HLA–DRB4 as a genetic risk factor for Churg‐Strauss syndrome

Vaglio, Augusto; Martorana, Davide; Maggiore, Umberto; Grasselli, Chiara; Zanetti, Adele; Pesci, Alberto; Garini, G; Manganelli, P; Bottero, Paolo; Tumiati, B; Sinico, Renato Alberto; Savi, M; Buzio, Carlo; Neri, Tauro Maria

doi:10.1002/art.22834

Cited by 175 publications

(90 citation statements)

References 43 publications

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“…HLA-DRB4 positivity may be a genetic risk factor for the development of CSS and may increase the likelihood of vasculitic manifestations of the disease. 5 Although this patient met only three of the six proposed ACR criteria, the clinical signs of her condition were most distinctive and in keeping with a diagnosis of CSS on clinical grounds. Indeed, Lanham et al have reported that although the classical histological picture comprises a necrotizing vasculitis, eosinophilic tissue infiltration and extravascular granulomas, it is only found in a minority of cases, and is not pathognomonic of the condition.…”

Section: To the Editorsupporting

confidence: 53%

“…1 The presence of four or more criteria yields a sensitivity of 85% and a specificity of 99.7%. These criteria include (1) asthma, (2) eosinophilia of more than 10% in the peripheral blood, (3) paranasal sinusitis, (4) pulmonary infiltrates (may be transient), (5) histological proof of vasculitis with extravascular eosinophils, and (6) mononeuritis multiplex or polyneuropathy. No causes of CSS are known, 2 although possible causes include allergic or autoimmune reactions to an environmental agent or drug (e.g., mesalazine, 3 propylthiouracil 4 ).…”

Section: To the Editormentioning

confidence: 99%

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Bilateral Subconjunctival Masses as a Rare Presentation of Churg-Strauss Syndrome

Manzouri

Shankar

Sim

et al. 2013

Ocular Immunology and Inflammation

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Section: To the Editorsupporting

confidence: 53%

Section: To the Editormentioning

confidence: 99%

Bilateral Subconjunctival Masses as a Rare Presentation of Churg-Strauss Syndrome

Manzouri

Shankar

Sim

et al. 2013

Ocular Immunology and Inflammation

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“…The HLA-DRB1 *04 and *07 alleles and the HLADRB4 gene are associated with an increased risk of developing EGPA [7,8]. The finding of an association with HLA, as in other autoimmune diseases, supports the hypothesis of an antigen-targeted disease.…”

Section: Genetic and Environmental Factorsmentioning

confidence: 58%

“…Since anti-neutrophil cytoplasmic antibodies (ANCA) have been found in a proportion of patients, EGPA has subsequently been included in the spectrum of ANCA-associated vasculitis (AAV), along with GPA and microscopic polyangiitis (MPA) [4]. Several studies have elucidated the role of immune mechanisms, identifying genetic associations with HLA-DRB4 while recognizing new diagnostic and follow-up biomarkers (e.g., eotaxin-3) [5][6][7][8][9][10][11]. Finally, the treatment approach has improved through the use of immunosuppressive drugs and biological treatments.…”

Section: Introductionmentioning

confidence: 99%

Churg-Strauss Syndrome or Eosinophilic Granulomatosis with Polyangiitis

et al. 2015

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Eosinophilic granulomatosis with polyangiitis (Churg-Strauss, EGPA) is a systemic small-to-medium-sized vasculitis associated with asthma and eosinophilia. Histologically EGPA presents tissue eosinophilia, necrotizing vasculitis, and granulomatous inflammation with eosinophil tissue infiltration. EGPA commonly involves the upper airway and lung parenchyma, peripheral neuropathy, cardiac disorders, and skin lesions. The anti-neutrophil cytoplasmic antibodies (ANCA) are positive in 40% of cases, especially in those patients with clinical signs of vasculitis. The pathogenesis of EGPA is multifactorial. The disease can be triggered by exposure to a variety of allergens and drugs, but a genetic background has also been described, particularly an association with HLA-DRB4. Th2 response is of special importance in the upregulation of different interleukins such as IL-4, IL-13, and IL-5. Th1 and Th17 responses are also of significance. Activated eosinophils have a prolonged survival and probably cause tissue damage by releasing eosinophil granule proteins, while their tissue recruitment can be regulated by chemokines such as eotaxin-3 and CCL17. Humoral immunity is also OPEN ACCESSSinusitis 2016, 1 25 abnormally regulated, as demonstrated by excessive responses of IgG4 and IgE. EGPA has a good respond to glucocorticoids, although the combination of glucocorticoids and immunosuppressants (e.g., cyclophosphamide, azathioprine) is needed in most of cases. Newer treatment options include anti-IL-5 antibodies (mepolizumab), whose efficacy has been described in clinical trials, and anti-CD-20, a B cell-depleting agent (rituximab), reported in several case series.

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“…Some studies, pooling CSS patients with WG and MPA, found a not significant association with a lower frequency of HLA-DRB1*03 (Boki KA, 1997). More recent genetic studies suggested some predisposing hereditary factors, like the HLA-DRB1*04 and HLA-DRB1*07 alleles and the HLA-DRB4 gene, which would be more frequent in Churg-Strauss syndrome patients than in healthy controls (Vaglio A. et al 2007). HLA-DRB4 positive patients were associated with a higher number of vasculitis symptoms, in particular in the ANCA positive group.…”

Section: Geneticsmentioning

confidence: 99%