IgM-positive ocular mucous membrane pemphigoid

IgM-positive ocular mucous membrane pemphigoid | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report IgM-positive ocular mucous membrane pemphigoid Richard Farnan, Kirsty Veitch, Kevin Culligan, Elizabeth McElnea This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7693526/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose Ocular mucous membrane pemphigoid involves chronic, relapsing-remitting, bilateral, cicatrizing conjunctivitis. Antibodies produced by activated B cells bind, in a linear fashion, to antigens on the basement membrane of the conjunctiva. We describe a patient with ocular mucous membrane pemphigoid who demonstrated deposition of only IgM along the conjunctival basement membrane. Methods The case of a 77-year lady with left lower eyelid cicatricial entropion secondary to inferior conjunctival forniceal shortening with symblepharon formation on a background of ocular mucous membrane pemphigoid is described. Results Linear deposition of only IgM and not IgG and/or IgA at the conjunctival basement membrane was identified by direct immunofluorescence. Conclusion IgM associated ocular mucous membrane pemphigoid is a rare clinical entity. Although not a new phenomenon, it is far less commonly observed than the deposition of IgG, IgA or C3. Outcomes of immunomodulatory therapy for these patients are, reportedly, comparable to those of the ‘general’ ocular mucous membrane pemphigoid patient population. Figures Figure 1 Figure 2 Figure 3 Introduction Mucous membrane pemphigoid (MMP) describes a group of autoimmune ‘blistering’ disorders that affect, for the most part, mucosal surfaces and, less commonly, skin. Inflammation develops in the oral, ocular, nasal, nasopharyngeal, anogenital, laryngeal, and oesophageal mucous membranes in descending order of involvement 1 . Cutaneous lesions involving the head and upper trunk also occasionally occur. Involvement of both mucous membranes and skin presents with erythema, ulceration, and scarring. Ocular mucous membrane pemphigoid (OMMP) refers to a form of MMP which involves chronic, relapsing-remitting, bilateral, conjunctivitis. It is a rare clinical entity with an incidence between 1 per 10,000 to 50,000 2 . It is believed however to account for 61% of newly diagnosed cases of cicatrizing conjunctivitis. Females are twice as commonly affected as males. Those affected are usually in the age range 60–80 years 3 . Approximately 60–70% of those with OMMP will have more generalized MMP 4 . Both are type II hypersensitivity reactions with antibody production against extracellular antigens resulting in tissue damage 5 . In OMMP, antibodies produced by activated B cells bind to antigens on the basement membrane of the conjunctiva 5 . Antibodies to beta-4 integrin have been associated with OMMP with antibody levels correlating with disease activity 6 , 7 . Other identified antigens include bullous pemphigoid (BP) 180 and several ectodomains of BP180, BP 230, and laminin 332 6 – 9 . Antibodies deposit in a linear fashion along the basement membrane zone (BMZ) in conjunction with these antigens. Although IgM is the initial antibody produced by B cells, interactions with CD4 + T helper cells and resultant cytokine production lead to immunoglobulin ‘class switching’ and the production of IgG and IgA 10 , 11 . Complement activation and cellular responses including the secretion of interferon-γ and TGF-β and fibroblast activation propagate the response resulting in conjunctival fibrosis and scarring. Conjunctival perilesional biopsy with immunofluorescence – direct or indirect or immunohistochemistry examinations are used to confirm OMMP. When ‘positive’, linear deposition of IgG, IgA and rarely IgM, individually or in combination, are shown in the BMZ. However, up to 40% of patients may have clinical signs of cicatrizing conjunctivitis but a ‘negative’ biopsy result 12 . Initially, patients affected by OMMP, may report a burning and/or foreign body sensation and photosensitivity suggestive of dry eye disease. Chronic conjunctival inflammation produces flattening of the plica and keratinisation of the caruncle, scarring with shortening of the fornices, symblepharon formation and eventually ankyloblepharon wherein the palpebral and bulbar conjunctiva fuse 13 . Corneal pathology includes superficial punctuate erosions, epithelial defects, and exposure keratitis which may progress to corneal scarring. Eyelid pathology occurs following subepithelial scarring and keratinisation of the eyelid margins and includes blepharitis, trichiasis and entropion. Although often not affecting the vision in the early stages of disease, unchecked progression of OMMP can lead to irreversible vision loss 14 . Its subtle presentation, usually with nonspecific symptoms and conjunctival erythema or ‘injection’ makes its initial diagnosis challenging. Fortunately, treatment with immunomodulatory medications has been shown to be successful in treating OMMP. We describe a patient with OMMP who demonstrated linear deposition of only