Anti–Saccharomyces cervisiae antibodies in hidradenitis suppurativa: More than a gut feeling
2020; Elsevier BV; Volume: 146; Issue: 2 Linguagem: Inglês
10.1016/j.jaci.2020.03.022
ISSN1097-6825
Autores Tópico(s)Autoimmune and Inflammatory Disorders
ResumoAnti–Saccharomyces cervisiae antibodies (ASCAs) are pANCA antibodies against the mannose portion (mannans) of the fungal cell wall.1Assan F, Gottleib J, Tubach F, Lebbah S, Guigue N, Hickman G, et al. Anti-Saccharomyces cerevisiae immunoglobulin G and immunoglobulin A antibodies are associated with systemic inflammation and advanced disease in hidradenitis suppurativa [published online ahead of print February 13, 2020]. J Allergy Clin Immunol. https://doi.org/10.1016/j.jaci.2020.01.045.Google Scholar They have a high sensitivity and specificity as a diagnostic biomarker for Crohn disease and as Assan et al1Assan F, Gottleib J, Tubach F, Lebbah S, Guigue N, Hickman G, et al. Anti-Saccharomyces cerevisiae immunoglobulin G and immunoglobulin A antibodies are associated with systemic inflammation and advanced disease in hidradenitis suppurativa [published online ahead of print February 13, 2020]. J Allergy Clin Immunol. https://doi.org/10.1016/j.jaci.2020.01.045.Google Scholar report are associated with severe disease activity in hidradenitis suppurativa (HS). HS is a chronic, inflammatory dermatoses manifesting in painful nodules and abscesses in intertriginous areas often with development of purulent chronically draining epithelialized dermal tunnels.2Frew JW, Jiang CS, Singh N, Grand D, Navrazhina K, Vaughan R, et al. Clinical response rates, placebo response rates, and significant covariates are dependent upon choice of outcome measurement in hidradenitis suppurativa: a post-hoc analysis of PIONEER 1 and 2 individual patient data [published online ahead of print December 24, 2019]. J Am Acad Dermatol. https://doi.org/10.1016/j.jaad.2019.12.044.Google Scholar Clinical outcome measures of disease activity and/or response to pharmacological intervention suffer from poor reproducibility and high placebo response rates.2Frew JW, Jiang CS, Singh N, Grand D, Navrazhina K, Vaughan R, et al. Clinical response rates, placebo response rates, and significant covariates are dependent upon choice of outcome measurement in hidradenitis suppurativa: a post-hoc analysis of PIONEER 1 and 2 individual patient data [published online ahead of print December 24, 2019]. J Am Acad Dermatol. https://doi.org/10.1016/j.jaad.2019.12.044.Google Scholar The identification of ASCAs as a potential diagnostic and disease activity biomarker is an encouraging result in HS, a disease in which biomarkers are sorely needed. However, a critical assessment of the validity of ASCAs in HS and identification of the potential confounding factors that may influence results is mandatory before the consideration of longitudinal, treatment-oriented biomarker validation studies. HS and Crohn disease have a known epidemiological association1Assan F, Gottleib J, Tubach F, Lebbah S, Guigue N, Hickman G, et al. Anti-Saccharomyces cerevisiae immunoglobulin G and immunoglobulin A antibodies are associated with systemic inflammation and advanced disease in hidradenitis suppurativa [published online ahead of print February 13, 2020]. J Allergy Clin Immunol. https://doi.org/10.1016/j.jaci.2020.01.045.Google Scholar and share a number of common inflammatory pathways.1Assan F, Gottleib J, Tubach F, Lebbah S, Guigue N, Hickman G, et al. Anti-Saccharomyces cerevisiae immunoglobulin G and immunoglobulin A antibodies are associated with systemic inflammation and advanced disease in hidradenitis suppurativa [published online ahead of print February 13, 2020]. J Allergy Clin Immunol. https://doi.org/10.1016/j.jaci.2020.01.045.Google Scholar The association of ASCAs in HS may be a product of the well-documented overlap in recruitment signaling between skin-homing and gut-homing lymphocytes and antibody-secreting cells in the setting of immune dysregulation such as Crohn disease.3Mann E.R. McCarthy N.E. Peake S.T. Milestone A.N. Al-Hassi H.O. Bernardo D. et al.Skin- and gut-homing molecules on human circulating γδ T cells and their dysregulation in inflammatory bowel disease.Clin Exp Immunol. 2012; 170: 122-130Crossref PubMed Scopus (26) Google Scholar The comparator population used by Assan et al1Assan F, Gottleib J, Tubach F, Lebbah S, Guigue N, Hickman G, et al. Anti-Saccharomyces cerevisiae immunoglobulin G and immunoglobulin A antibodies are associated with systemic inflammation and advanced disease in hidradenitis suppurativa [published online ahead of print February 13, 2020]. J Allergy Clin Immunol. https://doi.org/10.1016/j.jaci.2020.01.045.Google Scholar (psoriasis vulgaris) also has a comparable epidemiological association with Crohn disaese,4Alinaghi F. Tekin H.G. Burisch J. Wu J.J. Thyssen J.P. Egeberg A. Global prevalence and bidirectional association between psoriasis and inflammatory bowel disease—a systematic review and meta-analysis.J Crohns Colitis. 