Clinical and epidemiological research
Ann Rheum Dis 2012;71:390–393. doi:10.1136/ard.2011.155382390
ABSTRACT
Objective T-helper type 2 responses are crucial in
Churg–Strauss syndrome (CSS) and may enhance the
production of IgG4 antibodies. The authors assessed the
IgG4 immune response in CSS patients.
Methods The authors included 46 consecutive
patients with CSS (24 with active and 22 with quiescent
disease), 26 with granulomatosis with polyangiitis (GPA,
Wegener’s), 25 with atopic asthma and 20 healthy
controls and determined serum IgG, IgM, IgA, IgE and
IgG subclass levels. Tissue infi ltration by IgG4 plasma
cells was assessed in nine patients with CSS, 10 with
GPA, 22 with chronic sinusitis (11 with and 11 without
eosinophilia).
Results IgG4 levels were markedly higher in active CSS
patients than in controls (p<0.001 vs all control groups).
Serum IgG4 correlated with the number of disease
manifestations (r=0.52, p=0.01) and the Birmingham
vasculitis activity score (r=0.64, p=0.001). Longitudinal
analysis in 12 CSS cases showed that both the IgG4 level
and IgG4/IgG ratio dropped during disease remission
(p=3×10
−5
and p=6×10
−4
, respectively). Tissue
analysis did not show an increased IgG4 plasma cell
infi ltration in CSS biopsies compared with control groups.
Conclusions Serum IgG4 levels are markedly elevated
in active CSS and correlate with the number of organ
manifestations and disease activity.
Churg–Strauss Syndrome (CSS) is a rare vasculitis
occurring in patients with eosinophilia, a history of
asthma and frequently allergic rhinitis and sinusitis.
It is histologically characterised by eosinophil-rich
infi ltrates, eosinophilic (extravascular) granulomas
and small to medium-sized vessel vasculitis.
1 2
The
pathophysiology of CSS is largely unknown; genetic
association with HLA-DRB4 has been reported.
3
The allergic history of CSS patients strongly sug-
gests a T-helper (Th) type 2-mediated disease, a
view reinforced by the evidence that Th2 cytok-
ines (eg, interleukin (IL)-4, IL-5, IL-13 and IL-25)
and chemokines (eg, eotaxin-3, TARC/CCL17) are
involved in CSS.
4 5
The humoral immune response in CSS is rela-
tively unexplored. High serum IgE levels are found
in approximately 90% of active CSS patients.
6
On
the other hand, little is known about IgG production
and IgG subclass distribution. IgG subclass analysis
is often relevant to the pathogenesis of immune-
mediated diseases, as a skewing in Th responses
may affect IgG subclass switching. For example, in
allergic asthma, allergen-specifi c IgG4 can often be
found, although total IgG4 serum levels may not be
signifi cantly high.
7
A group of diseases characterised by fi brosis, tis-
sue eosinophilia, IgG4-positive plasma cell infi ltra-
tion and high serum IgG4 levels have recently been
grouped under the umbrella term ‘IgG4-related
systemic disease’.
8
This entity encompasses scle-
rosing pancreatocholangitis, retroperitoneal fi bro-
sis, chronic sialoadenitis and other manifestations,
most of which show Th2 and regulatory T-cell
responses.
9
Therefore, we hypothesised that CSS
may share a similar IgG4 overproduction pattern,
and decided to investigate local and systemic IgG4
responses in CSS patients.
METHODS
Study subjects and serum samples
We studied 24 consecutive patients with active
CSS, 22 with quiescent CSS, 26 with active gran-
ulomatosis with polyangiitis (GPA, Wegener’s),
25 with atopic asthma and 20 healthy controls.
The patients were recruited at the Department
of Internal Medicine 3, University of Erlangen-
Nurnberg, Germany, and the Department of
Clinical Medicine and Nephrology, University
Hospital of Parma, Italy. All patients fulfi lled the
1990 American College of Rheumatology criteria
and/or the Chapel Hill Consensus Conference defi -
nitions for CSS or GPA. The characteristics of the
active CSS patients are shown in table 1 and those
of GPA patients in supplementary table S1 (avail-
able online only). Six of the active CSS patients
and all but two patients with quiescent CSS were
receiving immunosuppressive therapies. The
healthy control group consisted of 10 men and 10
women (mean age 48±10.5 years).