IgM along the BMZ. Although this is not a new phenomenon, it is far less commonly observed than the deposition of IgG, IgA or C3 4 and literature on its presence, even for extraocular variants of pemphigoid is, as a result, scarce 15 , 16 . Case Presentation A 71 year-old lady was referred to the ophthalmology service with the complaint of ‘gritty’ foreign body sensation in both eyes for six weeks. She had previously had bilateral cataract surgery. She had a past medical history of psoriasis with associated spondyloarthritis, osteoporosis and hypertension. At examination her Snellen visual acuity was 6/6 bilaterally un-aided. There was left lower eyelid entropion secondary to inferior conjunctival forniceal shortening with symblepharon formation. Right lower eyelid symblepharon was also apparent. Punctate corneal epithelial erosions were noted inferiorly at the cornea bilaterally. Bilateral conjunctival biopsies were reserved and left lower eyelid entropion surgery performed wherein the lower eyelid retractors were accessed via a subciliary skin incision and reinserted to the tarsal plate and a lateral tarsal strip used to address horizontal eyelid laxity. Both conjunctival biopsy specimens showed conjunctiva with mixed inflammation of the submucosal tissue. Acute inflammation was demonstrated with neutrophil infiltration of the surface. Linear deposition of IgM at the BMZ was identified by direct immunofluorescence. No IgM monoclonal gammopathy was identified. Mycophenolate mofetil was commenced but gastrointestinal upset prevented its tolerance. Unfortunately, three months post-operatively, recurrence of left lower eyelid entropion was noted. Following discussion with dermatology and rheumatology colleagues, treatment with Adalimumab was ceased and treatment with Rituximab commenced. Repeat left lower eyelid entropion surgery was performed. Unfortunately, the patient developed multiple psoriatic plaques, onchyolysis and experienced a recurrence of joint pain in her hands. Rituximab was ceased and Adalimumab re-commenced along with oral prednisolone 60mg daily for one week and tapered by 10mg every week thereafter to a maintenance dose of 10mg daily. Six months after repeat left lower eyelid entropion surgery, recurrence of the same was not apparent. The patient’s skin, nail and joint disease were again in remission. Discussion Although isolated IgM deposition on the BMZ in patients with OMMP is not a new phenomenon 15 it is far less commonly observed than deposition of IgG, IgA, or C3 and literature on its presence is, as a result, limited. Our case shows linear positivity for IgM along the basement membrane in the absence of similar deposition of IgA, IgG and C3. This is illustrated in Fig. 1 . IgM positive OMMP is a rare clinical entity with only a minority of cases in the literature showing this pattern 14 . Hematoxylin and eosin (H & E) staining of the right eye conjunctiva showing inflammation along the basement membrane is illustrated in Fig. 2 . Figure 3 reveals a series of relevant findings which include left lower eyelid entropion (A) accompanied by right (B) and left (C) eye cicatrizing conjunctivitis with symblepharon formation. A single study investigated the prevalence of IgM along the BMZ of patients with OMMP 14 . A total of 817 patients with documented conjunctival biopsies were identified, with 93 (11.4%) positive for OMMP with linear IgM deposition along the BMZ at direct immunofluorescence or avidin–biotin complex immunohistochemistry evaluation of conjunctival specimens. This suggests that IgM positivity is seen in a minority of patients with OMMP. Very few case reports are present, even for extraocular pemphigoid variants although linear IgM deposition has been seen in dermatoses that include papules, plaques or blisters, all associated with Waldenstrӧm macroglobulinemia 17 – 19 . Immunoglobulin class switching i.e. from IgM, which is produced initially, to IgG and/or IgA, requires an interaction between a CD4 + T helper cell and the antigen specific B cell. This does not occur in patients with immunoglobulin deficiencies or IgM gammopathy such as Waldenstrӧm macroglobulinemia. IgM deposition in various nonlinear patterns has been observed in other autoimmune conditions such as systemic lupus erythematosus, dermatomyositis, and bullous pemphigoid 20 . A case of OMMP with IgM positivity, notable for having concurrent C3 positivity without IgA or IgG has been reported. The authors postulated that, in the absence of immunoglobulin deficiency or monoclonal gammopathy to prevent class switching, such IgM deposition may result from a T cell independent process involving a reaction to a polysaccharide-based antigen rather than a protein itself. Antibody formation against polysaccharide components is T cell independent. B cells are directly activated and so class switching from IgM to IgG and/or IgA is not seen 21 . This patient was treated with Rituximab with some effect. Further investigation into the antigens that precipitate the autoimmune response seen in IgM OMMP is warranted and