2020; 14: 351-360Crossref PubMed Scopus (23) Google Scholar supporting the validity of their conclusions of increased prevalence of ASCAs in severe HS.1Assan F, Gottleib J, Tubach F, Lebbah S, Guigue N, Hickman G, et al. Anti-Saccharomyces cerevisiae immunoglobulin G and immunoglobulin A antibodies are associated with systemic inflammation and advanced disease in hidradenitis suppurativa [published online ahead of print February 13, 2020]. J Allergy Clin Immunol. https://doi.org/10.1016/j.jaci.2020.01.045.Google Scholar The limitations to the study include the exclusion of patients with HS with inflammatory bowel disease or spondyloarthropathy, limiting the external validity of ASCAs as a potential biomarker as well as the moderate length of patient follow-up (17 months).1Assan F, Gottleib J, Tubach F, Lebbah S, Guigue N, Hickman G, et al. Anti-Saccharomyces cerevisiae immunoglobulin G and immunoglobulin A antibodies are associated with systemic inflammation and advanced disease in hidradenitis suppurativa [published online ahead of print February 13, 2020]. J Allergy Clin Immunol. https://doi.org/10.1016/j.jaci.2020.01.045.Google Scholar Longer follow-up may identify a subset of participants with emergence of Crohn disease. In addition, subclinical Crohn disease may exist in HS participants (as seen in spondyloarthropathy),5Rizzo A. Guggino G. Ferrante A. Ciccia F. Role of subclinical gut inflammation in the pathogenesis of spondyloarthritis.Front Med. 2018; 5 (63)Crossref Scopus (16) Google Scholar which would require histological investigation in future replication studies. An additional consideration in ASCAs as a potential HS biomarker is the significant cross-reactivity with fungal, bacterial, and mycobacterial species.6Schaffer T. Muller S. Flogerzi B. Seibold-Schmid B. Schoepfer A.M. Seibold F. Anti-Saccharomycets cerevisiae mannan antibodies (ASCA) of Crohn’s patients crossreact with mannan from other yeast strains, and murine ASCA IgM can be experimentally induced with Candida albicans.Inflamm Bowel Dis. 2007; 13: 1339-1346Crossref PubMed Scopus (28) Google Scholar,7Rangarajan M. Aduse-Opoku J. Hashim A. Paramonov N. Curtis M.A. Characterization of the α- and β-mannosidases of Porphyromonas gingivalis.J Bacteriol. 2013; 195: 5297-5307Crossref PubMed Scopus (16) Google Scholar Various Candida species cross-react with ASCAs via surface mannans, and an increase in gastrointestinal candida species results in ASCA titer elevation in murine models.6Schaffer T. Muller S. Flogerzi B. Seibold-Schmid B. Schoepfer A.M. Seibold F. Anti-Saccharomycets cerevisiae mannan antibodies (ASCA) of Crohn’s patients crossreact with mannan from other yeast strains, and murine ASCA IgM can be experimentally induced with Candida albicans.Inflamm Bowel Dis. 2007; 13: 1339-1346Crossref PubMed Scopus (28) Google Scholar Porphyromonas species (associated with complement activation and clinical disease activity in HS) use oligomannosidases (producing mannans) as virulence factors.7Rangarajan M. Aduse-Opoku J. Hashim A. Paramonov N. Curtis M.A. Characterization of the α- and β-mannosidases of Porphyromonas gingivalis.J Bacteriol. 2013; 195: 5297-5307Crossref PubMed Scopus (16) Google Scholar Emerging therapies for HS involve IL-17 blockade, which is known to increase the risk of cutaneous fungal infections. Therefore, although Assan et al’s work is an important first step in identifying potential biomarkers in HS, the effect of microbial (bacterial and fungal) colonization and IL-17–based therapy on ASCAs is an important area of future mechanistic and translational enquiry. Anti-Saccharomyces cerevisiae IgG and IgA antibodies are associated with systemic inflammation and advanced disease in hidradenitis suppurativaJournal of Allergy and Clinical ImmunologyVol. 146Issue 2PreviewHidradenitis suppurativa (HS) is a chronic inflammatory skin disease that affects 1% to 4% of the Western population and is associated with major impact on quality of life. Its pathogenesis, combining hair follicle dysregulation and both skin and systemic inflammation, involves a genetic background interacting with environmental factors (eg, bacterial skin dysbiosis, overweight, smoking).1 TNF-α, which is enhanced in HS, is upregulated in other immune-mediated inflammatory diseases (IMIDs) such as severe psoriasis vulgaris (PV), inflammatory bowel disease (IBD), and spondyloarthritis. Full-Text PDF ReplyJournal of Allergy and Clinical ImmunologyVol. 146Issue 2PreviewWe read with interest the correspondence by Frew1 about our article reporting an association between anti–Saccharomyces cerevisiae antibodies (ASCAs) and hidradenitis suppurativa (HS), especially in its severe and inflammatory forms, in comparison with healthy controls and those with severe psoriasis vulgaris.2 Full-Text PDF
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