Wolfgang L Gross

Publications of Wolfgang L Gross

• Increased frequency of CCR4+ and CCR6+ memory T-cells including CCR7+CD45RAmed very early memory cells in granulomatosis with polyangiitis (Wegener`s).

  Authors: Ursula Fagin, Silke Pitann, Wolfgang L Gross, Peter Lamprecht

  Arthritis research & therapy. 04/2012; 14(2):R73.

  ABSTRACT: INTRODUCTION: Chemokine receptors play an important role in mediating the recruitment of T-cells to inflammatory sites. Previously, small proportions of circulating Th1-type CCR5+ andABSTRACT: INTRODUCTION: Chemokine receptors play an important role in mediating the recruitment of T-cells to inflammatory sites. Previously, small proportions of circulating Th1-type CCR5+ and Th2-type CCR3+ have been shown in granulomatosis with polyangiitis (GPA). Wondering to what extent CCR4 and CCR6 expression could also be implicated in T-cell recruitment to inflamed sites in GPA, we investigated the expression of CCR4 and CCR6 on T-cells and its association with T cell diversity and polarization. METHODS: Multicolor flow cytometry was used to analyze CCR4, CCR6, and intracellular cytokine expression of T-cells from whole blood of GPA-patients (n=26) and healthy controls (n=20). CCR7 and CD45RA were included for phenotypic characterization. RESULTS: We found a significant increase in the percentages of circulating CCR4+ and CCR6+ cells within the total CD4+ T-cell population in GPA. In contrast, there was no difference in the percentages of CD8+CCR4+ and CD8+CCR6+ T-cells between GPA and healthy controls. CCR4 and CCR6 expression was largely confined to central (TCM) and effector memory T-cells (TEM, TEMRA). A significant increase in the frequency of CCR4+ and CCR6+ TEMRA and CCR6+ TCM was shown in GPA. Of note, we could dissect CCR4 and CCR6 expressing CCR7+CD45RAmed very early memory T-cells (TVEM) from genuine CCR7+CD45RAhigh naive T-cells lacking CCR4 and CCR6 expression for peripheral tissue-migration within the CCR7+CD45RA+ compartment. The frequencies of CCR4+ and CCR6+ TVEM were also significantly increased in GPA. An increased percentage of IL-17+ and IL-22+ cells was detected in the CCR6+ cell subsets and IL-4+ cells in the CRR4+ cell subset when compared with CD4+ cells lacking CCR4 and CCR6 expression. CONCLUSIONS: Increased frequencies of circulating CCR4+ and CCR6+ memory T-cell subsets including hitherto unreported TVEM suggest persistent T-cell activation with the accumulation of CCR4+ and CCR6+ cells in GPA. CCR4 and CCR6 could be involved in the recruitment of T-cells including cytokine-producing subsets to inflamed sites in GPA.

• Comparative analysis of different commercial ELISA systems for the detection of anti-neutrophil cytoplasm antibodies in ANCA-associated vasculitides.

  Authors: Julia U Holle, Kristine Herrmann, Wolfgang L Gross, Elena Csernok

  Clinical and experimental rheumatology. 03/2012;