may provide further insight into the aetiology of this disease 15 . More studies with larger sample sizes will be necessary to investigate the pathophysiologic basis of IgM deposition as compared to the more commonly encountered immune deposits in patients with OMMP 14 . The presence of IgM deposition along the BMZ in patients with OCP may not have a significant effect on treatment and outcomes. That study investigating the prevalence of IgM along the BMZ of patients with OMMP found that most of these patients attained remission at a frequency comparable to those without IgM along the BMZ when treated with immunomodulatory therapy 14 . Most were able to attain durable remission with first-line antimetabolite therapy with other patients achieving remission with other agents also often used in the treatment of OMMP. Put another way, outcomes are comparable for these patients to those of the ‘general’ OMMP patient population 22 , 23 . More studies with larger sample sizes, are necessary however to corroborate these findings 14 . Rituximab is a chimeric mouse-human monoclonal antibody which binds to the CD20 antigen on the surface of B lymphocytes and induces B cell death through antibody dependant cell-mediated cytotoxicity and apoptosis. It leads to rapid and sustained depletion of B cells. In our case, the patient was commenced on six monthly Rituximab infusions following cessation of Adalimumab therapy. Unfortunately, she failed to respond adequately, clinically to this therapy for which a role in the management of refractory OMMP has already been established 24 . Declarations Learning points IgM associated OMMP is a rare clinical entity. This does not appear to have a significant effect on treatment and outcome. Rather, outcomes of immunomodulatory therapy for these patients are comparable to those of the ‘general’ OMMP patient population. Patient consent to publish Written consent to publish this clinical case was obtained from the patient prior to submission. Patient consent to participate Written consent to participate in this clinical case was obtained from the patient prior to submission. Data Availability Statement All data underlying the results are available as part of the article and no further source data are required. Author contributions: RF - wrote the manuscript, edited the manuscript. KV - edited the manuscript, submitted the manuscript. KC - identified the clinical case, provided the images, edited the manuscript. EMcE - identified the clinical case, wrote the manuscript, edited the manuscript. Conflict of interest There are no conflicts of interest reported. Ethics Declaration Galway Research Ethics Committee waived the ethics declaration. Funding Declaration There was no funding required in writing this report. References Thorne JE, Anhalt GJ, Jabs DA. Mucous membrane pemphigoid and pseudopemphigoid. Ophthalmology., Korman NJ. Cicatricial pemphigoid. J Am Acad Dermatol. 2000;43(4):571 – 91; quiz 591-4. Foster CS. Cicatricial pemphigoid. Trans Am Ophthalmol Soc. 1986;84:527–663. Radford CF, Rauz S, Williams GP, Saw VP, Dart JK. Incidence, presenting features, and diagnosis of cicatrising conjunctivitis in the United Kingdom. Eye (Lond). 2012;26(9):1199–208. Chan LS, Ahmed AR, Anhalt GJ, Bernauer W, Cooper KD, Elder MJ, Fine JD, Foster CS, Ghohestani R, Hashimoto T, Hoang-Xuan T, Kirtschig G, Korman NJ, Lightman S, Lozada-Nur F, Marinkovich MP, Mondino BJ, Prost-Squarcioni C, Rogers RS 3rd, Setterfield JF, West DP, Wojnarowska F, Woodley DT, Yancey KB, Zillikens D, Zone JJ. 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Clinical Implications of Direct Immunofluorescence Findings in Patients With Ocular Mucous Membrane Pemphigoid. Am J Ophthalmol. 2017;183:48–55. Foster CS, De La Maza S. Ocular cicatricial pemphigoid review. Curr Opin Allergy Clin Immunol. 2004;4(5):435–9. Philip AM, Stephenson A, Al-Dabbagh A, Ramezani K, Fernandez-Santos CC, Foster CS. Ocular Cicatricial Pemphigoid With IgM-Positive Biopsy. Cornea. 2023;42(12):1503–5. Tazudeen N, Au S, Pewitt J, Tu E, Aronson IK. IgM ocular cicatricial pemphigoid: a unique insight into the immune system. Dermatol Online J. 2015;21(10):13030/qt40z314gz. Baardman R, Horváth B, Bolling MC, Pas HH, Diercks GFH. Immunoglobulin M bullous pemphigoid: An enigma. JAAD Case Rep. 2020;6(6):518–20. Whittaker SJ, Bhogal BS, Black MM. Acquired immunobullous disease: a cutaneous manifestation of IgM macroglobulinaemia. Br J Dermatol. 1996;135(2):283–6. Bernard P, Bazex J. Macroglobulinémie de Waldenström avec activité anti-membrane basale de l'immunoglobuline monoclonale [Waldenstrom's macroglobulinemia with antibasement membrane activity of monoclonal immunoglobulin]. Ann Dermatol Venereol. 1997;124(4):325–8. Chattopadhyay M, Rytina E, Dada M, Bhogal BS, Groves R, Handfield-Jones S. Immunobullous dermatosis associated with Waldenström macroglobulinaemia treated with rituximab. Clin Exp Dermatol. 2013;38(8):866–9. Kulthanan K, Pinkaew S, Suthipinittharm P. Diagnostic value of IgM deposition at the dermo-epidermal junction. Int J Dermatol. 