Serum levels of IgG, IgM, IgA, IgE and IgG sub-
classes were measured using standard nephelomet-
ric methods. Clinical manifestations and laboratory
markers were assessed as previously described;
3
the
criteria for organ involvement in CSS are reported in
the supplementary text (available online only). The
ethics committees of the University of Erlangen-
Nuremberg and of the University Hospital of
Parma approved the study, and written consent
was obtained from the study participants.
Tissue samples, histological and
immunohistochemical analyses
Nine biopsies obtained from the ear–nose–throat
(ENT) system (maxillary sinus n=6, ethmoid sinus
n=2, nasal septum n=1) of nine active CSS patients
were studied, together with ENT samples from 10
GPA patients and from 22 patients with chronic
sinusitis (11 with eosinophilia and 11 without).
▶ Additional supplementary
text, fi gures and tables are
published online only. To view
these fi les please visit the
journal online (http://ard.bmj.
com/content/71/3.toc)
1
Department of Clinical
Medicine, Nephrology and
Health Sciences, University of
Parma, Parma, Italy
2
Department of Pathology,
University of Erlangen-
Nuremberg, Erlangen, Germany
3
Department of Internal
Medicine 3 and Institute for
Clinical Immunology, University
of Erlangen-Nuremberg,
Erlangen, Germany
4
Nephrology and Clinical
Immunology Unit, San Carlo
Borromeo Hospital, Milan, Italy
5
Department of Laboratory
Medicine, University Hospital of
Parma, Parma, Italy
6
Ludwig Boltzmann Institute
of Osteology at the Hanusch
Hospital of WGKK and AUVA
Trauma Centre Meidling, 1st
Medical Department, Hanusch
Hospital, Vienna, Austria
Correspondence to
Jochen Zwerina, Department
of Medicine 3 and Institute for
Clinical Immunology, University
of Erlangen-Nuremberg,
Krankenhausstrasse 12,
D-91054 Erlangen, Germany;
jochen.zwerina@uk-erlangen.de
Received 4 April 2011
Accepted 6 October 2011
Published Online First
25 November 2011
CONCISE REPORT
IgG4 immune response in Churg–Strauss syndrome
Augusto Vaglio,
1
Johanna D Strehl,
2
Bernhard Manger,
3
Federica Maritati,
1
Federico Alberici,
1
Christian Beyer,
3
Jürgen Rech,
3
Renato A Sinico,
4
Francesco
Bonatti,
1
Luisita Battistelli,
5
Jörg H W Distler,
3
Georg Schett,
3
Jochen Zwerina
3,6
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Clinical and epidemiological research
Ann Rheum Dis 2012;71:390–393. doi:10.1136/ard.2011.155382 391
Detailed histological and immunohistochemical methods are
reported in the supplementary text (available online only).
Statistical analysis
Data are presented as mean±SEM, except where stated other-
wise. For group comparisons, we used one-way factorial analysis
of variance with the Bonferroni–Dunn test or the Mann–Whitney
U test. Categorical variables were compared with the Fisher’s
exact test. For correlations between IgG4 and the number of
involved organs or disease activity scores, Pearson’s correlation
coeffi cient was used. p Values less than 0.05 were considered
statistically signifi cant.
RESULTS
The clinical features of the 24 active CSS patients are given in
table 1.
Total immunoglobulin levels are shown in fi gure 1. IgG levels
were signifi cantly higher in active CSS patients than in healthy
controls (11709±384 mg/l vs 9631±405 mg/l, p=0.001), inac-
tive CSS (p<0.001) and controls with asthma (p=0.032). IgG
levels were also higher in GPA patients (11326±794 mg/l) than
in healthy subjects, but this difference was not statistically sig-
nifi cant (p=0.063); also, IgG levels were signifi cantly higher in
subjects with asthma (10769±271 mg/l) than in healthy con-
trols (p=0.033). With respect to IgM and IgA levels, no clinically
meaningful differences were detected between the groups. As
Table 1 Clinical characteristics of the 24 active Churg–Strauss
syndrome patients
M/F, n 15/9
Mean±SEM age at onset, years 47.3±2.8 (range 18–68)
ENT involvement, n (%) 23 (96)
Skin involvement, n (%) 8 (33)
Lung/lower airway tract involvement
Migratory lung infi ltrates, n (%) 13 (52)
Asthma, n (%) 24 (100)
Pleural effusions 3 (6.1)
Neurological manifestations
Peripheral neuropathy, n (%) 14 (58)
CNS involvement, n (%) 1 (4)
Gastrointestinal involvement, n (%) 3 (13)
Heart involvement 6 (25)
Renal involvement, n (%) 5 (21)
Mean±SEM eosinophil count, cells/µl 5607±2047
Mean±SEM C-reactive protein level, mg/l 25.6±6.4
ANCA positivity, n (%) 10 (42)
No (%) of treated patients 6† (25)
Mean±SEM BVAS 16.9±1.66
Patients with FFS ≥1 10 (42)
†Four patients were receiving corticosteroids alone, one prednisone and azathioprine
and one prednisone and cyclophosphamide.
