Wegener’s granuloma harbors B lymphocytes with specificities against a proinflammatory transmembrane protein and a tetraspanin

Thurner, Lorenz; Müller, Antje; Cérutti, Martine; Martin, Thierry; Pasquali, Jean‐Louis; Gross, Wolfgang L.; Preuss, Klaus‐Dieter; Pfreundschuh, Michael; Voswinkel, Jan

doi:10.1016/j.jaut.2010.09.002

Cited by 34 publications

(24 citation statements)

References 25 publications

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“…An analysis of the gene repertoire of the antibodyproducing immunoglobulin heavy chain of these B cells demonstrated a higher frequency of mutations than healthy controls, suggesting antigen-driven selection and affinity maturation. Some authors have suggested that the microenvironment of the endonasal granuloma may be responsible for PR3-driven B cell maturation and selection, break of tolerance, and development of overt autoimmunity (19,20). Targeting of these autoreactive B cells that may play a role in GPA pathogenesis might explain the observed effectiveness of RTX for granulomatous ENT disease in our study.…”

Section: Discussionsupporting

confidence: 51%

Effectiveness of Rituximab for the Otolaryngologic Manifestations of Granulomatosis With Polyangiitis (Wegener's)

Lally

Lebovics

Huang

et al. 2014

Arthritis Care & Research

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Objective. Ear, nose, and throat (ENT) involvement is the most prevalent manifestation of granulomatosis with polyangiitis (Wegener's) (GPA) and correlates with permanent damage and decreased quality of life. Although prior studies have evaluated the efficacy of rituximab (RTX) for granulomatous features of GPA, none have evaluated its efficacy solely for ENT manifestations. We compared the effectiveness of RTX to other therapies for the ENT manifestations of GPA in a large, well-characterized cohort. Methods. We performed a retrospective analysis of 975 visits from 99 GPA patients seen at a tertiary care ENT practice between 2003 and 2013. At each visit, subjects had a complete ENT examination, with ENT activity assessed by a single expert otolaryngologist. ENT disease activity during the observational period in subjects receiving RTX was compared to subjects receiving all other therapy. Results. In total, 48 subjects had never received RTX and 51 received RTX at least once. There was no active ENT disease during 92.4% of the observational period (days) for subjects receiving RTX, compared with 53.7% of the observational period for subjects not receiving RTX (odds ratio 11.0 [95% confidence interval 5.5-22.0], P < 0.0001). Subjects receiving RTX, compared with those receiving methotrexate, azathioprine, cyclophosphamide, or trimethoprim-sulfamethoxazole, were significantly more likely to have no active ENT disease (P < 0.0001 for each comparison). Conclusion. RTX is an effective treatment for ENT manifestations of GPA. Subjects treated with RTX were significantly less likely to have active ENT disease compared with those not receiving RTX. Patients being treated with RTX were 11 times less likely to have active ENT disease than patients being treated with other therapies.

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Section: Discussionsupporting

confidence: 51%

Effectiveness of Rituximab for the Otolaryngologic Manifestations of Granulomatosis With Polyangiitis (Wegener's)

Lally

Lebovics

Huang

et al. 2014

Arthritis Care & Research

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“…The baculovirus expression system has been used for basic research to analyze the molecular basis of specificity, 21,22,41,52 autoimmunity 32,33,36,39,41,42 or the function of intact antibodies or of isolated immunoglobulin domains. 18,40,[43][44][45][46] It is very easy and fast to generate recombinant viruses expressing H or L bearing specific mutations and to determine the impact of these mutations on the specificity or activity of a given antibody.…”

Section: Biological Activities Of Recombinant Antibodies Produced In mentioning

confidence: 99%

“…21,22,41 This strategy has been successfully used to analyze the catalytic activity of the 6D9 monoclonal antibody and the specificity of the PAC1 antibody that binds to the integrin αII b β3 on activated platelets. 18,52 Universal expression cassettes have also been designed either to directly clone the VH and VL domains of antibodies expressed by murine cells or by human B-cells isolated from patients 26,32,33,36,39 or to convert scFv or Fab fragments selected from phage-display libraries into an intact fully human or chimeric IgG. 29,34,35,37,38,42 The aim of many of these experiments was to isolate, characterize and validate antibodies for further therapeutic applications in the treatment of human diseases such as hemolytic disease of newborn, 31 cancer 23,27,[56][57][58] and infectious diseases, with the selection of neutralizing antibodies against hemorrhagic fever viruses (e.g., hantaan, Puumala viruses), 34,35,72 human cytomegalovirus, 37 influenza virus 38 or prion protein.…”

Section: Biological Activities Of Recombinant Antibodies Produced In mentioning

confidence: 99%

“…Several immunoglobulin isotypes from many different species, including murine IgG, 2,3,[21][22][23][24][25] chimeric IgG, [26][27][28][29][30] human IgG, [31][32][33][34][35][36][37][38][39] IgA, [40][41][42] IgM 41 and IgE, [43][44][45] as well as pig Igs 30,45 have been successfully expressed in insect cells. These molecules are all correctly processed (signal peptide cleaved), glycosylated and assembled (H2L2) with a production rate varying from 0.75 to 100 mg/l, depending on the antibody ( …”

Section: Introductionmentioning

confidence: 99%

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Lepidopteran cells, an alternative for the production of recombinant antibodies?

Cérutti

Golay

2012

mAbs

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“…It is usually associated with the detection of circulating ANCA (c-ANCA) against serine protease-3 (PR3). Its etiology and pathogenesis has not yet been fully elucidated, although various putative antigens have recently been invoked in the context of a local autoimmune reaction within the granuloma [3]. …”

Section: Introductionmentioning

confidence: 99%

‘Prostate Abscess' as the Initial Manifestation of Granulomatosis with Polyangiitis (Wegener's Granulomatosis)

Tsiodras

Poulakou²,

Leventakos³

et al. 2014

Urol Int

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Prostatic involvement in granulomatosis with polyangiitis (GWP), formerly known as Wegener's granulomatosis, is rare, mostly arising in the context of systemic involvement. Prostatic involvement as the first manifestation of this systemic disease is exceptionally rare. We hereby present the case of a 41-year-old male patient who underwent transurethral prostate resection for what was initially diagnosed as suppurative, focally necrotizing prostatitis. Prolonged postoperative fever that did not respond to various treatments, as well as the subsequent appearance of a left pleural effusion, a left upper pulmonary lobe lesion and cutaneous nodules, led to a reevaluation of histological slides which, along with the determination of serum c-ANCA/anti-PR3 antibody levels, established the diagnosis of GWP. Physicians, and especially urologists and infectious diseases specialists, should be aware of this rare association and consider GWP in the event of nonresolving prostatitis, especially when characteristic symptoms from other systems appear.

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Wegener’s granuloma harbors B lymphocytes with specificities against a proinflammatory transmembrane protein and a tetraspanin

Cited by 34 publications

References 25 publications

Effectiveness of Rituximab for the Otolaryngologic Manifestations of Granulomatosis With Polyangiitis (Wegener's)

Effectiveness of Rituximab for the Otolaryngologic Manifestations of Granulomatosis With Polyangiitis (Wegener's)

Lepidopteran cells, an alternative for the production of recombinant antibodies?

‘Prostate Abscess' as the Initial Manifestation of Granulomatosis with Polyangiitis (Wegener's Granulomatosis)

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