1998;37(3):201–5. Mond JJ, Vos Q, Lees A, Snapper CM. T cell independent antigens. Curr Opin Immunol. 1995;7(3):349–54. Foster CS, Wilson LA, Ekins MB. Immunosuppressive therapy for progressive ocular cicatricial pemphigoid. Ophthalmology. 1982;89(4):340–53. You C, Ma L, Anesi SD, Stephen Foster C. Long-term remission of ocular cicatricial pemphigoid off immunomodulatory therapy. Eur J Ophthalmol. 2018;28(2):157–62. Ruebsam A, Stefaniak R, Worm M. Uwe Pleyer; Rituximab for treatment refractory ocular cicatricial pemphigoid (OCP). Invest Ophthalmol Vis Sci. 2014;55(13):1494. Patient. consent to publish. Written consent to. publish this clinical case was obtained from the patient prior to submission. Patient. consent to participate. Written. consent to participate in this clinical case was obtained from the patient prior to submission. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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1","display":"","copyAsset":false,"role":"figure","size":823470,"visible":true,"origin":"","legend":"\u003cp\u003eA linear band of IgM deposition along the basement membrane in the right eye (A) and left eye (B) conjunctiva.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7693526/v1/7009d521db6934b3afe1b937.png"},{"id":96376967,"identity":"ee71943a-f0be-485e-8cfb-4effcba13d45","added_by":"auto","created_at":"2025-11-20 11:31:42","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1164094,"visible":true,"origin":"","legend":"\u003cp\u003eHematoxylin and eosin staining of right eye conjunctiva showing inflammation.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7693526/v1/7ff12806c9409736a0b618ed.png"},{"id":96376971,"identity":"55698b38-84bb-4d64-a900-216ebe78ceee","added_by":"auto","created_at":"2025-11-20 11:31:42","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":2322755,"visible":true,"origin":"","legend":"\u003cp\u003eLeft lower eyelid entropion (A). Right (B) and left (C) eye cicatrizing conjunctivitis with symblepharon formation.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-7693526/v1/f717fe419bf4605558a10c27.png"},{"id":97684667,"identity":"ab5f10f1-9df8-4fa3-a083-9375970282b5","added_by":"auto","created_at":"2025-12-08 10:07:48","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":5314863,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7693526/v1/420b1983-fca9-4472-9225-557261d6bb65.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"IgM-positive ocular mucous membrane pemphigoid","fulltext":[{"header":"Introduction","content":"\u003cp\u003eMucous membrane pemphigoid (MMP) describes a group of autoimmune \u0026lsquo;blistering\u0026rsquo; disorders that affect, for the most part, mucosal surfaces and, less commonly, skin. Inflammation develops in the oral, ocular, nasal, nasopharyngeal, anogenital, laryngeal, and oesophageal mucous membranes in descending order of involvement \u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. Cutaneous lesions involving the head and upper trunk also occasionally occur. Involvement of both mucous membranes and skin presents with erythema, ulceration, and scarring.\u003c/p\u003e\u003cp\u003eOcular mucous membrane pemphigoid (OMMP) refers to a form of MMP which involves chronic, relapsing-remitting, bilateral, conjunctivitis. It is a rare clinical entity with an incidence between 1 per 10,000 to 50,000 \u003csup\u003e2\u003c/sup\u003e. It is believed however to account for 61% of newly diagnosed cases of cicatrizing conjunctivitis. Females are twice as commonly affected as males. Those affected are usually in the age range 60\u0026ndash;80 years \u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. Approximately 60\u0026ndash;70% of those with OMMP will have more generalized MMP \u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eBoth are type II hypersensitivity reactions with antibody production against extracellular antigens resulting in tissue damage \u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. In OMMP, antibodies produced by activated B cells bind to antigens on the basement membrane of the conjunctiva \u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. Antibodies to beta-4 integrin have been associated with OMMP with antibody levels correlating with disease activity \u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. Other identified antigens include bullous pemphigoid (BP) 180 and several ectodomains of BP180, BP 230, and laminin 332 \u003csup\u003e6 \u0026ndash; 9\u003c/sup\u003e. Antibodies deposit in a linear fashion along the basement membrane zone (BMZ) in conjunction with these antigens. Although IgM is the initial antibody produced by B cells, interactions with CD4\u0026thinsp;+\u0026thinsp;T helper cells and resultant cytokine production lead to immunoglobulin \u0026lsquo;class switching\u0026rsquo; and the production of IgG and IgA \u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. Complement activation and cellular responses including the secretion of interferon-γ and TGF-β and fibroblast activation propagate the response resulting in conjunctival fibrosis and scarring.