ANCA, antineutrophil cytoplasmic antibodies; ANCA positivity was by
immunofl uorescence; BVAS, Birmingham vasculitis activity score; CNS, central nervous
system; ENT, ear– nose–throat; FFS, fi ve factor score.
Figure 1 Serum immunoglobulin and IgG subclass levels in Churg–Strauss syndrome (CSS) and control groups. Serum levels of total IgG, IgA, IgM
and IgE and IgG subclasses (IgG1, IgG2, IgG3, IgG4) were measured in the following groups: active CSS patients (n=24), CSS patients in remission
(n=22), active granulomatosis with polyangiitis (GPA, Wegener’s, n=26) patients, patients with asthma (n=25) and healthy subjects (n=20). Data
are given as box plots (median, 25th and 75th percentile, end of whiskers indicating 10th and 90th percentile). Statistically signifi cant p values are
hereafter reported. IgG, active CSS versus inactive CSS: p<0.001; active CSS versus healthy: p=0.001; active CSS versus patients with asthma:
p=0.032; GPA versus inactive CSS: p=0.024; asthma patients versus inactive CSS: p=0.002; asthma patients versus healthy: p=0.033. IgA:
active CSS versus inactive CSS: p=0.031; GPA versus inactive CSS: p=0.036. IgM: no signifi cant differences between the groups. IgE: active CSS
versus inactive CSS: p=0.005; active CSS versus GPA: p=0.001; active CSS versus healthy: p<0.001; asthma patients versus GPA, inactive CSS
and healthy: all p values <0.001. IgG4: active CSS versus inactive CSS, asthma patients, GPA and healthy: all p values <0.001; GPA versus healthy:
p=0.001; asthma patients versus healthy: p=0.033; inactive CSS versus healthy: p=0.013. GPA, granulomatosis with polyangiitis.
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Clinical and epidemiological research
Ann Rheum Dis 2012;71:390–393. doi:10.1136/ard.2011.155382392
IgG4/IgG ratio and IgG4 serum levels between antineutrophil
cytoplasmic antibody (ANCA)-positive and ANCA-negative
CSS patients (data not shown). IgE levels did not correlate with
IgG4 levels (r=0.23, p=0.270); also, they did not correlate with
the number of organ manifestations (r=−0.122, p=0.571) or the
BVAS (r=−0.72, p=0.738), nor did they differ in patients with
a FFS of 1 or greater versus a FFS of 0 (p=0.450). We also mea-
sured IgG4 serum levels longitudinally and the IgG4/IgG ratio
in 12 CSS patients at the time of active disease and during dis-
ease remission; notably, not only IgG4 levels but also the IgG4/
IgG ratio signifi cantly dropped during remission (p=3×10
-5
and
p=6×10
-4
, respectively; fi gure 2).
We next investigated differences in clinical characteristics
between patients with high (>1350 mg/l) and normal IgG4 levels
(see supplementary table S2, available online only). There were
no statistically signifi cant differences between the two groups.
Finally, we evaluated the degree of IgG4-bearing plasma cell
infi ltration in tissue biopsies obtained from the upper airway
tract of nine active CSS patients. All biopsies showed moderate
to severe lymphoplasmacellular infl ammation (grade 2 in fi ve
cases and grade 3 in four). Most biopsies also revealed moderate
to severe tissue eosinophilia (grade 1 in two cases, grade 2 in
three and grade 3 in four). Therefore, they were considered to be
representative of CSS-related chronic rhinosinusitis. The mean
IgG4/IgG-positive plasma cell ratio was 34.1±9.1%. Three of the
nine examined biopsies revealed an IgG4/IgG-positive plasma
cell infi ltration exceeding 30%, a cut-off ratio commonly used
to defi ne ‘IgG4-related systemic disorders’.