  OBJECTIVES: To assess the diagnostic performance of 11 commercial PR3- and MPO-ANCA ELISA systems (direct, capture and high sensitive [hs] ELISA). METHODS: Sera from 90 patients with AAV (GPA, MPAOBJECTIVES: To assess the diagnostic performance of 11 commercial PR3- and MPO-ANCA ELISA systems (direct, capture and high sensitive [hs] ELISA). METHODS: Sera from 90 patients with AAV (GPA, MPA and CSS) and 20 disease controls (SLE; RA) and healthy individuals were tested for the presence of ANCA by IFT and by different ELISAs for the presence of PR3-and MPOANCA, respectively. Furthermore, the binding capacity of the IUIS-CDC reference sera for PR3-/MPO-ANCA in different commercial assays was analysed. RESULTS: Commercial ELISA kits for PR3-ANCA differed moderately in their sensitivity (from 45% to 62.5%). The highest sensitivity for PR3-ANCA was obtained with hs ELISA (kit A) and capture ELISA (kit N). Testing for MPO-ANCA the highest sensitivity (85%) was obtained with direct ELISA (kit D and I). Specificity was high in all kits. Only three PR3-ANCA commercial kits and three MPO-ANCA kits produced binding at the expected value for the IUISCDC reference sera (100 U/ml). In all of the kits, serial dilutions of the reference sera did not yield linearity. CONCLUSIONS: Second (capture) and third (high sensitivity) generation PR3-ANCA ELISA kits are superior to conventional ELISAs. Direct and capture MPO-ANCA ELISAs showed a good overall performance in all kits. Most of the kits have not been standardised to allow their results to be compared.

• Cartilage Destruction in Granulomatosis with Polyangiitis (Wegener's Granulomatosis) Is Mediated by Human Fibroblasts after Transplantation into Immunodeficient Mice.

  Authors: Nina Kesel, Dorothee Köhler, Lena Herich, Martin Laudien, Konstanze Holl-Ulrich, Astrid Jüngel, Michel Neidhart, Steffen Gay, Renate E Gay, Elena Csernok, Peter Lamprecht, Wolfgang L Gross, Udo Schumacher, Sebastian Ullrich

  The American journal of pathology. 03/2012;

  A key feature of granulomatosis with polyangiitis (GPA; or Wegener's granulomatosis) is the granulomatous inflammation of the upper respiratory tract, which leads to the subsequent destruction ofA key feature of granulomatosis with polyangiitis (GPA; or Wegener's granulomatosis) is the granulomatous inflammation of the upper respiratory tract, which leads to the subsequent destruction of adjacent tissues. The aim of our work was to study the histopathological and cellular components of tissue destruction of human GPA tissue transplanted into immunodeficient mice. Biopsy specimens from patients with active GPA (n = 10) or sinusitis (controls, n = 6) were s.c. co-implanted with healthy allogeneic human nasal cartilage into immunodeficient pfp/rag2(-/-) mice. Transplants were examined for their destructive capability of the allografted human cartilage. In addition, nasal fibroblasts from patients with GPA (n = 8) and control healthy nasal fibroblasts (n = 5) were cultured, and cell proliferation and apoptosis were quantified. mRNA and protein levels of matrix metalloproteinases and cytokines were evaluated at baseline and after proinflammatory stimulation. GPA implants showed massive destruction of the co-implanted human cartilage, whereas cartilage destruction was only marginal in control samples. Destruction was mediated by human fibroblasts and could be inhibited by corticoid treatment. The up-regulated production of matrix metalloproteinases 1, 3, and 13 and cytokines IL-6 and IL-8 was found in vivo and in vitro. Although proliferation of isolated fibroblasts was comparable between GPA and controls, GPA samples showed a significant delay of apoptosis. The destruction of nasal cartilage in GPA is mainly mediated by fibroblasts that can be blocked by corticosteroids, and this tissue destruction is not dependent on the influx of leukocytes.

• Acute inflammatory syndrome with elevated procalcitonin induced by mycophenolate sodium.

  Authors: Jan Loock, Peter Lamprecht, Wolfgang L Gross

  The Journal of rheumatology. 03/2012; 39(3):658-9.

• Rituximab for refractory granulomatosis with polyangiitis (Wegener's granulomatosis): comparison of efficacy in granulomatous versus vasculitic manifestations.

  Authors: Julia U Holle, Christin Dubrau, Karen Herlyn, Martin Heller, Petra Ambrosch, Bernhard Noelle, Eva Reinhold-Keller, Wolfgang L Gross

  Annals of the rheumatic diseases. 03/2012; 71(3):327-33.