\u003c/p\u003e\u003cp\u003eConjunctival perilesional biopsy with immunofluorescence \u0026ndash; direct or indirect or immunohistochemistry examinations are used to confirm OMMP. When \u0026lsquo;positive\u0026rsquo;, linear deposition of IgG, IgA and rarely IgM, individually or in combination, are shown in the BMZ. However, up to 40% of patients may have clinical signs of cicatrizing conjunctivitis but a \u0026lsquo;negative\u0026rsquo; biopsy result \u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eInitially, patients affected by OMMP, may report a burning and/or foreign body sensation and photosensitivity suggestive of dry eye disease. Chronic conjunctival inflammation produces flattening of the plica and keratinisation of the caruncle, scarring with shortening of the fornices, symblepharon formation and eventually ankyloblepharon wherein the palpebral and bulbar conjunctiva fuse \u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. Corneal pathology includes superficial punctuate erosions, epithelial defects, and exposure keratitis which may progress to corneal scarring. Eyelid pathology occurs following subepithelial scarring and keratinisation of the eyelid margins and includes blepharitis, trichiasis and entropion. Although often not affecting the vision in the early stages of disease, unchecked progression of OMMP can lead to irreversible vision loss \u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. Its subtle presentation, usually with nonspecific symptoms and conjunctival erythema or \u0026lsquo;injection\u0026rsquo; makes its initial diagnosis challenging. Fortunately, treatment with immunomodulatory medications has been shown to be successful in treating OMMP.\u003c/p\u003e\u003cp\u003eWe describe a patient with OMMP who demonstrated linear deposition of only IgM along the BMZ. Although this is not a new phenomenon, it is far less commonly observed than the deposition of IgG, IgA or C3\u003csup\u003e4\u003c/sup\u003e and literature on its presence, even for extraocular variants of pemphigoid is, as a result, scarce \u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eA 71 year-old lady was referred to the ophthalmology service with the complaint of \u0026lsquo;gritty\u0026rsquo; foreign body sensation in both eyes for six weeks. She had previously had bilateral cataract surgery. She had a past medical history of psoriasis with associated spondyloarthritis, osteoporosis and hypertension.\u003c/p\u003e\u003cp\u003eAt examination her Snellen visual acuity was 6/6 bilaterally un-aided. There was left lower eyelid entropion secondary to inferior conjunctival forniceal shortening with symblepharon formation. Right lower eyelid symblepharon was also apparent. Punctate corneal epithelial erosions were noted inferiorly at the cornea bilaterally.\u003c/p\u003e\u003cp\u003eBilateral conjunctival biopsies were reserved and left lower eyelid entropion surgery performed wherein the lower eyelid retractors were accessed via a subciliary skin incision and reinserted to the tarsal plate and a lateral tarsal strip used to address horizontal eyelid laxity.\u003c/p\u003e\u003cp\u003eBoth conjunctival biopsy specimens showed conjunctiva with mixed inflammation of the submucosal tissue. Acute inflammation was demonstrated with neutrophil infiltration of the surface. Linear deposition of IgM at the BMZ was identified by direct immunofluorescence. No IgM monoclonal gammopathy was identified.\u003c/p\u003e\u003cp\u003eMycophenolate mofetil was commenced but gastrointestinal upset prevented its tolerance. Unfortunately, three months post-operatively, recurrence of left lower eyelid entropion was noted.\u003c/p\u003e\u003cp\u003eFollowing discussion with dermatology and rheumatology colleagues, treatment with Adalimumab was ceased and treatment with Rituximab commenced. Repeat left lower eyelid entropion surgery was performed.\u003c/p\u003e\u003cp\u003eUnfortunately, the patient developed multiple psoriatic plaques, onchyolysis and experienced a recurrence of joint pain in her hands. Rituximab was ceased and Adalimumab re-commenced along with oral prednisolone 60mg daily for one week and tapered by 10mg every week thereafter to a maintenance dose of 10mg daily.\u003c/p\u003e\u003cp\u003eSix months after repeat left lower eyelid entropion surgery, recurrence of the same was not apparent. The patient\u0026rsquo;s skin, nail and joint disease were again in remission.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eAlthough isolated IgM deposition on the BMZ in patients with OMMP is not a new phenomenon\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e it is far less commonly observed than deposition of IgG, IgA, or C3 and literature on its presence is, as a result, limited. Our case shows linear positivity for IgM along the basement membrane in the absence of similar deposition of IgA, IgG and C3. This is illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. IgM positive OMMP is a rare clinical entity with only a minority of cases in the literature showing this pattern \u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. Hematoxylin and eosin (H \u0026amp; E) staining of the right eye conjunctiva showing inflammation along the basement membrane is illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Figure\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e3\u003c/span\u003e reveals a series of relevant findings which include left lower eyelid entropion (A) accompanied by right (B) and left (C) eye cicatrizing conjunctivitis with symblepharon formation.