12
Representative
images are shown in supplementary fi gure S1 (available online
only).
Next, we compared the degree of IgG4-positive plasma cell
infi ltration of CSS biopsies with that of ENT biopsies taken from
active GPA patients and patients with chronic rhinosinusitis with
or without eosinophilia. No statistically signifi cant difference
was found in IgG4/IgG-positive plasma cell ratios between CSS
and GPA cases (p=0.278) and between CSS and chronic sinusitis
expected, IgE were higher in active CSS (761.5±246.6 IU/ml)
than in inactive CSS, GPA patients and healthy controls; equally,
they were higher in subjects with asthma (570.0±165.7 IU/ml)
than in healthy controls (p values in fi gure 1 legend).
IgG subclass analysis showed that serum IgG4 levels were
higher in active CSS patients (2732.2±363.3 mg/l) than in inac-
tive CSS (787.6±163.0 mg/l, p<0.001), GPA (1066.4±246.0 mg/l,
p<0.001), subjects with asthma (825.2±170.8 mg/l, p<0.001) and
healthy subjects (347.5±70.3 mg/l, p<0.001). IgG4 were also
higher in the GPA group and the group with asthma than in
healthy controls (p=0.001 and p=0.033; fi gure 1). Using 1350
mg/l as a cut-off value for IgG4, 18 active CSS patients (75%)
had elevated IgG4. We found no signifi cant alterations in IgG1,
IgG2 and IgG3 levels between the groups.
We also evaluated IgG4/IgG ratios to exclude the possibility
that the increase in serum IgG4 levels in active CSS was due to
the overall IgG increase (fi gure 1). Strikingly, the IgG4/IgG ratio
was higher in active CSS than in inactive CSS (22.0% vs 9.4%,
p=0.001), GPA (8.6%, p<0.001), subjects with asthma (7.5%,
p<0.001) and healthy subjects (3.6%, p<0.001).
Next, we explored the correlation between serum IgG4
levels and the number of organ manifestations as well as the
Birmingham vasculitis activity score (BVAS)
10
in active CSS; as
shown in fi gure 2, serum IgG4 strongly correlated with both
the number of organ manifestations (r=0.52, p=0.01) and the
BVAS (r=0.64, p=0.001). Likewise, the IgG4/IgG ratio in active
CSS also correlated with the number of organ manifestations
(r=0.44, p=0.034) and the BVAS (r=0.59, p=0.002). The fi ve fac-
tor score (FFS) is a well-established prognostic score in CSS,
based on the presence of heart, gastrointestinal and central ner-
vous system involvement, proteinuria greater than 1 g/24 h and
creatinine greater than 140 μmol/l.
11
Interestingly, the IgG4/IgG
ratio was higher in active CSS patients with a FFS of 1 or greater
compared with a FFS of 0 (p=0.046); IgG4 serum levels were
also higher in the former group, but the difference was not sta-
tistically signifi cant (p=0.053). There was no difference in the
Figure 2 IgG4 levels and disease activity in Churg–Strauss syndrome (CSS) patients. Upper panels: in CSS patients with active disease (n=24),
IgG4 serum levels signifi cantly correlate with disease activity, as assessed by the Birmingham vasculitis activity score (BVAS) and the number of
organ manifestations. Lower panels: IgG and IgG subclass serum levels were longitudinally measured in 12 patients during their active and remission
disease stages. A markedly signifi cant reduction is observed during remission in both the absolute IgG4 levels and the IgG4/IgG ratio (p=3×10
−5
and
p=6×10
−4
, respectively).
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Clinical and epidemiological research
Ann Rheum Dis 2012;71:390–393. doi:10.1136/ard.2011.155382 393
remains questionable.
20
Certainly, the possibility that IgG4-
related diseases and CSS have common immunopathogenetic
mechanisms has to be considered.
In conclusion, an increased IgG4 production is found in
active CSS. Serum IgG4 levels correlate with the extent of
organ involvement and with disease activity. Although a Th2-
dominated infl ammatory milieu may account for the enhanced
IgG4 production, further studies are needed to elucidate the
mechanisms underlying such immune response and to clarify
the potential pathogenetic role of IgG4 in CSS.