  First, to investigate the overall efficacy and safety of rituximab (RTX) in refractory granulomatosis with polyangiitis (GPA) in a tertiary referral centre. Second, to compare the efficacy of RTX inFirst, to investigate the overall efficacy and safety of rituximab (RTX) in refractory granulomatosis with polyangiitis (GPA) in a tertiary referral centre. Second, to compare the efficacy of RTX in granulomatous and vasculitic manifestations in GPA. This study comprised a retrospective, standardised data collection from all patients who received RTX for refractory Wegener's granulomatosis from 2002 to 2010. Patients were assessed by a standardised interdisciplinary diagnostic procedure (including ear, nose and throat and ophthalmology assessment, MRI, immunodiagnostics, B-cell levels and Birmingham Vasculitis Activity Score) and were treated by standardised therapeutic regimens according to available evidence. 59 patients received 75 cycles of RTX. 9.3% achieved complete remission. A response was documented in 61.3% (improvement in 52%, unchanged disease activity in 9.3%), 26.7% had refractory disease. Birmingham Vasculitis Activity Score, disease extent index, erythrocyte sedimentation rate, C-reactive protein and prednisolone demand decreased significantly. All patients achieved B-cell depletion. Granulomatous manifestations such as orbital granuloma and pachymeningitis were more frequently refractory to RTX than vasculitis or other granulomatous manifestations. Thus, for example, complete remission/improvement was found in 89.2% of patients with renal disease and in only 44.4% of those with orbital masses (p=0.003). The relapse rate was 44.4% after a median period of 13.5 months. Adverse events occurred in 29%, pneumonia in 15% and death in 3%. The overall response rate of refractory GPA to RTX was high (61.3% complete remission or improvement). Response rates of vasculitic manifestations were excellent; failure of response/progress was mostly due to granulomatous manifestations, especially orbital masses. Relapse rates were high (40%) despite maintenance treatment.

• Flow cytometric characterization of "early" and "late differentiated" T-cells including PR3-specific cells in granulomatosis with polyangiitis (Wegener's).

  Authors: Ursula Fagin, Silke Pitann, Wolfgang L Gross, Peter Lamprecht

  Cytometry. Part B, Clinical cytometry. 12/2011;

• Reply.

  Authors: Ronald J Falk, J Charles Jennette, Wolfgang L Gross, Loïc Guillevin, Gary S Hoffman, David R W Jayne, Cees G M Kallenberg, Raashid Luqmani, Alfred D Mahr, Eric L Matteson, Ulrich Specks, Peter A Merkel, Richard A Watts

  Arthritis and rheumatism. 09/2011; 63(9):2837.

• Rituximab in AAV: when and how to use it.

  Authors: Julia U Holle, Wolfgang L Gross

  Nature reviews. Rheumatology. 08/2011; 7(10):566-7.

• Conditions in subjects with rheumatic diseases: pulmonary manifestations of vasculitides.

  Authors: Julia U Holle, Frank Moosig, Klaus Dalhoff, Wolfgang L Gross

  Arthritis research & therapy. 06/2011; 13(3):224.

  Pulmonary involvement is a common complication of vasculitides, especially small vessel vasculitides. This review provides an overview of vasculitic manifestations of the lung as well as of otherPulmonary involvement is a common complication of vasculitides, especially small vessel vasculitides. This review provides an overview of vasculitic manifestations of the lung as well as of other organs involved in vasculitides. Furthermore, it provides the diagnostic procedures required to asses a patient with vasculitic lung involvement and gives an overview of current treatment strategies.

• Unclassified vasculitis.

  Authors: Peter Lamprecht, Nicolo Pipitone, Wolfgang L Gross

  Clinical and experimental rheumatology. 04/2011; 29(1 Suppl 64):S81-5.