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eA single study investigated the prevalence of IgM along the BMZ of patients with OMMP \u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. A total of 817 patients with documented conjunctival biopsies were identified, with 93 (11.4%) positive for OMMP with linear IgM deposition along the BMZ at direct immunofluorescence or avidin\u0026ndash;biotin complex immunohistochemistry evaluation of conjunctival specimens. This suggests that IgM positivity is seen in a minority of patients with OMMP.\u003c/p\u003e\u003cp\u003eVery few case reports are present, even for extraocular pemphigoid variants although linear IgM deposition has been seen in dermatoses that include papules, plaques or blisters, all associated with Waldenstrӧm macroglobulinemia \u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e \u0026ndash; \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e. Immunoglobulin class switching i.e. from IgM, which is produced initially, to IgG and/or IgA, requires an interaction between a CD4\u0026thinsp;+\u0026thinsp;T helper cell and the antigen specific B cell. This does not occur in patients with immunoglobulin deficiencies or IgM gammopathy such as Waldenstrӧm macroglobulinemia. IgM deposition in various nonlinear patterns has been observed in other autoimmune conditions such as systemic lupus erythematosus, dermatomyositis, and bullous pemphigoid \u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eA case of OMMP with IgM positivity, notable for having concurrent C3 positivity without IgA or IgG has been reported. The authors postulated that, in the absence of immunoglobulin deficiency or monoclonal gammopathy to prevent class switching, such IgM deposition may result from a T cell independent process involving a reaction to a polysaccharide-based antigen rather than a protein itself. Antibody formation against polysaccharide components is T cell independent. B cells are directly activated and so class switching from IgM to IgG and/or IgA is not seen \u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. This patient was treated with Rituximab with some effect.\u003c/p\u003e\u003cp\u003eFurther investigation into the antigens that precipitate the autoimmune response seen in IgM OMMP is warranted and may provide further insight into the aetiology of this disease \u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. More studies with larger sample sizes will be necessary to investigate the pathophysiologic basis of IgM deposition as compared to the more commonly encountered immune deposits in patients with OMMP \u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eThe presence of IgM deposition along the BMZ in patients with OCP may not have a significant effect on treatment and outcomes. That study investigating the prevalence of IgM along the BMZ of patients with OMMP found that most of these patients attained remission at a frequency comparable to those without IgM along the BMZ when treated with immunomodulatory therapy \u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. Most were able to attain durable remission with first-line antimetabolite therapy with other patients achieving remission with other agents also often used in the treatment of OMMP. Put another way, outcomes are comparable for these patients to those of the \u0026lsquo;general\u0026rsquo; OMMP patient population \u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e. More studies with larger sample sizes, are necessary however to corroborate these findings \u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eRituximab is a chimeric mouse-human monoclonal antibody which binds to the CD20 antigen on the surface of B lymphocytes and induces B cell death through antibody dependant cell-mediated cytotoxicity and apoptosis. It leads to rapid and sustained depletion of B cells. In our case, the patient was commenced on six monthly Rituximab infusions following cessation of Adalimumab therapy. Unfortunately, she failed to respond adequately, clinically to this therapy for which a role in the management of refractory OMMP has already been established \u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eLearning points\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIgM associated OMMP is a rare clinical entity.\u003c/p\u003e\n\u003cp\u003eThis does not appear to have a significant effect on treatment and outcome.\u003c/p\u003e\n\u003cp\u003eRather, outcomes of immunomodulatory therapy for these patients are comparable to those of the ‘general’ OMMP patient population.