Acknowledgement The authors would like to thank Veronika Gröger for excellent
technical assistance.
Competing interests None.
Ethics approval This study was conducted with the approval of the University of
Erlangen and the University of Parma.
Patient consent Obtained.
Provenance and peer review Not commissioned; externally peer reviewed.
REFERENCES
1. Pagnoux C, Guilpain P, Guillevin L. Churg–Strauss syndrome. Curr Opin Rheumatol
2007;19:25–32.
2. Vaglio A, Casazza I, Grasselli C, et al. Churg–Strauss syndrome. Kidney Int
2009;76:1006–11.
3. Vaglio A, Martorana D, Maggiore U, et al. HLA-DRB4 as a genetic risk factor for
Churg–Strauss syndrome. Arthritis Rheum 2007;56:3159–66.
4. Dallos T, Heiland GR, Strehl J, et al. CCL17/thymus and activation-related chemokine
in Churg–Strauss syndrome. Arthritis Rheum 2010;62:3496–503.
5. Zwerina J, Bach C, Martorana D, et al. Eotaxin-3 in Churg–Strauss syndrome:
a clinical and immunogenetic study. Rheumatology (Oxford) 2011;50:1823–7.
6. Bottero P, Bonini M, Vecchio F, et al. The common allergens in the Churg–Strauss
syndrome. Allergy 2007;62:1288–94.
7. de Moraes Lui C, Oliveira LC, Diogo CL, et al. Immunoglobulin G subclass
concentrations and infections in children and adolescents with severe asthma.
Pediatr Allergy Immunol 2002;13:195–202.
8. Khosroshahi A, Stone JH. A clinical overview of IgG4-related systemic disease.
Curr Opin Rheumatol 2011;23:57–66.
9. Zen Y, Fujii T, Harada K, et al. Th2 and regulatory immune reactions are increased
in immunoglobin G4-related sclerosing pancreatitis and cholangitis. Hepatology
2007;45:1538–46.
10. Suppiah R, Mukhtyar C, Flossmann O, et al. A cross-sectional study of the
Birmingham vasculitis activity score version 3 in systemic vasculitis. Rheumatology
(Oxford) 2011;50:899–905.
11. Guillevin L, Lhote F, Gayraud M, et al. Prognostic factors in polyarteritis nodosa and
Churg–Strauss syndrome. A prospective study in 342 patients. Medicine (Baltimore)
1996;75:17–28.
12. Zen Y, Onodera M, Inoue D, et al. Retroperitoneal fi brosis: a clinicopathologic study
with respect to immunoglobulin G4. Am J Surg Pathol 2009;33:1833–9.
13. Cartin-Ceba R, Keogh KA, Specks U, et al. Rituximab for the treatment of Churg–
Strauss syndrome with renal involvement. Nephrol Dial Transplant 2011;26:2865–71.
14. Pepper RJ, Fabre MA, Pavesio C, et al. Rituximab is effective in the treatment
of refractory Churg–Strauss syndrome and is associated with diminished T-cell
interleukin-5 production. Rheumatology (Oxford) 2008;47:1104–5.
15. Yamamoto M, Takahashi H, Suzuki C, et al. Analysis of serum IgG subclasses in
Churg–Strauss syndrome – the meaning of elevated serum levels of IgG4.
Intern Med 2010;49:1365–70.
16. Brouwer E, Tervaert JW, Horst G, et al. Predominance of IgG1 and IgG4 subclasses
of anti-neutrophil cytoplasmic autoantibodies (ANCA) in patients with Wegener’s
granulomatosis and clinically related disorders. Clin Exp Immunol 1991;83:379–86.
17. Sinico RA, Di Toma L, Maggiore U, et al. Prevalence and clinical signifi cance of
antineutrophil cytoplasmic antibodies in Churg–Strauss syndrome. Arthritis Rheum
2005;52:2926–35.
18. Nirula A, Glaser SM, Kalled SL,
et al. What is IgG4? A review of the biology of a
unique immunoglobulin subtype. Curr Opin Rheumatol 2011;23:119–24.
19. Smyrk TC. Pathological features of IgG4-related sclerosing disease.
Curr Opin Rheumatol 2011;23:74–9.