  Vasculitides are a heterogeneous group of inflammatory disorders of the blood vessels. The etiology and pathogenesis of vasculitides is incompletely understood, and the nomenclature andVasculitides are a heterogeneous group of inflammatory disorders of the blood vessels. The etiology and pathogenesis of vasculitides is incompletely understood, and the nomenclature and classification of vasculitides remains a challenge. A number of vasculitides were not included in the Chapel Hill Consensus (CHC) Conference definitions, thus, have remained 'unclassified', but may be included in a revised version of the nomenclature, e.g. Goodpasture's syndrome. In other cases the term 'unclassified' implies 'unclassifiable', i.e. a vasculitis cannot be assigned to any of the known entities. Vasculitis-induced acral necrosis including giant cell arteritis of small arteries as well as isolated forms of intestinal vasculitis including granulomatous giant cell polyphlebitis may belong to this category of rare 'unclassified' vasculitides. In some entities the relationship between vasculitis and other manifestations remains unclear, e.g. in Behçet's disease and IgG4-related systemic disease. In this review the clinical and pathological aspects of 'unclassified' vasculitides are briefly discussed.

• Granulomatosis with polyangiitis (Wegener's): an alternative name for Wegener's granulomatosis.

  Authors: Ronald J Falk, Wolfgang L Gross, Loïc Guillevin, Gary S Hoffman, David R W Jayne, J Charles Jennette, Cees G M Kallenberg, Raashid Luqmani, Alfred D Mahr, Eric L Matteson, Peter A Merkel, Ulrich Specks, Richard A Watts

  Arthritis and rheumatism. 04/2011; 63(4):863-4.

• Distinct proteinase 3-induced cytokine patterns in Wegener´s granulomatosis, Churg-Strauss syndrome, and healthy controls.

  Authors: Ursula Fagin, Elena Csernok, Antje Müller, Silke Pitann, Juliane Fazio, Kristina Krause, Philip Bremer, Edith Wipfler-Freissmuth, Frank Moosig, Wolfgang L Gross, Peter Lamprecht

  Clinical and experimental rheumatology. 04/2011; 29(1 Suppl 64):S57-62.

  To analyse whether a specific cytokine pattern is elicited in response to the autoantigen proteinase 3 (PR3) in active Wegener's granulomatosis (WG). Six-colour flow cytometry was used to analyseTo analyse whether a specific cytokine pattern is elicited in response to the autoantigen proteinase 3 (PR3) in active Wegener's granulomatosis (WG). Six-colour flow cytometry was used to analyse cytokine production and surface markers of the total CD4+ T-cell population ex vivo and in PR3-stimulated T-cell lines of patients with active PR3-ANCA-positive WG, PR3-ANCA-negative Churg-Strauss syndrome (CSS), and healthy controls (HC). The cytokine response of the total PB CD4+ T cell population was skewed towards distinct pro-inflammatory cytokine patterns in WG (Th1-type) and CSS (Th17, Th1-/Th2-type). Th2-type as well as Th17 cell populations including Th17/Th1, Th17/Th2 and Th22 cells were elicited in response to PR3 stimulation in WG. In contrast, CSS patients displayed a Th2-type dominated response following PR3 stimulation. These data suggest that the cytokine response of the total CD4+ T-cell population and PR3-specific cells is influenced by the underlying disorder.

• Granulomatosis with polyangiitis (Wegener's): an alternative name for Wegener's granulomatosis.

  Authors: Ronald J Falk, Wolfgang L Gross, Loïc Guillevin, Gary Hoffman, David R W Jayne, J Charles Jennette, Cees G M Kallenberg, Raashid Luqmani, Alfred D Mahr, Eric L Matteson, Peter A Merkel, Ulrich Specks, Richard Watts

  Journal of the American Society of Nephrology : JASN. 03/2011; 22(4):587-8.

• Improved outcome in 445 patients with Wegener's granulomatosis in a German vasculitis center over four decades.

  Authors: Julia U Holle, Wolfgang L Gross, Ute Latza, Bernhard Nölle, Petra Ambrosch, Martin Heller, Regina Fertmann, Eva Reinhold-Keller

  Arthritis and rheumatism. 01/2011; 63(1):257-66.

