the authors.
intensive immunosuppressive therapy, the disease progressed to ESKD
in many patients. Transplantation was not associated with recurrence in Declaration of Competing Interest
the kidney graft. Other cases of dual pathology with mesangial deposits
of IgA and linear glomerular deposits of IgG have been reported. In some All authors disclose that they do not have any financial or other re­
cases, pulmonary hemorrhage was present. Patients were treated with lationships, which might lead to a conflict of interest regarding this
methylprednisolone (MPP), with or without cyclophosphamide and/or article.
plasmapheresis with different outcomes ranging from complete kidney
recovery to stage 4 renal disease [110–115]. The pathogenesis of IgA- Data availability
mediated anti-GBM disease is still unknown. This condition may be
considered a different disease. No data was used for the research described in the article.

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