20. Strehl JD, Hartmann A, Agaimy A. Numerous IgG4-positive plasma cells are
ubiquitous in diverse localised non-specifi c chronic infl ammatory conditions and
need to be distinguished from IgG4-related systemic disorders. J Clin Pathol
2011;64:237–43.
without eosinophilia (p=0.112), whereas this ratio was lower in
CSS than in chronic sinusitis with eosinophilia (p=0.056) (see
supplementary fi gure S2, available online only).
DISCUSSION
Humoral immunity may be involved in the pathogenesis of
CSS. The effi cacy of B-cell depletion with rituximab in refrac-
tory CSS cases
13 14
supports the view that B cells and, possibly,
humoral responses, are instrumental in CSS. In this study, we
found highly elevated serum IgG4 levels in CSS patients with
active disease, thus extending preliminary fi ndings from a recent
small case series.
15
We also showed that the increased IgG4 pro-
duction is much more pronounced in CSS than in other diseases
with vasculitic or allergic features such as GPA or atopic asthma.
Previous reports showed that IgG4 are increased in GPA com-
pared with healthy controls.
16
This was also confi rmed by our
study; nevertheless, the difference between CSS and GPA was
highly signifi cant.
Serum IgG4 levels paralleled the disease course as they norma-
lised during remission; notably, the IgG4/IgG ratio also dropped
during remission, thus indicating that the IgG4 decrease was due
to the overall decrease in IgG levels, and that this subclass quite
specifi cally refl ected disease activity. Serum IgG4 levels also cor-
related with the number of organ manifestations and the BVAS,
a well-established disease activity score in vasculitis. In addition,
they tended to be higher in patients with an adverse prognosis,
as assessed using the FFS. ANCA, which are more frequent in
CSS patients with ‘vasculitic’ complications,
17
were detectable
in both IgG4-normal and IgG4-high patients. Probably due to
the relatively small sample size, we were unable to detect differ-
ences in clinical manifestations between IgG4-normal and IgG4-
high CSS patients. In-situ analysis of IgG4 immune responses in
tissue biopsies from active CSS patients showed marked IgG4
+
plasma cell infi ltration in only a few cases, suggesting that a sys-
temic rather than a local perturbation in IgG4 responses occurs
in CSS.
Whether IgG4 antibodies play any role apart from being a
potential biomarker in CSS is unclear. Compared with the other
IgG subclasses, IgG4 has a negligible ability to activate the clas-
sic complement pathway, and its binding to Fcγ receptors is
much lower than that of IgG1. IgG4 antibodies are thought to
be blocking antibodies neutralising antigens. Nevertheless, they
do play a pathogenic role in some autoimmune conditions (eg,
pemphigus vulgaris), or in the protective response against para-
sitic infections.
18
The shift towards IgG4 production seems to be
related to the infl ammatory milieu conditioning B-cell matura-
tion. Th2 responses certainly favour IgG4 production, as typical
Th2 cytokines such as IL-4, IL-5 and IL-13 promote IgG4 switch-
ing. However, also the immunoregulatory IL-10 and the Th1-
linked IL-12 contribute to such responses.
18
A new entity called IgG4-related disease has recently been
established.
8
The disorders included in this entity display ele-
vated serum IgG4 levels, tissue infi ltration by IgG4-bearing
plasma cells and eosinophils, obliterative phlebitis and marked
fi brosis.
19
Could CSS thus be considered a form of IgG4-related
disease? Indeed, a few of our cases had a strong local IgG4 pro-
duction in tissue biopsies, and serum IgG4 levels were elevated
in active patients. Also, allergic symptoms, eosinophil infi ltra-
tion and phlebitis are features of both diseases. However, as an
increased tissue IgG4 production may occur in diverse chronic
infl ammatory diseases (eg, rheumatoid arthritis), its specifi city
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syndrome
Strauss−IgG4 immune response in Churg
Jochen Zwerina
Francesco Bonatti, Luisita Battistelli, Jörg H W Distler, Georg Schett and
Federico Alberici, Christian Beyer, Jürgen Rech, Renato A Sinico,
Augusto Vaglio, Johanna D Strehl, Bernhard Manger, Federica Maritati,
doi: 10.1136/ard.2011.155382
25, 2011
2012 71: 390-393 originally published online NovemberAnn Rheum Dis
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