  To determine the long-term outcome in patients with Wegener's granulomatosis (WG) over 4 decades in an academic hospital unit specializing in rheumatology. We included 290 patients, divided them intoTo determine the long-term outcome in patients with Wegener's granulomatosis (WG) over 4 decades in an academic hospital unit specializing in rheumatology. We included 290 patients, divided them into 2 cohorts, and compared them with the historical cohort of 155 patients. Comparisons were retrospective regarding disease manifestations, therapy, mortality, and incidence of malignancies. The historical cohort (cohort 1) included 155 patients diagnosed between 1966 and 1993, cohort 2 included 123 patients diagnosed between 1994 and 1998, and cohort 3 included 167 patients diagnosed between 1999 and 2002. Over time, the interval between first symptoms and diagnosis was reduced by half (from 8 months to 4 months). Organ manifestations were similar in the 3 cohorts, and more than 80% of patients still required cyclophosphamide (CYC); however, the median cumulative dose was reduced significantly (from 67 gm in cohort 1 to 36 gm in cohort 2 and to 24 gm in cohort 3). The standardized mortality ratios (SMRs) declined (from 2.1 in cohort 1 to 1.41 in cohort 2 and to 1.03 in cohort 3), with fewer deaths related to WG and/or therapy (86.4% in cohort 1, 76.9% in cohort 2, 50% in cohort 3), decreasing relapse rates (63.9% in cohort 1, 51.2% in cohort 2, 35.3% in cohort 3), and no increased rate of malignancies. Compared with young females, young males had a considerably higher SMR (8.87 [95% confidence interval 4.05-16.8]) and more frequent renal manifestations (54.4% versus 33.8%). Mortality of WG patients declined over the last 4 decades, probably due to improved diagnostic and therapeutic procedures and increased awareness of WG, which led to earlier diagnosis and therapy, reduction in relapse rates, and lower cumulative CYC dose with fewer deaths related to therapy.

• Neurological involvement in Wegener's granulomatosis.

  Authors: Julia U Holle, Wolfgang L Gross

  Current opinion in rheumatology. 01/2011; 23(1):7-11.

  Wegener's granulomatosis is a rare autoimmune disease associated with granulomatous inflammation and antineutrophil cytoplasmic antibody-associated vessel vasculitis. Most commonly, upper and lowerWegener's granulomatosis is a rare autoimmune disease associated with granulomatous inflammation and antineutrophil cytoplasmic antibody-associated vessel vasculitis. Most commonly, upper and lower respiratory tract and kidneys are involved: alveolar hemorrhage and necrotizing glomerulonephritis are hallmarks of full-blown disease; yet, a significant proportion of patients presents with peripheral nervous system (PNS) involvement due to vasculitis or with central nervous system (CNS) involvement due to infiltrating granulomatous manifestations (10-45%). The purpose of this review is to give a systematic overview on Wegener's granulomatosis manifestations of the PNS and CNS and to highlight new findings regarding manifestations, diagnosis and therapy. So far, peripheral neuropathy has been recognized as a severe and frequently occurring organ manifestation in Wegener's granulomatosis which requires early introduction of highly potent immunosuppression to induce remission. Recently, the impact of granulomatous manifestations originating from the ear-nose-throat tract and frequently affecting CNS structures has moved into the focus of attention, first, because they are not uncommon (occurring in 10-45% of patients) and, second, because they are associated with a high frequency of refractory disease courses. For both CNS and PNS involvement, rituximab and infliximab have emerged as potential treatment options for refractory disease. CNS and PNS manifestation in Wegener's granulomatosis are less frequent than classical manifestations such as lung and kidney involvement in Wegener's granulomatosis; however, neurological manifestations - not only peripheral neuropathy but also granulomatous manifestations affecting CNS structures - necessitate a fast diagnostic work-up and therapeutic intervention in order to prevent or reduce potential damage.