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003ePatient consent to publish\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten consent to publish this clinical case was obtained from the patient prior to submission.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePatient consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten consent to participate in this clinical case was obtained from the patient prior to submission.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data underlying the results are available as part of the article and no further source data\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eare required.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRF - wrote the manuscript, edited the manuscript.\u003c/p\u003e\n\u003cp\u003eKV - edited the manuscript, submitted the manuscript.\u003c/p\u003e\n\u003cp\u003eKC - identified the clinical case, provided the images, edited the manuscript.\u003c/p\u003e\n\u003cp\u003eEMcE - identified the clinical case, wrote the manuscript, edited the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere are no conflicts of interest reported.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics Declaration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eGalway Research Ethics Committee waived the ethics declaration.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding Declaration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere was no funding required in writing this report.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eThorne JE, Anhalt GJ, Jabs DA. Mucous membrane pemphigoid and pseudopemphigoid. Ophthalmology., Korman NJ. Cicatricial pemphigoid. J Am Acad Dermatol. 2000;43(4):571\u0026thinsp;\u0026ndash;\u0026thinsp;91; quiz 591-4.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFoster CS. Cicatricial pemphigoid. Trans Am Ophthalmol Soc. 1986;84:527\u0026ndash;663.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRadford CF, Rauz S, Williams GP, Saw VP, Dart JK. Incidence, presenting features, and diagnosis of cicatrising conjunctivitis in the United Kingdom. Eye (Lond). 2012;26(9):1199\u0026ndash;208.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChan LS, Ahmed AR, Anhalt GJ, Bernauer W, Cooper KD, Elder MJ, Fine JD, Foster CS, Ghohestani R, Hashimoto T, Hoang-Xuan T, Kirtschig G, Korman NJ, Lightman S, Lozada-Nur F, Marinkovich MP, Mondino BJ, Prost-Squarcioni C, Rogers RS 3rd, Setterfield JF, West DP, Wojnarowska F, Woodley DT, Yancey KB, Zillikens D, Zone JJ. The first international consensus on mucous membrane pemphigoid: definition, diagnostic criteria, pathogenic factors, medical treatment, and prognostic indicators. Arch Dermatol. 2002;138(3):370\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKirzhner M, Jakobiec FA. Ocular cicatricial pemphigoid: a review of clinical features, immunopathology, differential diagnosis, and current management. Semin Ophthalmol 2011 Jul-Sep;26(4\u0026ndash;5):270\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eOyama N, Setterfield JF, Powell AM, Sakuma-Oyama Y, Albert S, Bhogal BS, Vaughan RW, Kaneko F, Challacombe SJ, Black MM. Bullous pemphigoid antigen II (BP180) and its soluble extracellular domains are major autoantigens in mucous membrane pemphigoid: the pathogenic relevance to HLA class II alleles and disease severity. Br J Dermatol. 2006;154(1):90\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRashid KA, G\u0026uuml;rcan HM, Ahmed AR. Antigen specificity in subsets of mucous membrane pemphigoid. J Invest Dermatol. 2006;126(12):2631\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTyagi S, Bhol K, Natarajan K, Livir-Rallatos C, Foster CS, Ahmed AR. Ocular cicatricial pemphigoid antigen: partial sequence and biochemical characterization. Proc Natl Acad Sci U S A. 1996;93(25):14714\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBhol KC, Dans MJ, Simmons RK, Foster CS, Giancotti FG, Ahmed AR. The autoantibodies to alpha 6 beta 4 integrin of patients affected by ocular cicatricial pemphigoid recognize predominantly epitopes within the large cytoplasmic domain of human beta 4. J Immunol. 2000;165(5):2824\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLetko E, Bhol K, Colon J, Foster CS, Ahmed AR. Biology of interleukin-5 in ocular cicatricial pemphigoid. Graefes Arch Clin Exp Ophthalmol. 2002;240(7):565\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSacks EH, Jakobiec FA, Wieczorek R, Donnenfeld E, Perry H, Knowles DM Jr. Immunophenotypic analysis of the inflammatory infiltrate in ocular cicatricial pemphigoid. Further evidence for a T cell-mediated disease. Ophthalmology. 1989;96(2):236\u0026ndash;43.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLabowsky MT, Stinnett SS, Liss J, Daluvoy M, Hall RP 3rd, Shieh C. Clinical Implications of Direct Immunofluorescence Findings in Patients With Ocular Mucous Membrane Pemphigoid. Am J Ophthalmol. 2017;183:48\u0026ndash;55.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFoster CS, De La Maza S. Ocular cicatricial pemphigoid review. Curr Opin Allergy Clin Immunol. 