• Successful use of bortezomib in a patient with systemic lupus erythematosus and multiple myeloma.

  Authors: Karen Fröhlich, Julia U Holle, Peer M Aries, Wolfgang L Gross, Frank Moosig

  Annals of the rheumatic diseases. 12/2010; 70(7):1344-5.

• CCL17/thymus and activation-related chemokine in Churg-Strauss syndrome.

  Authors: Tomáš Dallos, Gisela Ruiz Heiland, Johanna Strehl, Thomas Karonitsch, Wolfgang L Gross, Frank Moosig, Constanze Holl-Ulrich, Jörg H W Distler, Bernhard Manger, Georg Schett, Jochen Zwerina

  Arthritis and rheumatism. 11/2010; 62(11):3496-503.

  Churg-Strauss syndrome (CSS) is a Th2-mediated systemic vasculitis characterized by eosinophilic infiltration, blood eosinophilia, and high IgE levels. CCL17/thymus and activation-regulated chemokineChurg-Strauss syndrome (CSS) is a Th2-mediated systemic vasculitis characterized by eosinophilic infiltration, blood eosinophilia, and high IgE levels. CCL17/thymus and activation-regulated chemokine (TARC) is a chemokine responsible for the recruitment of Th2 cells. This study was undertaken to explore a possible role of CCL17/TARC in CSS. CCL17/TARC levels in serum from patients with active or inactive CSS, hypereosinophilic syndrome, systemic small-vessel vasculitis other than CSS, other types of eosinophilia, and healthy controls were determined by enzyme-linked immunosorbent assay. Biopsy samples of affected tissue from CSS patients were examined by immunohistochemical staining for Th2 infiltration and CCL17/TARC expression. Serum CCL17/TARC levels were significantly elevated in CSS patients with active disease (mean ± SEM 1,122.0 ± 422.7 pg/ml) compared with controls (220.6 ± 27.9 pg/ml) and patients with inactive disease (388.9 ± 72.6 pg/ml) (P < 0.001 and P < 0.05, respectively). These levels correlated with the clinical disease course of CSS and with absolute eosinophil counts as well as IgE levels. Infiltrating Th2 cells in active CSS lesions were evidenced by CD294 staining. CCL17/TARC in the affected tissue of CSS patients was readily identified by immunohistochemical analysis. Elevated CCL17/TARC levels were also noted in patients with hypereosinophilic syndrome (794.5 ± 294.8 pg/ml) and other disorders associated with eosinophilia (1,096.0 ± 345.3 pg/ml) (both P < 0.005 versus controls). CCL17/TARC may contribute to CSS pathogenesis by recruitment of Th2 cells into affected tissue. Serum CCL17/TARC levels reflect disease activity, and further studies to validate its use as an activity marker in CSS are warranted.

• Prospective long-term follow-up of patients with localised Wegener's granulomatosis: does it occur as persistent disease stage?

  Authors: Julia U Holle, Wolfgang L Gross, Konstanze Holl-Ulrich, Petra Ambrosch, Bernhard Noelle, Marcus Both, Elena Csernok, Frank Moosig, Susanne Schinke, Eva Reinhold-Keller

  Annals of the rheumatic diseases. 11/2010; 69(11):1934-9.