2004;4(5):435\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePhilip AM, Stephenson A, Al-Dabbagh A, Ramezani K, Fernandez-Santos CC, Foster CS. Ocular Cicatricial Pemphigoid With IgM-Positive Biopsy. Cornea. 2023;42(12):1503\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTazudeen N, Au S, Pewitt J, Tu E, Aronson IK. IgM ocular cicatricial pemphigoid: a unique insight into the immune system. Dermatol Online J. 2015;21(10):13030/qt40z314gz.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBaardman R, Horv\u0026aacute;th B, Bolling MC, Pas HH, Diercks GFH. Immunoglobulin M bullous pemphigoid: An enigma. JAAD Case Rep. 2020;6(6):518\u0026ndash;20.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWhittaker SJ, Bhogal BS, Black MM. Acquired immunobullous disease: a cutaneous manifestation of IgM macroglobulinaemia. Br J Dermatol. 1996;135(2):283\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBernard P, Bazex J. Macroglobulin\u0026eacute;mie de Waldenstr\u0026ouml;m avec activit\u0026eacute; anti-membrane basale de l'immunoglobuline monoclonale [Waldenstrom's macroglobulinemia with antibasement membrane activity of monoclonal immunoglobulin]. Ann Dermatol Venereol. 1997;124(4):325\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChattopadhyay M, Rytina E, Dada M, Bhogal BS, Groves R, Handfield-Jones S. Immunobullous dermatosis associated with Waldenstr\u0026ouml;m macroglobulinaemia treated with rituximab. Clin Exp Dermatol. 2013;38(8):866\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKulthanan K, Pinkaew S, Suthipinittharm P. Diagnostic value of IgM deposition at the dermo-epidermal junction. Int J Dermatol. 1998;37(3):201\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMond JJ, Vos Q, Lees A, Snapper CM. T cell independent antigens. Curr Opin Immunol. 1995;7(3):349\u0026ndash;54.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFoster CS, Wilson LA, Ekins MB. Immunosuppressive therapy for progressive ocular cicatricial pemphigoid. Ophthalmology. 1982;89(4):340\u0026ndash;53.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eYou C, Ma L, Anesi SD, Stephen Foster C. Long-term remission of ocular cicatricial pemphigoid off immunomodulatory therapy. Eur J Ophthalmol. 2018;28(2):157\u0026ndash;62.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRuebsam A, Stefaniak R, Worm M. Uwe Pleyer; Rituximab for treatment refractory ocular cicatricial pemphigoid (OCP). Invest Ophthalmol Vis Sci. 2014;55(13):1494.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePatient. consent to publish.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWritten consent to. publish this clinical case was obtained from the patient prior to submission.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePatient. consent to participate.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWritten. consent to participate in this clinical case was obtained from the patient prior to submission.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-7693526/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7693526/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e\u003cp\u003eOcular mucous membrane pemphigoid involves chronic, relapsing-remitting, bilateral, cicatrizing conjunctivitis. Antibodies produced by activated B cells bind, in a linear fashion, to antigens on the basement membrane of the conjunctiva. We describe a patient with ocular mucous membrane pemphigoid who demonstrated deposition of only IgM along the conjunctival basement membrane.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eThe case of a 77-year lady with left lower eyelid cicatricial entropion secondary to inferior conjunctival forniceal shortening with symblepharon formation on a background of ocular mucous membrane pemphigoid is described.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eLinear deposition of only IgM and not IgG and/or IgA at the conjunctival basement membrane was identified by direct immunofluorescence.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eIgM associated ocular mucous membrane pemphigoid is a rare clinical entity. Although not a new phenomenon, it is far less commonly observed than the deposition of IgG, IgA or C3. Outcomes of immunomodulatory therapy for these patients are, reportedly, comparable to those of the \u0026lsquo;general\u0026rsquo; ocular mucous membrane pemphigoid patient population.\u003c/p\u003e","manuscriptTitle":"IgM-positive ocular mucous membrane pemphigoid","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-20 11:31:38","doi":"10.21203/rs.3.rs-7693526/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"14062e11-43bc-4aaf-a5f1-833514291c9c","owner":[],"postedDate":"November 20th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-12-08T10:01:59+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-20 11:31:38","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7693526","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7693526","identity":"rs-7693526","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}