  To identify patients with localised Wegener's granulomatosis (locWG) to assess whether it occurs as a long-term disease stage or phenotype and to characterise its outcome. Patients in a 'localisedTo identify patients with localised Wegener's granulomatosis (locWG) to assess whether it occurs as a long-term disease stage or phenotype and to characterise its outcome. Patients in a 'localised stage' with histological criteria compatible with WG and a follow-up period of ≥1 year were included. They were prospectively followed at the Vasculitis Center Schleswig-Holstein from 1989 to 2009 and the clinical manifestations, antineutrophil cytoplasmic autoantibodies (ANCA) status and damage were evaluated. Immunosuppression was adapted to disease activity and severity in a step-up regimen. Of 1024 patients with suspected WG, 99 were clinically diagnosed with locWG and 50 fulfilled the inclusion criteria (72% women, median age 43 years, 46% ANCA-positive). The median follow-up was 48 months. All achieved a response to treatment, 34% achieved complete remission, 1-4 relapses occurred in 46%, 5 (10%) had generalised disease (median 6 years after onset). ANCA status was not associated with relapse (p=0.98), transition to generalised disease (p=0.51) or refractory manifestations (p=0.60). 47% required cyclophosphamide for localised manifestations, 36% of them for pulmonary masses and 24% for orbital masses. 66% developed organ damage, mostly due to bony destruction or space obturation (28% saddle nose, 24% septal perforation, 10% orbital wall destruction). There were two deaths that were not related to WG. There is evidence that locWG is a long-term disease stage or phenotype (5% of all patients with WG), 46% of whom are ANCA-positive. LocWG is characterised by destructive and/or space-consuming lesions associated with high relapse rates (46%) and local damage.

• Wegener's granuloma harbors B lymphocytes with specificities against a proinflammatory transmembrane protein and a tetraspanin.

  Authors: Lorenz Thurner, Antje Müller, Martine Cérutti, Thierry Martin, Jean-Louis Pasquali, Wolfgang L Gross, Klaus-Dieter Preuss, Michael Pfreundschuh, Jan Voswinkel

  Journal of autoimmunity. 10/2010; 36(1):87-90.

  Wegener's granulomatosis (WG) is a severe autoimmune disorder ranging from localized granulomatous disease to generalised anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. A previousWegener's granulomatosis (WG) is a severe autoimmune disorder ranging from localized granulomatous disease to generalised anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. A previous analysis of immunoglobulin heavy chain genes derived from tissue, i.e. Wegener's granuloma indicated selection and affinity maturation towards local antigen(s). The current study focused on determining the specificity of immunoglobulins from distinct B lymphocytes out of Wegener's granuloma. Four pairs of variable region immunoglobulin light and heavy chain genes, isolated before, were recombinantly expressed using the baculovirus/insect cell system. These immunoglobulins were then analysed for their antigenic target employing a protein macroarray based upon a human fetal brain tissue cDNA expression library. The lysosomal transmembrane protein 9B, a key regulator for TNFα activation, was identified as the putative antigenic target of two immunoglobulins and a tetraspanin, which might play a role in leukocyte activation and motility, was identified as the putative antigenic target of another one. Recombinant monoclonal antibodies out of Wegener's granuloma represent a new tool aiding in elucidation of its and WG immunopathogenesis.

• Clinical manifestations and treatment of Wegener's granulomatosis.

  Authors: Julia U Holle, Martin Laudien, Wolfgang L Gross

  Rheumatic diseases clinics of North America. 08/2010; 36(3):507-26.

  Wegener's granulomatosis (WG) is characterized by granulomatous lesions and vasculitic disease manifestations. Granulomatous lesions are found in the upper and lower respiratory tract (eg,Wegener's granulomatosis (WG) is characterized by granulomatous lesions and vasculitic disease manifestations. Granulomatous lesions are found in the upper and lower respiratory tract (eg, granulomatous sinusitis, orbital masses, and pulmonary granuloma), whereas vasculitic manifestations occur frequently in lung (alveolar hemorrhage) and kidney (glomerulonephritis). Vasculitis is typically associated with antineutrophil cytoplasmic antibodies (ANCA) directed against proteinase 3. WG has been traditionally associated with a poor outcome and increased mortality as documented by numerous studies; however, recent cohort studies report an improved outcome, probably a consequence of increased awareness leading to an earlier diagnosis, and to improved treatment strategies derived from evidence from controlled trials. Treatment regimens for WG, adapted to disease stage and activity, are reviewed and discussed in this article.